Search

Seyed Ali Mard, Samireh Ghafouri Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranCorrespondence: Samireh GhafouriDepartment of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, PO Box: 6135715753, Ahvaz IranTel +98-61 33112516Fax +98-61 33332036Email samireh.ghafoui@gmail.comBackground: Medical education is a dynamic process, which needs to be improved to meet the new expectations of medical practitioners, health workers, and communities from different countries. An important part of medical students’ education is to select an appropriate assessment method. In this regard, the objective structured practical examination (OSPE) can evaluate practical capabilities in a suitable step-wise, scientific, targeted and scheduled manner with direct consideration of student’s performance during programmed test stations. The purpose of this study is to investigate the outcomes of the OSPE utilization versus traditional practical examination (TPE) for evaluating students in experimental physiology.Methods: Totally, 120 medical students were chosen as the participants of this study: 1. TPE group (TPE used as a final exam; n=40); 2. TPE + OSPE group (TPE applied for half of topics and OSPE for another half; n=41); and 3. OSPE group (OSPE performed as a final exam; n=39). In order to evaluate the effect of OSPE, the average final grade of studied groups was compared. In addition, a 5-point Likert scale questionnaire, consisting of 10 questions was used to evaluate the students’ attitudes toward using this method.Results: The obtained results showed that the total grade in TPE group was significantly higher in comparison to TPE+OSPE and OSPE groups (respectively, P< 0.01 and P< 0.05), while according to students’ expression, the average score for all of the items in feedback questionnaire was increased significantly in TPE+OSPE and OSPE groups compared with TPE group (P< 0.001).Conclusion: In summary, feedback from students showed that they were in favor of OSPE compared with the TPE, and according to their statements in a feedback questionnaire, OSPE can improve learning in physiology as well as increasing students’ satisfaction.Keywords: OSPE, physiology, medical students, traditional practical examination, questionnaire, Ahvaz

Roya Rafie,1 Seyed Ahmad Hosseini,1 Eskandar Hajiani,2 Amal Saki Malehi,3 Seyed Ali Mard4 1Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 2Research Center for Infectious Diseases of the Digestive System, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 3Health Research Institute, Thalassemia and Hemoglobinopathy Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 4Alimentary Tract Research Center, Imam Khomeini Hospital Clinical Research Development Unit, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranCorrespondence: Seyed Ahmad HosseiniNutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranTel +98-6133367543Fax +98-6133720299Email Seyedahmadhosseini@yahoo.comBackground: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders. The main causes of NAFLD are associated with insulin resistance, severe lipid metabolism disorders, oxidative stress and inflammation. Previous studies have reported that ginger has positive metabolic results.Aim: The aim of this study was to determine the effect of ginger powder supplement on lipid profiles, insulin resistance, liver enzymes, inflammatory cytokines and antioxidant status in patients with NAFLD.Methods: In this randomized clinical trial, 46 people with NAFLD were parted into two groups and subjected to the ginger or placebo capsules (3 capsules daily, each containing 500 mg of ginger or wheat flour) over 12 weeks. All patients received a diet with balanced energy and physical activity during the intervention period. Liver ultrasonography, anthropometric indices and biochemical parameters were measured before and after intervention.Results: No significant difference was found between the two groups in the baseline variables at the beginning of the study. At the end of the study, serum levels of alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein (LDL-C), fasting blood glucose, and insulin resistance index (HOMA), C-reactive protein (hs-CRP), and fetuin-A in the group receiving a ginger supplement significantly decreased compared to placebo. However, there was no significant difference between the two groups in body weight, fasting insulin, HDL-C, triglyceride, adiponectin, alpha-tumor necrosis factor (TNF-α), total antioxidant capacity (TAC), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), fatty liver index (FLI), fatty liver grade and blood pressure.Conclusion: The ginger supplement may be used as a complementary therapy along with existing therapies to reduce insulin resistance, liver enzymes and inflammation in patients with non-alcoholic fatty liver.Keywords: ginger, liver enzymes, non-alcoholic fatty liver disease, lipid profiles, insulin resistance

Narjes Zaeemzadeh,1 Sanaz Taherpour,2 Noor Behzadian,2 Seyyed Ali Mard2 1Deparment of Phamacology, The School of Pharmacy, Medical Educational and Development Center (EDC), Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 2Physiology Research Center (PRC), Department of Physiology, School of Medicine, Medical Educational and Development Center (EDC), Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Purpose: The knowledge loss or longevity of taught lessons is a major concern in medical students and all medical practitioners. This study evaluated the physiology knowledge loss in medical students in Ahvaz Jundishapur University of Medical Sciences in Iran. Methods: A total of 265 volunteers from medical students who had previously passed the “general exam of medical basic sciences” at the end of fifth semester took a retention test (RT) to evaluate their knowledge loss of physiology. The candidates were divided into ten groups depending on the semester (S) they were passing at the time of study: 41 students in preclinical levels (S6 and S7), 123 students in externship levels (S8, S9, S10, S11 and S12), and 101 students in internship levels (S13, S14 and S15). The RT consisted of 20 multiple choice questions from all topics of medical physiology, including central nervous system, endocrine, gastrointestinal, cardiovascular, respiratory, renal, blood, and cellular. Results: Findings showed that there was a decreasing trend of knowledge loss from S6 to S15. The lowest level of knowledge loss was observed in S15 students. These results also demonstrated that knowledge loss in male medical students was more than that in female students. Conclusion: These findings indicated that the physiology knowledge loss trend is inversely correlated with the time passing. We conclude that the reason is that physiology is a basic science which is most applicable during medical students’ clinical years. Keywords: Ahvaz, Iran, medical students, physiology, knowledge loss, retention test, female student

Background: Allergic asthma is a destructive inflammatory process in the respiratory system. The anti-inflammatory and antioxidant effects of N-acetylcysteine (NAC) have been reported in patients with obstructive pulmonary disease. On the other hand, several studies have shown the modulatory effects of mesenchymal stem cells on the immune system and inflammatory responses. Accordingly, the purpose of the current study was to evaluate the effect of administration of adipose tissue-derived stem cells (ADSCs) plus NAC on regulatory T cell system balance in an allergic asthma model., Methods: Eighty Sprague- Dawley rats were randomly divided into the following groups: Control, Plasmalite, Allergic asthma, Allergic asthma + ADSCs, NAC, Allergic asthma + NAC, Allergic asthma + ADSCs + NAC and Allergic asthma + Prednisolone. at the end of the experiment, arterial blood gas analysis, inflammatory cell counts in bronchoalveolar lavage fluid (BALF), inflammatory cytokine concentration, total IgE and specific OVA-IgE levels, gene expression levels of CD4+-T cell subsets, pulmonary indicators, edema, and lung histopathology were evaluated in all groups., Results: Administration of NAC plus ADSCs demonstrated a significant decrease in total WBC and eosinophil counts, which was in line with remarkable decrease in IL-17 and TNF-α concentrations and increases in IL-10 level compared with other treated groups. NAC plus ADSC treatment showed significant increases in Treg gene expression, although Th17 and Th2 expression significantly decreased compared with that in prednisolone- treated rats., Conclusion: The results of the present study documented that the administration of ADSCs plus NAC has an inhibitory effect on the inflammation caused by allergic asthma in a rat model. The improvement of inflammatory indexes was significantly higher than that with prednisolone treatment.

Sleep deprivation increases stress, anxiety, and depression by altering the endocannabinoid system's function. In the present study, we aimed to investigate the anti-anxiety and anti-depressant effects of the endocannabinoid anandamide (AEA) in the chronic sleep deprivation (SD) model in rats. Adult male Wistar rats (200-250 g) were randomly divided into three groups: control + vehicle (Control), chronic sleep deprivation + vehicle (SD), and chronic sleep deprivation + 20 mg/kg AEA (SD + A). The rats were kept in a sleep deprivation device for 18 h (7 to 1 a.m.) daily for 21 days. Open-field (OFT), elevated plus maze, and forced swimming tests (FST) were used to assess anxiety and depression-like behavior. As well as the cortical EEG, CB1R mRNA expression, TNF-α, IL-6, IL-4 levels, and antioxidant activity in the brain were examined following SD induction. AEA administration significantly increased the time spent (p < 0.01), the distance traveled in the central zone (p < 0.001), and the number of climbing (p < 0.05) in the OFT; it also increased the duration and number of entries into the open arms (p < 0.01 and p < 0.05 respectively), and did not reduce immobility time in the FST (p > 0.05), AEA increased CB1R mRNA expression in the anterior and medial parts of the brain (p < 0.01), and IL-4 levels (p < 0.05). AEA also reduced IL-6 and TNF-α (p < 0.05) and modulated cortical EEG. AEA induced anxiolytic-like effects but not anti-depressant effects in the SD model in rats by modulating CB1R mRNA expression, cortical EEG, and inflammatory response., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Severe acute respiratory syndrome coronavirus 2 was first reported in December 2019 and it has spread globally ever since. The HLA system is crucial in directing anti-viral immunity and recent studies are investigating the possible involvement of the HLA genes on the severity of immune inflammation in different phases of COVID-19., Methods: In this cross-sectional study, peripheral blood-extracted genomic DNAs of 109 COVID-19 patients and 70 healthy controls were genotyped for different alleles of HLA-A, HLA-B, and HLA-DRB1 loci using sequence-specific primer PCR method., Results: The results indicated that frequencies of HLA-DRB1*11:01 and HLA-DRB1*04:03 were significantly higher in severe patients rather than moderates (p: <0.001 and 0.004, respectively). Also, it was observed that HLA-DRB1*04:01 was more frequent in moderate patients and healthy controls (p:0.002). In addition, HLA-B*07:35, and HLA-DRB1*07:01 showed higher frequencies in patients compared with controls (p: 0.031 and 0.003 respectively). Inversely, due to the higher frequencies of HLA-B*51:01 (p:0.027), HLA-DRB1*11:05 (p:0.003), HLA-DRB1*13:05 (p:0.022), and HLA-DRB1*14:01 (p:0.006) in healthy individuals rather than patients, they may be associated with COVID-19 resistance., Conclusion: The results show that, based on the population differences, the type of alleles related to the severity of COVID-19 is different, which should be clarified by designing large-scale studies in order to develop HLA-based treatments and vaccines., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Non-alcoholic steatohepatitis (NASH) is a subtype of nonalcoholic fatty liver disease and a progressive and chronic liver disorder with a significant risk for the development of liver-related morbidity and mortality. The complex and multifaceted pathophysiology of NASH makes its management challenging. Early identification of symptoms and management of patients through lifestyle modification is essential to prevent the development of advanced liver disease. Despite the increasing prevalence of NASH, there is no FDA-approved treatment for this disease. Currently, medications targeting metabolic disease risk factors and some antifibrotic medications are used for NASH patients but are not sufficiently effective. The beneficial effects of different drugs and phytochemicals represent new avenues for the development of safer and more effective treatments for NASH. In this review, different risk factors, clinical symptoms, diagnostic methods of NASH, and current treatment strategies for the management of patients with NASH are reviewed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Abstract: Shortness of breath and syncope are common symptoms of right ventricular failure caused by pulmonary arterial hypertension (PAH), which is the result of blockage and increased pressure in the pulmonary arteries. There is a significant amount of evidence supporting the idea that inflammation and vascular calcification (VC) are important factors in PAH pathogenesis. Therefore, we aimed to investigate the features of the inflammatory process and gene expression involved in VC in monocrotaline (MCT)-induced PAH rats. MCT (60 mg/kg, i.p.) was used to induce PAH. Animals were given normal saline or rosmarinic acid (RA) (10, 15, and 30 mg/kg, gavage) for 21 days. An increase in right ventricular systolic pressure was evaluated as confirming PAH. To determine the level of inflammation in lung tissue, pulmonary edema and the total and differential white blood cell counts in the bronchoalveolar lavage fluid were measured. Also, the expression of NFκB, OPG, Runx2, and P-selectin genes was investigated to evaluate the level of VC in the heart. Our experiment showed that RA significantly decreased right ventricular hypertrophy, inflammatory factors, NFκB, Runx2, and P-selectin gene expression, pulmonary edema, total and differential white blood cell count, and increased OPG gene expression. Therefore, our research showed that RA protects against MCT-induced PAH by reducing inflammation and VC in rats., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Organ ischemia-reperfusion (IR) is a common clinical condition associated with various situations such as trauma surgery, organ transplantation, and myocardial ischemia. Current therapeutic methods for IR injury have limitations, and nanotechnology, particularly zinc oxide nanoparticles (ZnO NPs), offers new approaches for disease diagnosis and treatment. In this study, we investigated the protective and anti-apoptotic effects of ZnO NPs in liver ischemia-reperfusion (IR) injury in rats., Methods: Forty-eight male rats were divided into six groups: sham, ZnO5, ZnO10, ischemia-reperfusion (IR), IR+ZnO5, and IR+ZnO10. The protective effect of ZnO NPs was evaluated by liver enzymes (AST, ALT, Bilirubin, ALP), biochemical (TAC, TNF-α, and MDA), molecular examinations (Bcl2, BAX), and histopathological evaluations (H&E, TUNEL)., Results: Pre-treatment with ZnO5 and ZnO10 improved hepatic function in IR liver injury, attenuated the levels of oxidants (P = 0.03) and inflammatory mediators, and reduced apoptosis (P = 0). ZnO10 was found to have a greater effect on ischemic reperfusion injury than ZnO5 did. Histopathological examination also showed a dose-dependent decrease in alterations in the IR+ZnO5 and IR+ZnO10 groups., Conclusion: Administration of ZnO5 and ZnO10 improved liver function after IR. The findings of this study suggest that ZnO NPs have a protective effect against oxidative stress and apoptosis in liver ischemia-reperfusion injury in rats. These results may have important implications for developing advanced methods in ischemia-reperfusion treatment., Competing Interests: The authors declare that they have no competing interests.

Objectives: Right ventricular hypertrophy (RVH) often results in failure of the right ventricle or even the left ventricle. Rosmarinic acid (RA), a natural polyphenol, is commonly found in Boraginaceae species and some species of ferns and hornworts. This study looked at how RA affects oxidative stress and left ventricular hemodynamic functions as well as RVH in monocrotaline (MCT) induced RVH model rats., Materials and Methods: To cause RVH, MCT (60 mg/kg) was intraperitoneally (IP) injected. Rats were given saline or RA (10, 15, and 30 mg/kg, gavage, over 21 days). In anesthetized rats, the lead II electrocardiogram was recorded. The hemodynamic functions of the isolated heart were measured using the Langendorff apparatus (at constant pressure). Investigations were made into the right ventricular hypertrophy index (RVHI), the activities of superoxide dismutase, catalase, glutathione, and Wnt and β-catenin gene expressions in the left ventricle. H&E staining was used., Results: A significant decline in electrocardiogram parameters and anti-oxidant enzyme activities, an increase in QTc (Q-T corrected) intervals, MDA (Malondialdehyde), RVHI, and Wnt/β-catenin gene expression, and also significant changes in the hemodynamic parameters were demonstrated in the MCT group. RA improved the above-mentioned factors., Conclusion: According to the findings, RA may act as a cardioprotective agent against cardiovascular complications brought on by RVH due to its capacity to boost the activity of cardiac anti-oxidant enzymes and decrease the expression of genes involved in vascular calcification., Competing Interests: All authors declare no conflicts of interest.

Sleep deprivation alters orexinergic neuronal activity in the lateral hypothalamus (LH), which is the main regulator of sleep-wake, arousal, appetite, and energy regulation processes. Cannabinoid receptor (CBR) expression in this area is involved in modulating the function of orexin neurons. In this study, we investigated the effects of endocannabinoid anandamide (AEA) administration on improving food intake and appetite by modulating the activity of orexin neurons and CB1R expression after chronic sleep deprivation. Adult male Wistar rats (200-250 g) were randomly divided into three groups: control + vehicle (Control), chronic sleep deprivation + vehicle (SD), and chronic sleep deprivation +20 mg/kg AEA (SD + A). For SD induction, the rats were kept in a sleep deprivation device for 18 h (7 a.m. to 1 a.m.) daily for 21 days. Weight gain, food intake, the electrical power of orexin neurons, CB1R mRNA expression in hypothalamus, CB1R protein expression in the LH, TNF-α, IL-6, IL-4 levels and antioxidant activity in hypothalamus were measured after SD induction. Our results showed that AEA administration significantly improved food intake (p < 0.01), Electrical activity of orexin neurons (p < 0.05), CB1R expression in the hypothalamus (p < 0.05), and IL-4 levels (p < 0.05). AEA also reduced mRNA expression of OX1R and OX2R (p < 0.01 and p < 0.05 respectively), also IL-6 and TNF-α (p < 0.01) and MDA level (p < 0.05) in hypothalamic tissue. As a consequence, AEA modulates orexinergic system function and improves food intake by regulating the expression of the CB1 receptor in the LH in sleep deprived rats., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

We aimed to investigate the probable protective effects of gallic acid (GA) on cognitive deficits, hippocampal long term potentiation (LTP) impairments, and molecular changes induced by cerebral ischemia/reperfusion (I/R) in rats following exposure to ambient dust storm. After pretreatment with GA (100 mg/kg), or vehicle (Veh) (normal saline, 2 ml/kg) for ten days, and 60 minutes' exposure to dust storm including PM (PM, 2000-8000 g/m3) every day, 4-vessel occlusion (4VO) type of I/R was induced. Three days after I/R induction, we evaluated behavioral, electrophysiological, histopathological, molecular and brain tissue inflammatory cytokine changes. Our findings indicated that pretreatment with GA significantly reduced cognitive impairments caused by I/R (P < 0.05) and hippocampal LTP impairments caused by I/R after PM exposure (P < 0.001). Additionally, after exposure to PM, I/R significantly elevated the tumor necrosis factor α content (P < 0.01) and miR-124 level (P < 0.001) while pre-treatment with GA reduced the level of miR-124 (P < 0.001). Histopathological results also revealed that I/R and PM caused cell death in the hippocampus CA1 area (P < 0.001) and that GA decreased the rate of cell death (P < 0.001). Our findings show that GA can prevent brain inflammation, and thus cognitive and LTP deficits caused by I/R, PM exposure, or both., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Oxidative stress and inflammation play a pivotal role in the pathogenesis of diabetic nephropathy (DN). Local renin-angiotensin systems (RAS) contribute to the pathogenesis and progression of DN by exacerbating oxidative stress and inflammation.Gentisic acid (GA), a phenolic compound and also a metabolite of aspirin, is reported to possess antioxidant and anti-inflammatory properties. However, the protective effects of GA against DN remain to be elucidated. Nicotinamide (120 mg/kg) and streptozotocin (65 mg/kg) were used to induce diabetes in male mice. Oral administration of GA once daily for 2 weeks (100 mg/kg) ameliorated diabetes-induced renal injury by reducing plasma creatinine, urea, blood urea nitrogen, and urinary albuminuria levels. Diabetic mice showed a significant increase in total oxidant status and malondialdehyde, along with decreased catalase, superoxide dismutase, and glutathione peroxidase in the kidney tissue, which was ameliorated in the GA-treated mice. Histopathological analysis showed that GA treatment reduced diabetes-induced renal injury. Furthermore, GA treatment was associated with the downregulation of miR-125b, nuclear factor kappa beta (NF-кB), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and upregulation of interleukin-10 (IL-10), miR-200a, and nuclear factor erythroid 2-related factor 2 (Nrf2) in the renal tissue. GA treatment also downregulated angiotensin-converting enzyme 1 (ACE1), angiotensin II receptor 1 (AT1R), and NADPH oxidase 2 (NOX 2) and upregulated angiotensin-converting enzyme 2 (ACE2). In conclusion, the ameliorative effects of GA against DN may be attributed to its powerful antioxidant and anti-inflammatory properties through the downregulation of NF-кB, upregulation of Nrf2, and modulation of RAS in renal tissue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Aims: There is a close link between oxidative stress, inflammation, and type 2 diabetes mellitus (T2DM). Gentisic acid (GA) is a di-phenolic compound and an active metabolite of aspirin that possesses antioxidant and anti-inflammatory properties, but its potential anti-diabetic effects have not been evaluated so far. Therefore, this study aimed to evaluate GA's potential antidiabetic effects through the Nuclear Factor Erythroid 2-Related Factor (Nrf2) and Nuclear Factor Kappa Beta (NF-кB) signaling pathways., Material and Methods: In this study, T2DM induced by a single intraperitoneal injection of STZ (65 mg/kg B.W) after 15 min nicotinamide (120 mg/kg B.W) injection. After seven days of injections, fasting blood glucose (FBS) was measured. Seven days after FBS monitoring treatments started. Grouping and treatments were as follows: 1) Normal control group; NC, 2) Diabetic control group; DC, 3) Metformin group; MT (150 mg/kg B.W, daily), 4) Test group; GA (100 mg/kg B.W, daily). Treatments continued for 14 consecutive days., Key Findings: Diabetic mice treatment with GA significantly decreased FBS, improved plasma lipid profiles and pancreatic antioxidant status. GA modulated Nrf2 pathway by upregulation of Nrf2 protein, NAD(P)H: quinone oxidoreductase 1 (Nqo1), and p21, and downregulation of miR-200a, Kelch-like ECH-associated protein 1 (Keap1), and nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX2). Also, GA attenuated inflammation by upregulation of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and interleukin-10 (IL-10) and downregulation of miR-125b, NF-кB, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß)., Significance: GA attenuates T2DM, possibly by improving antioxidant status through the Nrf2 pathway and attenuation of inflammation., Competing Interests: Declaration of competing interest No competing interests are declared., (Copyright © 2023. Published by Elsevier Inc.)

Increasing air pollution is associated with serious human health problems. P-coumaric acid (PC) is a herbal phenolic compound that exhibits beneficial pharmacological potentials. Here, the protective effect of PC on liver injury induced by air pollution was examined. Thirty-two adult male Wistar rats (200-250 g) were divided randomly into four groups (n = 8). The groups were; Control (rats received DMSO and then exposed to clean air), PC (rats received PC and then exposed to clean air), DMSO + Dust (rats received DMSO and then exposed to dust), and PC + Dust (the animals received PC and then exposed to dust). The clean air, DMSO, PC, and dust were administrated 3 days a week for 6 consecutive weeks. The rats were anesthetized and their blood samples and liver sections were taken to conduct molecular, biomedical, and histopathological tests. Dust exposure increased the liver enzymes, bilirubin, triglyceride, cholesterol, and the production of liver malondialdehyde, and decreased in liver total anti-oxidant capacity and serum high-density lipoprotein. It also increased the mRNA expression of inflammatory-related cytokines, decreased the mRNA expression of SIRT-1, decreased the expression levels of miR-20b5p, and MEG3 while increased the expression levels of miR-34a, and HOTAIR. Dust exposure also increased the liver content of three cytokines TNF-α, NF-κB, HMGB-1, and ATG-7 proteins. PC enhanced liver function against adverse effects of dust through recovering almost all the studied variables. Exposure to dust damaged the liver through induction of oxidative stress, inflammation, and autophagy. PC protected the liver against dust-induced cytotoxicity., (© 2023 Wiley Periodicals LLC.)

Background: Methylglyoxal (MG) has been reported to be a toxic by-product of glycolysis and intracellular stressor compound. This study investigated the effects of gallic acid (GA) against diabetic nephropathy (DN) induced by MG in male mice., Methods: DN was induced by methylglyoxal (600 mg/kg/day, p.o.) treated for 28 consecutive days. The animals received GA (30 mg/kg/day, p.o.) and metformin (MT) (150 mg/kg/day, p.o.) for 7 consecutive days after diabetes induction. Biochemical assays, antioxidant evaluation, microRNAs associated with fibrosis, endoplasmic reticulum stress, and histopathological analysis were examined., Results: MG increased malondialdehyde, albuminuria, Nrf2, miR-192 and miR-204 expression in diabetic groups and GA decreased them. Superoxide dismutase, catalase, glyoxalase1, and miR-29a expression decreased in diabetic groups and increased in treatment with GA., Conclusion: Our results revealed that GA has improved DN induced by MG via amelioration of biochemical indices, histopathological aspects, oxidative stress and microRNAs associated with endoplasmic reticulum stress and fibrosis.

Developmental morphine (MOR) exposure (DME) detrimentally affects the cognitive abilities of the next generation. It is shown that postnatal rearing environments and prenatal conditions effectively impact memory. The present study investigated the effects of DME, postweaning rearing, and sex on spatial learning and memory. At molecular level, we evaluated mRNA levels of brain-derived neurotrophic factor, cyclic AMP response element-binding protein (CREB), μ-opioid receptor, and ΔFosB in the hippocampus of male offspring. Female Wistar rats were treated with escalating doses of MOR or saline before mating, gestation, and lactation. On Postnatal Day 22, the male and female pups were divided into 12 groups and raised for 2 months under different conditions: standard, isolated (ISO), or enriched environment. Afterward, the Morris water maze task measured spatial learning and reference memory; rats were then sacrificed to assess hippocampus gene expressions. Results indicated the DME and isolated rearing increased latency to find the hidden platform in male offspring. DME was insignificant in female offspring, whereas rearing environments significantly altered escape latency in both sexes. We also found that the enriched environment upregulated the brain-derived neurotrophic factor mRNA in both saline and MOR groups, whereas it downregulated the mRNA levels of CREB1, μ-opioid receptor, and ΔFosB in the MOR group. In addition, the DME enhanced CREB1, μ-opioid receptor, and ΔFosB gene expression in the MOR + isolated group. Our findings signified the effects of DME, rearing environment, and sex on the spatial learning abilities of offspring. Also, we showed that DME and rearing conditions could manipulate hippocampal neurochemistry., (© 2022 International Society for Developmental Neuroscience.)

Background: Serum and glucocorticoid-induced kinase 1 (SGK1) is an enzyme that may play an important role in ischemic-reperfusion (I/R) injury and myocardial dysfunction. Although many studies have been conducted on individual antioxidants, little attention has been paid to the effects of co-administration of an antioxidant with an SGK1 inhibitor on cardiac function after I/R., Methods: This study aimed to determine the effects of gallic acid (as an antioxidant) combined with an SGK1 inhibitor on I/R-induced cardiac dysfunction and inflammation. Sixty male Wistar rats were randomized into 6 groups, pretreated with gallic acid or vehicle for 10 days. Subsequently, the heart was isolated and exposed to I/R. In groups that received the SGK1 inhibitor, the heart was perfused with the SGK1 inhibitor GSK650394, 5 min before induction of ischemia. After that, cardiac function, inflammatory factors, and myocardial damage were evaluated., Results: The combination of these two compounds improved cardiac contractility, heart rate, rate pressure product, left ventricular developed pressure, left ventricular systolic pressure, perfusion pressure, and QRS voltage significantly (P < 0.05). In addition, concomitant therapy of these two agents reduced tumor necrosis factor-alpha and interleukin-6, and the activity of creatine kinase-MB, lactate dehydrogenase, and troponin-I (P < 0.05)., Conclusion: The results indicated that administration of gallic acid with the SGK1 inhibitor may have a potentiating effect on the improvement of cardiac dysfunction and I/R-induced inflammation., Competing Interests: The authors have no relevant financial or non-financial interests to disclose.

Objectives: Oxidative stress and serum and glucocorticoid-induced Kinase 1 gene (SGK1) perform a central role in the consequences of ischemia in the heart. This research aimed to investigate the effect of coadministration of gallic acid and the GSK650394 (as SGK1 gene inhibitor) on the ischemic complications of a rat model of cardiac ischemia/reperfusion (I/R) injury., Materials and Methods: Sixty male Wistar rats were divided into 6 groups with or without pretreatment with gallic acid for 10 days. After that, the heart was isolated and perfused with Krebs-Henseleit solution. A 30 min of ischemia was performed followed by a 60 min reperfusion. In 2 groups, GSK650394 was infused 5 min before ischemia induction. Ten minutes after reperfusion commencement, cardiac marker enzyme (CK-MB, LDH, and cTn-I) activities were measured in the cardiac perfusate. At the end of reperfusion, the activity of anti-oxidant enzymes (Catalase, Superoxide dismutase, and Glutathione peroxidase), lipid peroxidation (MDA), total anti-oxidant capacity (TAC), intracellular reactive oxygen species (ROS), infarct size, and SGK1 gene expression were measured in the heart tissue., Results: The results indicated that dual therapy with both drugs significantly improved endogenous anti-oxidant enzyme activity and TAC more than each drug alone. However, the heart marker enzymes (CK-MB, LDH, and cTn-I), MDA, ROS, infarct size, and SGK1 gene expression were reduced significantly compared with the ischemic group., Conclusion: The results of this study suggest that concomitant administration of both drugs in the case of cardiac I/R injury may have a more beneficial effect than each one alone., Competing Interests: The authors have no relevant financial or non-financial interests to disclose.

Introduction: The neuropathology of Parkinson's disease (PD) is complex and affects multiple systems of the body beyond the central nervous system. This study examined the effects of gallic acid (GA) and gastrointestinal vagotomy (VG) on motor, cognitive, intestinal transit time, and thalamic nuclei electrical power in an animal model of PD induced by rotenone., Materials and Methods: Male Wistar rats were divided into 4 groups: Sham, ROT, ROT+GA, VG + ROT. Sham rats received vehicle, those in ROT received rotenone (5 mg/kg/2 ml, ig), PD rats in ROT+GA were treated with GA (100 mg/kg, gavage/once daily, for 28 days), and in VG + ROT, the vagal nerve was dissected. Stride length, motor coordination and locomotion, intestinal transit time, cognitive and pain threshold, and thalamic local EEG were evaluated. Oxidative stress indexes in striatal tissue were also measured., Results: Rotenone diminished significantly the stride length (p < 0.001), motor coordination (p < 0.001), power of thalamic EEG (p < 0.01) and pain (p < 0.001). MDA increased significantly (p < 0.001) while GPx activity decreased (p < 0.001). Intestinal transit time rose significantly (p < 0.01). PD rats treated with GA improved all above disorders (p < 0.001, p < 0.01). Vagotomy prevented significant alterations of motor and non-motor parameters by rotenone., Conclusion: According to current findings, rotenone acts as a toxin in GI and plays a role in the pathogenesis of PD through gastric vagal nerve. Thus, vagotomy could prevent the severity of toxicity by rotenone. In addition, GA improved symptoms of PD induced by rotenone. Therefore, GA can be regarded as a promising therapeutic candidate for PD patients., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Cytokines are the most important inflammatory mediators and are well-known as the main cause of emphysema. Adipose-derived stem cells (ADSCs) as a cell-based treatment strategy could play a pivotal role in lung regeneration through anti-inflammatory and paracrine properties. Accordingly, the aim of this study was to the comparison of inflammation markers' improvement in response to the intratracheal and systemic delivery method of adipose-derived mesenchymal stem cells in emphysema. Forty-eight rats were divided into five groups including Control, Elastase (25 IU/kg, Intratracheal, at day first and 10th), Elastase+PBS, Intratracheal cell therapy (1 ×10 7, at day 28th), and Systemic cell therapy groups (1 ×10 7, Jugular vein, at day 28th). After 3 weeks, the blood gas analysis (PO 2 , PCO 2 and pH), fibrinogen level, and C-reactive protein (CRP) concentrations were measured in all groups. In addition, inflammatory genes expression, and concentration levels of pro and anti-inflammatory cytokines (IL-6, IL-17, TNF-α, and TGF-β,) were evaluated using Real-time PCR and Elisa kits, respectively. The statistical analysis of our data shows that local administration leads to more significant treatment efficacy with decreased inflammation parameters such as WBC count and pro-inflammatory cytokines in comparison with systemic treatment. Besides, these results were approved by more reduction of CRP and fibrinogen concentration levels in blood samples of intra-tracheal AMSCs-treated rats compare with the systemic group. Moreover, the improvement in histopathology indexes of the local administrated group was significantly better than the systemic group. Accordingly, the obtained results suggest local administration as the most efficacious route for mesenchymal stem cells delivery in patients with emphysema., Competing Interests: Competing interests We know of no conflicts of interest with this publication., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Studies show that chronic injuries like air pollution or acute damage such as hepatic ischemia-reperfusion (IR) cause various cellular pathologies such as oxidative stress, apoptosis, autophagy, and inflammation in hepatocytes. p -Coumaric acid ( p- CA) is known as an antioxidant with many therapeutic impacts on inflammatory-related pathologies. In this experiment, we aimed to assess the hepatoprotective effects of p -CA on liver damage induced by dust and IR injury in adult male rats., Materials and Methods: Forty-eight adult male Wistar rats were divided into 6 groups; Control (CTRL); sham; DMSO+Dust+Laparotomy (LPT); DMSO+Dust+Ischemia-reperfusion (IR); p -CA+Dust+LPT; and p -CA+Dust+IR. Clean air, DMSO, p -CA, and dust were administrated 3 days a week for 6 consecutive weeks. Animals were sacrificed, the blood samples were aspirated and the liver sections were prepared for biochemical and histopathological assessments., Results: Significantly ( P <0.05), the results represented that dust and IR can potentially increase the levels of ALT, AST, direct and total bilirubin, triglyceride, and cholesterol in serum. Also, MDA, TNF-α , NF-κB . HMGB-1 and ATG-7 levels were increased in hepatocytes. Gene expression of Nrf2, HOX-1, IL-6, HOTAIR, and miR-34a showed an incremental trend in the liver tissue. Total antioxidant capacity (TAC) in hepatocytes was decreased following dust exposure and IR induction. Also, miR-20b-5p, MEG3, and SIRT1 in the liver were decreased in dust and dust+IR groups., Conclusion: p -CA alleviated pathological changes caused by dust exposure and IR injury. p -CA protected hepatic injury induced by dust and IR by inhibition of oxidative injury, inflammation, and autophagy., Competing Interests: The authors declare that they have no conflicts of interest.

Aim: This study aims to evaluate whether biochemical alterations caused by methylglyoxal (MG), improves by the administration of gallic acid (GA), crocin (Cr), and metformin (MT) in the liver., Background: MG is produced naturally through various physiological processes, but high levels of MG cause inflammation in hepatocytes. Normal liver function is essential for maintaining glucose homeostasis. Gallic acid and crocin can reduce inflammation., Methods: This experiment was done in 5 weeks. 50 male NMRI mice were randomly divided into 5 groups (n=10): 1) Control, 2) MG (600 mg/Kg/d, p.o.), 3) MG+GA (30 mg/kg/day, p.o.), 4) MG+Cr (60 mg/kg/day, p.o.), 5) MG+MT (150 mg/kg/day, p.o.). After one week of habituation, MG was administered for four weeks. Gallic acid, crocin, and metformin were administered in the last two weeks. Biochemical and histologic evaluations were assessed after plasma collection and tissue sample preparation., Results: Gallic acid and crocin-received groups significantly reduced fasting blood glucose, total cholesterol, triglyceride levels, and elevated insulin sensitivity. Administration of MG exerted a marked increase in the levels of hepatic enzymes. Treatment with gallic acid, crocin, and metformin significantly decreased them. The altered levels of inflammatory factors in the diabetic group were significantly improved in the diabetic-treated groups. High levels of steatosis and red blood cells (RBCs) accumulation in the MG group markedly recovered in other treated mice., Conclusion: Harmful effects of accumulated MG in the liver of diabetic mice were effectively attenuated by using gallic acid and crocin., Competing Interests: The authors have no conflict of interest in this study.

Background: Liver diseases and injuries are important medical problems worldwide. Acute liver failure (ALF) is a clinical syndrome characterized by severe functional impairment and widespread death of hepatocytes. Liver transplantation is the only treatment available so far. Exosomes are nanovesicles originating from intracellular organelles. They regulate the cellular and molecular mechanisms of their recipient cells and have promising potential for clinical application in acute and chronic liver injuries. This study compares the effect of Sodium hydrosulfide (NaHS) modified exosomes with non-modified exosomes in CCL4-induced acute liver injury to ascertain their role in ameliorating hepatic injury., Methods: Human Mesenchymal stem cells (MSCs) were treated with or without NaHS (1 μmol) and exosomes were isolated using an exosome isolation kit. Male mice (8-12 weeks old) were randomly divided into four groups (n=6): 1-control, 2-PBS, 3- MSC-Exo, and 4- H2S-Exo. Animals received 2.8 ml/kg body weight of CCL4 solution intraperitoneally, and 24 h later MSC-Exo (non-modified), H2S-Exo (NaHS-modified), or PBS, was injected in the tail vein. Moreover, 24 h after Exo administration, mice were sacrificed for tissue and blood collection., Results: Administration of both MSC-Exo and H2S-Exo reduced inflammatory cytokines (IL-6, TNF-α), total oxidant levels, liver aminotransferases, and cellular apoptosis., Conclusion: MSC-Exo and H2S-Exo had hepato-protective effects against CCL4-induced liver injury in mice. Modification of cell culture medium with NaHS as an H2S donor enhances the therapeutic effects of MSC exosomes., Competing Interests: The authors declare that they have no conflicts of interest.

Background: Diabetic nephropathy (DN) is a critical complication of diabetes mellitus. This study evaluates whether administration of conditioned medium from kidney tubular cells (KTCs-CM) has the ability to be efficacious as an alternative to cell-based therapy for DN., Materials and Methods: CM of rabbit kidney tubular cells (RK13; KTCs) has been collected and after centrifugation, filtered with 0.2 filters. Four groups of rats have been utilized, including control, DN, DN treated with CM, and sham group. After diabetes induction by streptozotocin (50 mg/kg body weight) in rats, 0.8 ml of the CM was injected to each rat three times per day for 3 consecutive days. Then, 24-h urine protein, blood urea nitrogen (BUN), and serum creatinine (Scr) have been measured through detection kits. The histopathological effects of CM on kidneys were evaluated by periodic acid-Schiff staining and the expression of microRNAs (miRNAs) 29a and 377 by using the real-time polymerase chain reaction. The expression of aquapurin-1 (AQP1) protein was also examined by Western blotting., Results: Intravenous injections of KTCs-CM significantly reduced the urine volume, protein 24-h, BUN, and Scr, decreased the miRNA-377, and increased miRNA-29a and AQP1 in DN treated with CM rats., Conclusion: KTCs-CM may have the potential to prevent kidney injury from diabetes by regulating the microRNAs related to DN and improving the expression of AQP1., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Advanced Biomedical Research.)

Introduction: Ischemia-reperfusion injury (IRI) by causing histopathological changes is considered one of the most important causes of liver failure and dysfunction after surgery which affect graft outcomes. Stem cells are new promising approaches to treating different diseases. One of the critical strategies to improve their function is the preconditioning of their culture medium. This study compared the effect of NaHS-modified and non-modified mesenchymal stem cell exosomes on liver ischemia-reperfusion injury in mice., Methods: Human umbilical cord-derived MSC (MSC) cultured in a 75 cm 3 flask and when confluency reached about 80%, the culture medium replaced with a serum-free medium, and 48 h later supernatants collected, concentrated, and then MSC-Exo extracted. To obtain H2S-Exo, MSC was treated with NaHS (1 μmol),the supernatant collected after 48 h, concentrated and exosomes extracted. Twenty-four male mice were randomly divided into four groups (n = 6) including: 1-ischemia, 2-sham-operated, 3- MSC-Exo, and 4- H2S-Exo. To induce ischemia, the hepatic artery and portal vein clamped using an atraumatic clip for 60 min followed by 3 h of reperfusion. Just upon ending the time of ischemia (removal of clamp artery), animals in MSC-Exo, and H2S-Exo groups received 100 μg exosomes in 100 μl PBS via tail vein. At the end of reperfusion, blood, and liver samples were collected for further serological, molecular, and histological analyses., Results: Administration of both MSC-Exo and H2S-Exo improved liver function by reducing inflammatory cytokines, cellular apoptosis, liver levels of total oxidant status, and liver aminotransferases. The results showed that protecting effect of MSC exosomes enhanced following NaHS preconditioning of cell culture medium., Conclusion: MSC-Exo and H2S-Exo had hepato-protective effects against injuries induced by ischemia-reperfusion in mice. NaHS preconditioning of mesenchymal stem cells could enhance the therapeutic effects of MSC-derived exosomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Background and Objective: Renal tissue injuries by free radicals are an essential reason in pathogenesis of urinary tract stones. Ethylene glycol is one of the toxic agents which can causes to the increases in biosynthesis of reactive oxygen species and oxidative stress condition. Natural antioxidants have been reported to protective efficacy against renal stones formation. Accordingly, the aim of the current experiment was to identify the renal protective effect of chlorogenic acid as a well-prominent antioxidant on ethylene glycol-induced renal stone model targeting the NFKB-RUNX2-AP1-OSTERIX signaling pathway., Materials and Methods: Renal stones model were established by ethylene glycol (Percent: 0.75) within the daily drinking water for rats. Treatment groups received cystone (750 mg/kg) and chlorogenic acid (100, 200, and 400 mg/kg, day: 15th to 28th, gavage). After 4 weeks, the renal function parameters (calcium, uric acid, creatinine, total protein, oxalate, and citrate) in plasma, urine, and renal tissue were measured. Moreover, oxidative stress factors and gene expression of NFKB, RUNX2, AP1, and OSTERIX were also evaluated., Results: The results showed improved renal function in chlorogenic acid-treated groups. The total proteins and creatinine excretion were decreased. Also the gene expression of oxidative stress pathway (NFKB-RUNX2-AP1-OSTERIX) were decreased which caused to increases of antioxidant enzymes., Conclusions: the antioxidant activity increases by chlorogenic acid treatment may have a critical role in prevention of calcium oxalate formation via inhibition of the NFKB-RUNX2-AP1-OSTERIX signaling pathway., Competing Interests: Conflict of interests We emphasize that there is not any conflict of interest with this publication., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Acute kidney injury (AKI) is identified by a progressive reduction in the glomerular filtration rate (GFR) and retention of nitrogenous waste products. Traumatic and nontraumatic rhabdomyolysis is recently considered the main cause of AKI. According to several studies, stem cell treatment is a promising therapeutic strategy for many types of disorders including AKI. The main limitation of mesenchymal stem cells (MSCs) therapy is reducing cell survival in response to oxidative stress products in injured organ areas. Gallic acid (GA) as a well-known antioxidant has been reported to confer potent-free radical scavenging and anti-inflammatory properties. Therefore, the aim of the current study was to assess the influence of MSCs and GA in acute renal injury following rhabdomyolysis induced by glycerol. A total of 70 healthy rats were divided into seven groups (10 in each group): control, AKI (glycerol, intramuscular), cell therapy (AKI + intravenous injection of mesenchymal stem cells derived from adipose tissue (AMCs), AKI + AMCs + GA (50, 100, and 200 mg/kg, intraperitoneally, 3 days a week for 3 consecutive weeks), and positive control group (the most effective dose of gallic acid). After the treatment, rats were sacrificed; blood, urine, and kidney tissues were collected; and qualitative and quantitative parameters (including blood urea nitrogen (BUN), creatine kinase (CK), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate transaminase (SGOT), oxidative stress markers kidney function parameters) and histopathological indexes were assayed. Our results revealed that co-treatment of AMCs plus GA into AKI rats decreased BUN and creatinine and ameliorated kidney injury parameters after 3 weeks. Improved oxidative stress markers such as decreased MDA and increased SOD and CAT were significant in the GA + AMCs group compared to the AMCs alone in AKI rats. Also, the histopathological appearances of AKI rats including renal tubule cavity expansion and renal tubular epithelial cell edema, and interstitial inflammation, were alleviated using GA + AMCs treatment compared to the control. The obtained results of the current study documented that antioxidants could make mesenchymal stem cells more resistant to the condition in which they are supposed to be transplanted and probably improve the efficacy of stem cell therapy in AKI patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Accumulation of methylglyoxal (MGO) occurs in diabetes. MicroRNA-204 is an important intracellular marker in the diagnosis of endoplasmic reticulum stress. Crocin (Crn) has beneficial effects for diabetes, but the effect of Crn on MGO-induced diabetic nephropathy has not been investigated. The current research evaluated the effects of Crn and metformin (MET) on diabetic nephropathy induced by MGO in male mice., Materials and Methods: In this experimental study, 70 male NMRI mice were randomly divided into 7 groups: control, MGO (600 mg/Kg/d), MGO+Crn (15, 30, and 60 mg/kg/d), MGO+MET (150 mg/kg/d), and Crn60 (60 mg/kg/d). Methylglyoxal was gavaged for four weeks. After proving hyperglycemia, Cr and MET were administered orally in the last two weeks. Biochemical and antioxidant evaluations, microRNA expression, and histological evaluation were assessed., Results: The fasting blood glucose, urine albumin, blood urea nitrogen, plasma creatinine, malondialdehyde, Nrf2, miR-204, and miR-192 expression increased in the MGO group. These variables decreased in Crn-treated animals. The decreased levels of superoxide dismutase, catalase, glyoxalase 1, Glutathione, and miR-29a expression in the MGO group improved in the diabetic-treated mice. Histological alterations such as red blood cell accumulation, inflammation, glomerulus diameter changes, and proximal cell damage were also observed., Conclusion: Our study indicated that Crn and MET attenuated renal damage by inhibiting endoplasmic reticulum stress., Competing Interests: There are no conflicts of interest in this study.

Background: The main aim of the present study is to investigate the independent association objectively measured level of physical activity (PA) and serum concentration of liver aminotransferases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) among seemingly healthy individuals., Materials and Methods: The current secondary study was conducted in the framework of Khuzestan Comprehensive Health Study, a large population-based multicentric cross-sectional study, conducted between 2016 and 2019 on 18,966 individuals living in Khuzestan province, southwestern Iran. International PA Questionnaire was used for evaluating PA levels, and participants were divided into three groups: low, moderate, and high PA, and ALT and AST were compared between these groups., Results: The mean ± standard deviation age of participants was 38.65 ± 11.40 years. The majority of participants were female (71%). The mean concentration of ALT in total sample was 18.22 ± 13.06 (male: 23.65 ± 16.26 and female: 15.57 ± 10.06), while the mean concentration of ALT in total sample was 19.61 ± 8.40 (male: 22.44 ± 10.03 and female: 18.23 ± 7.08). A statistically significant inverse correlation was found between AST ( r = -0.08, P = 0.02) and ALT ( r = -0.038, P < 0.001) with total PA score. The mean concentration of ALT was 19.96 ± 13.63 in people with low PA, 17.62 ± 12.31 with moderate PA, and 18.12 ± 13.47 with high PA ( P < 0.001). The mean concentration of AST in total sample was 20.37 ± 8.85 in people with low PA, 19.21 ± 8.83 with moderate PA, and 19.75 ± 8.85 with high PA ( P < 0.001). The difference between people in different levels of PA in terms of mean concentration of AST was remained significant ( P = 0.003); however, the difference for ALT was not remained significant after adjusting potential confounders., Conclusion: The current study based on large sample showed that PA had a statistically negative association with the concentration of liver aminotransferases in the seemingly healthy individuals; however, the observed associations were weak. People in the lowest levels of PA had the highest levels of ALT and AST., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Research in Medical Sciences.)

Nonalcoholic fatty liver disease (NAFLD), as the most common chronic liver disease, is rapidly increasing worldwide. This complex disorder can include simple liver steatosis to more serious stages of nonalcoholic fibrosis and steatohepatitis (NASH). One of the critical concerns in NASH research is selecting and confiding in relying on preclinical animal models and experimental methods that can accurately reflect the situation in human NASH. Recently, creating nutritional models of NASH with a closer dietary pattern in human has been providing reliable, simple, and reproducible tools that hope to create a better landscape for showing the recapitulation of disease pathophysiology. This review focuses on recent research on rodent models (mice, rats, and hamsters) in the induction of the dietary model of NAFLD /NASH. This research tries to compile the different dietary compositions of NASH, time frames required for disease development, and their impact on liver histological features as well as metabolic parameters., (©The Author(s) 2022. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Introduction: Bisphosphonates can severely slow down orthodontic tooth movement (OTM) by reducing bone turnover. This calls for materials and methods to reverse or neutralize their effects on OTM. We propose systemic vitamin D3 (D3) for this purpose., Methods: Thirty-two male Wistar rats were randomized into 4 groups of 8 each. Three groups were administered D3 (3 systemic doses of 24,000 IU/kg each), alendronate (ALN) (5 doses of 7 mg/kg each), and ALN+D3 (same doses as mentioned above). One group served as the negative control. The incisors were distalized at 30 g of force for 2 weeks. OTMs were measured blindly. Radicular pressure areas were searched histologically (blindly) for capillaries, Howship's lacunae, osteoclasts, and osteoblasts. Data were analyzed statistically (α = 0.05, α = 0.0083, β <0.1)., Results: OTMs in the groups D3, ALN+D3, ALN, and control were 1.900 ± 0.237, 1.629 ± 0.219, 0.975 ± 0.145, and 1.565 ± 0.324 mm (analysis of variance, P <0.001), respectively. OTM in the ALN group was smaller than all other groups (Tukey, P <0.001). OTM in the D3 group was greater than in the control group (P = 0.054). The ALN+D3 group had greater OTM than the ALN group (P <0.001) but was not significantly different from the D3 (P = 0.153) or control (P = 0.951) groups. All histologic variables were significantly different across groups (Kruskal-Wallis, P <0.001). All the markers in the D3 group were more frequent than those of the other groups (Mann-Whitney U, P <0.001). There were fewer markers in the ALN group than in the control group (P ≤0.001). The ALN+D3 group had more markers than the ALN group in terms of capillaries, osteoclasts, and osteoblasts (P ≤0.007). The ALN+D3 group was similar to the control group regarding capillaries, osteoclasts, and osteoblasts (P ≥0.382)., Conclusions: Systemic vitamin D3 may accelerate OTM and increase histologic biomarkers of bone turnover. ALN reduces OTM and its histologic biomarkers. Systemic vitamin D3 can reverse this inhibitory effect of ALN on OTM back to normal., (Copyright © 2022 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Background: The role of hepatocyte apoptosis and inflammation has been implicated in the progression of nonalcoholic steatohepatitis (NASH). Overproduction of reactive oxygen species (ROS) appears to accelerate these pathways through the activation of Fas receptor signaling. Therefore, we explored the hepatoprotective effects of crocin as a strong free radical scavenger against oxidative damages leading to NASH development., Methods: Thirty-two male mice were randomly divided into control, NASH, NASH + crocin, and crocin groups. They received an intraperi- toneal injection of crocin twice a week, for 3 weeks. For NASH model induction, the animals were fed with a Western diet and exposed to cigarette smoke for 8 weeks. At the end of the experiment, liver histology, biochemical, and biomolecular analyses were done to evaluate the antioxidant, anti-inflammatory, and anti-apoptotic activities of crocin in the NASH model., Results: Evaluation of the features of the NASH model revealed steatosis, inflammatory infiltrate, and ballooning degeneration. Metabolic dysfunction was associated with elevated serum levels of the lipid profile and decreased hepatic liver enzymes. The increased content of malondialdehyde (MDA) and reduced antioxidant activities confirmed hepatotoxicity induction. There was a significant increase in expression level of Fas, caspase 3, and NF-κB genes that was also associated with elevation in hepatic TNF-α content. Moreover, expression the of Fas receptor protein was significantly detected on the hepatocyte membrane. Treatment with crocin effectively improved NASH-related parameters, and the histopathological findings were also parallel with the resulting changes., Conclusion: Crocin can be introduced as a candidate hepatoprotective agent against NASH by virtue of its anti-inflammatory, antioxi- dant, and anti-apoptotic properties, possibly through regulation of the Fas death receptor pathway.

Cisplatin, an antineoplastic drug used in cancer therapy, -induced nephrotoxicity mediated by the production of reactive oxygen species (ROS). Gallic acid (GA) is identified as an antioxidant substance with free radical scavenging properties. This research was designed to examine the ameliorative impact of GA caused by cisplatin-induced nephrotoxicity through apoptosis and long non-coding RNA (lncRNA) Taurine-upregulated gene 1 (TUG1) expression. Thirty-two male Sprague Dawley rats (200 - 220 g) were randomly allocated to four groups: (1) control group; (2) rats treated with cisplatin (7.5 mg/kg, i.p.) on the fourth day; and the two other groups include rats pretreated with GA (20 and 40 mg/kg by gavage) for s7 days and cisplatin (7.5 mg/kg, i.p.) at the fourth day. The rats were anesthetized and sacrificed for collecting samples, 72 h after cisplatin administration. The blood samples were used to investigate biochemical factors and kidney tissue was evaluated for measuring oxidative stress and inflammatory factors and the gene expression of molecular parameters. The results indicated that GA administration increased the B-cell lymphoma-2 (Bcl-2) mRNA and lncRNA TUG1 expression, and reduced Bcl-2-associated x protein (Bax), and caspase-3 expression. Likewise, the TAC level increased, and kidney MDA content decreased by administration of GA. GA also decreased the inflammatory factor levels, including IL-1β and TNF-α. Moreover, GA led to the improvement of kidney dysfunction as evidenced by reducing plasma BUN (blood urea nitrogen) and Cr (creatinine). Taken together, GA could protect the kidney against cisplatin-induced nephrotoxicity through antioxidant, anti-inflammatory, and anti-apoptosis properties and reduction of lncRNA TUG1 expression., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Exposures to particulate matter (PM) have been related to increased risk for cardiovascular health effects and can promote cardiac ischemia and oxidative stress. Crocin has strong antioxidant properties and stress-reducing effects. Therefore, this study considered the effect of crocin on cardiovascular parameters in rats exposed to PM 10 ., Materials and Methods: Forty Wistar rats (male, 250-300 g) were grouped as control, receiving normal saline and crocin, receiving PM 10 , receiving PM 10 +Crocin. Instillation of PM 10 into the trachea was done. Forty-eight hours after exposure to the normal saline or PM, the heart was separated. Hemodynamic and electrophysiological factors were measured. The levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase activity (CAT), malondialdehyde (MDA), xanthine oxidase, were evaluated by kits., Results: The voltage of the QRS complex was significantly reduced and PR and QTc intervals increased in PM 10 groups. Hemodynamic parameters before ischemia and in the ischemic-reperfusion stage, in the PM 10 group, showed a significant decrease. In the ischemic hearts of the PM 10 group, a significant decline in the activity of CAT, SOD, and GPx, and a significant increase in MDA and XOX enzymes activity were observed, and crocin improved all of these factors., Conclusion: Cardiac ischemia causes abnormal hemodynamic factors of the heart, which are exacerbated by PM 10 and further reduce the heart's contractile strength. Increased oxidative stress due to PM 10 is probably one of the important reasons for these changes. This study suggests that the use of antioxidants such as crocin improves the cardiovascular adverse effects of myocardial ischemia and PM 10 exposure., Competing Interests: The authors declare no conflicts of interest.

Objectives: Methylglyoxal (MG) provokes endoplasmic reticulum (ER) stress in β-cells and triggers pancreatic β-cell dysfunction. Crocin has anti-diabetic properties. The present study investigated whether crocin prevented pancreas damages induced by MG., Materials and Methods: Diabetes was induced by MG administration (600 mg/kg/day, PO). On the fourteenth day, after proving hyperglycemia, crocin (15, 30, and 60 mg/kg) and metformin (MT) (150 mg/kg) were used for detoxification of MG until the end of the experiment. The animals were divided into 6 groups: 1) control, 2) diabetic by MG, 3) MG + crocin 15 mg/kg, 4) MG + crocin 30 mg/kg, 5) MG + crocin 60 mg/kg, and 6) MG + MT. The data were analyzed by one-way analysis of variance and significant differences were compared by Tukey and Bonferroni tests ( P <0.05). Biochemical assays, antioxidant evaluation, and microRNAs expression associated with ER stress were assessed., Results: MG induced hyperglycemia, insulin resistance, and dyslipidemia ( P <0.001). Crocin and MT significantly ameliorated β-cell function through reduction of fasting blood glucose, malondialdehyde levels ( P <0.001), and significant elevation of anti-oxidant enzyme activity accompanied by regulation of glutathione and glyoxalase1-Nrf2 in MG induced diabetic mice. Crocin and MT significantly down-regulated microRNAs 204, 216b, 192, and 29a expression ( P <0.001). Crocin (60 mg/kg) ( P <0.01) and MT ( P <0.001) could improve diameter of pancreatic islets in MG treated mice., Conclusion: Crocin prevents the progression of diabetes through modulating ER stress-associated microRNAs and GLO1 activity with the helpful effects of glutathione and Nrf2., Competing Interests: There are no conflicts of interest, and all authors support the submission to this journal.

Objective: One of the severe complications and well-known sources of end stage renal disease (ESRD) from diabetes mellitus is diabetic nephropathy (DN). Exosomes secreted from diverse cells are one of the novel encouraging therapies for chronic renal injuries. In this study, we assess whether extracted exosomes from kidney tubular cells (KTCs) could prevent early stage DN in vivo ., Materials and Methods: In this experimental, exosomes from conditioned medium of rabbit KTCs (RK13) were purified by ultracentrifuge procedures. The exosomes were assessed in terms of morphology and size, and particular biomarkers were evaluated by transmission electron microscopy (TEM), scanning electron microscopy (SEM), Western blot, atomic force microscopy (AFM) and Zetasizer Nano analysis. The rats were divided into four groups: DN, control, DN treated with exosomes and sham. First, diabetes was induced in the rats by intraperitoneial (i.p.) administration of streptozotocin (STZ, 50 mg/kg body weight). Then, the exosomes were injected each week into their tail vein for six weeks. We measured 24-hour urine protein, blood urea nitrogen (BUN), and serum creatinine (Scr) levels with detection kits. The histopathological effects of the exosomes on kidneys were evaluated by periodic acid-Schiff (PAS) staining and expressions of miRNA-29a and miRNA-377 by quantitative real-time polymerase chain reaction (qRT-PCR)., Results: The KTC-Exos were approximately 50-150 nm and had a spherical morphology. They expressed the CD9 and CD63 specific markers. Intravenous injections of KTC-Exos potentially reduced urine volume (P<0.0001), and 24- hour protein (P<0.01), BUN (P<0.001) and Scr (P<0.0001) levels. There was a decrease in miRNA-377 (P<0.01) and increase in miRNA-29a (P<0.001) in the diabetic rats. KTC-Exos ameliorated the renal histopathology with regulatory changes in microRNAs (miRNA) expressions., Conclusion: KTC-Exos plays a role in attenuation of kidney injury from diabetes by regulating the miRNAs associated with DN., Competing Interests: There is no conflict of interest in this study., (Copyright© by Royan Institute. All rights reserved.)

Introduction: Little is known about the laboratory and radiological characteristics and clinical significance of peripheral immune alterations in patients with coronavirus disease 2019 (COVID-19). This study aims to clarify these aspects in children and adults with COVID-19. Methods: In this consecutive pilot study, COVID-19 patients with the confirmed pneumonia and real-time RT-PCR were recruited prospectively in June 2020. The clinical, chest CT, and laboratory features, such as lymphocyte subpopulations, were analyzed for each individual. Results: Forty confirmed COVID-19 patients, 11 severe children, 12 severe adults, and 17 critical adult patients, besides 20 healthy pediatrics and 14 healthy adults as controls, were enrolled prospectively. Adult patients, especially critical ones, had a much higher prevalence of laboratory and chest CT abnormalities. Data regarding immune cell subsets in children patients, compared with matched controls, had higher CD3+ CD8+ T cells ( p = 0.004) and lower CD4+/CD8+ ratio ( p = 0.042), while adult patients, compared with matched controls, had lower CD14+ monocytes ( p = 0.032). Adult patients were also categorized as experiencing critical or severe illness on admission and, compared with severe patients, had lower total lymphocytes ( p < 0.047), CD3+ T-lymphocytes ( p < 0.002), and CD3+ CD8+ T cells ( p = 0.001) and, on the other hand, had higher CD3+ CD4+ T cells ( p = 0.012) and CD4+/CD8+ ratio ( p = 0.003). Non survived adults, compared with survived patients, had significantly lower CD3+ T-lymphocyte ( p = 0.005). Conclusion: Unlike adult patients, who compared with matched controls and had more comorbidities, higher frequency of severe clinical symptoms, laboratory abnormalities, and immune cells alteration, clinical manifestations of COVID-19 in children (compared with matched controls) were relatively mild, and fewer clinical complications were seen either, perhaps because of a milder inflammatory response following their peripheral innate and adaptive immune cell alteration pattern., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shokati Eshkiki, Shahriari, Seyedtabib, Torabizadeh, Assarehzadegan, Nashibi, Khosravi, Neisi, Mard and Shayesteh.)

Background: Little is known regarding the impact of quantity and quality of sleep on the incidence of cardiovascular disease. The aim of this study was to investigate the possible independent association of late bedtime and premature coronary artery disease (PCAD)., Methods: Between October 2016 and November 2019, we conducted a cross-sectional population-based study on 30101 participants aged 20-65 years in Khuzestan Comprehensive Health Study (KCHS). Data on major risk factors of cardiovascular disease, habit history, physical activity, and sleep behavior was gathered and participants underwent blood pressure, anthropometric, and serum lipid and glucose profile measurements. PCAD was defined as documented history of developing obstructive coronary artery disease before 45 years in men and before 55 years in women., Results: Of a total of 30101 participants (64.1% female, mean age: 41.7±11.7 years) included in this study, 1602 (5.3%, 95% confidence interval: 5.1%-5.6%) had PCAD. Late bedtime was reported in 7613 participants (25.3%, 95% confidence interval: 24.9%-25.8%). Age-sex standardized prevalence for PCAD and late bedtime were 3.62 (3.43-3.82) and 27.8 (27.2-28.4), respectively. There was no significant difference ( P =0.558) regarding prevalence of PCAD between those with late bedtime (5.5%, 95% CI: 4.9%-6.0%) and those with early bedtime (5.3%, 95% CI: 5.0%-5.6%). However, after adjustment for potential confounders, late bedtime was independently associated with PCAD (OR=1.136, 95% CI=1.002-1.288, P =0.046)., Conclusion: In this study, late bedtime was significantly associated with presence of PCAD. Future prospective studies should elucidate the exact role of late bedtime in developing coronary atherosclerosis prematurely., (© 2021 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Objective: Destruction of pancreatic beta-cells induces an insulin deficiency and causes type 1 diabetes. The role of autophagy in inducing insulin-secreting cells (ISCs) from adipose-derived mesenchymal stem cells (AMSCs) was investigated in the current study., Materials and Methods: In this experimental study, the isolated AMSCs were characterization and exposed to a cocktail differentiation medium (CDM) in the absence or presence of 3-methyladenine (3MA), an autophagy inhibitor. The differentiation of ISCs was confirmed by the evaluation of the expression of beta-cell-specific genes including pancreatic and duodenal homeobox 1 ( PDX1 ), musculoaponeurotic fibrosarcoma oncogene homolog A (MAF-A), Nk class of homeodomain-encoding genes 6.1 and 2.2 ( NKX6-1 and NKX2.2 ), Glucose transporter 2 (GLUT-2) and INSLIN. Using Newport Green (NG), insulin-positive cells were identified. Insulin secretion in response to various glucose concentrations was measured. Autophagy was evaluated by Acridine orange (AO) staining. Also, expression of autophagy-associated genes, including autophagy-related gene 5 ( ATG-5 ), autophagy-related gene 7 ( ATG-7 ), BECLIN-1 , and mammalian target of rapamycin ( mTOR ), was evaluated by Real-time polymerase chain reaction (PCR) method., Results: We observed a significant increase of beta-cell specific genes expression in the CDM-treated cells (P<0.01 or P<0.001), whereas the expression of these genes was down-regulated in 3MA-exposed cells. Expression of INSULIN and GLUT-2 genes (P<0.01 and P<0.05, respectively), insulin secretion in response to glucose (P<0.01), and percentage of NG-positive cells (P<0.05) in the 3MA-exposed cells were considerably lower than the cells treated with CDM. The percentage of AO-positive cells (P<0.01) and the expression of autophagy-related genes (P<0.001) was significantly enhanced in the CDM group. These events were significantly prevented by the 3MA., Conclusion: Our data showed that autophagy is necessary for beta-cell differentiation, and preventing autophagy by 3MA causes the reduction of beta-cell differentiation and insulin secretion., Competing Interests: There is no conflict of interest in this study., (Copyright© by Royan Institute. All rights reserved.)

Emphysema is associated with an abnormal airspace enlargement distal to the terminal bronchioles accompanied by destructive changes in the alveolar walls and chronic inflammation. Air pollution can cause respiratory diseases such as chronic obstructive pulmonary disease (COPD) and emphysema in urban areas. As a natural antioxidant compound, gallic acid may be effective in controlling inflammation and preventing disease progression. In this research, we investigated the protective role of gallic acid in the inflammatory process and the possible signaling pathway in the elastase-induced emphysema. Forty-eight rats were divided into six different groups including the following: control, gallic acid (7.5, 15, and 30 mg/kg), porcine pancreatic elastase (PPE), and PPE+gallic acid 30 mg/kg. Oxidative stress indexes such as malondialdehyde and antioxidant enzyme activity were measured in all groups. The gene expression levels of heme oxygenase-1 (HO-1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were determined as key regulators of antioxidant and inflammation system. The PPE group showed pulmonary edema and a significant change in arterial blood gas values, which was associated with decreased antioxidant activity of enzymes and changes in NF-κB, HO-1, and Nrf2 gene expression in comparison to the control group. Co-treatment with gallic acid preserved all these changes approximately to the normal levels. The results confirmed that elastase-induced emphysema leads to lung injuries, which are associated with oxidative stress and inflammation. Also, the results suggested that gallic acid as a natural antioxidant agent can modulate the Nrf2 signaling pathway to protect the lung against elastase-induced emphysema. Therefore, we documented the evidence for the importance of NF-κB inhibitors and Nrf2 activators as a target for new treatments in respiratory dysfunction caused by oxidative agents., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The burden of diseases and death related to environmental pollution is becoming a major public health challenge. This study was designed to evaluate the deleterious effects of a combination of dust exposure and high-fat diet on liver function. Gallic acid as a potent antioxidant was used to prevent/alleviate non-alcoholic fatty liver disease (NAFLD) in rats exposed to dust and HFD., Materials and Methods: 24 rats were randomly divided into 3 experimental groups: HFD+Clean air, HFD+N/S+Dust and HFD+gallic acid+Dust. Animals were exposed to CA/ dust for six weeks on alternate days. At the end of the experiments, rats were anesthetized and samples were taken to perform molecular, biomedical, and histopathological evaluations., Results: Dust exposure induced NAFLD features in rats under HFD. Dust exposure and HFD disrupted liver enzymes and lipid profile. Dust exposure and HFD increased liver MDA level, mRNA expression of NF-Kβ , TNF-α , IL-6 , Nrf2 , HO1 and miRs122, and 34a. Dust+HFD also decreased liver total antioxidant capacity level. Pretreatment with GA improved almost studied variables in the HFD+GA+Dust group., Conclusion: The present study showed that HFD given for 6 weeks and dust exposure induced NAFLD in Wistar rats through inducing oxidative stress. Oxidative stress through activating the inflammatory pathways caused NAFLD features. GA pretreatment by inhibiting oxidative stress, effectively protected liver functions against HFD+Dust induced inflammation., Competing Interests: The authors have declared that there is no conflict of interest.

Background: Chronic kidney disease (CKD) is a growing global health problem with faster progression in developing countries such as Iran. Here we aimed to evaluate the prevalence and determinants of CKD stage III+., Methods: This research is part of the Khuzestan Comprehensive Health Study (KCHS), a large observational population-based cross-sectional study in which 30,041 participants aged 20 to 65 were enrolled. CKD was determined with estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73m 2 , based on two equations of Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The multivariate logistic regression was used to evaluate the CKD stage III+ determinants., Results: Prevalence of CKD stage III+ is estimated to be 7.1, 5.5, and 5.4% based on MDRD, CKD-EPI, and combination of both equations, respectively. More than 89% of CKD subjects aged higher than 40 years. In regression analysis, age more than 40 years had the strongest association with CKD stage III+ probability (OR: 8.23, 95% CI: 6.91-9.18). Higher wealth score, hypertension, High-Density Lipoprotein levels less than 40 mg/dl, and higher waist to hip ratio were all associated with CKD stage III+ while Arab ethnicity showed a protective effect (OR: 0.69, 95% CI: 0.57-0.78)., Conclusion: Our findings provide detailed information on the CKD stage III+ and its determinants in the southwest region of Iran. Due to strong association between age and CKD stage III+, within a few decades we might expect a huge rise in the CKD prevalence., (© 2021. The Author(s).)

Background: Nucleus tractus solitarius (NTS) is a brain area that plays a key role in kidney and cardiovascular regulation via baroreceptors impulses., Objectives: The aim of this study was to evaluate the effect of naringin (NAR) and trimetazidine (TMZ) alone and their combination on NTS electrical activity and baroreceptor sensitivity (BRS) in renal ischemia- reperfusion (I/R) injury., Methods: Forty male Sprague-Dawley rats (200- 250 g) were allocated into 5 groups with 8 in each. 1) Sham; 2) I/R; 3) TMZ 5 mg/kg; 4) NAR 100 mg/kg; and 5) TMZ5+ NAR100. The left femoral vein was cannulated to infuse saline solution or drug and the BRS was evaluated. I/R was induced by occlusion of renal pedicles for 45 min, followed by 4 hours of reperfusion. The NTS local electroencephalogram (EEG) was recorded before, during ischemia and throughout the reperfusion. Phenylephrine was injected intravenously to evaluate BRS at the end of reperfusion time. The data were analyzed by two-way repeated measurement ANOVA followed by Tukey's post hoc test. A p-value <0.05 was considered significant., Results: NTS electrical waves did not change during ischemia time, while they significantly decreased during the entire reperfusion time. NTS electrical activity and BRS dramatically reduced in rats with I/R injury; however, administration of NAR, TMZ alone or their combination significantly improved these changes in rats with I/R injury., Conclusions: The results showed that I/R injury leads to reduced BRS and NTS electrical activity and there may be an association between I/R and decreased BRS. In addition, NAR and TMZ are promising agents to treat I/R complications.

Background: The effect of total suspended particulate matter (TSP) was investigated on the expression of inflammatory and apoptotic factors in diabetic rats, and the effect of crocin and insulin was examined on these factors., Methods: Fifty-four adult male wistar rats were divided into nine experimental groups: control group, crocin group (received crocin, 50 mg/kg), diabetic group (received a single dose of alloxan at 120 mg/kg, IP), TSP group (5 mg/kg TSP instilled intratracheally), diabetic-crocin group (received crocin at 50 mg/kg after the induction of diabetes by alloxan (120 mg/kg)), diabetic-insulin group (received regular insulin (5 U/kg), crocin-TSP group (received crocin at 50 mg/kg, IP, and then 5 mg/kg TSP was instilled intratracheally), diabetic-TSP-insulin group (after receiving alloxan (120 mg/kg) and instilling TSP (5 mg/kg, intratracheally), a single dose (5 U/kg) of regular insulin), and diabetic-TSP-crocin group (after receiving alloxan (120 mg/kg) and instilling TSP (5 mg/kg, intratracheally), a single dose of crocin (50 mg/kg, IP)). Quantitative real-time PCR was performed to measure the expression of the mRNAs of apoptotic (Bax and Bcl2) and inflammatory mediators (TNFα, COX2, iNOS/eNOS) in Wistar rats., Results: In diabetic and TSP groups the inflammatory factors and BAX/Bcl2 ratio significantly increased compared to the control group. In diabetic-TSP-insulin and diabetic-TSP-crocin, a significant decrease was observed in the rate of inflammatory factors and BAX/Bcl2 ratio., Conclusion: The results suggested that diabetes and exposure to TSP increase the rate of apoptosis and inflammation, and also demonstrated the anti-apoptotic and anti-inflammation role of insulin and crocin.

Background: The Middle East and North Africa (MENA) is postulated to have the highest increase in the prevalence of diabetes by 2030; however, studies on the epidemiology of diabetes are rather limited across the region, including in Iran., Methods: This study was conducted between 2016 and 2018 among Iranian adults aged 20 to 65 years residing in Khuzestan province, southwestern Iran. Diabetes was defined as the fasting blood glucose (FBG) level of 126 mg/dl or higher, and/or taking antidiabetic medications, and/or self-declared diabetes. Prediabetes was defined as FBG 100 to 125 mg/dl. Multinomial logistic regression models were used to examine the association of multiple risk factors that attained significance on the outcome., Results: Overall, 30,498 participants were recruited; the mean (±SD) age was 41.6 (±11.9) years. The prevalence of prediabetes and diabetes were 30.8 and 15.3%, respectively. We found a similar prevalence of diabetes in both sexes, although it was higher among illiterates, urban residents, married people, and smokers. Participants aged 50-65 and those with Body Mass Index (BMI) 30 kg/m 2 or higher were more likely to be affected by diabetes [RR: 20.5 (18.1,23.3) and 3.2 (3.0,3.6)]. Hypertension [RR: 5.1 (4.7,5.5)], waist circumference (WC) equal or more than 90 cm [RR: 3.6 (3.3,3.9)], and family history [RR: 2.3 (2.2,2.5)] were also significantly associated with diabetes. For prediabetes, the main risk factors were age 50 to 65 years [RR: 2.6 (2.4,2.8)], BMI 30 kg/m 2 or higher [RR: 1.9 (1.8,2.0)], hypertension and WC of 90 cm or higher [RR: 1.7 (1.6,1.8)]. The adjusted relative risks for all variables were higher in females than males, with the exception of family history for both conditions and waist circumference for prediabetes., Conclusions: Prediabetes and diabetes are prevalent in southwestern Iran. The major determinants are older age, obesity, and the presence of hypertension. Further interventions are required to escalate diabetes prevention and diagnosis in high-risk areas across Iran.

Background: In 2017, the American College of Cardiology/American Heart Association (ACC/AHA) provided a new guideline for hypertension prevention and management. We aimed to update the prevalence, awareness, control, and determinants of hypertension based on this guideline in Khuzestan province, southwest of Iran, and to estimate the number of people who are eligible for non-pharmacologic and pharmacologic intervention., Methods: This population-based cross-sectional study was conducted in Khuzestan, a large province in the southwest of Iran. Comprehensive information about the potential relating factors of hypertension was collected, blood pressure was measured, and anthropometric measurements were obtained. Moreover, the dietary pattern was evaluated in 2830 individuals, using a qualitative food frequency questionnaire., Results: Among 30,506 participants, 30,424 individuals aged 20-65 years were eligible for the study. In comparison with the previous guideline released by the Joint National Committee (JNC8), the prevalence of hypertension in Khuzestan dramatically increased from 15.81 to 42.85% after implementation of the ACC/AHA guideline, which was more dominant in the male population and the 45-54 age group. The sex and age adjustment of the hypertension prevalence was estimated to be 39.40%. The percentage of hypertension awareness, treatment, and control were 45.85%, 35.42%, and 59.63%, which dropped to 22.72%, 26.37%, and 28.94% after implementation of new guideline, respectively., Conclusions: In the ACC/AHA guideline, a higher number of individuals with the pre-hypertension condition were shifted into the hypertension category and the level of awareness, treatment, and control were dramatically decreased, which highlight a great need to expand the public health infrastructure for further managing the substantial increased burden on healthcare system. However, further studies with population over 65 years are required to estimate the eligibility for antihypertensive treatment in this province after implementation of new guideline.

Aims: Cardiovascular diseases (CVDs) are the leading cause of death in the world. Many modifiable risk factors have been reported to synergistically act in the development of CVDs. We aimed to compare the predictive power of anthropometric indices, as well as to provide the best cut-off point for these indicators in a large population of Iranian people for the prediction of CVDs and CVD risk factors., Methods and Results: All the data used in the present study were obtained from Khuzestan comprehensive health study (KCHS). Anthropometric indices, including BMI (body mass index), WC (waist circumference), HC (hip circumference), WHR (waist-to-hip ratio), WHtR (waist-to-height ratio), ABSI (a body shape index), as well as CVD risk factors [dyslipidaemia, abnormal blood pressure (BP), and hyperglycaemia] were recorded among 30 429 participants. WHtR had the highest adjusted odds ratios amongst anthropometric indices for all the risk factors and CVDs. WC had the highest predictive power for dyslipidaemia and hyperglycaemia [area under the curve (AUC) = 0.622, 0.563; specificity 61%, 59%; sensitivity 69%, 60%; cut-off point 87.95, 92.95 cm, respectively], while WHtR had the highest discriminatory power for abnormal BP (AUC = 0.585; specificity 60%; sensitivity 65%; cut-off point 0.575) and WHR tended to be the best predictor of CVDs (AUC = 0.527; specificity 58%; sensitivity 64%; cut-off point 0.915)., Conclusion: In this study, we depicted a picture of the Iranian population in terms of anthropometric measurement and its association with CVD risk factors and CVDs. Different anthropometric indices showed different predictive power for CVD risk factors in the Iranian population., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)