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Toll-like receptors (TLRs) are known to have an important role in triggering the innate immune response and in priming antigen-specific adaptive immunity and inflammation. The differences in synovial tissue expression of the TLRs between seronegative and seropositive rheumatoid arthritis (RA) were examined from 9 seropositive RA, 5 seronegative RA and 4 osteoarthritis (OA) patients. Synovitis status was assessed using Krenn's scoring and TLR 1–9 expression by immunohistochemistry. Tissue citrulline content was analysed by HPLC method. In RA TLR expression was generally higher than in OA. TLR2 expression was higher in both seronegative and seropositive RA compared to OA. TLR 1, 4 and 8 expressions were higher in seropositive RA than in seronegative RA or in OA. For TLRs 3, 5, 6, 7 and 9 local differences of expression were found between groups. TLR 1–9 expression correlated with the synovitis grade. No statistical difference was found in synovial tissue citrulline content between the groups. In seropositive RA, the TLR repertoire in the synovial tissue differs from seronegative RA and could explain differences in disease outcomes. The high expression of protein sensing (TLR1, TLR2 and TLR4) and nucleic acid sensing TLRs (TLR7, TLR8 and TLR9) in the seropositive RA could make the synovium primed for reacting to citrullinated proteins and nucleic acids that could be released to extracellular space in formation of neutrophil extracellular traps. This reactivity could be augmented by Fc receptor activation by anti-citrullinated protein antibody immunocomplexes associated with seropositive RA. [ABSTRACT FROM AUTHOR]

Omega‐3 fatty acids are gaining attention as a therapeutic agent of many diseases. Their protective effect in a variety of diseases has been demonstrated. To the best of our knowledge, this is the first study on omega‐3 fatty acids related to acute cold‐restraint stress (CRS) induced hepatic dysfunction in rats. Forty adult male Sprague–Dawley albino rats were used and classified into: control, omega‐3 group, each rat was pretreated with omega‐3 fatty acids; CRS group, rats were subjected to acute CRS for 6 hr; and CRS group pretreated with omega‐3 fatty acids. Serum was obtained to determine corticosterone (CORT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor‐α (TNF‐α) levels. Hepatic malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were measured. Also, liver tissues were taken for histological examination and immunohistochemical assessment of the apoptotic marker, caspase‐3. Results showed that pretreatment of stressed rats with omega‐3 fatty acids led to significant decrease in hepatic MDA and increase in TAC levels. They reduced serum levels of CORT, ALT, AST, and TNF‐α. Also, they improved liver damage and suppressed hepatic caspase‐3 expression. In conclusion, pretreatment of stressed rats with omega‐3 fatty acids has ameliorated stress‐induced liver damage due to their antioxidant, anti‐inflammatory, and antiapoptotic effects. So, they can be used to minimize stress complications on the liver. Omega‐3 fatty acids are gaining attention as a therapeutic agent of many diseases. Their protective effect in a variety of diseases has been demonstrated. To the best of our knowledge, this is the first study on omega‐3 fatty acids related to acute cold‐restraint stress (CRS) induced hepatic dysfunction in rats. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is closely associated with male infertility and sexual dysfunction. Recent data indicate that the proinsulin C‐peptide (CP) exerts important physiological effects and shows the characteristics of an endogenous peptide hormone. So, this study was done to investigate the effect of C‐peptide with or without insulin treatment on testicular function and architecture in diabetic rats. Rats were divided into the following groups: control, diabetic, and diabetic groups treated with either CP alone or combined with insulin. Tested parameters included, estimation of serum follicle‐stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and glucose levels, testicular samples for histopathology and estimation of malondialdehyde (MDA), total antioxidant capacity (TAC), and B‐cell leukemia/lymphoma‐2 (BCL‐2) levels as well as sperm count and motility. Results showed that DM caused a severe alteration in hormonal profile and reduced sperm parameters along with increased MDA and decrease in both TAC and BCL‐2 levels. CP alone or with insulin treatment efficiently reversed all the negative effects of DM on rat testes, with maximum improvement in the combined regimen. Proposed mechanisms may involve its hypoglycemic, antioxidant, and antiapoptotic properties. Thus, CP could substitute for or better combined with insulin to prevent or retard diabetic‐induced testicular dysfunction. Diabetes mellitus (DM) has a detrimental effect on rat testicular function and architecture including hypogonadism and decreased sperm count and motility. C‐peptide with or without insulin treatment efficiently reversed all negative effects of DM on rat testes, probably via its hypoglycemic, antioxidant, and antiapoptotic mechanisms with subsequent improvement in testicular function and architecture. [ABSTRACT FROM AUTHOR]

Aging is a biological process with gradual decrease of cell function. Kidneys are one of the organs with higher susceptibility to the development of age-dependent tissue damage. Intermittent fasting has several beneficial effects on age-related degenerative changes. The aim of this study was to investigate the possible beneficial effect of intermittent fasting in delaying age-related renal changes and the possible mechanisms of this effect. Thirty male albino rats were classified into three groups: control, adult rats aged 3 months; aged group, 15-month-old rats and maintained until the age of 18 months; and intermittent fasting-aged groups, 15-month-old rats maintained on intermittent fasting for 3 months. Kidneys were processed for histological and immunohistochemical study. Aging resulted in a significant reduction in renal function and significant several degenerative changes in renal corpuscles and tubules which showed abnormal histological structure with increased collagen deposition. Aging caused significant reduction in the expression of autophagic marker light chain 3 with increased expression of active caspase-3 and inducible nitric oxide synthase. Intermittent fasting significantly improved these age-related renal changes. Intermittent fasting effectively prevents age-related renal changes through the reduction of age-related oxidative stress, inflammation, apoptosis, and activation of autophagy., Competing Interests: Conflict of Interest The authors declare that they have no competing interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Microscopy Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)