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Introduction: Human aortic tissues in vitro are tools to clarify the pathophysiological mechanisms of the cardiovascular system, cell culture, and transplants. Therefore, this study aims to analyze and compare the preservation of human aneurysmatic aortic tissues in three different solutions., Methods: Six human abdominal aortic aneurysms were obtained from patients after surgical ablation. The aorta samples were incubated in different solutions - 0.9% normal physiological saline solution, Ringer's lactate solution, and histidine-tryptophan-ketoglutarate solution (Custodiol®). Segments were collected at 0, 6, 24, and 48 hours. Creatine kinase and nitrate/nitrite were quantified for each incubation time. The tissue's alpha-smooth muscle actin was analyzed by immunofluorescence., Results: There was a significant increase in creatine kinase formation in the normal saline group at 0 and 48 hours and in the Ringer's lactate group at 0 and 48 hours (P=0.018 and P=0.028). The lower levels of creatine kinase and nitrate/nitrite and the aortic tissues' morphological integrity show that histidine-tryptophan-ketoglutarate has better tissue protection. These data suggest that histidine-tryptophan-ketoglutarate induces a protective effect on smooth muscle cells, with less tissue depletion in the aortic aneurysm., Conclusion: This study compared three preservation solutions with the potential for human abdominal aortic aneurysm tissue preservation. The histidine-tryptophan-ketoglutarate solution reduced tissue injury and improved tissue preservation in human abdominal aortic aneurysm tissue samples.

Objective: To compare the ability of bioreactance noninvasive cardiac output (BR-NICO) with thermodilution cardiac output (TDCO) for the measurement of cardiac output (CO) in healthy adult horses receiving 2 different IV volume replacement solutions., Design: Prospective randomized crossover study from September to November 2021., Setting: University teaching hospital., Animals: Six university-owned adult horses., Interventions: Horses were randomly assigned to receive 7.2% hypertonic saline solution (HSS) or 6% hydroxyethyl starch (130/0.4) solution (HETA). BR-NICO and TDCO were measured simultaneously at baseline, 10, 20, 30, 40, 50, 60, 90, and 120 minutes before fluid administration and again at the same times after starting a bolus infusion of IV volume replacers. All solutions were administered within 10 minutes., Measurements and Main Results: BR-NICO and TDCO were strongly correlated (Pearson r 2  = 0.93; P < 0.01). Regression analysis showed the relationship between TDCO and BR-NICO was BR-NICO = 0.48 × TDCO + 0.6. For the corrected BR-NICO values, the Bland-Altman agreement mean bias and lower/upper limits of agreement were -0.62 and -5.3 to 3.9 L/min, respectively. Lin's concordance (95% confidence interval) between methods was 0.894 (0.825-1.097). Compared with baseline, HSS increased the CO at 10 and 20 minutes (TDCO and BR-NICO). Compared with baseline, HETA decreased the CO at 10 and 20 minutes (TDCO and BR-NICO) and increased the CO at 90 (TDCO only) and 120 minutes (TDCO and BR-NICO)., Conclusions: BR-NICO strongly agreed with TDCO in the measurement of CO in healthy unsedated adult horses. HSS administration significantly increased CO in the first 30 minutes, while HETA initially decreased CO at 10 minutes but increased CO to above baseline values by 90 minutes., (© Veterinary Emergency and Critical Care Society 2024.)

Abstract: Sepsis causes dysfunction in different organs, but the pathophysiological mechanisms behind it are similar and mainly involve complex hemodynamic and cellular dysfunction. The importance of microcirculatory dysfunction in sepsis is becoming increasingly evident, in which endothelial dysfunction and glycocalyx degradation play a major role. This study aimed to investigate the effects of hydrogen-rich saline (HRS) on renal microcirculation in septic renal failure, and whether Sirt1 was involved in the renoprotective effects of HRS. Rats model of sepsis was established by cecal ligation and puncture, and septic rats were intraperitoneal injected with HRS (10 mL/kg). We found that in sepsis, the degree of glycocalyx shedding was directly proportional to the severity of sepsis. The seven-day survival rate of rats in the HRS+CLP group (70%) was higher than that of the CLP group (30%). HRS improved acidosis and renal function and reduced the release of inflammatory factors (TNF, IL-1β, and IL-6). The endothelial glycocalyx of capillaries in the HRS+CLP group (115 nm) was observed to be significantly thicker than that in the CLP group (44 nm) and EX527 (67.2 nm) groups by electron microscopy, and fewer glycocalyx metabolites (SDC-1, HS, HA, and MMP9) were found in the blood. Compared with the CLP group, HRS reduced renal apoptosis and upregulated Sirt1 expression, and inhibited the NF-κB/MMP9 signaling pathway. In addition, HRS did not damage immune function in septic rats as well. Generally speaking, our results suggest that HRS can alleviate the inflammatory response, inhibit glycocalyx shedding, improve septic kidney injury, and enhance survival rate., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Objectives: Intestinal ischemia-reperfusion (I/R) injury is a multifactorial and complex clinical pathophysiological process. Current research indicates that the pathogenesis of intestinal I/R injury involves various mechanisms, including ferroptosis. Methane saline (MS) has been demonstrated to primarily exert anti-inflammatory and antioxidant effects in I/R injury. In this study, we mainly investigated the effect of MS on ferroptosis in intestinal I/R injury and determined its potential mechanism., Methods: In vivo and in vitro intestinal I/R injury models were established to validate the relationship between ferroptosis and intestinal I/R injury. MS treatment was applied to assess its impact on intestinal epithelial cell damage, intestinal barrier disruption, and ferroptosis., Results: MS treatment led to a reduction in I/R-induced intestinal epithelial cell damage and intestinal barrier disruption. Moreover, similar to treatment with ferroptosis inhibitors, MS treatment reduced ferroptosis in I/R, as indicated by a decrease in the levels of intracellular pro-ferroptosis factors, an increase in the levels of anti-ferroptosis factors, and alleviation of mitochondrial damage. Additionally, the expression of Nrf2/HO-1 was significantly increased after MS treatment. However, the intestinal protective and ferroptosis inhibitory effects of MS were diminished after the use of M385 to inhibit Nrf2 in mice or si-Nrf2 in Caco-2 cells., Discussion: We proved that intestinal I/R injury was mitigated by MS and that the underlying mechanism involved modulating the Nrf2/HO-1 signaling pathway to decrease ferroptosis. MS could be a promising treatment for intestinal I/R injury.

Objective: To evaluate the topical antiseptic activity of saline, chlorhexidine (CHX), and povidone-iodine (PI) scrubs on the skin of chickens with or without the addition of DuraPrep (DP)., Animals: 7 healthy adult Orpington hens (Gallus gallus domesticus)., Methods: The right apterium corporale laterale was swabbed for standard aerobic bacterial culture and colony-forming unit (CFU) determination. The apterium was divided into 3 areas and treated with sterile saline, CHX, or PI. Samples were collected by swabbing each area before and after additional treatment with DP. CFU's were counted after 48 hours of incubation. Statistical analysis was performed using a linear mixed model with a continuous outcome., Results: Compared to saline, CHX and PI treatment without DP decreased CFU count by 119 (95% CI, 55 to 183; P < .001) and 123 (95% CI, 58 to 187; P < .001), respectively. The application of DP after CHX and PI further decreased CFU counts by 6 (P = .01) and 9 (P = .01), respectively. DP after saline treatment decreased counts by 128 CFU (95% CI, 63 to 192; P < .001). No significant difference was detected between saline, PI, or CHX after DP application (-1.0 CFU; 95% CI, 63.4 to -65.4; P = .98 for both PI and CHX)., Clinical Relevance: CHX or PI provided greater reductions in bacterial CFU than saline, and all combinations with DP provided similar results. No notable cutaneous reactions were detected at any point. This data suggests that a scrub protocol including CHX or PI with DP is acceptable in surgical site preparation of chickens.

The occurrence of major depressive disorder is widespread and can be observed in individuals belonging to all societies. It has been suggested that changes in the NO pathway and heightened oxidative stress may play a role in developing this condition. Anethole is a diterpene aromatic compound found in the Umbelliferae, Apiaceae, and Schisandraceae families. It has potential pharmacological effects like antioxidant, anxiolytic, analgesic, anti-inflammatory, antidiabetic, gastroprotective, anticancer, estrogenic, and antimicrobial activities. This study aimed to investigate the potential antidepressant properties of Anethole in a mouse model experiencing maternal separation stress while also examining its impact on oxidative stress and nitrite levels. The research involved the participation of 40 male NMRI mice, separated into five distinct groups to conduct the study. The control group was administered 1 ml/kg of normal saline, while the MS groups were given normal saline and Anethole at 10, 50, and 100 mg/kg doses. The study comprised various behavioural tests, including the open field test (OFT), forced swimming test (FST), and splash test, to assess the effects of Anethole on the mice. In addition to the behavioural tests, measurements were taken to evaluate the total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrite levels in the hippocampus of the mice. According to the findings, maternal separation stress (MS) led to depressive-like conduct in mice, including a rise in immobility duration during the FST and a reduction in the duration of grooming behaviour in the splash test. Additionally, the results indicated that MS correlated with an increase in the levels of MDA and nitrite and a reduction in the TAC in the hippocampus. However, the administration of Anethole resulted in an increase in grooming activity time during the splash test and a decrease in immobility time during the FST. Anethole also exhibited antioxidant characteristics, as demonstrated by its ability to lower MDA and nitrite levels while increasing the TAC in the hippocampus. The results suggest that Anethole may have an antidepressant-like impact on mice separated from their mothers, likely partly due to its antioxidant properties in the hippocampus., (© 2024. The Author(s).)

Objectives: Despite the use of multimodal analgesia, patients undergoing knee arthroplasty still encounter residual moderate pain. The addition of betamethasone to local anesthetic has been shown to improve postoperative pain. However, it remains uncertain whether the positive effects of perineural or intravenous administration of betamethasone on analgesia outcomes lead to better early mobility and postoperative recovery., Methods: Between June 2022 and February 2023, a total of 159 patients who were undergoing knee arthroplasty were included in this study. These patients were allocated randomly into three groups: (i) the NS group, received ropivacaine 0.375% and intravenous 3mL 0.9% normal saline; (ii) the PNB group, received ropivacaine 0.375% plus perineural betamethasone (12mg) 3mL and intravenous 3mL 0.9% normal saline; and (iii) the IVB group, received ropivacaine 0.375% and intravenous betamethasone (12mg) 3mL., Results: Both perineural and intravenous administration of betamethasone led to improved median (IQR) numeric rating scale (NRS) scores on the 6-meter walk test, with a score of 1.0 (1.0-2.0) for both groups, compared with 2.0 (1.0-2.0) for the NS group (p = 0.003). Compared to the NS group, both the PNB and IVB groups showed significant reductions in NRS scores at 24 and 36 h after surgery, along with a significant increase in ROM at 24, 36, and 48 h post-operation. Additionally, it exhibited lower levels of cytokine IL-1β and TNF-α in fluid samples, as well as lower level of HS-CRP in blood samples in the PNB and IVB groups compared to the NS group., Conclusion: The administration of perineural and intravenous betamethasone demonstrated an enhanced analgesic effect following knee arthroplasty. Furthermore, it was associated with reduced levels of IL-1β, TNF-α, and HS-CRP, as well as enhanced knee ROM, which is conducive to early ambulation and postoperative rehabilitation after knee arthroplasty., (© 2024 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Objective: One of the most critical reasons for limiting cancer treatment is the toxic effects of anti-cancer drugs on healthy tissues and organs. This study aims to investigate the possible protective effects of misoprostol (MS) against the damage that arises from paclitaxel (PT), an anti-cancer pharmacological agent, in the rat heart using histopathological and biochemical analyses., Methods: In this study, four groups, each containing seven animals, were formed by random selection from 28 Sprague Dawley female rats. Control group rats were administered 1 ml of normal saline orally and intraperitoneally (i.p.) for six days. While the PT group rats were administered PT at a dose of 2 mg/kg intraperitoneally (i.p.) on days 0, 2, 4, and 6, the MS group was administered MS at a dose of 0.2 mg/kg in 1 ml normal saline by oral gavage for six days. PT and MS were administered to the PT + MS group rats in the same dose and route as the previous groups., Results: Administration of PT increased serum lactate dehydrogenase (LDH), cardiac troponin I (cTn-I), creatine kinase isoenzyme MB (CK-MB), and brain natriuretic peptide (BNP) levels. PT administration also decreased the levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in the heart tissue while increasing the level of malondialdehyde (MDA) (p < 0.05). In histopathological examinations, pathological changes, such as edema, congestion, hemorrhage, apoptosis, and degeneration, occurred in the heart tissue of PT-treated rats. The negative changes in histopathological and biochemical parameters that occurred in the PT group were almost not observed in the PT + MS group (p < 0.005)., Conclusion: When the findings were evaluated, it was concluded that MS protects the heart tissue from the harmful effects of PT, probably due to its antioxidant, anti-apoptotic and TNF-alpha suppressive effects., Competing Interests: Declaration of Competing Interest There is no conflict of interest between the authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Ischemia-reperfusion (IR) injury is a major concern that frequently occurs during vascular surgeries. Hydrogen-rich saline (HRS) solution exhibits antioxidant and anti-inflammatory properties. This study aimed to examine the effects of HRS applied before ischemia in the lungs of rats using a lower extremity IR model., Material and Methods: After approval was obtained from the ethics committee, 18 male Wistar albino rats weighing 250-280 g were randomly divided into three groups: control (C), IR and IR-HRS. In the IR and IR-HRS groups, an atraumatic microvascular clamp was used to clamp the infrarenal abdominal aorta, and skeletal muscle ischemia was induced. After 120 min, the clamp was removed, and reperfusion was achieved for 120 min. In the IR-HRS group, HRS was administered intraperitoneally 30 min before the procedure. Lung tissue samples were examined under a light microscope and stained with hematoxylin-eosin (H&E). Malondialdehyde (MDA) levels, total sulfhydryl (SH) levels, and histopathological parameters were evaluated in the tissue samples., Results: MDA and total SH levels were significantly higher in the IR group than in the control group ( p  < 0.0001 and p  = 0.001, respectively). MDA and total SH levels were significantly lower in the IR-HRS group than in the IR group ( p  < 0.0001 and p  = 0.013, respectively). A histopathological examination revealed that neutrophil infiltration/aggregation, alveolar wall thickness, and total lung injury score were significantly higher in the IR group than in the control group ( p  < 0.0001, p  = 0.001, and p  < 0.0001, respectively). Similarly, alveolar wall thickness and total lung injury scores were significantly higher in the IR-HRS group than in the control group ( p  = 0.009 and p  = 0.004, respectively). A statistically significant decrease was observed in neutrophil infiltration/aggregation and total lung injury scores in the IR-HRS group compared to those in the IR group ( p  = 0.023 and p  = 0.022, respectively)., Conclusion: HRS at a dose of 20 mg/kg, administered intraperitoneally 30 min before ischemia in rats, reduced lipid peroxidation and oxidative stress, while also reducing IR damage in lung histopathology. We believe that HRS administered to rats prior to IR exerts a lung-protective effect., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: The aim of the present study was to examine donkey sperm quality after intratesticular injection of hypertonic mannitol (HM) and saline (HS)., Methods: Randomly assigned to five treatment groups were 15 adult male donkeys: (1) Control group (no treatment), (2) Surgery group (surgical castration for testosterone control), (3) NS group (normal saline intratesticular injection), (4) HS group (hypertonic saline), and (5) HM group. We injected 20 mL per testicle. We took 5 mL blood from all donkeys before injection. Castration was performed under general anesthesia 60 days later. Samples included blood and testicular tissue. Total motility (TM), progressive motility (PM), movementy features, DNA damage, morphology, viability, and plasma membrane functionality were evaluated. Hormone analyses, histomorphometric studies and oxidative stress indices including total antioxidant capacity (TAC), glutathione peroxidase (GPx), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and NADP+/NADPH were evaluated. Apoptosis, pyroptosis-related Bax, Caspase-1, GSDMD, and Bcl-2 expression were also assessed., Results: In HS and HM groups, testosterone, epididymal sperm count, motility, viability, and plasma membrane functionality dropped while sperm DNA damage increased. HS and HM groups had significantly lower histomorphometric parameters, TAC, GPx, SOD, GSH, and Bcl-2 gene expression. MDA, NADP + /NADPH, Bax, Caspase-1, and GSDMD gene expression were substantially higher in the HS and HM groups than in the control group., Conclusions: Toxic effects of hypertonic saline and mannitol on reproductive parameters were seen following, hence, they might be considered as a good chemical sterilizing treatment in donkeys., (© 2024. The Author(s).)

Although it is well established that fibromyalgia (FM) syndrome is characterized by chronic diffuse musculoskeletal hyperalgesia, very little is known about the effect of this pathology on muscle tissue plasticity. Therefore, the present study aimed to characterize the putative alterations in skeletal muscle mass in female rats subjected to a FM model by inducing chronic diffuse hyperalgesia (CDH) through double injections of acidic saline (pH 4.0) into the left gastrocnemius muscle at 5-day intervals. To determine protein turnover, the total proteolysis, proteolytic system activities and protein synthesis were evaluated in oxidative soleus muscles of pH 7.2 (control) and pH 4.0 groups at 7 days after CDH induction. All animals underwent behavioural analyses of mechanical hyperalgesia, strength and motor performance. Our results demonstrated that, in addition to hyperalgesia, rats injected with acidic saline exhibited skeletal muscle loss, as evidenced by a decrease in the soleus fibre cross-sectional area. This muscle loss was associated with increased proteasomal proteolysis and expression of the atrophy-related gene (muscle RING-finger protein-1), as well as reduced protein synthesis and decreased protein kinase B/S6 pathway activity. Although the plasma corticosterone concentration did not differ between the control and pH 4.0 groups, the removal of the adrenal glands attenuated hyperalgesia, but it did not prevent the increase in muscle protein loss in acidic saline-injected animals. The data suggests that the stress-related hypothalamic-pituitary-adrenal axis is involved in the development of hyperalgesia, but is not responsible for muscle atrophy observed in the FM model induced by intramuscular administration of acidic saline. Although the mechanisms involved in the attenuation of hyperalgesia in rats injected with acidic saline and subjected to adrenalectomy still need to be elucidated, the results found in this study suggest that glucocorticoids may not represent an effective therapeutic approach to alleviate FM symptoms., (© 2024 John Wiley & Sons Australia, Ltd.)

This study was conducted to evaluate how sterubin affects rotenone-induced Parkinson's disease (PD) in rats. A total of 24 rats were distributed into 4 equal groups: normal saline control and rotenone control were administered saline or rotenone (ROT), respectively, orally; sterubin 10 received ROT + sterubin 10 mg/kg po; and sterubin alone was administered to the test group (10 mg/kg). Rats of the normal saline and sterubin alone groups received sunflower oil injection (sc) daily, 1 h after receiving the treatments cited above, while rats of the other groups received rotenone injection (0.5 mg/kg, sc). The treatment was continued over the course of 28 days daily. On the 29th day, catalepsy and akinesia were assessed. The rats were then euthanized, and the brain was extracted for estimation of endogenous antioxidants (MDA: malondialdehyde, GSH: reduced glutathione, CAT: catalase, SOD: superoxide dismutase), nitrative (nitrite) stress markers, neuroinflammatory cytokines, and neurotransmitter levels and their metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), dopamine (DA), norepinephrine (NE), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA)). Akinesia and catatonia caused by ROT reduced the levels of endogenous antioxidants (GSH, CAT, and SOD), elevated the MDA level, and altered the levels of nitrites, neurotransmitters, and their metabolites. Sterubin restored the neurobehavioral deficits, oxidative stress, and metabolites of altered neurotransmitters caused by ROT. Results demonstrated the anti-Parkinson's activities of sterubin in ROT-treated rats.

This study observed the protective effect of resveratrol(Res) on ovarian function in poor ovarian response(POR) mice by regulating the Hippo signaling pathway and explored the potential mechanism of Res in inhibiting ovarian cell apoptosis. Female mice with regular estrous cycles were randomly divided into a blank group, a model group, and low-and high-dose Res groups(20 and 40 mg·kg~(-1)), with 20 mice in each group. The blank group received an equal volume of 0.9% saline solution by gavage, while the model group and Res groups received suspension of glycosides of Triptergium wilfordii(GTW) at 50 mg·kg~(-1) by gavage for two weeks to induce the model. After modeling, the low-and high-dose Res groups were continuously treated with drugs by gavage for two weeks, while the blank group and the model group received an equal volume of 0.9% saline solution by gavage. Ovulation was induced in all groups on the day following the end of treatment. Finally, 12 female mice were randomly selected from each group, and the remaining eight female mice were co-housed with male mice at a ratio of 1∶1. Changes in the estrous cycle of mice were observed using vaginal cytology smears. The number of ovulated eggs, ovarian wet weight, ovarian index, and pregnancy rate of mice were measured. The le-vels of anti-Mullerian hormone(AMH), follicle-stimulating hormone(FSH), estradiol(E&#95;2), and luteinizing hormone(LH) in serum were determined using enzyme-linked immunosorbent assay(ELISA). Ovarian tissue morphology and ovarian cell apoptosis were observed using hematoxylin-eosin(HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) staining, respectively. The protein expression levels of yes-associated protein(YAP) 1 and transcriptional coactivator with PDZ-binding motif(TAZ) were detected by immunohistochemistry(IHC), while the changes in protein expression levels of mammalian sterile 20-like kinase(MST) 1/2, large tumor suppressor(LATS) 1/2, YAP1, TAZ, B-cell lymphoma-2(Bcl-2), and Bcl-2 associated X protein(Bax) were determined by Western blot. The results showed that compared with the blank group, the model group had an increased rate of estrous cycle disruption in mice, a decreased number of normally developing ovarian follicles, an increased number of blocked ovarian follicles, increased ovarian granulosa cell apoptosis, decreased ovulation, reduced ovarian wet weight and ovarian index, increased serum FSH and LH levels, decreased AMH and E&#95;2 levels, decreased protein expression levels of YAP1 and TAZ in ovarian tissues, increased relative expression levels of MST1/2, LATS1/2, and Bax proteins, and decreased relative expression levels of YAP1, TAZ, and Bcl-2 proteins. Additionally, the number of embryos per litter significantly decreased after co-housing. Compared with the model group, the low-and high-dose Res groups exhibited reduced estrous cycle disruption rates in mice, varying degrees of improvement in the number and morphology of ovarian follicles, reduced numbers of blocked ovarian follicles, improved ovarian granulosa cell apoptosis, increased ovulation, elevated ovarian wet weight and ovarian index, decreased serum FSH and LH levels, increased AMH and E&#95;2 levels, elevated protein expression levels of YAP1 and TAZ in ovarian tissues, decreased relative expression levels of MST1/2, LATS1/2, and Bax proteins, and increased relative expression levels of YAP1, TAZ, and Bcl-2 proteins. Furthermore, the number of embryos per litter increased to varying degrees after co-housing. In conclusion, Res effectively inhibits ovarian cell apoptosis in mice and improves ovarian responsiveness. Its mechanism may be related to the regulation of key molecules in the Hippo pathway.

Introduction: EDTA plays a crucial role in regenerative endodontic therapy (RET) because of its significant biological effects. However, EDTA is also recognized as the preferred anticoagulant for hematologic tests. Thus, this study aimed to assess the influence of different EDTA activation techniques on the morphology of blood clots after conditioning the root canal dentin., Methods: Forty extracted human teeth were prepared to simulate immature teeth and divided into the following 5 groups: (1) saline solution (negative control), (2) EDTA 17% + saline solution (CNI), (3) CNI + ultrasonic activation, (4) CNI + Easy clean activation, and (5) CNI + XP-endo Finisher activation. After irrigation, the roots were cleaved, and the root canals were filled with human blood to clot formation. The morphology and density of erythrocytes, platelets, and the fibrin network were observed using a scanning electron microscope. The fibrin network density was classified using a 4-point scale. Data were analyzed using the Friedman test and the Kruskal-Wallis test with Bonferroni adjustment (α = 5%)., Results: All groups exhibited consistent blood clot morphology characterized by a high density of erythrocytes, platelets, and white blood cells throughout the entire length of the root canal. The negative control group showed statistically significant high scores of fibrin density compared with the CNI group in all root thirds (P < .05). However, there was no statistical difference in the scores for the fibrin network density between the groups irrigated with EDTA with and without activation (P > .05)., Conclusions: EDTA may impair the fibrin network formation compared with the saline group. However, EDTA activation did not significantly change the effects on the blood clot in contact with the conditioned intraradicular dentin., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Objective: To elucidate the mechanism of the nourishing Yin and purging fire Chinese herbal mixture (NYPF) in delaying light-induced premature puberty in rats., Methods: Twenty-one days old female Sprague-Dawley rats were randomly assigned to normal group (N), long light exposure group (L), NYPF and normal saline group (NS). Rats in the L, NYPF and NS groups were exposed to 16 h: 350 lux light/8 h: dark, while rats in the N group were exposed to 12 h: 50 lux light/12 h: dark. NYPF and normal saline was administered to the rats in the NYPF group or NS group, respectively, from day 21. Five rats in every group were sacrificed at 9 p.m. on day 28 (P28), on the day when rat's vulva opened in the L group (L-VO), on the day when the first estrous interphase occurred in rats of L group (L-E1), and on the day when the second estrous interphase occurred in rats of L group (L-E2), respectively., Resulits: On day 34, all rats in the L group, 80% of rats in the NS group, 40% of rats in the N group, and 20% of rats in the NYPF group showed complete opening of the vulva. At P28, mRNA level of hypothalamic kisspeptin (Kiss-1) in the L group was significantly higher than that in the N group ( P < 0.05). The rats in the L and NS groups had significantly lower hypothalamic arginine-phenylalanine-amide (RFamide)-related peptide 3 (RFRP-3) mRNA levels than those in the N group ( P < 0.05), whereas RFRP-3 mRNA level was significantly higher in the NYPF group than that in the L group ( P < 0.05). At L-VO, the ovarian index of the L and NS groups was significantly higher than that of the N group ( P < 0.05) and estradiol (E2) level of the NYPF group was significantly lower than that of the N and NS groups ( P < 0.05); hypothalamic Kiss-1 mRNA level in the L and NS groups was significantly higher than that in the N and NYPF groups ( P < 0.05), whereas hypothalamic RFRP-3 mRNA level in the L, NYPF, and NS groups was significantly lower than that in the N group ( P < 0.05). At L-E1, E2 level of the L and NS groups was significantly higher than that of the N group ( P < 0.01), whereas it was significantly lower in the NYPF group than that of the N, L, and NS groups ( P < 0.01), and serum luteinizing hormone level of the L and NS groups was significantly higher than that of the N group ( P < 0.05); levels of serum melatonin and ovarian melatonin receptor 1 (MT-1) mRNA in the L, NYPF, and NS groups were significantly lower than those in the N group ( P < 0.05). At L-E2, the uterine organ index of the NYPF group was significantly lower than that of the L group ( P < 0.05); and ovarian MT-1 mRNA level of the L and NS groups was significantly lower than that in the N group ( P < 0.05)., Conclusions: NYPF can delay puberty onset in rats exposed to strong light for a prolonged duration, and regulation of the gene expression of Kiss-1 and RFRP-3 in the hypothalamus has been suggested as one of the mechanisms.

Objective: To investigate the effects of long-term administration of tacrolimus (also known as FK506) on the pain-related behaviors in mice and to study the underlying mechanism of pain induced by FK506 via measuring the effect of FK506 on the synaptic expression and phosphorylation of alpha-amino-3-hyroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor in the spinal cord dorsal horn of mice., Methods: 1) A total of 24 mice were evenly and randomly assigned to two groups, a FK506 group and a Saline group. The FK506 group was given daily intraperitoneal injection of FK506 and the Saline group received normal saline. Both groups received injection once a day for 7 days in a row. Some of the mice ( n =6 in each group) were monitored for the changes in the paw withdrawal threshold (PWT), the paw withdrawal latency (PWL), and the spontaneous pain behaviors to establish the pain model. The other mice ( n =6 in each group) of each group underwent isolation of the dorsal horn when obvious pain symptoms were induced on day 7 of injection. Then, immunoblotting was performed to determine the synaptic expression and phosphorylation levels of GluA1 and GluA2 subunits of AMPA receptors. 2) The mice were randomly divided into two groups, FK506+calcineurin (CaN) group and FK506+Saline group ( n =6 in each group). After the pain model was constructed, the mice were given intrathecal injection of recombinant CaN (also know as 33 U) or normal saline. Then, 60 minutes later, the PWT and the PWL of the mice were measured to investigate the role of CaN in FK506-induced pain. 3) Another18 mice were selected. The mice were randomly and evenly assigned to three groups, a control group (receiving intraperitoneal injection of normal saline followed by intrathecal injection of normal saline), FK506+Saline group (receiving intraperitoneal injection of FK506 followed by intrathecal injection of normal saline) and FK506+CaN group (receiving intraperitoneal injection of FK506 followed by intrathecal injection of CaN). Then, 60 minutes later, the spinal cords were isolated and subjected to immunoblotting assay to determine the role of CaN in FK506-induced AMPA receptor modification., Results: 1) After 7 consecutive days of intraperitoneal injection of FK506, the PWT and PWL of mice dropped significantly, reaching on day 7 as low as 22.3%±0.05% and 66.6%±0.05% of the control group, respectively ( P <0.01). The FK506-treated mice displayed evident spontaneous pain behavior, presenting significantly increased licking activities ( P <0.01). These results indicated that FK506-induced pain model was successfully established. Immunoblotting assay showed that the total expressions of GluA1 and GluA2 subunits in the spinal dorsal horn of the FK506 group remained unchanged in comparison with those of the Saline group. However, FK506 specifically induced an increase in the synaptic expression of GluA1. In addition, the phosphorylation levels of GluA1 at Ser845 and Ser831 in FK506-treated mice were significantly increased in comparison with those of the control group ( P <0.05). 2) Compared with those of the mice in the FK506+Saline group, the PWT and the PWL of mice in the FK506+CaN group were significantly increased ( P <0.05). 3) Compared with those of the FK506+Saline group, the synaptic expression of GluA1 were decreased in FK506+CaN group ( P <0.01) and the phosphorylation levels of GluA1 at Ser845 and Ser831 were significantly downregulated ( P <0.001)., Conclusion: The hyper-expression and hyperphosphorylation of GluA1 subunit in the spinal cord dorsal horn resulting from CaN inhibition contributes to the FK506-induced pain syndrome. FK506 induces the synaptic hyper-expression and hyperphosphorylation of GluA1 in the dorsal horn of the spinal cord through CaN inhibition, thereby inducing pain., Competing Interests: 利益冲突 　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Board of Journal of Sichuan University (Medical Sciences).)

Background: Stellate ganglion block (SGB) has been shown to reduce perioperative complications in various surgeries. Because laparoscopic techniques and instruments have advanced during the past two decades, laparoscopic liver resection is being increasingly adopted worldwide. Lesser blood loss, fewer postoperative complications, and shorter postoperative hospital stays are the advantages of laparoscopic liver resection, as compared to conventional open surgery. There is an urgent need for an effective intervention to reduce perioperative complications and accelerate postoperative recovery. This study investigated the effect of ultrasound-guided SGB on enhanced recovery after laparoscopic partial hepatectomy., Methods: We compared patients who received SGB with 0.5% ropivacaine (group S) with those who received SGB with 0.9% saline (group N). A total of 58 patients with partial hepatectomy were enrolled (30 S) and (28 N). Before induction of anesthesia, SGB was performed with 0.5% ropivacaine in group S and 0.9% saline in group N., Main Outcome: Comparison of serum inflammatory cytokines concentration at each time point., Results: Main outcome: When comparing IL-6 and IL-10 concentrations among groups, group S showed less variation over time compared to group N. For comparison between groups, the serum IL-6 concentration in group S was lower than that in group N at 6 and 24 h after operation (P < 0.01), and there was a significant linear relationship between serum IL-6 concentration at 24 h after operation and hospitalization situation., Conclusions: Ultrasound-guided SGB can stabilize perioperative inflammatory cytokines plays a positive role in the enhanced recovery of patients after laparoscopic partial hepatectomy. The serum IL-6 level within 24 h after surgery may be used as a predictor of hospitalization., Trial Registration: The study was registered at the ClinicalTrials.gov (Registration date: 13/09/2021; Trial ID: NCT05042583)., (© 2023. The Author(s).)

Objective: To assess the effect of an injection of botulinum toxin A (BoNT/A) at the epicenter of the spinal cord injury (SCI) site on the recovery of lower urinary tract function in female rats with thoracic SCI., Materials and Methods: Twenty-four female Wistar rats with Sham (laminectomy at T8/T9 level) or SCI (at T8/T9; 30 g compression for 5 s) were assigned into Sham-SS (injected with 5 µL of saline solution), Sham-BoNT/A (injected with 15 pg/rat, equivalent to 7.5 Units/kg of BoNT/A in 5 µL volume), SCI-SS (injured and injected with saline), SCI-BoNT/A (injured and injected with BoNT/A), N = 6 per group. Weekly evaluation of stereotyped micturition behavior, hind-limb nociception, and locomotor activity was performed 1 week before and during 6 weeks after surgery. Subsequently, all groups underwent simultaneous electromyography of the external urethral sphincter (EUS-EMG) and cystometric (CMG) studies., Results: A compression SCI at the T8/T9 thoracic level significantly impairs sensory and locomotive functions, as well as stereotyped micturition behavior. However, these impairments were improved by BoNT/A injection after SCI. Neither injections of saline solution nor BoNT/A had an appreciable effect on the same parameters evaluated in the Sham groups. The combined EUS-EMG and CMG evaluations revealed important improvements of lower urinary tract physiology, particularly a reduction in the frequency of non-voiding contractions and the properties of EUS bursting activity indicated as the amplitude of the EUS-EMG signal and duration of burst electrical activity during effective voiding., Conclusion: The severe impairments on sensory and locomotive functions as well stereotyped micturition caused by an SCI could be potentially attenuated by an injection of a small amount of BoNT/A directly into the epicenter of the SCI region. A reduction in the release of neurotoxic neurotransmitters requiring the SNARE complex may be the mechanism triggered by BoNT/A to reduce neurotoxicity and hyperexcitability created in the SCI area to improve the survival of spinal cord cells involved in micturition., (© 2023 Wiley Periodicals LLC.)

N-acetylcysteine (NAC) is a recommended drug for treating acetaminophen (APAP) intoxication. Due to NAC's low bioavailability, this study aimed to use polyrhodanine (PR) nanoparticles (NPs) as a drug carrier to improve the effectiveness of NAC. After preparation and characterization of NAC loaded on PR, 30 rats were randomly divided into five groups of six. The first group (control) received normal saline. Groups 2-5 were treated with normal saline, PR, NAC, and NAC loaded on PR, respectively. The treatments were started 4 h after oral administration of APAP (2000 mg kg -1 ). After 48 h, the animals were anesthetized, and liver function indices and oxidative stress were measured in tissue and serum samples. The APAP administration can increase aminotransferases and alkaline phosphatase enzymes in serum, decreasing the total antioxidant capacity and thiol groups and increasing lipid peroxidation in liver tissue. Administration of PR-NAC could effectively improve the level of serum-hepatic enzymes, total antioxidant capacity and thiol groups, lipid peroxidation, and pathological changes in liver tissue in animals poisoned with APAP. PR-NAC has a significant therapeutic effect on preventing acute hepatotoxicity caused by APAP, and its effectiveness can be associated with an improvement in the oxidant/antioxidant balance of liver tissue., (© 2023 John Wiley & Sons Ltd.)

Purpose: Previous research has highlighted the impact of X-ray irradiation-induced organ damage, on cancer patients after radiation therapy. The ionizing radiation-induced oxidative stress causes injury to the pancreatic islet cells of Langerhans. We used histopathological, immunohistochemical, and biochemical analyses to examine α- and β-cells in the islets of Langerhans in rats undergoing whole-body x-ray ionizing radiation, a group of which was treated with NAC., Material and Methods: Twenty-four male rats were randomly divided into 3 groups, one control, and two experimental groups. Group I (Control) was administered only saline solution (0.09% NaCl) by oral gavage for 7 days. Group II (IR) was administrated whole body single dose 6 Gray ionizing radiation (IR) and saline solution (0.09% NaCl) by oral gavage for 7 days. Group III (IR + NAC) was administered 300 mg/kg NAC (N-acetylcysteine) by oral gavage for 7 days, 5 days before, and 2 days after 6 Gray IR application., Results: In the X-ray irradiation group, we observed diffuse necrotic endocrine cells in the islets of Langerhans. In addition, we found that Caspase-3, malondialdehyde (MDA) levels increased, and insulin, glucagon, and glutathione (GSH) levels decreased in the IR group compared to the control group. In contrast, we observed a decrease in Caspase-3, and MDA levels in necrotic endocrine cells, and an increase in insulin, glucagon, and GSH levels in the IR + NAC group compared to the IR group., Conclusion: This study provides evidence for the beneficial effects of N-acetyl cysteine on islets of Langerhans cells with X-ray ionizing-radiation-induced damage in a rat model., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Respiratory mechanics are often significantly altered in morbidly obese patients and magnesium sulfate (MgSO4) is a promising agent for managing several respiratory disorders. This study aimed to examine the effects of MgSO4 infusions on arterial oxygenation and lung mechanics in patients with morbid obesity undergoing laparoscopic bariatric surgery., Methods: Forty patients with morbid obesity aged 21-60 years scheduled for laparoscopic bariatric surgery under general anesthesia were randomly allocated to either the control (normal saline infusion) or MgSO4 group (30 mg/kg lean body weight [LBW] of 10% MgSO4 in 100 ml normal saline intravenously over 30 min as a loading dose, followed by 10 mg/kg LBW/h for 90 min). The primary outcome was intraoperative arterial oxygenation (ΔPaO2/FiO2). Secondary outcomes included intraoperative static and dynamic compliance, dead space, and hemodynamic parameters., Results: At 90 min intraoperatively, the Δ PaO2/FiO2 ratio and the Δ dynamic lung compliance were statistically significantly higher in the MgSO4 group (mean ± SE: 16.1 ± 1.0, 95% CI [14.1, 18.1] and 8.4 ± 0.5 ml/cmH2O, 95% CI [7.4, 9.4]), respectively), and the Δ dead space (%) was statistically significantly lower in the MgSO4 group (mean ± SE: -8.0 ± 0.3%, 95% CI [-8.6, -7.4]) (P < 0.001). No significant differences in static compliance were observed., Conclusions: Although MgSO4 significantly preserved arterial oxygenation and maintained dynamic lung compliance and dead space in patients with morbid obesity, the clinical relevance is minimal. This study failed to adequately reflect the clinical importance of these results.

Gallic acid (GA) is known to be a natural phenolic compound with antioxidant and neuroprotective effects. This study aims to investigate the impact of GA against restraint stress-induced oxidative damage, anxiety-like behavior, neuronal loss, and spatial learning and memory impairment in male Wistar rats. The animals were divided into four groups (n = 8) and subjected to restraint stress for 4 h per day for 14 consecutive days or left undisturbed (control without inducing stress). In the treatment group, the animals were treated with 2 mL normal saline plus 100 mg/kg GA per day for 14 consecutive days (STR + GA group). The animals received the drug or normal saline by gavage 2 h before inducing restraint stress. ELISA assay measured oxidative stress factors. Elevated-plus maze and Morris water maze tests assessed anxiety-like behavior and spatial learning and memory, respectively. Also, neuronal density was determined using Nissl staining. Restraint stress significantly increased MDA and reduced the activities of GPX and SOD in the stressed rats, which were reserved by treatment with 100 mg/kg GA. Restraint stress markedly enhanced the anxiety-like behavior and spatial learning and memory impairment that were reserved by GA. In addition, treatment with GA reduced the neuronal loss in the stressed rats in the hippocampus and prefrontal cortex (PFC) regions. Taken together, our findings suggest that GA has the potential to be used as a good candidate to attenuate neurobehavioral disorders as well as neuronal loss in the hippocampus and PFC induced by restraint stress via reducing oxidative damage., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Valproic acid (VPA) is a commonly used drug for management of epilepsy. Prolonged VPA administration increases the risk of hepatotoxicity. Liraglutide is a glucagon-like peptide 1 receptor (GLP-1R) agonist that act as a novel antidiabetic drug with broad-spectrum anti-inflammatory and antioxidant effects. This study tested the protective effect of liraglutide against VPA-induced hepatotoxicity elucidating the possible underlying molecular mechanisms. Forty adult male rats were allocated in to four equally sized groups; Group I (control group) received oral distilled water and subcutaneous normal saline for 2 weeks followed by subcutaneous normal saline only for 2 weeks. Group II (liraglutide group) received subcutaneous liraglutide dissolved in normal saline daily for 4 weeks. Group III (valproic acid-treated group) received sodium valproate dissolved in distilled water for 2 weeks. Group IV (Combined valproic acid & liraglutide treated group) received valproic acid plus liraglutide daily for 2 weeks which was continued for additional 2 weeks after valproic acid administration. The hepatic index was calculated. Serum AST, ALT, GGT, and ALP activities were estimated. Hepatic tissue homogenate MDA, GSH, SOD, HMGB1, MAPK, RIPK1, and RIPK3 levels were evaluated using ELISA. However, hepatic RAGE and MLKL messenger RNA expression levels using the QRT-PCR technique. Hepatic NF-κB and TNF-α were detected immunohistochemically. Results proved that liraglutide coadministration significantly decreased liver enzymes, MDA, HMGB1, MAPK, RIPK1 RIPK3, RAGE, and MLKL with concomitant increased GSH and SOD in comparison to the correspondent values in VPA-hepatotoxicity group. Conclusions: Liraglutide's protective effects against VPA-induced hepatotoxicity are triggered by ameliorating oxidative stress, inflammation, and necroptosis., (© 2023 John Wiley & Sons Ltd.)

Background: The reactive oxygen species generated by numerous xenobiotic substances has as consequences the impairment of different organs normal function. Many plants pose antioxidant activity to counteract oxidative stress, among them being the chokeberry (Aronia melanocarpa). The purpose of present study was to determine if the use of A. melanocarpa extract can counteract the oxidative stress induced by cisplatin administration in rats., Material and Methods: The study was made on forty Wistar rats divided in four groups as follows: C (control): receiving i.p. 1 mL of saline solution; E1: receiving cisplatin 20 mg/kg bw, i.p.; E2: receiving cisplatin 20 mg/kg bw, i.p and A. melanocarpa berry 6 % aqueous extract as drinking water, and CB (control blank): i.p 1 mL saline solution and A. melanocarpa 6 % aqueous extract for four weeks., Results: Administration of Cisplatin was followed by the increase of serum superoxide dismutase (+21.18 %, P < 0.05), catalase (+25.44 %, P < 0.001), glutathione peroxidase (+17.88 %, P < 0.05) and thiobarbituric reactive substances (+28.17 %, P < 0.01) but significantly decreased glutathione reductase (-22.35 %, P < 0.001) level comparative to control, pointing out that administration of cisplatin induced oxidative stress in rats. In groups that received A. melanocarpa extract as drinking water, we noted that the levels of the oxidative stress biomarkers tended to be restored almost to normal levels, which could be a possible good antioxidant used in condition to cisplatin use. Also, we noted a significant (P < 0.001) decrease of total antioxidant capacity in liver and kidney of rats exposed to cisplatin, recovered in those that received chokeberry. Studied trace elements important for the stress oxidative enzymes (Cu, Zn, Fe and Mn) were decreased in cisplatin exposed groups compared to control and mainly all were almost to normal level in groups receiving A. melanocarpa., Conclusion: A. melanocarpa extract due to its antioxidants content could offer protection against free radicals produced as a consequence of cisplatin use., 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 The Authors. Published by Elsevier GmbH.. All rights reserved.)

This study aims to observe the effect and explore the mechanism of Qirong Tablets in the treatment of premature ovarian insufficiency(POI) in mice via the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/hypoxia inducible factor 1(HIF-1) signaling pathway. Sixty SPF female BALB/c mice were randomly divided into normal group, model group, positive control group, Qirong Tablets low-, medium-and high-dose group. The normal group was intraperitoneally injected with the same amount of normal saline, and the other groups were intraperitoneally injected with cyclophosphamide 120 mg·kg~(-1)·d~(-1) once to establish a POI animal model. After the model was successfully established, the low-, medium-and high-dose groups of Qirong Tablets were administered orally with 0.6, 1.2, 2.4 mg·kg~(-1)·d~(-1) respectively. The positive control group was given 0.22 mg·kg~(-1)·d~(-1) Clementine Tablets by intragastric administration, and the normal group and model group were given intragastric administration with the same amount of normal saline, and the treatment was 28 d as a course of treatment. After drug intervention, enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of estradiol(E&#95;2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-mullerian hormone(AMH) in peripheral blood, and hematoxylin-eosin(HE) staining to observe the ovarian tissue. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay was used to detect the apoptosis of granulosa cells, and Western blot to determine the expression levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), caspase-3, PI3K, Akt, and HIF-1. Compared with the normal group, the modeling of POI caused loose or destroyed ovarian tissue with vacuolar structures, edema and fibrosis in the ovarian interstitium, disordered or loose arrangement of granulosa cells, and reduced normal follicles. Compared with the model group, drug interventions restored the ovarian tissue and follicles at all the development stages and reduced atretic follicles. Compared with the normal group, the modeling of POI lowered the serum level of E&#95;2 and AMH(P&lt;0.01), and elevated the level of FSH and LH(P&lt;0.01). Compared with the model group, high-dose Qirong Tablets elevated the levels of E&#95;2 and AMH(P&lt;0.05), and lowered the levels of FSH and LH(P&lt;0.05). Compared with the normal group, the modeling of POI up-regulated the protein levels of PI3K, Akt, HIF-1, Bax, and caspase-3 and down-regulated the protein level of Bcl-2 in the ovarian tissue(P&lt;0.01). Compared with the model group, low-, medium-, and high-dose Qirong Tablets down-regulated the protein levels of PI3K, Akt, HIF-1, Bax, and caspase-3 proteins and up-regulated the protein level of Bcl-2 in the ovarian tissue(P&lt;0.05). In conclusion, Qirong Tablets can up-regulate the expression Bcl-2, down-regulate the expression of Bax and caspase-3 in POI mice. Qirong Tablets may inhibit the apoptosis of follicular granulosa cells in mice, thereby delaying ovarian aging, improving reproductive axis function, and strengthening ovarian reserve capacity, which may be associated with the inhibition of PI3K/Akt/HIF-1 pathway.

This study aimed to investigate the potential of nebivolol in preventing doxorubicin-induced cardiotoxicity by targeting the inflammatory, oxidative, and apoptotic pathways. Twenty-eight male rats were randomly divided into four groups, each consisting of seven rats. The control group received standard diets and unrestricted access to water. The rats in the normal saline (N/S) group were administered a 0.9% normal saline solution for two weeks. The doxorubicin group (the "induced group") received doxorubicin at a dosage of 2.5 mg/kg three times per week for two weeks. The nebivolol group received an oral dose of 4 mg/kg of nebivolol for the same duration. The cardiac tissues of rats treated with doxorubicin exhibited increased levels of tumor necrosis factor, interleukin-1, malondialdehyde, and caspase-3 compared to the normal saline control group (p<0.05), along with decreased levels of total antioxidant capacity and Bcl-2. These results show that doxorubicin is harmful to the heart. The administration of nebivolol significantly reduced the cardiotoxic effects induced by doxorubicin, as indicated by a statistically significant decrease in the levels of inflammatory markers, specifically tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) (p<0.05). The nebivolol group exhibited a significant decrease in malondialdehyde levels, which serves as a signal of oxidation, in cardiac tissue compared to the doxorubicin-only group (p<0.05). Additionally, the nebivolol group showed a significant increase in overall antioxidant capacity. Nebivolol dramatically attenuated doxorubicin-induced cardiotoxicity in rats, likely by interfering with oxidative stress, the inflammatory response, and the apoptotic pathway., Competing Interests: The authors declare no conflict of interest., (©2023 JOURNAL of MEDICINE and LIFE.)

Background : Hydrogen peroxide (H 2 O 2 ) is used as a topical antiseptic in contaminated wounds caused by road traffic accidents. It kills bacteria by producing oxidation through local, nascent, free oxygen radicals. It also removes dirt from the wound due to its frothing action. H 2 O 2 is synthesized by various cells as an active biochemical agent that affects cell biological behavior through complex chemical reactions. H 2 O 2 has also been used as a wound cleaning agent, removing debris, preventing infection, and causing hemostasis due to its exothermic reaction with blood. Despite its widespread use, there is scanty literature on its use to promote granulation tissue formation. Objective : In the orthopaedics literature, studies on H 2 O 2 use are very limited and its potential is underestimated. In the present study, we would like to report our protocol of use of H 2 O 2 for its tremendous potential for stimulating granulation and early wound healing. Material and Methods : A total of 53 patients with large acute extensive lower limb contaminated wounds reported to the emergency department have been included with and without lower limb fracture. In group A (43 patients) wound management was done using 7% H 2 O 2 and group B (10 patients) was treated by only saline dressing as a control group. Results : In the present study, daily dressing by 7% H 2 O 2 solution and provide solution gives excellent results compared to the Saline group. Granulation tissue appeared much earlier with a mean SD 6.3 ± 6.8 days in the hydrogen peroxide group as compared to the Saline group where granulation tissue appeared in 9.3 ± 8.4 days. Conclusion : Spontaneous wound healing is a controlled balance between destructive and healing processes. It is mandatory to remove damaged tissue to promote healing by secondary intention and minimize infection. The dynamic effect of H 2 O 2 promotes faster healing, stimulates granulation, and minimizes infection by oxidative stress.

This study aimed to compare the effect of sodium hypochlorite (NaOCl) and calcium hypochlorite [Ca(OCl) 2 ] on the bond strength to pulp chamber dentin when followed or not by the use of sodium thiosulfate (Na 2 S 2 O 3 ). The pulp chamber of fifty human molars were divided into five groups (n = 10) according to the immersion protocol: 2.5% NaOCl; 2.5% NaOCl + 5% Na 2 S 2 O 3 ; 2.5% Ca(OCl) 2 ; 2.5% Ca(OCl) 2 + 5% Na 2 S 2 O 3 ; and 0.9% sodium chloride (NaCl; control). Subsequently, the samples were restored with resin composite. Three sticks each were obtained and subjected to microtensile testing. SEM/EDS analyses of the pulp chamber roof (n = 8) were carried out for mineral quantification. Elemental analysis data were investigated via one-way ANOVA and Tukey's post hoc, and bond strength data by post hoc pairwise comparisons using the Kruskal-Wallis test. Use of 2.5% NaOCl was associated with the lowest value of bond strength, while 2.5% Ca(OCl) 2 had similar bond strength to that of the 0.9% NaCl control. Using 5% Na 2 S 2 O 3 was able to increase the bond strength after 2.5% NaOCl, but not after 2.5% Ca(OCl) 2 . The group treated only with 2.5% Ca(OCl) 2 had a higher Ca/P ratio on the dentin surface. Dentin treated with Ca(OCl) 2 was not affected by Na 2 S 2 O 3 and showed bond strength similar to the 0.9% NaCl., (© 2023 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.)

Introduction: Achieving stable adhesion between fiber post and interradicular dentin is a challenging process in the restoration of endodontically treated teeth. This study was conducted to investigate the effect of surface pretreatment with cold atmospheric plasma (CAP) on improving the bond strength between them., Materials and Methods: Forty-eight single-canal mandibular premolars were cut 1 mm above the cementoenamel junction to keep the root length of 14 mm or more. After endodontic treatment and preparation of the post space, the teeth were divided into four groups regarding the pretreatment of dentin surfaces, including normal saline, ethylenediaminetetraacetic acid (EDTA), CAP, and CAP + EDTA groups. The data were analyzed using paired and independent t-test and one-way analysis of variance and the significance level was set at p < .05., Results: The bond strength was significantly higher in the coronal third than in the apical third in all the groups. Moreover, the bond strength was significantly higher in the CAP + EDTA-treated group. The bond strength increased significantly in the CAP group compared to the normal saline group. In addition, the bond strength increased significantly in the CAP or EDTA groups compared to the control group. The lowest bond strength belonged to the control group (normal saline)., Conclusion: The surface pretreatment with CAP (alone or in combination with EDTA) played a significant role in improving the bond strength of fiber post and root canal dentin., (© 2023 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Carbon tetrachloride (CCl 4 ) is a potent liver toxin. Diclofenac (Dic), leading adverse effects on the liver, is used among the employees of the industries that use CCl 4 . The increased use of CCl 4 and Dic in industrial workers has prompted us to investigate their synergistic effect on the liver using male Wistar rats as a model. Male Wistar rats were divided into seven groups ( n = 6), and the exposure was by intraperitoneal injection for 14 days as follows. Group 1: Control, 2: Olive oil, 3: CCl 4 (0.8 mL/kg/day (3 times per week)), 4: Normal saline, 5: Dic (1.5 mg/kg/day per day), 6: Olive oil with normal saline, 7: CCl 4 (0.8 mL/kg/day (3 times per week)) and Dic (1.5 mg/kg/day daily). At the end of day 14, the heart blood was collected to measure the liver enzymes, alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), blood alkaline phosphatase (ALP), albumin (ALB), direct bilirubin, and total bilirubin. A pathologist examined the liver tissue. Prism software was used to analyze data using ANOVA and Tukey statistical tests. ALT, AST, ALP, and Total Bilirubin enzymes were increased significantly in the co-administered CCl 4 and Dic group, while the ALB levels decreased ( p < 0.05). The histological findings reported liver necrosis, focal hemorrhage, adipose tissue change, and lymphocytic portal hepatitis. In conclusion, using Dic while exposed to CCl 4 may exacerbate hepatotoxicity in rats. Therefore, it is suggested that more severe restrictions and safety regulations be placed on using CCl 4 in the industry, and caution is advised to these industry workers to use Diclofenac.

Paraquat (PQ) is a widely used herbicide that can cause severe oxidative and fibrotic injuries in lung tissue. Due to the antioxidant and anti-inflammatory properties of chlorogenic acid (CGA), the present study investigated its effects on PQ-induced pulmonary toxicity. To this end, 30 male rats were randomly categorized into five groups of six. Initially, the first and third groups were treated intraperitoneally (IP) with normal saline and CGA (80 mg/kg) for 28 consecutive days, respectively. The second, fourth, and fifth groups were treated with normal saline and 20 and 80 mg/kg of CGA for 28 consecutive days, respectively, and received a single dose of PQ (IP, 20 mg/kg) on Day 7. Then, the animals were anesthetized with ketamine and xylazine, and lung tissue samples were collected for biochemical and histological examinations. The results showed that PQ significantly increased hydroxyproline (HP) and lipid peroxidation (LPO) and decreased the lung tissue antioxidant capacity. In addition, myeloperoxidase (MPO) activity increased significantly, while glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) activity declined substantially. The administration of therapeutic doses of CGA could prevent the oxidative, fibrotic, and inflammatory effects of PQ-induced lung toxicity, and these changes were consistent with histological observations. In conclusion, CGA may improve the antioxidant defense of lung tissue and prevent the spread of inflammation and the development of PQ-induced fibrotic injuries by enhancing antioxidant enzymes and preventing inflammatory cell infiltration., (© 2023 Wiley Periodicals LLC.)

New Findings: What is the central question of this study? Although the involvement of reactive oxidative species in triggering hypertension has been documented, there are no data about the role of antioxidant enzymes in the heart and aorta of borderline hypertensive rats kept in baseline conditions or exposed to high salt with or without repeated stress. What is the main finding and its importance? In borderline hypertensive rats, high salt intake and stress contribute significantly to increase blood pressure and antioxidative defence in the aorta but decrease it in the heart. Elucidating the early changes that accompany elevated blood pressure could provide new therapeutical venues for prevention and treatment of the condition., Abstract: Hypertension and its complications are a leading cause of death in the human population. Several factors can contribute to development of hypertension, such as genetic predisposition, high salt intake and environmental stressors, underlying oxidative stress as one of its key trademarks. We studied the effects of increased salt intake and chronic stress on blood pressure parameters and the activity and protein levels of antioxidant enzymes in the heart and aorta of borderline hypertensive rats (BHRs) with genetic susceptibility to hypertension. All animals were randomized into four groups: (1) Wistar rats kept in baseline conditions; (2) BHRs kept in baseline conditions; (3) BHRs drinking 0.9% saline solution; and (4) BHRs drinking 0.9% saline solution and exposed to repeated heterotypic stress. The BHRs exhibited significantly higher blood pressure, mitochondrial superoxide dismutase (SOD2) and catalase (CAT) protein levels and lower glutathione peroxidase (GPx) and glutathione reductase (GR) activities in the aorta, followed by lower CAT and GPx protein levels and higher CAT and GR activities in the heart, compared with normotensive Wistar rats. In the BHR aorta, high salt intake elevated CAT and GPx activities, and when combined with stress it increased GPx and GR activities. In BHR hearts, high salt intake provoked lower CAT activity. Adding repeated stress to salt treatment further decreased CAT activity, in addition to Cu 2+ -Zn 2+ superoxide dismutase (SOD1) and GR activities. The protein level of CAT was lower, whereas SOD2 and GPx increased. Overall, our results suggest that BHR hearts are better adapted to oxidative pressure, compared with the aorta, when exposed to salt and stress., (© 2023 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Objective: To investigate the efficacy of hydrodilatation with 40 mg triamcinolone acetonide (TA) compared with the same procedure with 10 mg TA in patients with adhesive capsulitis (AC) of the shoulders., Design: Prospective, double-blind, randomized controlled trial with 12 weeks of follow-up., Setting: Tertiary care rehabilitation center., Participants: Eighty-four patients diagnosed with AC (N=84)., Interventions: Ultrasound guidance using (A) hydrodilatation with 4 mL of TA (40 mg)+4 mL 2% lidocaine hydrochloride+12 mL normal saline or (B) hydrodilatation with 1 mL of TA (10 mg)+4 mL 2% lidocaine hydrochloride+15 mL normal saline through the posterior glenohumeral recess., Main Outcome Measures: Shoulder Pain and Disability Index (SPADI), visual analog scale (VAS) for pain, and range of motion (ROM) at baseline and at 6 and 12 weeks after injection., Results: Both groups experienced improvements in the SPADI score, VAS scores for pain, and ROM throughout the study period. However, group-by-time interactions were not significant for any outcome measurement at any follow-up time point. No adverse events were reported in either group., Conclusion: Ultrasound-guided hydrodilatation with 40 and 10 mg TA yielded similar improvements in SPADI, VAS score, and ROM at the 12-week follow-up. Considering the potential detrimental effects of corticosteroids on the adjacent cartilage and tendons, a low dose of TA would be preferable for ultrasound-guided hydrodilatation for AC., (Copyright © 2022 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Hexavalent chromium salt, like potassium dichromate (PD), is chromium's most precarious valence state in industrial wastes. Recently, there has been increasing interest in β-sitosterol (BSS), a bioactive phytosterol, as a dietary supplement. BSS is recommended in treating cardiovascular disorders due to its antioxidant effect. Trimetazidine (TMZ) was used traditionally for cardioprotection. Through the administration of BSS and TMZ, the cardiotoxic effects of PD were to be countered in this study, in addition to examining the precise mechanism of PD-induced cardiotoxicity. Thirty male albino rats were divided into five groups; the control group: administered normal saline daily (3 mL/kg); the PD group: administered normal saline daily (3 mL/kg); BSS group: administered BSS daily (20 mg/kg); TMZ group: administered TMZ daily (15 mg/kg); and the BSS + TMZ group: administered both BSS (20 mg/kg) and TMZ (15 mg/kg) daily. All experimental groups, except the control, received on the 19th day a single dose of PD (30 mg/kg/day, S.C.). Normal saline, BSS, and TMZ were received daily for 21 consecutive days p.o. The exposure to PD promoted different oxidative stresses, pro-inflammatory, and cardiotoxicity biomarkers. BSS or TMZ succeeded solely in reducing these deleterious effects; however, their combination notably returned measured biomarkers close to normal values. The histopathological investigations have supported the biochemical findings. The combination of BSS and TMZ protects against PD cardiotoxicity in rats by reducing oxidative stress and apoptotic and inflammatory biomarkers. It may be promising for alleviating and protecting against PD-induced cardiotoxicity in people at an early stage; however, these findings need further clinical studies to be confirmed. HIGHLIGHTS: • Potassium dichromate induces cardiotoxicity in rats through the upregulation of oxidative stress, proinflammatory, and apoptotic pathways biomarkers. • β-Sitosterol possesses a possible cardioprotective effect by modulating several signaling pathways. • Trimetazidine, the antianginal agent, has a potential cardioprotective impact on PD-intoxicated rat model. • The combination of β-Sitosterol and trimetazidine was the best in modulating different pathways involved in PD cardiotoxicity in rats via the interplay between NF-κB/AMPK/mTOR/TLR4 and HO-1/NADPH signaling pathways., (© 2023. The Author(s).)

Introduction: Extracorporeal blood purification systems represent a promising alternative for treatment of blood stream infections with multiresistant bacteria., Objectives: The aim of this study was to analyse the binding activity of S. aureus to Seraph affinity filters based on heparin coated beads and to identify effectors influencing this binding activity., Results: To test the binding activity, we used gfp-expressing S. aureus Newman strains inoculated either in 0.9% NaCl or in blood plasma and determined the number of unbound bacteria by FACS analyses after passing through Seraph affinity filters. The binding activity of S. aureus was clearly impaired in human plasma: while a percent removal of 42% was observed in 0.9% NaCl (p-value 0.0472) using Seraph mini columns, a percent removal of only 10% was achieved in human plasma (p-value 0.0934). The different composition of surface proteins in S. aureus caused by the loss of SarA, SigB, Lgt, and SaeS had no significant influence on its binding activity. In a clinically relevant approach using the Seraph® 100 Microbind® Affinity Filter and 1000 ml of human blood plasma from four different donors, the duration of treatment was shown to have a critical effect on the rate of bacterial reduction. Within the first four hours, the number of bacteria decreased continuously and the reduction in bacteria reached statistical significance after two hours of treatment (percentage reduction 64%, p-value 0.01165). The final reduction after four hours of treatment was close to 90% and is dependent on donor. The capacity of Seraph® 100 for S. aureus in human plasma was approximately 5 x 108 cells., Conclusions: The Seraph affinity filter, based on heparin-coated beads, is a highly efficient method for reducing S. aureus in human blood plasma, with efficiency dependent on blood plasma composition and treatment duration., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Seffer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: This study was aimed at evaluating the effects of dexpramipexole (DPX) - a mitochondrial protectant that sustains mitochondrial function and energy production - on cognitive function in a mouse model of sepsis-associated encephalopathy (SAE) induced by peripheral administration of lipopolysaccharide (LPS) and examining the potential mechanisms., Methods: C57BL/6 male mice were randomized into one of four treatment protocols: Con+Sal, Con+DPX, LPS+Sal or LPS+DPX. The mice were intraperitoneally (i.p.) injected with LPS or equivalent volumes of normal saline once daily for 3 consecutive days. To evaluate the protective effects of DPX, we administered DPX or normal saline i.p. to the mice once daily for 6 consecutive days. Six mice in each group were decapitated on day 7, and each brain was rapidly removed and separated into two halves for biochemical and histochemical analysis. The remaining surviving mice in each group were subjected to behavioral tests from days 7 to 10., Results: Peripheral administration of LPS to mice led to learning and memory deficits in behavioral tests, which were associated with mitochondrial impairment and ATP depletion in the hippocampus. Repeated DPX treatment protected the mitochondria against LPS-induced morphological and functional impairment; inhibited the activation of the Nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome-caspase-1-dependent pyroptosis pathway and cytochrome c (Cyt-c)-caspase-3-dependent apoptosis pathway; and attenuated LPS-induced neuroinflammation and cell death in the hippocampus in SAE mice., Conclusions: Mitochondria-mediated pyroptosis and apoptosis are involved in the pathogenesis of cognitive deficits in a mouse model of SAE and DPX protects mitochondria and suppresses the mitochondria-medicated pyroptosis and apoptosis pathways, and ameliorates LPS-induced neuroinflammation and cognitive deficits. This study provides theoretical evidence supporting DPX for the treatment of SAE., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To explore the effects of heat-inactivated Streptococcus thermophilus MN-ZLW-002(MN002) on glucose metabolism, lipid metabolism, gut microbiota and bile acids in high-fat diet fed obese mice., Methods: Sixty 3-week-old male C57BL/6 mice were randomly divided into control group, high-fat group and intervention group(n=20). After 1 week of adaptive feeding, the control group was fed with normal chow and continued intragastric administration of normal saline for 12 weeks, the high-fat group was fed with high-fat diet and continued intragastric administration of normal saline for 12 weeks, and the intervention group was fed with high-fat diet and continued intragastric of MN002 for 12 weeks. During the experiment, the body weight, food intake, fasting blood glucose content of mice were measured and feces were collected. At the end of the experiment, the oral glucose tolerance of mice was measured and blood, periintestinal fat, peritestosterone fat and perirenal fat samples were collected. The histopathological changes of liver were observed by hematoxylin-eosin staining. Triglyceride, low density lipoprotein, high density lipoprotein and total cholesterol were detected by automatic biochemical analyzer, bile acids content in feces was detected by liquid chromatography-mass spectrometry, gut microbiota structure of mice was analyzed by 16S rDNA sequencing., Results: Compared with high fat group, serum triglyceride, total cholesterol and perirenal fat in intervention group were significantly decreased(P&lt;0.05), the content of fossil cholic acid sulfate in feces was significantly increased, while the content of ursodeoxycholic acid, porcine deoxycholic acid and deoxycholic acid were significantly decreased(P&lt;0.01). Heat inactivation of MN002 could significantly increase the relative abundance of Ruminiclostridium and Alistipes and reduce the relative abundance of Lactobacillus(P&lt;0.01)., Conclusion: Heat-inactivated Streptococcus thermophilus MN002 can regulate the gut microbiota structure and bile acid composition and content of high-fat diet fed mice, thereby alleviating the lipid metabolic disorders caused by high-fat diet.

Background and Objectives : Gentamicin (GM) is a nephrotoxic aminoglycoside. Neutral electrolyzed saline (SES) is a compound with anti-inflammatory, antioxidant, and immunomodulatory properties. The objective of the present study was to evaluate whether kidney damage by GM can be prevented and/or reversed through the administration of SES. Materials and Methods : The study was carried out as a prospective, single-blind, five-arm, parallel-group, randomized, preclinical trial. The nephrotoxicity model was established in male BALB/c mice by administering GM at a dose of 100 mg/kg/day intraperitoneally for 30 days, concomitantly administering (+) SES or placebo (physiologic saline solution), and then administering SES for another 30 days after the initial 30 days of GM plus SES or placebo. At the end of the test, the mice were euthanized, and renal tissues were evaluated histopathologically. Results : The GM + placebo group showed significant tubular injury, interstitial fibrosis, and increased interstitial infiltrate of inflammatory cells compared with the group without GM. Tubular injury and interstitial fibrosis were lower in the groups that received concomitant GM + SES compared with the GM + placebo group. SES administration for 30 days after the GM administration periods (GM + placebo and GM + SES for 30 days) did not reduce nephrotoxicity. Conclusions : Intraperitoneal administration of SES prevents gentamicin-induced histologic nephrotoxicity when administered concomitantly, but it cannot reverse the damage when administered later.

Background: The molecular mechanisms by which exercise improves brain function and capillaries in the cerebral cortex are unclear. Exercise can increase the expression of nitric oxide (NO) in the brain, and endogenous NO is thought to exert beneficial effects on proangiogenic factors, antiangiogenic factors and brain function. Therefore, we hypothesized that running exercise might improve brain function and enhance angiogenesis through endogenous NO., Methods and Results: The following three groups of rats were administered intracerebroventricular (i.c.v.) injections before running exercise each day for 4 weeks: exercise+L-NAME group (i.c.v. L-NAME, an NO synthase blocker, dose: 1 μmol/μl and 5 μl/day; treadmill exercise, 20 min/day), exercise group (i.c.v. normal saline, 5 μl/day; treadmill exercise, 20 min/day), and sham group (i.c.v. normal saline, 5 μl/day; no treadmill exercise). Subsequently, the spatial learning and memory abilities were tested using a Morris water maze, and the nitric oxide synthase (NOS) activity in the cerebral cortex in each group of rats was measured using a method involving nitric acid reductase and metabolic chemistry. The parameters of the cortical capillaries were quantitatively investigated using an immunohistochemistry technique and stereological methods. The expression levels of proangiogenic factors (VEGF and FGF-2) and an antiangiogenic inhibitor (endostatin) in the cerebral cortex were tested using a Western blot analysis. Running exercise significantly improved the rats' spatial learning and memory abilities and increased NOS activity in the cortex. Running exercise also subsequently improved the expression of proangiogenic factors (VEGF and FGF-2) and the length, volume and surface area of capillaries and reduced the expression of antiangiogenic factors (endostatin) in the cortex. In contrast, the L-NAME treatment attenuated the effects of running exercise., Conclusions: Running exercise regulates proangiogenic factors, antiangiogenic factors and angiogenesis in the cerebral cortex via a partially NO-dependent mechanism, and influencing endogenous NO might potentially affect the exercise-related beneficial effects on cognitive ability and cortical capillaries., Competing Interests: Declaration of Conflict of Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Alcohol-induced aggression and related violence is a serious and common social problem globally. Alcohol use is increasingly found in the form of alcoholic herbal mixtures (AHM) with indiscriminate and unregulated alcohol content. This study investigated the effects of AHM on aggressive-like, neurocognitive impairment and brain biochemical alteration in mice. Thirty-two male resident mice were paired housed with female mice for 21 days in four groups (n = 8). Resident mice were treated orally with normal saline, AHM, ethanol and AHM + ethanol daily for 14 days. Aggressive-like behaviour was scored based on the latency and frequency of attacks by the resident mouse on the intruder. Neurocognitive impairment was determined using the Y-maze test (YMT) and novel object recognition test (NORT). Acetylcholinesterase, glutamic acid decarboxylase (GAD), pro-inflammatory and oxidative stress parameters were determined in the prefrontal cortex (PFC). Neuronal morphology, cytochrome c (Cyt-c) and nuclear factor-kappa B (NF-ĸB) expressions were determined. AHM and in combination with ethanol showed an increased index of aggression typified by frequency of attack and reduced latency to attack when compared to normal saline-treated animals. Co-administration of AHM and ethanol significantly reduced cognitive correct alternation (%) and discrimination index in the YMT and NORT, respectively. AHM and ethanol increased acetylcholinesterase, Pro-inflammatory cytokines and oxidative stress parameters while they reduced GAD. There were significantly reduced neuronal counts and increased expression of Cyt-c and NF-ĸB, respectively Alcoholic herbal mixture increased aggressiveness and caused neurocognitive impairment via increased oxido-inflammatory stress in the prefrontal cortex., (© 2022 Wiley Periodicals LLC.)

Background: Chronic steroid intake has been associated with attenuation of neuromuscular block. Despite some promising animal and adult studies, the effect of a single dose of intravenous dexamethasone on neuromuscular blockers is not well established. Thus, the present study aimed to demonstrate the effect of dexamethasone given at the time of induction for the prevention of PONV on the action of neuromuscular blockers in children undergoing elective surgery., Method: After obtaining approval from the Institute Ethics Committee and written informed parental consent, 100 ASA I and II children aged 4-15 years undergoing elective surgery randomized to receive either: 0.15 mg/kg (maximum of 5 mg) of dexamethasone diluted to a total volume of 2 ml with 0.9% saline (n = 50) or 2 ml of 0.9% saline (n = 50) at the time of induction. The time interval between application of atracurium and maximum T1 depression, 25% twitch height recovery of T1, amid 25% and 75% twitch height recovery of T1, amid the 25% twitch height recovery of T1 and recovery of the neuromuscular block to a TOF ratio of 0.9, and in between the initiation of atracurium injection till the recovery of the neuromuscular block to a TOF ratio of 0.9 was defined as onset time, clinical duration, recovery index, recovery time, and total recovery period, respectively, and recorded., Results: The onset time and recovery index time were lower (1.96 ± 0.39, 8.04 ± 2.14, respectively) with dexamethasone in comparison with saline (2.01 ± 0.51, 8.9 ± 3.4, respectively) but not statistically significant. The clinical duration, recovery time, and total recovery period were similar., Conclusion: Application of a single bolus dose (0.15 mg/kg) of dexamethasone during induction does not attenuate atracurium-induced neuromuscular blockade in children., (© 2022 John Wiley & Sons Ltd.)

For centuries, diverse mouthrinses have been applied for medicinal purposes in the oral cavity. In view of the growing resistance of oral microorganisms against conventional antimicrobial agents e.g. chlorhexidine, the implementation of alternative treatments inspired by nature has lately gained increasing interest. The aim of the present study was to compare in vitro biofilm models with in situ biofilms in order to evaluate the antimicrobial potential of different natural mouthrinses. For the in vitro study a six-species supragingival biofilm model containing A. oris , V. dispar , C. albicans , F. nucleatum , S. mutans and S. oralis was used. Biofilms were grown anaerobically on hydroxyapatite discs and treated with natural mouthrinses Ratanhia, Trybol and Tebodont. 0.9% NaCl and 10% ethanol served as negative controls, while 0.2% CHX served as positive control. After 64h hours, biofilms were harvested and quantified by cultural analysis CFU. For the in situ study, individual test splints were manufactured for the participants. After 2h and 72h the biofilm-covered samples were removed and treated with the mouthrinses and controls mentioned above. The biofilms were quantified by CFU and stained for vitality under the confocal laser scanning microscope. In the in vitro study, 0.2% CHX yielded the highest antimicrobial effect. Among all mouthrinses, Tebodont (4.708 ± 1.294 log10 CFU, median 5.279, p<0.0001) compared with 0.9% NaCl showed the highest antimicrobial potential. After 72h there was no significant reduction in CFU after 0.2% CHX treatment. Only Trybol showed a statistically significant reduction of aerobic growth of microorganisms in situ (5.331 ± 0.7350 log10 CFU, median 5.579, p<0.0209). After treatment with the positive control 0.2% CHX, a significant percentage of non-vital bacteria (42.006 ± 12.173 log10 CFU, median 42.150) was detected. To sum up, a less pronounced effect of all mouthrinses was shown for the in situ biofilms compared to the in vitro biofilms., 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 © 2023 Schönbächler, Thurnheer, Paqué, Attin and Karygianni.)

Introduction: The aim of the study was to explore the analgesic mechanism of effects of intrathecally administered interferon a (IFN-a) on chronic constriction injury (CCI) model rats., Material and Methods: 24 rats were divided into 6 groups, with 4 rats in each group, including the negative control group (Group N, no operation or treatment), the sham operation group (Group S, only the left sciatic nerve of the rats was exposed without ligation, 0.9% NaCl was intrathecally administered), and four experimental groups (CCI model was established first and then different drugs were intrathecally administered respectively), including 0.9% NaCl (Group C), IFN-a (Group CI), morphine (Group CM), and IFN-a combined with morphine (Group CIM). The mRNA levels of G proteins in both the spinal cord and dorsal root ganglia (DRG), as well as the content of amino acid and chemokine (C-X-C motif) ligand 6 (CXCL-6) in the cerebrospinal fluid were measured and analysed in each group., Results: Intrathecal administration of IFN-a increased the mechanical pain threshold in CCI rats (33.32 ±1.36 vs. 21.08 ±1.59, p < 0.001), achieving the effect comparable to that of morphine (33.32 ±1.36 vs. 32.44 ±3.18, p > 0.05), increased the mRNA expression level of Gi protein (0.62 ±0.04 vs. 0.49 ±0.05, p = 0.006), and decreased the mRNA expression level of Gs protein in the spinal cord (1.80 ±0.16 vs. 2.06 ±0.15, p = 0.035) and DRG (2.11 ±0.10 vs. 2.79 ±0.13, p < 0.001). The intrathecal administration of both IFN-a and morphine can reduce the glutamate content in the cerebrospinal fluid (261.55 ±38.12 vs. 347.70 ±40.69, p = 0.012), but without any statistically significant difference in the content of CXCL-6 across all groups ( p > 0.05)., Conclusions: Intrathecal injection of IFN-a improved the mechanical pain threshold in CCI rats, so we inferred that intrathecal administration of IFN-a had analgesic effects on neuropathic pain, possibly related to the activation of G-proteincoupled µ receptors in the spinal cord and the inhibition of glutamate release.

Purpose: To investigate vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) immunoreactivities, as well as apoptosis and oxidative stress levels in Streptozotocin (STZ)-induced diabetic rats, and determine how neferine affected these parameters., Methods: Thirty-five male Sprague Dawley rats were divided into five groups of seven. Fasting blood glucose was measured 72 h after diabetes mellitus (DM) induction in 21 rats using 60 mg/kg STZ dissolved in 0.4 ml (0.1 M) sodium-citrate buffer (pH:4.5), with values > 250 mg/dl considered diabetic. Group 1 received no treatment. Group 3 (healthy rats) received daily intraperitoneal (IP) 4 mg/kg neferine. Following DM induction: Group 2 (sham) received daily IP 0.25 ml/kg 0.9% normal saline; Group 4 received single IP 0.01 mL (2.5 mg/kg) bevacizumab, followed by daily IP 0.25 mL/kg 0.9% normal saline; and Group 5 received daily IP 4 mg/kg neferine. Total antioxidant capacity (TAC) and total oxidative stress (TOS) levels in serum and ocular tissue homogenates were evaluated using ELISA. TUNEL method was used for determining apoptosis and immuno-histochemical staining for PCNA and VEGF immunoreactivities., Results: Group 5 had significantly higher TAC and lower TOS in serum and ocular tissue homogenates than Group 4 (p < 0.05). Despite significantly lower VEGF levels and apoptosis (p < 0.05), there was no significant change in PCNA immunoreactivity in Group 5 (p > 0.05)., Conclusions: DM was associated with lower TAC, higher TOS and apoptotic cells, as well as VEGF and PCNA immunoreactivities in the retina. Neferine altered parameters other than PCNA in the opposite direction, demonstrating reductive effects on DM., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The aim of this study was to examine the effects of hyperhomocysteinemia and aerobic physical activity on changes of cardiovascular biomarkers in sera, oxidative stress in cardiac tissue, and histomorphometric parameters of heart and aorta in rats. Experiments were conducted on male Wistar albino rats organized into four groups (n = 10, per group): C (control group): 0.9% NaCl 0.2 mL/day; H (homocysteine group): homocysteine 0.45 µmol/g b.w./day; CPA (control + physical activity group): 0.9% NaCl 0.2 mL/day and a program of physical activity on a treadmill; and HPA (homocysteine + physical activity group) homocysteine 0.45 µmol/g b.w./day and a program of physical activity on a treadmill. Substances were applied subcutaneously twice a day. Lipid peroxidation and relative activity of Mn-superoxide dismutase isoform were significantly higher in active hyperhomocysteinemic rats in comparison to sedentary animals. Atherosclerotic plaques were detected in aorta samples of active hyperhomocysteinemic rats and also, they had increased left ventricle wall and interventricular septum, and transverse diameter of cardiomyocytes compared to sedentary groups. Aerobic physical activity in the condition of hyperhomocysteinemia can lead to increased oxidative stress in cardiac tissue and changes in histomorphometric parameters of the heart and aorta, as well increased lipid parameters and cardiac damage biomarkers in sera of rats., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Regarding neurocognitive and immunomodulatory properties of cinnamon (Cinn) we aimed to investigate whether cinnamon regulates acetylcholinesterase (AChE) activity, and oxidative abnormalities with concomitant memory dysfunction in streptozotocin (STZ)-induced diabetes., Methods: Forty-seven male adult rats were divided into seven groups (n=8 animals): Control group: in these non-diabetic rats only saline 0.9% NaCl was gavaged, Diabetic (Dia) group: diabetic rats in them saline 0.9% NaCl was gavaged for six weeks. Dia-Cinn 100, Dia-Cinn 200, and Dia-Cinn 400, Dia-Met groups: in these diabetic rats the extract (100, 200, 400 mg/kg respectively) or metformin (300 mg/kg) was gavaged for six weeks. Passive avoidance performance, AChE enzyme activity, and oxidative indicators were examined among the groups., Results: Vs. the control group, blood glucose level and stay time in the dark were remarkably increased in Dia group whereas the latency time was decreased. Meanwhile, antioxidant levels (superoxide dismutase, catalase, and thiols) noticeably decreased in the Dia group compared to the Control group. On the other hand, Cinn extract espicailly at the highest dose recovered the changes similar to those found in the metformin-treated group., Conclusions: These findings proposed that the cinnamon hydro-ethanolic extract promotes memory recovery in diabetic conditions through the atteuation of the AChE activity and oxidative injury., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Abstract: Introduction: Intraoperative irrigation, usually with normal saline (NS), aids in bleeding identification and management. We investigated the effect of different irrigation fluids, with additives, on hemostasis using two bleeding models. Methods: C57BL/6 J mice were subjected to a tail bleed model or uncontrolled abdominal hemorrhage via liver laceration followed by abdominal cavity irrigation. We compared NS, lactated Ringer's (LR), and PlasmaLyte. We examined NS and LR at different temperatures. Normal saline or LR with calcium (Ca 2+ ) or tranexamic acid (TXA) was studied. Results: Compared with room temperature (RT), increasing the temperature of the irrigation fluid to 37°C and 42°C reduced tail vein bleeding times substantially in both NS and LR (all P < 0.001), with no significant differences between the two fluids. At RT, LR, but not PlasmaLyte, substantially reduced bleeding times in comparison to NS ( P < 0.0001). Liver injury blood loss was lower with LR ( P < 0.01). Normal saline supplemented with 2.7 mEq/L of Ca 2+ decreased bleeding time and blood loss volume ( P < 0.001 and P < 0.01, respectively) to similar levels as LR. Normal saline with 150 mg/mL of TXA markedly reduced bleeding time ( P < 0.0001), and NS with 62.5 mg/mL TXA decreased blood loss ( P < 0.01). Conclusion: Whereas Ca 2+ - and TXA-supplemented NS reduced bleeding, LR remained superior to all irrigation fluid compositions. As LR contains Ca 2+ , and Ca 2+ -supplemented NS mirrored LR in response, Ca 2+ presence in the irrigation fluid seems key to improving solution's hemostatic ability. Because warming the fluids normalized the choice of agents, the data also suggest that Ca 2+ -containing fluids such as LR may be more suitable for hemostasis when used at RT., Competing Interests: M.D.N. serves on the scientific advisory board of Haima Therapeutics with equity stake. He has received research funding from Haemonetics, Instrumentation Laboratories, and Janssen Pharmaceuticals, and he has received honoraria from Haemonetics and Janssen. The other authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

The purpose of this study is to assess the effect of fluid bolus in response to a hypotensive episode by evaluating high-fidelity hemodynamic data obtained from children with single-ventricle anatomy and parallel circulation. Single center, retrospective analysis of hemodynamic and oximetric data after fluid bolus administrations within the first 2 weeks post-surgery. A baseline (- 60 to - 10 min), hypotensive episode (- 10 to 0 min), and response interval (0 to 60 min) were defined to quantify the dynamics of vital signs. The responses assessed include heart rate, blood pressure, oxygen saturation, oxygen extraction ratios, and pulmonary-to-systemic flow ratios. Mixed effects models were used to account for the repeated measures over the response interval. The analysis included 67 fluid boluses. There is a decrease in heart rate and an increase in blood pressure during the response in comparison to the hypotensive time. These vitals rapidly return to the baseline values. The boluses induced a significant decrease in renal and cerebral oxygen extraction ratios, with no significant change in arterial oxygen saturation or pulmonary-to-systemic flow ratio. The type of bolus (normal saline versus albumin) did not affect the response in blood pressure. However, in comparison with albumin, normal saline had a more favorable effect on the renal and cerebral oxygen extraction ratios. This study demonstrates that fluid boluses are an effective rescue medication for hypotensive episodes in children with parallel circulation by improving hemodynamics, as well as markers of oxygen delivery. The type of bolus (normal saline versus albumin) did not affect the blood pressure response. However, normal saline had a more pronounced effect on the renal and cerebral oxygen extraction ratios than albumin., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Plasma activated liquids have demonstrated antimicrobial effects and receive increasing attention due to the potential to strengthen the armoury of novel approaches against antibiotic resistant bacteria. However, the antibacterial activity and cytotoxic effects of these solutions need to be understood and balanced before exposure to humans. In this study, the antibacterial effects of plasma activated saline (PAS) were tested against Gram negative and positive bacteria, and HaCaT keratinocytes were used for cytotoxicity studies. For the first time, a co-culture model between these bacteria and eukaryotic cells under the influence of PAS has been described. Exposure of saline to plasma resulted in high concentrations of nitrate, hydrogen peroxide and a reduction of pH. PAS caused high antibacterial effects in the co-culture model, accompanied by high cytotoxic effects to the monolayer of mammalian cells. We present evidence and provide a deeper understanding for the hypothesis that upon treatment with PAS, chemical species generated in the liquid mediate high antimicrobial effects in the co-culture setup as well as mitochondrial depolarization and glutathione depletion in HaCaT cells and cell lysis due to acidic pH. In conclusion, PAS retains strong antibacterial effects in a co-culture model, which may have unintended negative biological effects on mammalian cells., (© 2022. The Author(s).)

Objective: To determine whether dobutamine, norepinephrine or phenylephrine infusions alleviate hypotension in isoflurane-anaesthetized dogs administered dexmedetomidine with vatinoxan., Study Design: Balanced, randomized crossover trial., Animals: A total of eight healthy Beagle dogs., Methods: Each dog was anaesthetized with isoflurane (end-tidal isoflurane 1.3%) and five treatments: dexmedetomidine hydrochloride (2.5 μg kg -1 ) bolus followed by 0.9% saline infusion (DEX-S); dexmedetomidine and vatinoxan hydrochloride (100 μg kg -1 ) bolus followed by an infusion of 0.9% saline (DEX-VAT-S), dobutamine (DEX-VAT-D), norepinephrine (DEX-VAT-N) or phenylephrine (DEX-VAT-P). The dexmedetomidine and vatinoxan boluses were administered at baseline (T0) and the treatment infusion was started after 15 minutes (T15) if mean arterial pressure (MAP) was < 90 mmHg. The treatment infusion rate was adjusted every 5 minutes as required. Systemic haemodynamics were recorded at T0 and 10 (T10) and 45 (T45) minutes. A repeated measures analysis of covariance model was used., Results: Most dogs had a MAP < 70 mmHg at T0 before treatment. Treatments DEX-S and DEX-VAT all significantly increased MAP at T10, but systemic vascular resistance index (SVRI) was significantly higher and cardiac index (CI) lower after DEX-S than after DEX-VAT. CI did not significantly differ between DEX-S and DEX-VAT-S at T45, while SVRI remained higher with DEX-S. Normotension was achieved by all vasoactive infusions in every dog, whereas MAP was below baseline with DEX-VAT-S, and higher than baseline with DEX-S at T45. Median infusion rates were 3.75, 0.25 and 0.5 μg kg -1 minute -1 for dobutamine, norepinephrine and phenylephrine, respectively. Dobutamine and norepinephrine increased CI (mean ± standard deviation, 3.35 ± 0.70 and 3.97 ± 1.24 L minute -1 m -2 , respectively) and decreased SVRI, whereas phenylephrine had the opposite effect (CI 2.13 ± 0.45 L minute -1 m -2 )., Conclusions and Clinical Relevance: Hypotension in isoflurane-anaesthetized dogs administered dexmedetomidine and vatinoxan can be treated with either dobutamine or norepinephrine., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)