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Objectives: To determine the neuroprotective effects of berberine hydrochloride (BBR) against lead-induced injuries on the hippocampus of rats. Methods: Wistar rats were exposed orally to doses of 100 and 500 ppm lead acetate for 1 and 2 months to develop subchronic and chronic lead poisening models, respectively. For treatment, BBR (50 mg/kg daily) was injected intraperitoneally to rats poisoned with lead. At the end of the experiment, the spatial learning and memory of rats were assessed using the Morris water maze test. Hippocampal tissue changes were examined by hematoxylin and eosin staining. The activity of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels as parameters of oxidative stress and antioxidant status of the hippocampus were evaluated. Results: BBR reduced cognitive impairment in rats exposed to lead (P<0.05 or P<0.01). The resulting biochemical changes included a decrease in the activity of antioxidants and an increase in lipid peroxidation of the hippocampus of lead-exposed rats (P<0.05 or P<0.01), which were significantly modified by BBR (P<0.05). BBR also increased the density of healthy cells in the hippocampus of leadexposed rats (P<0.05). Significant changes in tissue morphology and biochemical factors of the hippocampus were observed in rats that received lead for 2 months (P<0.05). Most of these changes were insignificant in rats that received lead for 1 month. Conclusion: BBR can improve oxidative tissue changes and hippocampal dysfunction in lead-exposed rats, which may be due to the strong antioxidant potential of BBR. [ABSTRACT FROM AUTHOR]

Background and Aim: Stressful conditions have become integral to people's lives and are among the destructive factors affecting brain function. These conditions are often more severe and damaging in military environments. Crocin possesses anti-inflammatory, antioxidant, and neuroprotective properties. However, it has limitations, such as instability in varying pH levels, rapid absorption, and low bioavailability. The aim of the study was to enhance the efficacy of crocin by encapsulating it in chitosan and utilizing it as a nanocarrier to treat the effects of chronic stress in a male rat model. Methods: Thirty-five adults male Wistar rats (weighing between 220 and 250 grams) were randomly divided into five groups of seven each: a control group (not exposed to stress or drugs), a stress group (subjected to immobility stress), an immobility stress group receiving crocin nanoparticles (administered 180 mg/kg), a crocin group (administered 6 mg/kg), and a chitosan group (administered 160 mg/kg). The open field test was conducted to evaluate anxiety-like behaviors. Serum oxidative stress factors (GPX, MDA, and CAT) and inflammatory serum factors (IL-6, IL-10, and TNFα) were evaluated using the ELISA method. Additionally, cresyl violet and G-fab staining were performed to assess cell damage in the hippocampus. Results: The findings of this study indicated that stress induction was associated with increased anxiety behaviors, and the administration of crocin nanoparticles can effectively improve these behavioral disorders. Crocin nanoparticles significantly reduced inflammatory factors and oxidative stress and also demonstrated substantial healing effects compared to the crocin (P<0.05) and chitosan (P<0.001) treatment groups. The results of tissue staining revealed that chronic stress significantly decreased the number of neurons in the stained areas, while the administration of crocin nanoparticles mitigated this reduction in cell count in the hippocampus, showing a significant difference compared to the crocin group (P<0.05). Conclusion: Our study demonstrates that crocin encapsulated in chitosan can overcome the limitations of low bioavailability associated with this substance and yields better results compared to the free form of crocin. [ABSTRACT FROM AUTHOR]

Introduction: Physical activity causes cardiac hypertrophy by a non-pathological change in cardiac structure, called physiological hypertrophy. Several molecular changes are involved in this process. Insulin-like growth hormone-1 (IGF-1) is an important hormone involved in hypertrophy of cardiomyocytes. Also, the role of GATA4 as a possible gene involved in cardiac hypertrophy is controversial. Therefore, the present study was conducted to find the effect of aerobic and interval training on IGF-1, GATA4 gene, and cardiac tissue. Methods: Eighteen male Wistar rats (243.72 ± 23.41 g) were randomly divided into control, aerobic, and interval training groups (n = 6). The aerobic group trained for 8 weeks/4 days a week/38 minutes/ 65% of maximum oxygen consumption (VO2 max). The intermittent group trained 8 weeks/4 days a week/5 set/4 minutes/85-90% of VO2 max running with 2 minutes rest between the sets. The weight of the heart and left ventricle, IGF-1 concentration, and GATA4 gene expression were measured 48 hours after the training. The evaluation was conducted with a one-way analysis of variance and Tukey's post hoc test at a significance level of 0.05. Results: The weight of the heart and left ventricle increased significantly in trained groups. IGF1 and GATA4 gene expression increased in both the training groups than the control group. Conclusions: Aerobic and Interval training increases IGF-1, GATA4 gene, left ventricle, and heart weight. Considering the shorter time interval training takes, it seems that interval training is more beneficial than aerobic training. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate the effect of moderate exercise on the healing of acetic acid-induced gastric ulcers in male rats. Background: Gastric ulcers include benign mucosal and submucosal lesions of the gastric wall. Exercise regulates a wide range of physiological processes. Methods: 48 male Wistar rats were randomly divided into three experimental groups (n=16 per group) as follows: control, which was left untreated after causing stomach ulcers; experimental group 1, the rats were first exercised and then received acetic acid; experimental group 2, the rats received acetic acid, and then exercised. The ulcer was caused by injecting 0.12 ml of a 60% acetic acid solution after 24 hours of not eating. The rats had a period of moderate treadmill activity either before or after the development of ulcers, lasting for a duration of 30 days. On the seventh and fourteenth days after the experiment, the rats were sacrificed, their stomach was removed, and the wound healing parameters, and wound depth were determined. Results: Exercise before and after inducing gastric ulcers significantly decreased the depth of gastric ulcers in the experimental groups. The average number of PMN in the control group decreased in comparison to the seventh and fourteenth days following the experiment. Conversely, the number of fibroblasts, epithelialization, and new vessels increased. It seems that exercise before the appearance of ulcers has a greater effect on gastric ulcers compared to exercise after inducing gastric ulcers. Conclusion: Exercise can prepare the gastric mucosa for forthcoming injuries, and heal gastric ulcers. Moderate aerobic exercise has significant restorative effects on gastric ulcers caused by acetic acid and is recommended. [ABSTRACT FROM AUTHOR]

Background: Methamphetamine is a commonly abused drug, and its neurotoxic effects have increased in recent years. There is growing evidence that buprenorphine, a widely used drug for pain management, reduces the harmful effects of addiction and is effective in treating opioid dependence. Objectives: This study aimed to investigate the interaction between methamphetamine and buprenorphine on analgesia and the expression of BDNF and CREB genes in the spinal cords of rats. Methods: In this study, 56 male Wistar rats (200 ± 50 g) were randomly assigned to eight groups: Control, sham, methamphetamine, two buprenorphine groups, two methamphetamine + buprenorphine groups, and a deprivation group. A one-way ANOVA test was used to analyze the data. Results: Intraperitoneal injection of methamphetamine (10 mg/kg) induced analgesia (P < 0.05) and increased CREB gene expression in the lumbar spinal cord (P < 0.01), whereas buprenorphine alone (6 and 10 mg/kg) did not induce significant analgesia or alter BDNF gene expression in the spinal cord. Pharmacological interactions revealed that buprenorphine (6 and 10 mg/kg, i.p.) enhanced the analgesic effect of methamphetamine. Additionally, while the lower dose of buprenorphine reduced methamphetamine's effect on CREB gene expression (P < 0.05), the higher dose potentiated the effect of methamphetamine on BDNF gene expression (P < 0.01) without significantly affecting CREB gene expression. Conclusions: The findings suggest that buprenorphine may enhance the analgesic effects of acute methamphetamine administration and modulate gene expression in the lumbar spinal cord of male Wistar rats. [ABSTRACT FROM AUTHOR]

Objective: Scar tissue formation, as a normal part of wound healing, initiates in the proliferation phase, continues after the remodelling phase, and may cause an unpleasant appearance or disruption in normal functioning. This study investigated the effects of a topical gel on acute wound healing and reducing scars in a rat model. Method: ChitoScar (ChitoTech Company, Iran), a commercial scar-reducing gel based on chitosan, was analysed for antibacterial and antiviral activity through a quantitative suspension test. Its cytotoxic effect was investigated, and then irritation and delayed-type hypersensitivity tests were carried out on rabbits through direct application of the gel. Furthermore, the effect of the chitosan-based gel on wound healing and scar tissue formation was studied in rats with an acute wound in two groups: the treatment group (topical application of the chitosan-based gel); and the control group (without treatment). Histopathological examination was carried out based on the inflammatory cells, collagen fibre, keratinocytes and fibroblasts. Results: Analysis revealed that the chitosan-based gel had no cytotoxicity and caused no erythema, oedema, local or other systemic adverse response. Wound healing occurred earlier in the treatment group, which was a result of a significant increase in re-epithelialisation, angiogenesis, fibroblast population and collagen fibre thickness (p<0.05). In the treatment group, wounds healed completely after 21 days and scars totally disappeared after 28 days, while in the control group, wound healing remained incomplete with distinct scar tissue. Conclusion: The results demonstrated the positive effect of the chitosan-based gel on the duration and quality of the wound healing process, as well as minimising the scar tissue formation in this in vivo study. Declaration of interest: All authors are employees of ChitoTech Company, Iran, but have no other conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Background. Rattus norvegicus (R. norvegicus) population plays a significant role in the spread of numerous diseases in urban environments. The present study is aimed at investigating the presence of Campylobacter jejuni (C. jejuni), C. coli, Clostridium difficile (C. difficile), C. difficile toxigenic, and C. perfringens in R. norvegicus captured from urban areas of Tehran, Iran. Methods. From October 2021 to October 2022, 100 urban rats were trapped in 5 different districts of Tehran, Iran. The genomic DNA was extracted from fecal samples, and the presence of C. jejuni, C. coli, C. perfringens, and C. difficile species was evaluated using PCR assay. Moreover, PCR was used to assess the toxicity of C. difficile isolates. Results. Overall, 30% (n = 30 / 100) of fecal samples were positive for zoonotic pathogens. Based on the PCR on hippuricase (hipO), glycine (gly), CIDIF, and phospholipase C (plc) genes, C. perfringens and C. difficile were isolated from 18.2% (n = 14 / 77) and 5.2% (n = 4 / 77) of male rats. The highest frequency of C. perfringens and C. jejuni was 25% (n = 5 / 20) related to the south of Tehran. Toxigenic C. difficile was not detected in all regions. Conclusion. According to the findings, rats are the main reservoirs for diseases. Therefore, rodent control coupled with the implementation of surveillance systems should be prioritized for urban health. [ABSTRACT FROM AUTHOR]

Background & Objective: The efficacy of escitalopram, a pharmaceutical antidepressant, and exercise, a lifestyle intervention, in mitigating depressive symptoms has been established. This study investigated the impact of varying doses of escitalopram and the combination of forced exercise with escitalopram on stress-induced depressive-like behavior in male rats. Materials & Methods: Sixty-four male rats were allocated into eight groups: control (Co), sham (Sh), depression without treatment (Dep-WT), depression with exercise (Dep-Exe), depression with escitalopram at 10 mg/kg (Dep-Esc10), depression with escitalopram at 20 mg/kg (Dep-Esc20), depression with escitalopram at 10 mg/kg combined with exercise (Dep-Esc10-Exe), and depression with escitalopram at 20 mg/kg combined with exercise (Dep-Esc20-Exe). To induce depression, chronic restraint stress was administered for 6 hours per day over a period of 14 days. Following the stress induction period, rats were administered escitalopram (at doses of 10 or 20 mg/kg, i.p), subjected to treadmill running (20-21 m/min for 1 h/day), or subjected to a combination of both interventions. Depressive-like behaviour induced by stress and locomotor activity were assessed using the forced swimming test (FST) and the open field test (OFT), respectively. Results: In the FST, the immobility time significantly increased in the Dep-WT, Dep-Exe, and Dep-Esc10 groups, while it significantly decreased in the Dep-Esc20, Dep-Esc10-Exe, and Dep-Esc20-Exe groups compared to the Dep-WT group. In the OFT, the central time and total travelled distance significantly decreased in the Dep-WT group. Conversely, central time significantly increased in the Dep-Esc10-Exe and Dep-Esc20-Exe groups, and all treatment groups exhibited a significant increase in central time compared to the Dep-WT group. Conclusion: The findings suggest that combining exercise with escitalopram yields additive effects, representing a promising treatment protocol for anxiety, depression, and locomotor activity. [ABSTRACT FROM AUTHOR]

The combination of hyaluronic acid and iodine (Hyodine) has sparked interest in wound care and could have valuable applications in treating burn injuries. We aimed to provide valuable insight into the potential advantages, limitations, and implications of using Hyodine in burn wound management. We studied 25 male rats to assess the clinical outcomes and wound‐healing effects of Hyodine. Each rat received a deep second‐degree burn wound on their back using metal stamps. Subsequently, the rats were then randomly split into two groups. The first group was treated with a layer of Hyodine gel, while the second group received Vaseline. The burn sites were photographed on days 1, 7, 14, and 21 using a digital camera. After excision of the burn wounds, histopathology slides were stained and evaluated in terms of the degree of epithelialization, angiogenesis, inflammatory cells' infiltration, and collagen amount and arrangement. Despite a non‐significant difference regarding the extent of burn wound area between intervention and control groups in the first day of experiment, the rats that were treated with Vaseline showed a significant decrease compared to those who received Hyodine in the second and third weeks (p = 0.02). On the other hand, epithelialization, pathology score, and collagen synthesis were significantly different between days 7, 14, and 21 of each group. However, collagen arrangement and neovascularization were only significantly different between days 7, 14, and 21 in Hyodine group (p = 0.02 and p = 0.03, respectively). The Hyodine gel may offer beneficial outcomes in patients with a burn wound. Based on our findings, despite a non‐significant difference in the extent of burn wound area, using Hyodine revealed a significant improvement in different histopathological variables including neovascularization, and collagen arrangement. [ABSTRACT FROM AUTHOR]

Objective of the Research: Air pollution is a universal issue and has significant deleterious effects on both human health and also environment. The important indicators of air pollution include ozone (O3), particulate matter (PM), nitrogen dioxide (NO2), and sulfur dioxide (SO2). This research aims to investigate the impacts of ambient air pollution (AAP), SO2, and O3 on oxidative stress parameters, liver tissue histopathology, and expression of some carcinogenesis-related genes in the hepatic tissue of rats. Materials and Methods: 32 Wistar rats were randomly allocated to four groups: the control group, the AAP group, the SO2 group (10 ppm), and the ozone group (0.6 ppm). Over a period of five consecutive weeks, the rats were exposed to the specified pollutants for 3 h daily; liver tissues were harvested and instantly fixed with formalin. Pathological changes were assessed in the tissue samples. Additionally, the RT-qPCR technique was utilized to investigate Expression alterations of BAX, p-53, BCL2, caspase-3, caspase-8 and caspase-9. Furthermore, 30 milligrams of hepatic tissues were extracted to assess the activities of oxidative stress enzymes. Results: The liver catalase and MDA activity were elevated in the air pollution (p <.05). Also, liver GPx activity in air pollution and ozone groups was significant in comparison to the control group (p <.05). The SO2 group exhibited severe lesions in histopathology examinations. Conclusions: The findings revealed an alteration in liver histopathology, an induction of oxidative stress, and the expression of some apoptosis-related genes in hepatic tissues after exposure to AAP, SO2, and O3. [ABSTRACT FROM AUTHOR]

Background: Capecitabine (CAPE), an antimetabolite chemotherapy, can induce hepatic and renal toxicity. Melatonin (MEL), a neurohormone, possesses antioxidant, anti-apoptotic and anti-inflammatory effects. This study investigated the impact of MEL on capecitabine-induced hepatic and renal toxicity. Methods and materials: Twenty-five male Wistar rats were categorized into five groups for the study. The groups included a control group, MEL10 group (rats receiving daily intraperitoneal injections of 5 mg/kg MEL), CAPE 500 group (rats receiving weekly intraperitoneal injections of 500 mg/kg CAPE), CAPE + MEL five group, and CAPE + MEL 10 group. All groups were treated for a duration of 6 weeks. Various hematological, serological, biochemical, and histopathological assessments were conducted to evaluate the objective of the study. Results: The administration of CAPE led to significant liver and kidney toxicity, as evidenced by elevated levels of malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), as well as serological markers including AST, ALT, ALP, BUN, and creatinine. CAPE exposure also resulted in a reduction in total antioxidant capacity (TAC) and glutathione peroxidase (GPx) levels. Histological examination revealed hyperemia in both liver and kidney tissues exposed to CAPE. However, treatment with MEL demonstrated positive effects. MEL administration alleviated oxidative stress, reduced levels of liver enzymes, BUN, and creatinine, and ameliorated histopathological degenerations. MEL also increased GPx and TAC levels. Moreover, MEL treatment aided in restoring the body weight that was lost due to CAPE exposure. Conclusion: Our findings indicated that the administration of MEL in rats significantly reduced the hepatic and renal toxicity induced by CAPE. [ABSTRACT FROM AUTHOR]

Background and Objective: Bisphenol A [BPA; 2,2-bis-(4 hydroxyphenyl) propane] is an environmental estrogenic and endocrine-disrupting compound that exerts its destructive effects through increasing oxidative stress, but the mechanisms underlying this effect have not yet been fully explained. This study evaluates BPA toxicity in muscle cells and the therapeutic potential of adiponectin (APN) and quercetin (QUER). Materials & Methods: Confluent L6 rat muscle cells were exposed to BPA (50 and 100 μM) with APN (10 and 100 ng/ml) and QUER (10 and 25 mM) for 24 and 48 hours. Cell viability, pro-oxidant/antioxidant balance (PAB), catalase (CAT) activity, and KEAP1/Nrf2 gene expression were analyzed using desired methods. Results: BPA in high doses (100 mM) significantly reduced the viability of the muscle cells, while APN and QUER increased cell survival in a time-dependent manner. The effect of QUER also was dose-dependent, while APN in high doses decreased the viability of the muscle cells. APN and QUER also reduced BPA-associated oxidative stress. These changes were significant in the case of QUER. The CAT activity was reduced in BPA-treated cells, which was notably increased with APN and QUER treatment. A decrease in Nrf2 gene expression of BPA-treated muscle cells improved by treatment with QUER and APN in a dose-dependent manner. Conclusion: Our results hinted that APN and QUER could modulate BPA-induced oxidative stress in muscle cells through KEAP1/Nrf2 pathways. Accordingly, it can also be concluded that APN in low doses and QUER may significantly reduce muscle toxicity caused by BPA. [ABSTRACT FROM AUTHOR]

Background & Objective: Toll-like receptors (TLRs) are proteins that play key roles in inflammation. METH and buprenorphine (BUP) both modulate pain, but the exact mechanism underlying their antinociceptive effects is unknown. As a result, the expression of TLR1 and TLR2 genes was examined in METH rats that had been treated with or without BUP. Materials & Methods: A total of 77 rats were classified into 11 subtypes (n = 7): control (saline), BUP 6 or 10 mg/kg, METH (10 mg/kg), METH+BUP 6 or 10 mg/kg, or withdrawal groups. The treatments were intraperitoneally administered for 5 or 14 days. RT-PCR evaluated genes expressed in the brain stem area. Results: The results showed that TLR1 gene expression in the METH group (10 mg/kg; 5 days) considerably improved compared with the control group. Furthermore, BUP injection (10 mg/kg) acutely decreased TLR2 gene expression compared with the METH group. In the METH + BUP (10 mg/kg; 14 days) group, TLR1 expression was higher than in the METH group. The coadministration of METH+BUP (10 mg/kg) acutely decreased TLR2 gene expression compared with METH. Conclusion: There are limited changes in these genes, and their role in METH consumption and inflammation is unclear. Due to the presence of these two genes in the inflammatory pain and addiction signaling pathways, they may have more clear roles in other parts of the nervous system. [ABSTRACT FROM AUTHOR]

Background and Aim: Chronic neuropathic pain is one of the common and debilitating problems of human societies and is a challenge in health care Valerian officinalis has been used in the treatment of pain and anxiety due to its antioxidant effects and multiple mechanisms. Also, the medicinal form of emulsion is studied to increase the bioavailability and absorption of herbal products. The present study was conducted to determine the analgesic and anti-anxiety effects of the oral emulsion of the extract and compare it with the effects of the extract in adult male rats. Methods: First, the oral emulsion of the extract was formulated with the help of similar studies and Design Expert software, and the best formulation was selected. Then, neuropathic pain was induced in the animals with the help of a sciatic nerve chronic obstructive lesion (CCI) neuropathy surgical model. The extract and emulsion were given orally (gastric gavage) to the animals for 30 days, after which behavioral tests were performed, to investigate thermal allodynia, and elevated plus maze (EPM), to investigate induced anxiety behaviors, one day before Induction of neuropathy and on days 2, 4, 6, 10, 14, 21, 30 after neuropathy were investigated, and at the end, the effects of oral emulsion gavage of extract and extract on lipid peroxidation of malondialdehyde (MDA) in brain tissue were investigated and compared. Results: Separate administration of valerian extract and emulsion reduced cold allodynia in all days after CCI surgery compared to the neuropathy group (P<0.05). In addition, CCI surgery caused anxiety in rats. Administration of valerian emulsion and its extract were able to significantly reduce anxiety in the behavioral test of the plusshaped elevated maze. The difference is that this reduction process started earlier with the administration of the extract emulsion (P<0.001). Also, the administration of the extract and emulsion significantly reduced the amount of malondialdehyde in the brain tissue in neuropathic rats compared to the neuropathy group (P<0.001), with the difference that the emulsion of the extract caused a greater decrease in the amount of malondialdehyde compared to the extract. Conclusion: Valerian extract and emulsion have analgesic and anti-anxiety effects. In addition, the administration of valerian emulsion in neuropathic rats has significantly more anti-anxiety and analgesic effects compared to the administration of valerian extract. [ABSTRACT FROM AUTHOR]

Introduction: On average, patients suffering from non-alcoholic steatohepatitis after about seven years, their disease turns into fibrosis and reversibility at this stage becomes very difficult because this disease is an irreversible stage of the disease. Therefore, the effect of eight weeks of high-intensity interval training in water on inflammatory factors in patients with nonalcoholic steatohepatitis was investigated. Methods: In this study, eight-week-old male Sprague-Dawley rats were divided into healthy (n=20) and high-fat diet (HFD) (n=20) groups. After eight weeks and proof of disease induction, the HFD group was randomly divided into two groups: control-disease (n=9) and exercisedisease (n=9); Also, the healthy group was divided into two groups: control-healthy (n=9) and exercise-healthy (n=9). The rats in the training group performed HIIT swimming training, including 20 times of 30 seconds of swimming with 30 seconds of rest between each time, for eight weeks (three days a week). One-way ANOVA and Bonferroni's post hoc test (P<0.05) were used to determine the difference between groups. The proposal of this study has been approved by the Ethics Committee of Shiraz University of Medical Sciences (IR.SUMS.REHAB.REC.1400.008). Results: As shown in diagram 1; Based on the results of the one-way analysis of variance test, it can be said that there was a significant difference between the mean TNF-α blood serum (P=0.001). According to the results of Bonferroni's post hoc test, there was a significant increase in the patient-control group compared to the healthy-control group (P=0.001) and also a significant decrease in the patient-exercise group compared to the patient-control group (P=0.012). Also, a significant decrease was observed in the exercise-healthy group compared to the control-patient group (P=0.001) and the exercise-patient group (P=0.002). Conclusions: The results of the present research showed that high-intensity intermittent swimming exercises reduce inflammatory and fibrotic factors, and in general, it can be concluded that eight weeks of high-intensity intermittent swimming exercises improve the inflammatory and fibrotic factors associated with non-alcoholic steatohepatitis. . However, to obtain a definitive result, this type of exercise should be studied in human studies in this patient community. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the combined effects of resveratrol (RES) and saroglitazar (SARO) on a high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in a rat model. Methods: In this animal study, rats were treated with RES, SARO, or a combination of both. Male rats were fed with an HFD to induce nonalcoholic steatohepatitis (NASH) and then divided into 4 groups: RES treatment, SARO treatment, combined RES and SARO treatment, and no treatment. Various parameters were measured, including body and liver weight, liver enzymes, gene expression of inflammatory markers and reactive oxygen species (ROS), protein expression levels of transforming growth factor-beta (TGF-β) and p-Smad3, and liver histology. Results: The combination of RES and SARO significantly reduced blood and hepatic lipids, attenuated weight gain, and decreased inflammatory cytokine production in a NAFLD study. The combination diminished hepatic lipid accumulation, oxidative stress, and TGF-β1 expression, suggesting antifibrotic effects. Histological evaluations showed antisteatotic and antifibrotic outcomes of the combined treatment. Improved glycemic index, blood lipids, and reduced NASH indicators (i.e., aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) were observed after 6 weeks. The treatment also decreased ROS and NOX family expression, lessening oxidative stress. The inhibition of the TGF-β-Smad3 pathway in HFD-induced rats resulted in reduced NASH(P< 0.05). Conclusions: The results indicated that the group receiving the combination of RES and SARO showed a more efficient reduction in fibrosis and steatosis in the NASH model induced by an HFD than the groups receiving RES or SARO alone. [ABSTRACT FROM AUTHOR]

Exercise is assumed to attenuate age-related neuronal apoptosis, but the detailed mechanism(s) is not fully understood. α1-Adrenergic receptors (ARs) can either trigger or suppress apoptosis, therefore, here we determined the impact of treadmill exercise on the expression of the apoptosis regulatory proteins as well as α1-AR subtypes α1A- and α1B-ARs, in order to elucidate a possible association between apoptosis and the hippocampal expression of α1-ARs in aged male rats. Twenty-one male Wistar rats were divided into 3 groups (n=7): young control, aged sedentary, and aged + exercise. Western blot for α1A- and α1B-ARs as well as pro-(Bax and p53) and anti-apoptotic (Bcl2) proteins was conducted. An 8-week regular moderate-intensity treadmill exercise intervention was carried out in exercise group. In aged rats, α1A-AR expression in the hippocampus was significantly increased, and exercise markedly prevented this event. While α1B-AR expression was no altered with aging, a marked reduction in α1B-AR level was detected in exercise group when compared to aged group. Furthermore, pro-apoptotic protein levels of Bax and p53 were upregulated and anti-apoptotic protein Bcl2 was downregulated in the aging hippocampus, but could be reversed by treadmill exercise. In the present research, exercise-induced reduction in α1A- and α1B-ARs was associated with an obvious downregulation of Bax/Bcl2 ratio in aged rats, suggesting that exercise may inhibit apoptosis through regulating α1-ARs, particularly α1A-AR. Our study suggests that manipulations attenuating α1-AR activity, including nonselective α1-adrenergic antagonists, may protect against hippocampal neurodegeneration in aging brains. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a rapidly progressive neurodegenerative disease characterized by the gradual loss of dopaminergic (DA) neurons in the substantia nigra (SNpc) and reduced DA innervation in the striatum. Objectives: This study aimed to investigate the impact of rilmenidine on DA neurons in the SNpc using a rat model of PD induced by 6-hydroxydopamine. Methods: A total of thirty Wistar rats were randomly assigned to three groups: Sham, lesion, and treatment. In each group, a behavioral evaluation utilizing apomorphine was conducted one week prior to surgery and repeated four weeks after the procedure. In the treatment group, 10 mg/kg rilmenidine was injected intraperitoneally four times a week after surgery. Microscopic examination of the SNpc was performed after the preparation of brain tissue blocks, Nissl staining, photography of slides, and counting of neurons. The number of rotations and neurons in the SNpc were analyzed after surgery using ANOVA and Tukey's test. The number of rotations before and after surgery and the number of cells in the right and left hemisphere were compared using the paired t-test. The significance level was set at P = 0.05. Results: The number of rotations significantly decreased, and the number of neurons in the SNpc significantly increased in the treatment group compared to the lesion group (P = 0.001). Conclusions: Rilmenidine can reduce the neuronal damage induced by 6-hydroxydopamine in the SNpc. [ABSTRACT FROM AUTHOR]

Background: There is considerable evidence suggesting that exposure to bisphenol-A (BPA) may affect the dopaminergic system. Objectives: This study aimed to investigate the effect of pre-and postnatal BPA exposure on the severity of experimental Parkinson's disease in adult male rats. Methods: Four groups of pregnant Wistar rats (200 - 230 g) were used: (1) control; (2) sham (solvent); (3) prenatal BPA (50 µg/rat, 10 days), and 4. pre-and postnatal BPA (from 8 - 30 days). Bisphenol-A or its solvent was injected intraperitoneally into the mothers from days 8 to 18 of gestation and into the neonates from days 10 to 30 of life. Thirty days after birth, eight males were randomly selected from each group. At 120 days after birth, the Parkinson-like behavior of the rats was assessed by injecting 6-hydroxydopamine (6-OHDA) into the right striatum. Results: The outcomes showed that exposure to BPA during embryonic and/or fetal periods, especially concurrently, significantly increased the rate of apomorphine-induced rotations and muscle rigidity compared to the control group and decreased the number of neurons in the substantia nigra. Conclusions: Based on the results, exposure to BPA during the pre- and/or neonatal period affects dopaminergic neurons and can exacerbate the effects of 6-OHDA toxicity. [ABSTRACT FROM AUTHOR]

Background: Although most of the metabolism of local anesthetics (LAs) takes place in the liver, no study has investigated the effect of these anesthetics on the kidney function of single-kidney humans or animals. The present study was conducted to examine the effect of LAs on renal function in single-kidney rats. Materials and Methods: The present experimental animal study with two control groups was done in an animal laboratory. Forty-two rats were randomly assigned to seven groups of six rats, including two control groups and five experimental groups. The experimental groups underwent intraperitoneal anesthesia with 2% lidocaine, 2% lidocaine with 1:80,000 epinephrine, 4% articaine, 3% prilocaine with 0.03 IU Felypressin, and 3% mepivacaine, respectively. Unilateral nephrectomy was done. After 24 h, the rats' blood urea nitrogen (BUN), serum creatinine (Cr), and blood specific gravity (BSG) were measured. A standard dose of anesthetics was injected into the peritoneum for 4 days afterward. Then, these indices were measured again 24 h after the last injection. Data were analyzed using IBM SPSS (version 21.0). One-way analysis of variance, Tukey's honestly significant difference post hoc, and paired t-tests were used for statistical analysis. P < 0.05 was considered statistically significant. Results: The results indicated significant differences among groups in the rats' BUN and serum Cr 24 h after nephrectomy (P < 0.05). However, there were no significant differences in BUN, BSG, and Cr among groups after the interventions. Conclusion: LAs did not affect renal function in single-kidney rats. Therefore, dentists can use the anesthetics in single-kidney people. [ABSTRACT FROM AUTHOR]

Introduction: This study investigates the impact of two high-intensity interval training (HIIT) programs on PGC-1a, p53, and citrate synthase (CS) proteins within cardiomyocytes of male type 2 diabetic rats, aiming to discern potential molecular mechanisms influencing cardiac health. Material & Methods: Twenty-four male Wistar rats were randomly assigned to control (NC), diabetic control (DC), diabetic with type 1 HIIT (HIIT-1), and diabetic with type 2 HIIT (HIIT-2) groups. Streptozotocin (STZ) induced type 2 diabetes, excluding the NC group. A four-week HIIT intervention, six sessions per week, preceded the analysis of heart tissue for PGC-1a, p53, and CS protein levels. Statistical analysis employed GraphPad Prism software version 8 and one-way ANOVA (P < 0.05). Results: Both HIIT-1 (p=0.004) and HIIT-2 (p=0.007) groups exhibited significantly elevated cardiac PGC-1a levels compared to DC. CS levels increased notably in HIIT-1 (p=0.001) and HIIT-2 (p<0.001), with HIIT-2 surpassing HIIT-1 significantly (p=0.010). Concurrently, p53 levels significantly decreased in both HIIT-1 (p=0.005) and HIIT-2 (p=0.001) groups compared to DC. Conclusion: Exercise training (HIIT) positively influences cardiac metabolism, evident in PGC-1a and CS upregulation and p53 downregulation. While these findings provide valuable insights, further exploration is crucial for a comprehensive understanding of the underlying molecular mechanisms. This study advances our understanding of optimizing exercise interventions for improved cardiac health in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background. Cardiac ischemia is the major cause of morbidity and mortality which can be increased by Statins. This study aimed to increase the effectiveness of simvastatin in the form of niosomes. Methods. In this study, 25 male Wistar rats were divided into 5 groups: control, ischemia (induced by closed LAD), ischemia receiving nano-niosomes, ischemia receiving simvastatin, and ischemia receiving simvastatin-loaded nano-niosomes. One month after the drug injection, RNA was extracted from the heart tissue of the studied groups, cDNA was synthesized, and a real-time PCR test was performed using specific primers. SPSS 21.0 software was used for statistical analysis. Analysis of variance was used to investigate the effect of the interventions, and Tukey's post hoc test was used to investigate a significant difference (P<0.05) between the control groups and other groups as well as between intervention groups. Results. Apoptosis and autophagy increased significantly in the ischemia group compared to the control group (P<0.05). In the simvastatin-loaded nano-niosomes group, compared to the simvastatin group, apoptosis and autophagy showed a significant decrease (P<0.05), and also in both simvastatin-loaded nano-niosomes and simvastatin group, compared to the control group, apoptosis and autophagy showed a significant decrease. (P<0.05). Conclusion. Simvastatin is an effective drug in the recovery of cardiac ischemia, but the main problem in using simvastatin is its instability and degradability, and the use of its niosomes form solves this problem properly. Practical Implications. Simvastatin‑loaded nano‑niosomes is more effective in reducing heart ischemia damage compared to simvastatin. [ABSTRACT FROM AUTHOR]

Background & Aims: Pain is divided into two main types, fast and slow. Pain receptors are composed of free nerve endings and use two separate pathways to transmit pain signals to the CNS. Sharp pain signals are produced by mechanical and thermal pain stimuli. These signals are transmitted to the spinal cord by peripheral nerves through Aδ fibers at a speed of 3-15 m/s. On the contrary, slow and chronic pain signals are mainly produced by chemical pain stimuli, but sometimes stable mechanical or thermal stimuli can also produce these signals. These signals are transmitted to the spinal cord by C-type fibers at a speed of 0.5 to 2 m/s (1). The mechanisms of neuropathic pain are not fully known, but the mechanisms proposed in the pathogenesis of this pain include the role of glial cells as supporting cells of the central nervous system, changes in sodium and potassium voltage-dependent channels, afferents adjacent to the neuron. It is damaged. Different neural pathways are affected differently. Therefore, identification of these pathways is important in determining the analgesic and medicinal mechanisms from physiological aspects. Although there are many studies in this field, one of the existing problems is the rate of recovery and return of nerve activity after injury. The results of researchers' research have brought relatively acceptable results, which were not without problems. In the present research, due to the high incidence of peripheral nerve injuries caused by blows and fractures in humans and animals, efforts will be made to find a drug or drug combination to accelerate the healing process of damaged nerves following experimental sciatic nerve injury in the rat animal model. Therefore, the present study will be conducted in order to investigate the analgesic effects of simvastatin and its neurophysiological interaction with the involved systems following experimental sciatic nerve ligation in rats. Methods: This research was used in 2 experimental phases on 85 adult male rats weighing 180-200 grams. These animals were transferred to the laboratory animal breeding and maintenance center of the veterinary school and were kept in standard mouse cages under standard conditions. All animals were evaluated for motor health before surgery, and then all mice were anesthetized by intraperitoneal injection of ketamine hydrochloride (60 mg/kg) and xylazine (10 mg/kg), and after scrubbing and initial leg preparation The animals were placed on their left side and an incision was made in the posterior-external skin of the thigh area of the left leg. The muscles and fascia were gently removed and after exposing the sciatic nerve, the sciatic nerve was compressed for 60 seconds using a micro hemostat. In order to trace, the injury site is marked by suturing the muscle closest to the crush site using non-absorbable silk suture (0-5) and then the muscles are placed together and the subcutaneous tissue and skin are The sequence was stitched using vicryl thread (0-4) and nylon (0-3) in a simple all round and single stitch method. Then formalin test was done and licking time was measured. The animals were divided into 4 groups: group 1: nerve damage without treatment, group 2, 3 and 4 were treated with simvastatin. Mice in group 2 (with a dose of 2 mg/kg), group 3 (with a dose of 4 mg/kg) and group 4 (with a dose of 8 mg/kg) were treated with Sivastatin. There were 5 mice in each group and they were evaluated in two time intervals of 2 and 4 weeks. Results: As seen in Figure 1, the injection of morphine (5 mg/kg) significantly reduced the pain time caused by the formalin test compared to the control group (P<0.05). The level of 4 and 8 mg/kg simvastatin significantly decreased the pain time caused by the formalin test compared to the control group (P<0.05). According to the results of the statistical analysis of repeated measurements of one factor, the summary of the analysis of variance of the changes in the duration of the animal's response to the stimulating effects of formalin affected by the effective dose (8 mg/kg) of simvastatin compared to naloxone during the acute and chronic phases is presented in Figure 2. Naloxone injection (2 mg/kg) had no effect on pain time caused by formalin test compared to the control group (P>0.05). The level of 8 mg/kg simvastatin significantly decreased the pain time caused by the formalin test compared to the control group (P<0.05). The combined injection of naloxone plus simvastatin significantly reduced the analgesic effects of simvastatin compared to the simvastatin alone group (P<0.05). According to the results of the statistical analysis of the repeated measurements of one factor, the summary of the analysis of variance of the changes in the duration of the animal's response to the stimulating effects of formalin affected by the effective dose (8 mg/kg) of simvastatin compared to speroheptadine during the acute and chronic phases is presented in Figure 3. According to the results of the statistical analysis of the repeated measurements of one factor, the summary of the analysis of variance of the changes in the duration of the animal's response to the stimulating effects of formalin affected by the effective dose (8 mg/kg) of simvastatin compared to cimetidine during the acute and chronic phases is presented in graph No. 4 . Conclusion: The aim of this study is the analgesic effects of simvastatin following experimental sciatic nerve ligation in rats. According to the obtained results, it was determined that the analgesic effects of simvastatin are dose-dependent and the findings of this test show that the effective dose (8 mg/kg) of simvastatin alone has been able to create a significant effect in reducing the painful effects of formalin in animals. It has also caused a significant decrease in the response time to formalin pain stimulus in animals. Antagonists naloxone, cyproheptadine and cimetidine were able to inhibit the analgesic effects in acute and chronic phase. Simvastatin activates the PI3K/AKt pathway and increases neurogenesis through BDNF and (Vascular endothelial growth factor) (12). Simvastatin increases the phosphorylation and expression of BDNF and VEGF gene in (Dentate gyrus) DG. As a result, cell proliferation increases and differentiation occurs in the DG area and brain recovery increases (14). Therefore, simvastatin may cause gene expression of growth factors, production of protein kinases, and subsequent induction of neurogenesis in the DG of the hippocampus, increasing dendritic branches through the activation of AKt through the signaling pathway (15). The effects of simvastatin on ischemia-reperfusion injury of the sciatic nerve in adult rats, as a result, administration of simvastatin before ischemia shows protective properties in nerve re-injury and improves blood supply again (16). [ABSTRACT FROM AUTHOR]

Background & Aims: Diabetes mellitus is a disease that, is affected by environment and also genetics. The pathophysiological changes of diabetes are caused by dysfunction of peripheral β cells and ROSdependent inflammation produced by tissues, all of these factors underlie insulin resistance and chronic inflammation, which gradually impairs blood glucose control (1). GATA4 is a cardiac-enriched transcription factor that is essential for various physiological and adaptive responses of cardiomyocytes. Recent studies have shown that GATA4 was able to protect cardiomyocytes from DOX-induced apoptosis, indicating that GATA4 also conveys a survival signal for cardiomyocytes (4). Recent studies have shown that physical activity has a significant effect on improving type 2 diabetes, reducing the risk of insulin resistance, metabolic syndrome and type 2 diabetes, and improving insulin sensitivity (8). Many studies show that by consuming more energy and training intensities, including high-intensity intermittent exercise, there is a greater response to insulin sensitivity throughout the body. During exercise, with muscle contraction and increased AMPK activity, stimulation of insulin sensitivity increases. After exercise, an increase in Akt inactivates TCB1D4 and thus increases the transport of glucose transporter (GLUT4) to the cell membrane, resulting Increases in absorption glucose (9). In recent years, in addition to the emphasis on exercise and physical activity, attention has been paid to dietary supplements and some herbs for the treatment of diabetes, among which there is great interest in the use of honey (15). Honey is primarily rich in carbohydrates and is also abundant in flavonoids and phenolic acids; thus, it is a promising therapeutic antioxidant for various disorders. it is a promising antidiabetic agent. Although the use of honey due to its therapeutic and nutritional value has long been considered and approved in scientific texts, but its use in modern medical sciences is debatable (17). Therefore, considering the known physiological positive effects and protection of the heart, periodic exercise and thyme honey, as well as their positive role in improving cardiac function and the possibility of stimulating GATA4 gene expression in line with positive physiological adaptations of the heart, especially cardiomyocyte hypertrophy, we hypothesized that: 1- HIIT, Thyme honey and The combination of both can be effective in increasing the expression of GATA4 gene in male type 2 diabetic rats. Therefore, the aim of the present study was to investigate the effects of eight weeks of HIIT and thyme honey on GATA4 gene expression in male type 2 diabetic rats. Methods: In this experimental study, 36 young male Wistar rats, as a statistical sample, were purchased from Royan Research Institute and were move to the Razi Laboratory of Azad University of Science and Research. After two weeks of getting acquainted with the laboratory environment and reaching a weight of 197± 20, undergo a high-fat diet (HFD) for 20 weeks on a high-fat diet prepared by the Royan Biotechnology Research Institute, which 45% HFD was given for 3 months and 60% HFD was given for 2 months (20, 21). Then Rats were randomly divided into four groups: control (n=8), HIIT (n=10), thyme honey (n=8) and HIIT*thyme honey (n=10) groups. At the end of the protocol, 28 rats were survived. In each group 2 rats died. To induce diabetes, a high-fat diet is used for 20 weeks and then intraperitoneal injection (25 mg / kg) of STZ solution is used. The HIIT training intervention of 8 weeks, with 2 min running at 80-90% VO2max and 1 min at 50-56% VO2max, was performed for 5 sessions per week including 2 to 8 intervals 16 Up to 34 minutes was done running on a treadmill, so that running time increased from 16 minutes in the first week to 34 minutes in last week. Additionally, during the 8 weeks of intervention, 3 g/kg of diluted thyme honey consumed, 5 days/week in supplement groups, honey and HIIT*honey groups. Cardiac tissue was isolated and transferred to a negative 80 freezer to measure the expression of genes. In the next step, the RNA is extracted by RiboEX Total RNA isolation solution (GeneAll) and finally the quantitative and qualitative study of the RNA by Nanodrop device is evaluated. After ensuring the quality of RNA, it was extracted, cDNA made using the TAKARA kit and transferred to negative 20 freezer . AMPLIQON Master Mix Cybergreen was used for real-time reverse transcription-polymerase chain reaction (real-time RT-PCR). In the present study, the GAPDH reference gene was used as a house keeping gene and the Delta Delta CT method was used to quantitatively analyze the Real Time PCR data. The expression of the GATA4 genes in heart tissue. The primers used in this study were designed by Allel ID6 software and synthesized by Sinaclon Biotechnology Company. The sequence of primers is given in Table 2. Temperature gradient was set. All samples were repeated 2 times in a real-time PCR machine. Also, the temperature and time program of Real Time PCR reaction in the present study is according to Table 3. Data were analyzed using SPSS22 software. Shapiro-Wilk test to determine the normality of data distribution and Levin test for homogeneity of variances and inferential statistics of one-way analysis of variance and tukey post hoc test were used to compare the differences between groups. Significance level in the tests was considered α 05 0.05. Results: According to the results of descriptive statistics, the scores of HIIT in the insulin resistance index are lower than the other groups. Also, the GATA4 scores in the HIIT and Theym honey are higher than the other groups. ANOVA Analysis revealed that there was a significant difference between the groups in the variable of HOMA-IR (P = 0.001) and GATA4 gene expression (P = 0.016).The results of Tukey post hoc test showed that HOMA-IR was significantly decreased only in HIIT group when compared with other groups, whereas this finding was not repeated in other intervention groups (p>0.05).and expression of GATA4 gene was significantly increased in HIIT and Theym honey (p <0.05). Conclusion: The aim of this study was to evaluate the effect of HIIT and thyme honey on insulin resistance index and expression of GATA4 gene in heart tissue of type 2 male diabetic rats. The results of the present study revealed that HOMA-IR were significantly decrease on the HIIT group when compared with others groups, though, there were no significant difference on the insulin resistance index in thyme honey and HIIT*thyme honey groups. These results were consistent with the study of Nova et al. (2017), Farazmandi and Rezaian (1399), Jelstad et al. (2021). also, Su et al. (2011) showed that exercise and physical activity can significantly reduce the insulin resistance index (34). Azimi Dokht et al. (2015) also showed in a study that eight weeks of intermittent exercise has a positive effect on fat profile and insulin resistance in type 2 diabetic men (35). Although, in concern with expression of GATA4 gene there are significantly increase in HIIT group in compared others group, there is no significant difference in the other intervention groups. These results are consistent with the findings of Hemmati et al. (2019), Xu et al. (2018), Naderi et al. (2019), Xiao et al. (2014). Xu et al. (2018) demonstrated GATA4 had a protective effect against endothelial dysfunction induced by hyperglycemia. Overexpression of GATA4 was demonstrated to lead to increased expression of NOX4 mRNA and protein. Furthermore, GATA4 overexpression resulted in increased nitric oxide (NO) production through the upregulation of endothelial NO synthase phosphorylation (38). Exercise imposes a higher cardiac workload, inducing angiogenesis and hypertrophy of cardiomyocytes, and GATA4 triggers this physiological process. However, overexpression of GATA4 is also associated with decompensated cardiac hypertrophy, as it occurs in neuroendocrine overactivation-induced HF. On the other hand, in postnatal hearts, GATA4 is essential for cardiomyocyte survival after injury or stress (38). For years, people have believed that diabetics cannot consume honey because honey is high in sugar. Regarding honey, it should be noted that according to the standard, the acceptable limit for the ratio of fructose to glucose of honey is a minimum of 0.9 (40).Due to the fact that the glycemic index of fructose is very low. These findings show that honey causes fewer changes in blood sugar compared to glucose and can prevent the adverse effects of postprandial hypertension (41) and therefore this ability It increases the expression of GATA4 gene. Therefore, it seems that interval exercise and consumption of thyme honey can be used in type 2 diabetes. [ABSTRACT FROM AUTHOR]

In traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear. Aim of the study: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. The effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. In the fasting state, T. b, S. h , and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90–97% and 80–91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b , S. h , and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b , S. h , and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. The present study supports the traditional use of T. b , E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p , showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models. [Display omitted] • Eryngium bungei , Tragopogon buphthalmoides , and Salvia hydrangea regulated blood glucose levels in hyperglycemic rats. • All extracts showed no signs of acute toxicity. • The extracts suppressed the enzymatic activity of G6Pase, FBPase, and PTP-1B in vitro as possible mechanisms of action. • Phenolic acid and flavonoid glycosides were identified by HPLC-SQ-TOF as the major compounds in three extracts. [ABSTRACT FROM AUTHOR]

Background & Aims: Type 2 diabetes is the most common endocrine disease occurs due to glucose intolerance due to imbalance between reserves and insulin demand. Diabetes can also cause damage and cell death or apoptosis (1, 2).Recent research shows the vital role of p53 in the development of diabetes. The aim of this study was to study changes in p53 gene expression in liver tissue and insulin resistance index after HIIT and Zataria multiflora (Thyme) extract in obese type 2 diabetic rats. Methods: The statistical population of the study consisted of male Wistar rats from Royan Institute. All rats were fed a high-fat diet (45 to 60% fat) for 5 months or 20 weeks. after the Rats became obese and reached an average weight of about 407 ± 50 g, to create a type 2 diabetic model, 25mg/kg STZ was injected intraperitoneally. Rats with fasting glucose between 150 to 400 mg/dl was considered as a criterion for diabetes and all rats were diabetic divided into 4 groups control, HIIT, Thyme, HIIT-Thyme. HIIT protocol, performed for five sessions per week with 2-minute alternation of 2 and 8 intervals with 80 to 90% VO2max and a one-minute rest cycle with 50 to 56% vo2max. Running time increased from 16 minutes in the first week to 34 minutes in the eighth week. Thyme extract was given by gavage at a dose of 200 mg / kg 5 days a week for eight week. At the end of the training period and 48 hours after the last training session, the experimental training groups and after 12 hours of fasting, the rats were anesthetized and sacrificed by ether anesthetic. Blood samples were collected from the heart. Glucose was measured using an auto-analyzer. Insulin measured by a special kit of Pars Azmoun Company. The insulin resistance index was calculated using the formula and the expression of liver tissue P53 genes expression was also measured by RT-PCR. Statistical analyze performed with one-way ANOVA and two-factor analysis of variance test for comparison between groups and determination of the effect size and post-hoc method. Results: According to the results, these findings were observed: The mean weight in the experimental groups of exercise, thyme and HIIT-Thyme groups increased slightly compared to control group. The mean concentration of glucose in the exercise group was significantly lower than the control group (P = 0.001) and also in the HIIT-Thyme group, there was no significant difference (P = 0.99) compared to the thyme group. Moreover, in the Thyme-HIIT group there was a significant decrease (P = 0.001) compared to the control group. Also, HIIT led to a significant reduction in glucose and insulin resistance index (P<0.05). The mean insulin concentration in the HIIT group was significantly higher than the control group (P = 0.005) group and in the HIIT-Thyme group was not significantly different compared to the thyme group (P = 0.218); however, the Thyme group had a significant increase compared to the control group. The mean insulin resistance index in the HIIT group (2.04) and ThymeHIIT was significantly lower than the control group but Thyme group was not significantly different from the control group (P = 0.994).HIIT reduced P53 gene expression in hepatocytes compared with controls (P <0.009). HIIT and consumption of Thyme extract also significantly reduced P53 gene expression in hepatocytes compared with the control group (P <0.05). Conclusion: The P53 gene, which is a tumor suppressor gene, is mutated and inactive in a wide range of cancers, this gene has been given the title of "protector of the genome", now new research shows that this gene has profound effects on metabolism and other Its activation can lead to obesity and type 2 diabetes, and for this reason another name was given to this gene "protector against obesity" (11). While the role of this gene is well known during decades of cancer research, little information is available about its role in metabolism. Previous studies have shown that the role of P53 in metabolism and its function is important for tumor suppression (12), this gene also has effects on heart disease, obesity and type 2 diabetes (13).P53 gene regulates glucose transporters. Maintaining proper function of glucose transporters is crucial in glucose homeostasis and suppression of diabetes (11). P53 regulates the function of glucose transporters by influencing their transcription and transport. For example, p53 activated by genotoxic stress can directly bind to GLUT1 and GLUT4 promoters and repress their transcription. P53 also suppresses GLUT3 expression, but this occurs through an indirect mechanism by inhibiting IkB kinase or IKK (11). P53 gene negatively regulates glycolysis. It affects glucose levels by directly regulating degradation (glycolysis) and synthesis (gluconeogenesis). Following DNA damage, p53 can reprogram the cell's energy production strategies from glycolysis to mitochondrial respiration (or oxidative phosphorylation) in order to suppress tumor progression (11). The first p53 target gene identified to inhibit glycolysis is TIGAR (TP53-induced glycolysis and apoptosis regulator) (30). TIGAR overexpression reduces the level of fructose 2, 6-bisphosphate (Fru-2, 6-P2), which activates the glycolysis promoter PFK1 (6-phosphofructo-1-kinase). P53 also regulates the stability of phosphoglycerate mutase (PGM), another enzyme important for the completion of glycolysis through the conversion of 3-phosphoglycerate (3-PG) to 2- phosphoglycerate (2-PG). It has been shown that the pentose phosphate pathway (PPP), an alternative mechanism for glucose consumption for energy production, is partially blocked by p53 through a direct interaction between p53 and its rate-limiting enzyme, glucose 6-phosphate dehydrogenase (G6PD). 30). P53 also negatively regulates pyruvate dehydrogenase kinase-2 (PDK2) through both transcriptional and post-translational mechanisms to activate the PDH complex that converts pyruvate to acetyl-CoA to shift the balance from glycolysis to mitochondrial respiration (28, 31). The results of the present study show a significant decrease in the expression of the P53 gene in the liver tissue in the intense interval training group, and also the decrease in the expression of this gene in the interaction group of interval training - thyme can indicate the effect of interval training on the decrease in the expression of the P53 gene in the liver tissue. According to the mentioned regulatory pathways, but in the thyme group alone, no significant decrease in the expression of this gene was observed, which can be inferred that when using thyme extract to use its medicinal, antioxidant and anti-inflammatory properties, performing periodic exercises its effectiveness can be improved by further reducing the expression of the P53 gene. Suppression of hepatic glucose production by reducing the expression of the P53 gene can effectively improve diabetes and be used to treat it, in a way, it can be said that targeting components in the gluconeogenic pathway can improve hyperglycemia (10, 11). HIIT with thyme extract in diabetic rats led to improved glycemic profile and changes in glucose and insulin levels, as well as positive and appropriate changes in the expression of P53 gen expression in hepatic tissue. [ABSTRACT FROM AUTHOR]

Background: Heart rate variability (HRV) is calculated by electrocardiography (ECG-HRV) or blood pressure (BP-HRV). The purpose of this study was to determine the validity of the above methods in rats with normal and ischemic hearts during the baroreflex maneuver. Methods: The study was conducted at Shiraz University of Medical Sciences, Shiraz, Iran, in 2021. Sprague-Dawley rats were divided into a sham group and an isoproterenol-mediated cardiac ischemia (ISO) group. Saline and isoproterenol (150 mg/kg) injected subcutaneously for 2 consecutive days in the sham and ISO groups, respectively. Then, the animals were anesthetized with an intraperitoneal injection of sodium thiopental (60 mg/kg), and the femoral artery and vein were cannulated. Baroreflex was activated using an intravenous injection of phenylephrine (10 µg/100 µL saline). ECG, BP, and heart rate (HR) were recorded, and the time domain of HRV and baroreflex gain were calculated. Results: Baroreflex gain in the ISO group (male, weight=275.8±2.8 g, n=8) was lower than that in the sham group (male, weight=258±2.3 g, n=8) (P<0.05). ECG-HRV indicated an increase in the standard deviation of the RR interval (SDRR), the index of overall HRV, and the parasympathetic index of the root mean square of successive differences (RMSSD) in both groups. However, the rise in SDRR and RMSSD in the ISO group was less than that in the sham group (P<0.05). SDRR and RMSSD obtained from BP did not show a difference between the sham and ISO groups, nor did they correspond with the results seen in baroreflex gain. Conclusion: BP-HRV was not as valuable as ECG-HRV in assessing cardiac ischemia. [ABSTRACT FROM AUTHOR]

Background and Aim: Zhumeria majdae, a unique native plant of southern Iran, has been traditionally used to treat various health issues. Preclinical studies suggest its therapeutic potential for immunological and inflammatory disorders. This study investigates the effect of Z. majdae essential oil (ZMEO) on TNBS-induced colitis in rats, focusing on the NF-κB/p38 MAPK/Nrf-2 pathway., Experimental Procedure: Forty-eight male Wistar rats were used, with all groups except the sham group receiving a single intra-rectal dose of TNBS. Three different doses of ZMEO and also 1 mg/kg dexamethasone were administered orally for 2 weeks. Colon tissue was analyzed for ulcer index, histological changes, inflammatory cytokines, apoptotic factors, and levels of NF-κB, p38 MAPK, and Nrf-2., Key Results: GC-mass analysis identified 25 compounds with linalool (52.01%) and camphor (31.01%) as the major compounds in ZMEO. ZMEO ameliorated colon injuries, reduced ulcer index, and prevented the elevation of pro-inflammatory cytokines and pro-apoptotic proteins. It also increased the levels of IL-10 and Bcl-2 proteins. Furthermore, ZMEO decreased the expression of p-NF-κB and p38 MAPK while increasing the expression of pNrf-2., Conclusions: ZMEO mitigates colon damage associated with IBD by suppressing inflammatory cytokines and pro-apoptotic proteins possibly through modulating the NF-κB/p38 MAPK/Nrf-2 signaling pathway., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Although a substantial body of research suggests curcumin (CUR) has the preventive potential in memory impairment, the mechanism by which CUR prevents memory loss is still being investigated. This study employs an inhibitory avoidance (IA) model to investigate whether CUR can prevent morphine (Mor)-induced memory impairment as well as the possible role of cAMP-response element binding (CREB) protein, and nitric oxide (NO) signaling in this mechanism. Methods: This experimental study was conducted at the Animal Lab of the Physiology Research Center, Kashan University of Medical Sciences (Kashan, Iran) in 2018. Forty rats were randomly divided into four groups: control, CUR (pretreatment gavage of CUR [10 mg/Kg] for 35 days), Mor (7.5 mg/Kg, i.p.), and CUR+Mor (n=10 per group). Following the evaluation of the IA memory and locomotor activity of the animals, the CREB protein expression in the hippocampus and NO metabolites (NOx) level in the brain tissue were also investigated. The data were analyzed using Sigmaplot software (version 14.0) by using the ANOVA, Kruskal-Wallis, Holm-Sidak, and Dunn's post hoc tests. P<0.05 was considered to be statistically significant. Results: In the Mor group, the IA memory of the rats was significantly impaired (P=0.001). CUR prevented the Mor-induced IA memory impairment (P=0.075). While the Mor treatment decreased the phosphorylated CREB (p-CREB) expression, the CUR+Mor cotreatment increased p-CREB expression (P=0.010). Nevertheless, the Mor treatment increased the total CREB expression (P=0.010). The NOx concentration in the brain tissue was decreased following the Mor treatment (P=0.500) but increased after the CUR+Mor cotreatment (P=0.001). Conclusion: The present findings suggest that CUR prevents the memory impairment of rats, possibly through NO and its downstream CREB signaling. [ABSTRACT FROM AUTHOR]

Objective: For a long time, natural compounds have been used to accelerate wound healing. In this study, the topical effects of ammoniacum gum extract on wound healing were investigated in white male rats. Method: Following skin wound induction in aseptic conditions, 48 Wistar rats were divided into six equal groups; phenytoin cream 1% (standard), untreated (control), Eucerin (control), and 5%, 10% and 20% ointments of Dorema ammoniacum gum extract (treatment groups). All experimental groups received topical drugs daily for 14 days. The percentage of wound healing, hydroxyproline content, histological parameters, and growth factors (endothelial growth factor (EGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-α) were measured in experimental groups. Results: The areas of the wounds in the treatment groups were significantly decreased compared with the wound areas of control groups at 5, 7 and 10 days after wounding. On the 12th day, the wounds in the treatment groups were completely healed. Hydroxyproline contents were significantly increased in the treatment groups compared with the control groups (p<0.001). In histological evaluation, the re-epithelialisation, increasing thickness of the epithelial layer, granulation tissue and neovascularisation parameters in the treatment groups showed significant increases compared with the control groups. Also, serum levels of TGF-β, PDGF, EGF and VEGF in the treatment groups were significantly increased compared to the control groups. Conclusion: The topical application of ammoniacum gum extract significantly increases the percentage of wound healing in rats and reduces the time of wound closure. [ABSTRACT FROM AUTHOR]

Introduction: Tissue dysfunction might be the result of reactions between free radicals and cell membranes. The purpose of this study was the evaluation of cell vulnerability and assessment of the effect of intense intermittent exercise and curcumin supplementation on apoptotic and antiapoptotic factors in Wistar rats. Materials and Methods: For the study, 60 adult male Wistar rats were randomly divided to 5 groups (n = 8) of saline, hydrogen peroxide (H2O2), high intensity interval training (HIIT) + oxygenated Water, Curcumin Supplement + Oxygenated Water, and HIIT + Curcumin Supplement + Oxygenated Water. Rats were treated with H2O2 in the amount of 1 mmol/kg of body weight three times a week on even days and curcumin, 150 m g/kg of body weight, daily. Treadmill running program was performed for 8 weeks. Real-time PCR was applied to assess Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2) genes expression. Data were analyzed by using the Two-way ANOVA. Results: The induction of oxidative stress by H2O2 increased expression of Bax, and decreased expression of Bcl-2 in hippocampus of rats (P = 0.0001). HIIT and curcumin supplementation decreased expression of Bax, and increased expression of Bcl-2, Also, decreased the Bax/Bcl-2 ratio (P = 0.0001). [ABSTRACT FROM AUTHOR]

Introduction. The importance of women's health and the quality of life after menopause is a critical issue. To prevent disability and menopause complications as well as avoid the side effects of hormone replacement therapy (HRT), in this study, licorice hydroalcoholic extract (Glycyrrhiza uralensis roots) was evaluated as a natural remedy. Methods. Seventy-two female Sprague-Dawley rats were divided into six groups: control group, Sham-operated group, Glycyrrhiza (Gly) 30% group, and ovariectomized group as well as two ovariectomized groups treated with Gly 10% and Gly 30%. Normal saline and different treatments were administered orally for 8 weeks. At the end of the study, calcium, alkaline phosphatase, estrogen, and progesterone levels in the ovariectomized rats were determined. Moreover, the stereological and histopathological changes in uterine tissue in all groups were determined. Phytochemical analyses were also performed to determine the total phenolic content and antioxidant potential of the extract. Result. The hydroalcoholic extract of licorice root exhibited considerable effect to improve calcium, estrogen, and progesterone levels in the ovariectomized rats. Also, hydroalcoholic extract of licorice root successfully decreases the amount of alkaline phosphatase (ALP) level. The stereological and histopathological findings confirmed the therapeutic potential of this extract. The considerable effects of hydroalcoholic extract of licorice root could be due to high amounts of phytoestrogens with similar estrogen-like structures. Considerable total phenolic content and antioxidant activity were also seen in licorice root extract. Conclusion. Hydroalcoholic extract of licorice root due to containing high amounts of phytoestrogens with similar chemical structures to estradiol notably improves biochemical parameters as well as stereological and histopathological markers of uterine tissues in ovariectomy rats, so it could be a potential agent for prevention and/or treatment as hormone replacement therapy in healthy middle-aged and/or older women. [ABSTRACT FROM AUTHOR]

Background: Cirrhotic cardiomyopathy is a well-recognized cardiac dysfunction in cirrhotic patients. Studies have confirmed the protective effects of silymarin in different types of cardiac injury. This study aimed to examine the effectiveness and molecular mechanism of silymarin against myocardial dysfunction and hypertrophy in a rat model of cirrhosis. Methods: The experiment was performed at Alborz University of Medical Sciences (Karaj, Iran) during 2020-2021. Thirty- two male Wistar rats were randomly divided into four groups of Sham-operated (control group for surgical procedures), Bile Duct Ligated (BDL), and two Silymarin extract (SE)-treated groups of 300 and 600 mg/Kg/day. After 28 days, serum levels of AST, ALT, GGT, and ALP, liver histopathological status, as well as cardiac mechanical function, were assessed. Cardiac β1-adrenergic receptors (β1-AR), L-type voltage-dependent calcium channels (L-VDCC), and GATA4 mRNA expression were also determined using real-time RT-PCR. Data analysis was performed using the one-way ANOVA followed by Duncan's multiple range test. Histological data has been analyzed with Kruskal-Wallis nonparametric test. The analysis was performed at P≤0.05. Results: BDL was associated with a significant elevation in serum AST, ALT, GGT, and ALP, development of necrosis and fibrosis of the liver texture, increased Heart Weight and Heart Weight to Body Weight ratio, enhanced cardiac mechanical function as well as a significant up-regulation of ventricular β1-AR and L-VDCC. Administration of SE600, but not SE300, significantly reduced the serum levels of the enzymes and alleviated signs of liver necrosis and fibrosis. Cirrhotic-induced cardiac dysfunction was also restored by SE600, but not by the lower dose. In addition, cardiac expression of the β1-AR and L-VDCC was down-regulated toward normal values by either higher or lower doses of the SE. Conclusion: Silymarin treatment in higher dose attenuated cirrhosis-associated cardiac remodeling and reduced cardiac mechanical dysfunctions. [ABSTRACT FROM AUTHOR]

Background: The lateral hypothalamus (LH), which produces orexin, is vital for body solution homeostasis. Lateral hypothalamus (LH) lesion causes adipsia and its stimulation increases water intake. Objective: This study aimed to investigate the effect of an intracerebroventricular (ICV) injection of orexin-A (OXA) on water-drinking behavior in water-deprived rats. Metods: A total of 32 male Wistar rats (220-250 g) were used and divided into 4 groups, control (no injection), vehicle (Normal saline, 5 µL), OXA (30 µg/rat), SB-334867 (OXA receptor selective antagonist, 30 µg/rat). After the microinjection of drugs or vehicles in the right lateral ventricle, each rat was placed individually into the metabolic cage and the amount of water intake, the delay time for the first water intake, and the referral number for water intake were recorded for 4 h. Findings: This study showed that ICV administration of OXA increased both water intake and the referral number for water intake in water-deprived animals (P<0.05). On the other hand, ICV administration of SB-334867 decreased water intake compared to vehicle and control groups. Conclusion: It can be concluded that OXA has a regulatory role in water drinking behavior in water-depriving states. [ABSTRACT FROM AUTHOR]

Background: The Paraventricular Hypothalamic Nucleus (PVN) coordinates autonomic and neuroendocrine systems to maintain homeostasis. Microinjection of angiotensin II (AngII) into the PVN has been previously shown to produce pressor and bradycardia responses. Anatomical evidence has indicated that a substantial proportion of PVN neurons is connected with the neurons in the central amygdala (CeA). The present study aimed to examine the possible contribution of the CeA in cardiovascular responses evoked by microinjection of AngII into the parvocellular portion of PVN (PVNp) before and after microinjection of cobalt chloride (CoCl2) into the CeA. Methods: The experiments were conducted at the Department of Physiology of Shiraz University of Medical Sciences, from April 2019 to November 2019. There were two groups of 21 eight-week-old urethane anesthetized male rats, namely saline (n=9 rats) and AngII (n=12 rats) groups. Drugs (100 nL) were microinjected via a single-glass micropipette into the PVNp and CeA. Their blood pressure (BP) and heart rate (HR) were recorded throughout the experiments. The mean arterial pressure (MAP) and heart rate (HR) were compared to the pre-injection values using paired t test, and to those of the saline group using independent t test. Results: Microinjection of AngII into the PVNp produced pressor response (P<0.0001) with no significant changes in HR (P=0.70). Blockade of CeA with CoCl2 attenuated the pressor response to microinjection of AngII into the PVNp (P<0.001). Conclusion: In the PVNp, Ang II increased the rats' blood pressure. This response was in part mediated by the CeA. Our study suggested that these two nuclei cooperate to perform their cardiovascular functions. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes is a major risk factor for cardiovascular diseases. Endurance training and empagliflozin were reported to have notable effects on heart structure and function. This study aimed to investigate the effect of six weeks of endurance training and empagliflozin intake on some structural and functional indicators of the heart in diabetic male rats. Material & Methods: In this study, a total of 40 male Wistar rats (mean±SD weight: 253.09±12.92 g, aged: 8-10 weeks) were randomly divided into five equal groups, 1) healthy control, 2) diabetic control, 3) diabetic+empagliflozin, 4) diabetic+endurance training, and 5) diabetic+endurance training+empagliflozin and kept in laboratory conditions. Induction of diabetes was performed in rats after completion of the familiarization protocol for two weeks and after 12 h of food deprivation by intraperitoneal injection of streptozotocin (STZ) solution at a dose of 50 mg /kg. The glucose level of 300 mg/dL was considered diabetic. The training groups practiced endurance training, five days per week for six weeks. The drug groups also received empagliflozin (10 mg/kg) daily by gavage. The animals were anesthetized 48 h after the end of the protocol and cardiac function was recorded using echocardiography. Subsequently, cardiac tissue was isolated and dissected. One-way analysis of variance (ANOVA) and Kruskal-Wallis tests were used for statistical analysis of data in SPSS software (version 27) and Graph Pad Prism software (version 9). (Ethic code: LU.ECRA.2021.63) Findings: The results showed significant differences between study groups in terms of left ventricular end-systolic thickness (P=0.011) and left ventricular end-systolic volume (P=0.008). The results of the post-hoc test showed that left ventricular end-systolic thickness in the diabetic control group was significantly higher, compared to the healthy control group (P=0.012). On the other hand, left ventricular end-systolic thickness in diabetes+exercise+empagliflozin was significantly lower, compared to the diabetic control group (P=0.020). Moreover, left ventricular end-systolic volume in the diabetic control group was significantly higher, compared to healthy controls (P=0.006), and left ventricular end-systolic volume in the diabetes+exercise+empagliflozin group was significantly lower than that in the diabetic control group (P=0.017). No significant differences were observed in other structural and functional indices of the heart (P≥0.05). Discussion & Conclusion: The results of the present study showed that the combination of empagliflozin use and endurance training has a positive impact on the structure and function of the heart compared to the adoption of each (empagliflozin use and training) alone. [ABSTRACT FROM AUTHOR]

Background & Aims: One of the tissues that is affected by physical activity is bone. Bone is one of the tissues that needs to receive mechanical load to have normal function as a key factor in strengthening bone mass (2). Evidence shows that the mechanical load resulting from physical activity activates a set of proteins involved in the process of osteoblast activation and inhibits osteoclasts. One of these proteins is osteonectin. It is commonly used as a serum marker of osteoblastic bone formation and is believed to regulate minerals in the bone matrix, but now new genetic and pharmacological evidence also points to the hormonal role of this protein (5). Osteopointin, on the other hand, accounts for about 2% of non-collagenous bone proteins and is synthesized mainly by osteoblasts as well as bone-forming cells, bone cells and other hematopoietic cells in the bone marrow (7). Another important factor in the ossification process is ALP, a membrane-bound tetrameric enzyme found in the plasma membrane of osteoblasts. This substance plays an important role in the formation of osteoids and mineralization by degrading enzymes inhibiting minerals, pyrophosphate at alkaline pH (8). Also, due to their active phytochemical compounds, medicinal plants can affect the formation and destruction of bone tissue through various mechanisms. One of the plants used in traditional medicine for various therapeutic purposes is palm tree pollen. This plant is used to improve infertility and impotence in men and women. Phytochemical compounds such as estrone, α-amirin, triterpenoidal, saponins, flavonoids, estrone, estradiol and estriol are abundant in this plant (15). Therefore, the researcher seeks to answer the question whether resistance training and date pollen extract affect bone tissue density and osteoblast cell proliferation in young males? Methods: For the present experimental study, 36 8-week-old male rats with a weight range of 220 20 20 g were purchased from the Pasteur Institute of Iran and randomly divided into 6 groups: 1) sham, 2) exercise, 3) palm pollen, 4) testosterone. 5) Exercise + palm pollen and 6) Exercise + Testosterone were divided. After one week of adaptation, groups 2, 4 and 6 performed resistance training for four weeks and five sessions per week. Groups 3 and 5 performed 100 mg / kg of date fertilization pollen five days a week. Gavage was also given. Groups 4 and 6 also received 2 mg / kg of testosterone propionate per week peritoneally. Finally, descriptive statistics, Shapiro-Wilk test, two-way analysis of variance and Benferroni post hoc using SPSS software at a significance level of p <0.05 were used for statistical analysis of data. Results: The results showed that resistance training and drug administration significantly increased osteocalcin gene expression, ALP concentration, ALP gene expression and osteopontin and osteogenesis of femoral bone tissue. Although the highest expression of osteocalcin gene was observed in the group of resistance training and date palm pollen or testosterone enanthate, but the interaction of these two interventions was not statistically significant. It was also found that resistance training (palm pollen and testosterone enanthate) significantly reduced serum ALP. The interaction of these two interventions on serum ALP concentration was significant. Simultaneous resistance training and medication enhanced the reducing effect of each intervention. Conclusion: In this study, due to resistance training, osteocalcin, osteopontin, ALP, RUNX2 gene expression, ALP protein expression and osteogenesis were significantly increased. While serum ALP showed a significant decrease. The expression of bone matrix proteins, alkaline phosphatase, and osteocalcin appears to increase with the differentiation of osteoblasts, which may lead to bone mineralization and formation. Another reason for the increased expression of acetocalcin gene in this study can be explained by the change in cytokine changes caused by resistance training, especially interleukin-6. Much of IL-6 has been reported to be secreted into the bloodstream from muscle during physical activity, an increase that is essential for increasing physical function capacity. IL-6, on the other hand, triggers signals in osteoblasts to stimulate osteoclast differentiation and the secretion of the bioactive form of osteocalcin into the bloodstream. In general, an increase in interleukin-6 is necessary to increase circulating osteocalcin levels during physical activity (28). Another mechanism of increased expression of osteocalcin gene induced by resistance training in this study can be explained based on the effect of resistance training on oxidative stress. Evidence suggests that regular resistance training can increase antioxidant capacity and reduce oxidative stress (29). On the other hand, increasing oxidative pressure can reduce the process of osteoblast differentiation by activating apoptotic processes in bone (30). In the present study, resistance training increased the expression of osteopontin gene. Along with osteocalcin, acetaminophen is involved in the organization of the extracellular matrix, the coordination of bone cell interactions with the extracellular matrix, and the matrix minerals. Both proteins also play a structural role in bone and determine the tendency of bone to break. As a result, these proteins may regulate the structure and morphology of the entire bone and affect the mechanical properties of bone (36, 37). Like osteocalcin, the mechanical load resulting from resistance training appears to stimulate the expression of the osteopontin gene. It has been shown that the application of mechanical load on bone increases the periosteal of bone by increasing the activation of bone formation processes. In these conditions, mechanical load can stimulate both gene expression and ALP protein expression by activating adult osteoblasts and increase They become (26). On the other hand, date palm extract could increase the expression of the studied genes and the process of osteogenesis. The effect of date palm extract on increasing gene expression of osteocalcin, osteopontin, alkaline phosphatase and osteogenesis can be examined from two perspectives. The first view is the effect of this extract on the motility of LH followed by stimulation of testicular Leydig cells to produce and secrete circulating testosterone. Numerous studies have reported stimulation of testosterone secretion after induction of date palm pollen (45, 46). The view on the effect of date pollen extract on the process of outcomes measured in this study is the antioxidant and anti-inflammatory role of the compounds in this plant material (47, 48). As mentioned about the antioxidant and anti-inflammatory effect of physical exercise and its role on acetoblasts, increasing oxidative stress and inflammation has an inhibitory effect on the differentiation and proliferation of osteoblasts (30). Induction of date palm pollen extract in this way can develop the process of bone formation. [ABSTRACT FROM AUTHOR]

Background & Aims: There is a close relationship between obesity and type 2 diabetes, so that the risk of developing type 2 diabetes in obese people is higher than people with normal weight (2, 3). Both type 2 diabetes and obesity are associated with changes in the body's metabolism, which is a determining factor in the development of insulin resistance (4, 5). Studies show that adipose tissue is a central metabolic organ in regulating energy homeostasis throughout the body and plays an important role in the development of insulin resistance and type 2 diabetes (6). It also secretes various hormones, cytokines, and metabolites that control systemic energy balance by regulating appetite signals from the central nervous system and metabolic activity in peripheral tissues (8). One of the peptide hormones expressed by various body tissues, including adipose tissue in animal and human samples, is adropin, which is involved in energy homeostasis, metabolic adaptation, and modulation of insulin sensitivity and obesity (9). Increased adropin levels have been reported following aerobic exercise (17). also, Abbasian et al. (2016) observed increase in serum adropin levels in overweight and obese men after 8 weeks of intense intermittent exercise (18). However, in the study of Alizadeh et al. (2015) following a session of aerobic exercise, no significant change in glucose and adropin factors was observed in overweight women (19). The effects of exercise training on changes of factors involved in energy metabolism in obese diabetic subjects have been less studied, therefore, the present study intends to investigate the question of whether six weeks of aerobic training affect the on adipose tissue energy homeostasis index in obese diabetic rats? Methods: This is an experimental study. This research was conducted on Wistar rats at Islamic Azad University, Marvdasht Branch. 32 obese male wistar rats (weight 320±20 gr) after induction of diabetes randomly were divided into 4 groups including obese control, shem (obese), obese diabetic, obese aerobic training - obese diabetic. Rats were exposed to a high-fat controlled diet in the form of pellets for 4 weeks to gain weight (20). In this study, the rats were type 2 diabetic using peritoneal injection nicotinamide-STZ (21). Aerobic training program was performed on treadmill 4 days a week with intensity of 70% VO2max for six weeks (22). Blood samples were used to measure fasting glucose by enzymatic colorimetric method with glucose oxidase technology by Pars Azmoun Tehran kit company. Insulin was measured by ELISA method using a laboratory kit (Demeditec insulin ELIZA DE2935, Germany). Insulin resistance index was measured after Calculated fasting glucose and fasting insulin concentrations using the homeostasis model (HOMA-IR) and according to the formula. Also, the amount of adropine in adipose tissue of rats was measured using a special kit (Phoenix Pharmaceuticals, Inc. USA) by ELISA method. Adropin level were measured using ELISA kit. Data were analyzed by One-way ANOVA and Tukey post hoc test at the P<0.05. Results: Mean and standard deviation of variables in adipose tissue of different research groups are presented in Table 2. The results showed that the adropin level in adipose tissue in the obese diabetic group was significantly lower than the obese control group (P=0.001). Also, insulin resistance was significantly higher in the obese diabetic group than the obese control groups (P=0.004). Aerobic training was associated with significant increase of adropin in adipose tissue and decrease of insulin resistance in obese diabetic rats (P=0.001). Conclusion: The findings of this study were consistent with the results of Previous research (17, 23, 24). Insulin resistance, fasting glucose and insulin have a negative correlation with adropin levels (29). In the present study, a negative relationship was observed between adropin levels of adipose tissue and insulin and insulin resistance index, which may be one of the effective factors in increasing adropin levels of adipose tissue after aerobic training in the obese-diabetic exercise group. The molecular mechanism by which fat causes insulin resistance is unclear. Inflammation due to lipid accumulation, inhibitory effect of fatty acid oxidation on glucose oxidation, and secretion of adipocytokines are all associated with the development of local and systemic insulin resistance (36). Improvements in insulin resistance following exercise may be due in part to the potential effect of adropine on vasodilation. This improvement can facilitate access to glucose and enhance glucose metabolism (9). There were some limitations in the present study, such as the lack of measurement of other indicators of associated with energy homeostasis and metabolic adaptation in adipose tissue. According to the results, it seems that Aerobic training may be able to help reduce the effects of obesity in diabetes by improving adropin levels in adipose tissue and insulin resistance. [ABSTRACT FROM AUTHOR]

Peptic ulcer disease (PUD) is an important cause of morbidity and mortality throughout the world affecting lives of millions of people. Hyssopus officinalis L. have been used as carminative and antispasmodic stomachic in Iran and Indian traditional systems of medicine. Thus, present study was aimed to evaluate gastroprotective activity of ethanolic extract of Hyssopus officinalis L. leaves (EEHO) in indomethacin-induced gastric ulcer in experimental rats. Female Sprague Dawley rats of groups I, II, III, IV, V, and VI received orally 1 mL/kg/day 1% CMC (carboxy methylcellulose), 1 mL/kg/day 1% CMC, 250 mg EEHO/kg/day, 500 mg EEHO/kg/day, 50 mg ranitidine/kg/day and 500 mg EEHO/kg/day respectively for 10 days. Then, all the groups except groups I and VI were orally administered with 20 mg indomethacin/kg b.wt on 11th day. Ulcer index and mucus barrier were determined. Antioxidant parameters thiobarbituric acid reactive substances (TBARS), glutathione-reduced (GSH), catalase and superoxide dismutase (SOD) were evaluated. Stomach was examined for histopathology also. EEHO in groups III and IV significantly (p < 0.01) increased the mucus barrier, SOD, GSH, and catalase while significantly (p < 0.01) decreased the ulcer index and TBARS as compared to ulcer control group II. Histopathological findings showed that indomethacin administration in group II caused PUD (gastric ulcer) and the gastric ulcer was protected by pretreatment with EEHO in groups III and IV. Thus, EEHO possesses gastroprotective activity where the gastroprotection is by strengthening of the gastric mucosa and reduction of oxidative stress. The gastroprotective activity of EEHO was comparable to that of standard drug ranitidine. [ABSTRACT FROM AUTHOR]

Gheiasvand et al. (2020) use the two larger benthic foraminifera species Simplorbitolina manasi Ciry & Rat and Mesorbitolina parva (Douglass) (Orbitolinidae) as upper Aptian "potential index fossils" for parts of the Taft Formation in Central Iran. This age assignment is accompanied by changes to well-established orbitolinid biozonations (e.g. occurrence of Praeorbitolina in the late Aptian) with far-reaching implications. These data were also used in a later "multidisciplinary study" (Gheiasvand et al., 2021) for isotopic correlations (e.g., location of OAE's), delimitation of palaeobiogeographic faunal provinces and related migration patterns. It is shown herein that the taxa identified as S. manasi and M. parva belong to Iraqia simplex Henson and Palorbitolina lenticularis (Blumenbach) respectively documenting a lower and not an upper Aptian age. This revised age and the different taxononomic inventory do not question all results obtained by Gheiasvand et al. (2020, 2021), but provide a revised basis interpretation. [ABSTRACT FROM AUTHOR]

Background: Paricalcitol has been proposed for the treatment of secondary hyperparathyroidism in patients with renal failure and vitamin D deficiency (VDD); however, VDD is related to a range of clinical complaints. We aimed to investigate the effects of paricalcitol on body composition in VDD rats. Methods: Thirty adult male rats aged 10 weeks were randomly divided into three groups of 10, comprising control, VDD, and VDD plus paricalcitol32) ng/rat intraperitoneal injection) (VDD+P), at the Animal Lab of the Endocrinology and Metabolism Research Center, Shiraz, Iran, in 2020. Body composition was assessed after three weeks via serum biochemical tests and dual-energy X-ray absorptiometry. Finally, the data were analyzed by using the paired-sample t test, the one-way ANOVA, and the Tukey post hoc test. Results: Global lean mass and fat mass were lower in the VDD and VDD+P groups than in the controls (P<0.001). Global fat percentage was reduced significantly in the VDD+P group (P=0.029). Conclusion: Paricalcitol reduced global fat mass and fat percentage in a rat model with VDD. Evaluation of insulin and adiponectin levels is suggested to clarify the physiology of paricalcitol in VDD states. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The aim of this study was to evaluate the effects of hydro-alcoholic extract of spinach (HES) on hepatic and serum measurements of NAFLD in a rat model. Methods: In the prevention phase, 18 Sprague–Dawley rats were fed a high-fat diet, a high-fat diet plus 400 mg/kg HES, or a chow diet for seven weeks. For the treatment phase, after the induction of NAFLD, they were fed a high-fat diet, a high-fat diet plus 400 mg/kg HES, a chow diet, or a chow diet plus 400 mg/kg HES for four weeks (n = 6). Results: Administration of HES combined with high-fat diet in rats was associated with decreased food intake (P < 0.01), weight loss (P = 0.01), and increased superoxide dismutase (SOD) (P = 0.02) enzyme activity in the liver, at the end of the prevention phase. hs-CRP (P < 0.05), PTX-3 (P < 0.05), and TNF-α (P < 0.05) gene expression in the liver were decreased and PPAR-γ (P < 0.05) gene expression in the liver was increased by spinach intake, both in the prevention and treatment phases. Furthermore, administration of spinach in the treatment phase increased serum TAC (P = 0.03) and hepatic GPX (P = 0.01) enzyme activity. Conclusion: Taking into account the potential beneficial effects of HES on prevention and treatment of NAFLD in the present study, to confirm these findings, we propose that further clinical trials be conducted on human subjects with NAFLD. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a degenerative joint disease that causes a variety of adverse health effects. Considering the need to identify additional effective therapeutic options for OA therapy, we investigated the effect of co-injection of apigenin and synovial membrane-derived mesenchymal stem cells (SMMSCs) on OA in male rats' knee joints. Methods: The study was performed in 2019 at the Department of Pharmacology, Shiraz University of Medical Sciences, Shiraz, Iran. Anterior cruciate ligament transection (ACLT) was used to induce OA. For three weeks, male Sprague-Dawley rats (eight groups, n=6 each) were treated once-weekly with intra-articular injections of apigenin alone or in combination with SMMSC (three million cells), phosphate-buffered saline, or hyaluronic acid. After three months, the interleukin 1 beta (IL-1β), tumor necrosis factor-alpha (TNF- α), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured in the cartilage homogenate. The expression of extracellular matrix (ECM) components including collagen 2a1, aggrecan, IL-1β, TNF-α, inducible nitric oxide synthase (iNOS), transcription factor SOX-9, and matrix metalloproteinases 3 and 13 were assessed using real-time polymerase chain reaction (RT-PCR) analysis. Radiological evaluation and histopathological assessment were used to evaluate the knees. Results: Levels of TNF-α (P=0.009), MDA (P0.001>), and IL-1β (P<0.001) decreased and the level of SOD increased (P=0.004) in the apigenin 0.3 µM with SMMSCs group. RT-PCR analysis indicated that IL-1β in the apigenin 0.3 µM with SMMSCs group reduced significantly (P>0.001). This group also exhibited increased expression levels of SOX-9, collagen 2a1, and aggrecan (P>0.001). Conclusion: Apigenin may have supplementary beneficial effects on cell therapy in a rat model of OA due to its possible effect on the reduction of oxidative stress, suppression of inflammation, and promotion of production of ECM components. [ABSTRACT FROM AUTHOR]

Rodents are considered as reservoir hosts for various pathogens (such as Toxoplasma gondii) and have been revealed to play an important role in the spread of several infectious diseases to humans and other animals. The aim of this investigation was to survey the prevalence of anti-T. gondii IgG antibodies in wild rats in Northern Iran. One hundred rats were caught using rat traps set in different areas in Northern Iran (September 2017). The thoracic cavity of each rat was opened, and then the blood sample was collected from the heart. IgG anti-Toxoplasma gondii antibodies were detected using the modified agglutination test (MAT) with a cutoff value equal to 1 : 40. Overall, 56% of rats were infected by T. gondii. Considering the sex of rats, 45% of male and 55% of female rats were seropositive, but the differences were not statistically significant. There was a significant difference between seropositivity and habitat types and age of rodents. Our findings have public health implications and confirm the high seroprevalence of T. gondii infection in northern Iran. The study established that wild rats represent an important and persistent wildlife intermediate host reservoir for T. gondii. [ABSTRACT FROM AUTHOR]

Background: Punica granatum L. (pomegranate) with astringent activities and Matricaria chamomilla L. (chamomile) with anti-inflammatory and antioxidant properties are natural remedies used for various skin disorders, including wound healing. Objectives: This study was conducted to evaluate the individual and combined wound healing activity of the methanol extracts of pomegranate and chamomile flowers. Methods: After preparing the menthol fraction of pomegranate and chamomile flowers, the content of total phenols, total tannins, and total flavonoids of fractions was measured. For standardization of pomegranate and chamomile fractions, Gallic acid and apigenin-7-O-glucoside contents of them were determined using high-performance liquid chromatography (HPLC). Moreover, their antioxidant activities were examined using DPPH and FRAP tests. The antimicrobial assay was performed against Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa. Three different concentrations of methanol fraction of each plant and one combination dose of fractions were investigated for their wound healing activities in an excision wound model on the rats' dorsum. Finally, histopathological studies were done at the end of the experiment. Results: Phytochemical examinations showed high amounts of phenolic compounds in pomegranate flowers, while chamomile flower fractions contained a high amount of total flavonoids. Both fractions, especially pomegranate, had potent antioxidant activity. The best results for wound closure were observed 7 days after wound induction. All treated groups exhibited superior wound contraction compared to their placebo at all measurement times. The combined form of pomegranate and chamomile had better wound healing properties compared to a single therapy, especially on time earlier to wound induction. Conclusion: This study represented high antioxidant and wound healing activities for methanol fraction of pomegranate and chamomile flowers, which could be related to their high content of phytochemicals. In comparison with single herb treatment, the combined form of these two fractions in lower concentrations accelerated wound closure. [ABSTRACT FROM AUTHOR]

Background: Bisphenol A (BPA) is a widely used chemical with toxic effects on the liver. Resveratrol (RES) is an herbal compound with protective properties. This study aimed to investigate the protective effects of RES on the liver in rats exposed to BPA. Methods: This study was conducted in 2018 in Shiraz, Iran. Thirty Sprague-Dawley male rats were divided into five groups: a control group (distilled water), a sham group (olive oil as a BPA solvent), a BPA group (50 mg/kg), an RES group (100 mg/ kg), and a RES+BPA group (50 mg/kg+100 mg/kg). Olive oil, BPA, and RES were administered to the animals via gavage for eight weeks. After eight weeks, the animals' livers were removed, and stereological measurements were made to obtain the total liver volume, portal triad volumes, hepatocyte nucleus and cytoplasm volumes, hepatocyte numbers, sinusoidal space volumes and lengths, and Kupffer cell (KC) numbers. The data were analyzed using the one-way analysis of variance test. Results: The hepatocyte number, the total liver volume, and hepatocyte nucleus and cytoplasm volumes in the BPA group decreased by 41% (P<0.001), 18% (P<0.001), 32% (P=0.030), and 37% (P=0.014), respectively. The number of KCs and the length of sinusoids in the BPA group were increased compared with all the other groups (P<0.001). Our histological study revealed vacuolization, sinusoidal space dilatation, and congestion in the BPA group. Conclusion: In this study, the RES group, compared with the BPA group, exhibited a decrease in the total volume and length of sinusoids and the number of KCs. Additionally, the RES group showed an increase in the total liver volume, hepatocyte nucleus and cytoplasm volumes, portal triad volumes, and hepatocyte numbers after oral administration. [ABSTRACT FROM AUTHOR]

Background and purpose: Dracocephalum kotschyi (Zaringiah) is a fragrant wild medicinal plant found in Iran. Traditionally, it is used for the treatment of rheumatism, asthma, and gastrointestinal ailments. So far no investigation has been done on the beneficial or side effects of D. kotschyi on peptic ulcer. Therefore, this research was performed to find out whether D. kotschyi extract would induce peptic ulcer or could alleviate existing peptic ulcer. Experimental approach: Effect of hydroalcoholic (DKHE) and flavonoid extracts (DKFE) of D. kotschyi were determined in normal or indomethacin-induced gastric ulcer rats (n = 6) and compared with the vehicle and ranitidine treated controls. All the treatments were carried out orally and 24 h later the stomach mucus was visually examined for peptic ulcers. A section of the stomach was taken for microscopic histopathological examinations while another section of the stomach was used for measurement of myeloperoxidase (MPO) and malondialdehyde (MDA) activities. Findings/Results: Oral administration of the DKHE and DKFE alone, did not cause any sign of gastric ulcer induction. The D. kotschyi extracts not only didn't aggravate the induced ulcer but also significantly prevented the severity of gastric ulcer induction by indomethacin. In addition, DKHE and DKFE inhibited MPO (up to 58.2%) and MDA (up to 44.2%) activities indicating their anti-inflammatory and antioxidant potential action on the stomach-induced ulcer. Conclusion and implication: Usage of D. kotschyi extracts is not associated with gastric ulcer induction and its co-administration with NSAIDs would be beneficial for controlling both the inflammation and preventing gastric ulcer in diseases such as rheumatism. [ABSTRACT FROM AUTHOR]

Background: One of the major indices of immunodeficiency is lymphoid organ atrophy. Some trace elements are candidates for the treatment of this defect. These conditions may induce structural changes in the sub-components of lymphoid organs. Therefore, this study evaluated the effect of selenium on volumetric changes in dexamethasone (DEX)-induced lymphoid organ atrophy in an animal model. Methods: This study was conducted at Histomorphometry and Stereology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran, in September 2016 to September 2017. Thirty-two male rats were divided into four groups: Group I; control (normal saline, 0.5 mL/kg, intraperitoneally), Group II; DEX (0.4 mg/kg; intraperitoneally), Group III; selenium plus DEX (similar to Group II and Group IV), and Group IV; selenium (0.1 mg/kg; orally). At the end of the experiment, the rats' thymus, spleen, and lymph nodes were removed, processed, and stained by hematoxylin and eosin (H&E). The volume and volume density of theses organs were estimated by stereology. The results were analyzed using the Mann--Whitney U-test and the Kruskal--Wallis test. Results: The volume of the thymus as well as its cortex and medulla; the volume of the spleen as well as the volume density of its white pulp, periarterial lymphatic sheath zone, and follicles; and the volume of the lymph nodes as well as their inner (P=0.001) and outer (P=0.007) cortices showed a significant reduction in the DEX-treated animals in comparison with the controls. In the DEX plus selenium-treated animals, maximum effects were observed on the increment in the thymic cortex (P=0.001), the outer cortex of the lymph nodes (P=0.012), and the splenic follicles (P=0.018) in comparison with the DEX group. There was no significant difference between the animals receiving selenium treatment and the controls in terms of lymphoid organs. Conclusion: Selenium may improve lymphoid organ structures in an immunodeficiency rat model but has no effect on normal lymphoid tissues. [ABSTRACT FROM AUTHOR]

Brucellosis, caused by various Brucella species, poses a significant threat to global public health and livestock industries. This study aims to fill the knowledge gap concerning the presence of Brucella spp. in rodents on livestock farms in Iran. Both bacteriological and molecular surveys were conducted to assess the prevalence of Brucella spp. in these rodent populations. A total of 16 rodents were captured in four seropositive dairy cattle farms (n = 7) and two seropositive sheep farms (n = 9) and were then examined for the presence of the Brucella-infection. Five cow milk samples and 53 bovine lymph node samples from these farms were also tested for Brucella spp. Lymph node samples from dairy cattle farms contained 32 B. abortus biovar 3 isolates and one B. melitensis Rev1 vaccine isolate. The bacterial culture of rodents identified 12.5% of them (Mus musculus and Rattus norvegicus) harboring Brucella strains in dairy cattle farms. The rodents had B. abortus biovar 3 and B. melitensis biovar 1, suggesting a reservoir for these bacteria. A two-step molecular assay, utilizing the Omp28 sequences in tissue samples of rodents, demonstrated that 68.75% (n = 11) of the tested rodents yielded positive results. Bruce-ladder PCR and wboA typing on isolated bacteria revealed a close relationship to field strain of Brucella species. The study reveals that rodents on seropositive livestock farms in Iran harbor Brucella spp., indicating a potential reservoir for these bacteria. This highlights the importance of monitoring rodent populations through the molecular and bacterial methods to manage and control brucellosis in livestock., Competing Interests: Declaration of competing interest Authors confirm that they have no conflict of interest of any sort with any one., (Copyright © 2024 Elsevier Ltd. All rights reserved.)