Chronic niacin administration ameliorates ovulation, histological changes in the ovary and adiponectin concentrations in a rat model of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common ovarian diseases among women of reproductive age. The reproductive and metabolic traits of PCOS are underpinned by adipocyte dysfunction, especially diminished adiponectin secretion. Based on evidence that niacin stimulates adiponectin secretion, this study evaluated the effects of niacin on adiponectin concentrations and reproductive traits in a rat model of PCOS. PCOS was induced by single injection of 4mg kg-1 oestradiol valerate (i.m.), and PCOS groups were administered orally with saline or niacin (10 or 25mg kg-1) daily for 30 days after PCOS induction. The control group received 0.2mL sesame oil (i.m.) only. At the end of the experimental period, serum samples and ovaries were collected for adiponectin, histological and molecular analyses. Niacin reduced the bodyweight gain and increased ovary weights in PCOS rats. Niacin also increased the number of normal antral follicles and corpora lutea while reducing the number of cystic follicles and the thickness of theca interna. Moreover, niacin significantly increased serum adiponectin concentration and the gene expression of adiponectin and its type 1 receptor. In conclusion, this study indicates that niacin reduces cystic follicles and improves ovulation in PCOS rats. Adiponectin signalling may have contributed, in part, to the beneficial effects.

Use of zona pellucida-bound spermatozoa as a natural selection in improvement of ICSI outcomes: A systematic review and meta-analysis.

Zona pellucida (ZP)-bound spermatozoa have normal morphology and motility and can enhance the ICSI outcomes. Selection of zona pellucida-bound spermatozoa is recently considered to find functional spermatozoa for ICSI. This study reviewed the efficacy of ZP-bound sperm selection on the ICSI outcomes includes fertilisation rate, embryo quality, embryo transfer rate and clinical pregnancy rate. The databases searched include PubMed, Scopus and Cochrane databases up to January 2019. All research reports with full text and in English language that addressing the relation between ZP-sperm selection and ICSI outcomes were included. Fifty studies were suitable after screening of the 845 identified articles. After exclusions, five of these studies were included. Meta-analytic pooling of data indicated no association between the ICSI outcomes and ZP-bound sperm selection except a marginal effect on implantation rate. Eliminating one study indicated that ZP-bound sperm selection technique improves embryo quality, implantation rate and clinical pregnancy rate. This study revealed that ZP-bound sperm selection produces only a slight improvement in implantation rate. However, further studies with a large number of couples must be done to clarify the potential beneficial effect of ZP-bound spermatozoa on ICSI outcomes.

Resveratrol suppresses interleukin-6 expression through activation of sirtuin 1 in hypertrophied H9c2 cardiomyoblasts.

Inflammatory cytokine, interleukin-6 (IL-6), plays an important role in the pathogenesis of cardiac hypertrophy. Recent studies have documented that resveratrol exhibits cardioprotective effects. The present study attempts to explore whether resveratrol suppreses IL-6 in hypertrophied H9c2 cardiomyoblasts through histone deacetylase, sirtuin 1 (SIRT1). To induce hypertrophy, the cells were incubated with angiotensin II (Ang II). Treatment groups were treated with different doses (1, 10, 25, 50, 75, and 100 µM) of resveratrol (R). Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell size was determined using crystal violet staining. Gene expression was assessed by real-time polymerase chain reaction technique. Enzyme-linked immunosorbent assay was used to measure IL-6 concentration. The results showed that cell area and ANP messenger RNA (mRNA) levels decreased significantly in R25+Ang, R50+Ang, and R100+Ang groups, as compared with Ang group. Therefore, 10, 20, 30, 40, and 50 µM of resveratrol were used to to evaluate its anti-inflammatory effects. The results revealed that Ang II upregulated IL-6 at both mRNA and protein levels (p < .001 vs. normal) and resveratrol (50 µM) decreased IL-6 mRNA (p < .01) and protein (p < .05) significantly in comparison to Ang group. However, in groups in which the cells were pretreated with SIRT1 inhibitor, EX-527, the response of resveratrol was partially reversed. Transcription levels of IL-6 receptor components (gp130 and gp80) did not change significantly among the experimental groups. The current data suggests that resveratrol protects H9c2 cells against Ang II-induced hypertrophy by suppression of IL-6 through SIRT1 activation.

Involvement of central TRPV1 receptors in pentylenetetrazole and amygdala-induced kindling in male rats.

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel that is involved in modulation of diverse physiological processes. The role of this receptor in epilepsy has not been studied well. Therefore, we investigated the role of central TRPV1 receptors on the development of pentylenetetrazole (PTZ) and amygdala-induced kindling in rats. Male Wistar rats received subconvulsive dose of PTZ intraperitoneally, every other day. TRPV1 receptor agonist, OLDA and its antagonist, AMG-9810 were injected intracerebroventricularly 30 min prior to PTZ administration. In electrical kindling, stimulating and recording electrodes were implanted in the right amygdala of male rats. After kindling, the effect of TRPV1 receptor agonist or antagonist on afterdischarge duration (ADD), latency to the onset of bilateral forelimb clonuses (S4L) and duration of loss of equilibrium (stage 5 seizures, S5D) were measured. The results demonstrated that, OLDA at the doses of 0.01, 0.1 and 1 µg/rat, significantly accelerated the incidence of all seizure stages, increased S5D and decreased S4L in the PTZ model of kindling. Also, in amygdala kindling, S5D and ADD were significantly reduced following the administration of AMG-9810. In contrast, OLDA significantly aggravated the indices of seizure in both models of epileptic seizure. This study demonstrated that central TRPV1 receptors may be involved in the development of electrical and PTZ-induced kindling.

Morphine Reduces Expression of TRPV1 Receptors in the Amygdala but not in the Hippocampus of Male Rats.

BACKGROUND: Chronic use of opioids usually results in physical dependence. The underlying mechanisms for this dependence are still being evaluated. Transient receptor potential vanilloid type 1 (TRPV1) are important receptors of pain perception. Their role during opioid dependence has not been studied well. The aim of this study was to evaluate the effect of morphine-dependence on the expression of TRPV1 receptors in the amygdala and CA1 region of the hippocampus. METHODS: This study used four groups of rats. Two groups of rats (morphine and morphine+naloxone) received morphine based on the following protocol: 10 mg/kg (twice daily, 3 days) followed by 20, 30, 40 and 50 mg/kg (twice daily), respectively, for 4 consecutive days. Another group received vehicle (1 ml/kg) instead of morphine given using the same schedule. The morphine+naloxone group of rats additionally received naloxone (5 mg/kg) at the end of the protocol. The control group rats received no injections or intervention. The amygdala and CA1 regions of the morphine, saline-treated and intact animals were isolated and prepared for real-time PCR analysis. RESULTS: Administration of naloxone induced withdrawal signs in morphine-treated animals. The results showed a significant decrease in TRPV1 gene expression in the amygdala (P<0.05) but not the CA1 region of morphine dependent rats. CONCLUSION: TRPV1 receptors may be involved in morphine-induced dependence.

Possible Impact of Human ß-defensin 1 on sperm motility in infertile men with abnormal sperm parameters.

Human ß-defensins and interleukins may be auxiliary in sperm maturation. This cross-sectional study aimed to evaluate the expression of Human ß-defensins 1 and 2, interleukins (ILs)- 10 and -18 genes in sperm, as well as seminal plasma levels of these two cytokines in subfertile men with different types of sperm abnormalities compared to those with normozoospermic men. Participants were separated into two experimental groups: the control group (n = 25) and the group with sperm abnormalities (SA) (n = 45). SA participants were further subdivided into the following groups with n = 15 individuals each: Teratozoospermia (T), Asthenoteratozoospermia (AT), and Oligoasthenoteratozoospermia (OAT) groups. The quantitative real-time polymerase chain reaction was used to quantify the mRNA levels of hBDs 1 and 2, IL-10, and IL-18 in sperm. The seminal plasma concentrations of IL-10 and IL-18 were measured by using the enzyme-linked immunosorbent assay technique. The mRNA expression of hBD-1 and IL-10 showed a significant decrease in the OAT compared to the controls (P < 0.0001 and P = 0.02, respectively). The lowest seminal plasma concentration of IL-10 belonged to the OAT (P = 0.04). ROC curve analysis showed a sensitivity, specificity, and cutoff value of 82.35%, 86.67%, and 0.63 for hBD-1 levels, respectively. A positive and significant correlation was found between hBD-1 expression and sperm motility and IL-10 expression rate and normal sperm morphology.Therefore, hBD-1 could be considered as the alternative biomaterial to pre-treatments of infertile men with abnormal sperm parameters, specifically OAT men, which led to improving the assisted reproduction success rate.

Effect of vitamin C on histomorphometric changes of testis, epididymis, prostate, and seminal vesicle induced by acrylamide in rat.

Acrylamide (ACR) has adverse effects on the rat testis. This study aimed to assess the impact of ACR and vit C exposure on reproductive organs in rats. In this experimental study, 32 adult male rats were used. The animals were divided into 4 groups (n = 8): (1) control group, (2) ACR (10 mg/kg) group, (3) vit C (200 mg/kg), (4) ACR (10 mg/kg) + vit C (200 mg/kg) daily for 5 weeks by gavage. After the administration period, testis, prostate, seminal vesicle, and epididymis of animals are removed; after preparing tissue sections, the structural changes of the tissues are examined by stereology. Data were analyzed using one-way ANOVA followed by the Tukey test in SPSS software. A value of p ≤ 0.05 was considered significant. The testis weight, volume (mm3), and the mean Johnsen score showed a significant decrease in comparison with the control group and vit C-treated group. These parameters were increased in ACR + vit C group. The number of spermatogonia, spermatocyte, spermatid, and Sertoli and Leydig cells in ACR-treated group showed a significant decrease in comparison with the control and vit C-treated groups. The number of these cells was increased in the ACR + vit C group. Epithelium height and folding of prostate and seminal vesicle in the ACR-treated group were decreased. Epithelium lost its integrity. In the ACR + vit C group, histopathological changes were decreased. Seminal vesicle of ACR + vit C-treated group showed mild degeneration and rupture in epithelium integrity. The epididymis of ACR + vit C group also showed mild degeneration and rupture in epithelium integrity.

Methane-rich saline ameliorates depressive-like behaviors during chronic unpredictable mild stress (CUMS).

Depression, considered the most prevalent neuropsychiatric disorder, is multifactorial and complex. Oxidative stress and inflammation significantly contribute to its etiology. Conversely, methane, a novel therapeutic gas, has demonstrated efficacy in enhancing tissue resilience against ischemic injuries and inflammation. In this study, we investigated the effect of methane-rich saline (MRS) on depression using the chronic unpredictable mild stress (CUMS) model. Depressed rats received MRS treatment, and depression-like behaviors and cognitive function were assessed through sucrose preference, open field, forced swimming, and Morris water maze tests. Additionally, we measured serum corticosterone levels, antioxidant enzyme activity, hippocampal malondialdehyde (MDA), and TNFα levels, and investigated histological changes in the hippocampus. Our findings revealed that MRS significantly ameliorated Depressive-like behaviors and cognitive impairment. Furthermore, MRS administration regulated serum corticosterone levels and also MRS reduced hippocampal lipid peroxidation, TNFα, and hippocampus tissue damage. MRS likely exerts its effects by reducing oxidative stress and inflammatory factors and modulating the function of the hypothalamus-pituitary-adrenal (HPA) axis. These results demonstrate the protective effects of MRS on the hippocampus in CUMS animals.

Sperm Selection Using Zona Pellucida-Binding Enhanced Embryo Morphokinetic and Clinical Outcomes in ICSI: A Sibling Oocytes Study.

The objective was to investigate the embryo morphokinitics using a time-lapse monitoring (TLM) system and assessment of clinical outcomes following intracytoplasmic sperm injection (ICSI) with zona pellucida (ZP)-bound sperm selection and conventional methods. A total of 371 metaphase II (MII) oocytes from 50 ICSI cycles were studied. Sibling oocytes were randomly divided into control (n = 199) and ZP-bound group (n = 172). All resulting zygotes were cultured and monitored in the TLM system up to Day 3 after ICSI. Fertilization rate, early embryo development, and clinical outcomes were evaluated. No significant differences were found in fertilization rate, time-lapse qualitative and quantitative measures, pronuclear fading time (PNF) t2, t3, t4, t5, t6, and t7 (times of cleavage to 2, 3, 4, 5, 6, and 7 cells), respectively. However, the t8 (time of cleavage to eight cells) and cc3 (duration of third cell cycle) revealed a significant difference between control and ZP-bound groups (p < .05). A significant difference between the two groups (p < .05) in the rates of Grade A embryos (according to Basile algorithm), chemical pregnancy, clinical pregnancy, and implantation was observed. Sperm selection using biological materials, such as ZP, improved both embryo quality and pregnancy outcomes, despite not affecting the early embryo development and morphokinetic parameters up to t8. This prospective randomized sibling oocyte trial was registered in October 2020 to January 2022 (IRCT20200705048021N1).

Antidepressant-like effect of endogenous SO2 on depression caused by chronic unpredictable mild stress.

Sulfur dioxide (SO2) is a toxic gas with harmful effects on various organs. However, recent studies have confirmed the protective effect of SO2 on ischemic heart disease, atherosclerosis, and lung infections. Therefore, the present study was designed to investigate the effect of endogenous SO2 on depression. The chronic unpredictable mild stress (CUMS) model was performed to cause depression. Depression-like behaviors in animals were determined using an open-field test, forced swimming test, and sucrose consumption. Animal spatial learning and memory were also assessed using the Morris water maze. Besides, the oxidative status of the hippocampus and serum corticosterone level were evaluated. A reduction in the tendency to consume sucrose, mobility, and curiosity, as well as learning and memory disorders were observed in CUMS animals. Depressed animals treated with SO2 revealed a significant improvement in behavioral and cognitive functions. SO2 also reduced neuronal damage and lipid peroxidation of the hippocampus and serum corticosterone level in the CUMS group. Various shreds of evidence support a mutual relationship between inflammation and depression; also, growing studies show the role of oxidative stress in the pathogenesis of mood-related disorders such as depression. This study indicated that increased hippocampal malondialdehyde (MDA) and serum corticosterone levels can be due to the existence of oxidative stress and possible activation of inflammatory processes. SO2 donors diminished MDA and corticosterone levels in depressed animals. According to the study results, SO2 may be able to reduce tissue damage and eventually behavioral disorders caused by depression by lowering oxidative stress and inflammation.

Mesenchymal stem cells-derived exosomes as a promising new approach for the treatment of infertility caused by polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a multifactorial metabolic and most common endocrine disorder that its prevalence, depending on different methods of evaluating PCOS traits, varies from 4% to 21%. Chronic low-grade inflammation and irregular apoptosis of granulosa cells play a crucial role in the pathogenesis of PCOS infertility. Mesenchymal stem cells (MSCs)-derived exosomes and extracellular vesicles (EVs) are lipid bilayer complexes that act as a means of intercellular transferring of proteins, lipids, DNA and different types of RNAs. It seems that this nanoparticles have therapeutic effects on the PCOS ovary such as regulating immunity response, anti-inflammatory (local and systemic) and suppress of granulosa cells (GCs) apoptosis. Although there are few studies demonstrating the effects of exosomes on PCOS and their exact mechanisms is still unknown, in the present study we reviewed the available studies of the functions of MSC-derived exosome, EVs and secretome on apoptosis of granulosa cells and inflammation in the ovary. Therefore, the novel cell-free therapeutic approaches for PCOS were suggested in this study.

Ferulic Acid Ameliorates Cell Injuries, Cognitive and Motor Impairments in Cuprizone-Induced Demyelination Model of Multiple Sclerosis.

OBJECTIVE: Ferulic acid (FA) is a phenolic compound that exhibits neuroprotective effects in the central nervous system (CNS). This study was conducted to evaluate the potential effects of FA on the cognitive and motor impairments in the cuprizone-induced demyelination model of multiple sclerosis (MS). MATERIALS AND METHODS: In this experimental study, demyelination was induced in mice by feeding them with chow containing cuprizone (CPZ) 0.2% for 6 weeks. Mice in the control group received normal chow. Mice in the CPZ+Veh, CPZ+FA10, and CPZ+FA100 groups received saline, and FA at a dose of 0, 10, or 100 mg/kg (intraperitoneal, I.P., daily) respectively. After cognitive and motor assessments, under anaesthesia, animal brains were removed for evaluating the histological, apoptosis, and molecular changes. RESULTS: The results showed that FA increased freezing behaviour in contextual (P<0.05) and cued freezing tests (P<0.05). FA also reduced the random arm entrance (P<0.01) and increased spontaneous alternations into the arms of Y-maze compared to the CPZ+Veh group (P<0.05). Time on the rotarod was improved in rats that received both doses of FA (P<0.01). Demyelination, apoptosis, and relative mRNA expression of p53 were lower in the FA-treated groups relative to the CPZ+Veh group (P<0.01). In addition, FA increased mRNA expression of brain-derived neurotrophic factor (Bdnf), Olig2, and Mbp (P<0.05) but decreased GFAP mRNA expression compared to the CPZ+Veh group (P<0.01). CONCLUSION: The results of this study showed that FA plays a significant neuroprotective role in CPZ models of demyelination by reducing neuronal apoptosis and improving oligodendrocytes (OLs) growth and differentiation.

The G-Protein-Coupled Estrogen Receptor Agonist Prevents Cardiac Lipid Accumulation by Stimulating Cardiac Peroxisome Proliferator-Activated Receptor α: A Preclinical Study in Ovariectomized-Diabetic Rat Model.

Background: Type 2 diabetes mellitus (T2DM) is associated with cardiometabolic changes, and menopause exacerbates these conditions, leading to a greater risk of cardiovascular diseases (CVDs). The G protein-coupled estrogen receptor (GPER), which mediates the rapid effects of estrogen, has beneficial cardiac effects in both T2DM and menopause, but its mechanism of action is not well understood. Objectives: This study aimed to determine whether G1 as a selective GPER-agonist has beneficial effects on cardiac lipid metabolism in ovariectomized rats with T2DM. Methods: Female Wistar rats were divided into 5 groups (n = 7 in each group): Sham-control (Sh-Ctl), T2DM, ovariectomized-T2DM (OVX-T2DM), OVX-T2DM-G1 (GPER-agonist), and OVX-T2DM-vehicle (OVX-T2DM-Veh). After stabilization of T2DM, G1 (200 µg/Kg) was administrated for 6 weeks. Then, the levels of free fatty acids (FFAs), CD36, peroxisome proliferator-activated receptor α (PPARα), and lipid accumulation in the cardiac tissue were determined. Results: Compared with the Sh-Ctl group, cardiac FFAs (P < 0.001), CD36 (P < 0.05), and lipid accumulation (P < 0.001) increased, and cardiac PPARα (P < 0.01) decreased in T2DM animals; ovariectomy intensified these changes. Also, cardiac FFAs, PPARα, and lipid accumulation (P < 0.05) significantly decreased in the OVX-T2DM-G1 group compared to the OVX-T2DM-Veh group. However, cardiac CD36 levels did not change. Conclusions: G1 as a selective GPER-agonist affects lipid metabolism in T2DM animals. It also plays a vital role in improving cardiac metabolism during postmenopausal diabetic conditions.

Anticonvulsant and depressant effects of aqueous extracts of Carum copticum seeds in male rats.

In this study, the effects of aqueous extracts of Carum copticum seeds (CCS) were evaluated in kindling models of epilepsy. Additionally, the sedative and anxiolytic effects of the extract were assessed. For pentylenetetrazole (PTZ) kindling, rats received a subconvulsant dose of PTZ (40 mg/kg, ip) every second day and seizure stages were recorded. CCS aqueous extract (200, 400, or 600 mg/kg, ip) was injected 30 minutes prior to each PTZ injection. In electrical kindling, bipolar stimulating and monopolar recording electrodes were implanted stereotaxically in the right basolateral amygdala of male Sprague-Dawley rats. After kindling, the effect of aqueous extracts of CCS (200, 400, or 600 mg/kg, ip) on afterdischarge duration, duration of rearing, forelimb clonus, and loss of equilibrium (stage 5 seizure), and latency to the onset of bilateral forelimb clonus were measured. The sedative and the anxiolytic effects of CCS extracts were evaluated in an open-field apparatus and elevated plus maze, respectively. The results indicate that aqueous extracts of CCS have a significant anticonvulsant effect. Different doses of extract significantly delayed the incidence of every seizure stage in the PTZ model of kindling. Moreover, CCS extract (400 and 600 mg/kg, ip) suppressed afterdischarge duration, latency to the onset of bilateral forelimb clonus, and stage 5 seizure in the electrical kindling model. These results suggest that CCS extract has remarkable antiepileptic and central depressant effects.

Mesenchymal Stem-Cell Derived Exosome Therapy as a Potential Future Approach for Treatment of Male Infertility Caused by Chlamydia Infection.

Some microbial sexually transmitted infections (STIs) have adverse effects on the reproductive tract, sperm function, and male fertility. Given that STIs are often asymptomatic and cause major complications such as urogenital inflammation, fibrosis, and scarring, optimal treatments should be performed to prevent the noxious effect of STIs on male fertility. Among STIs, Chlamydia trachomatis is the most common asymptomatic preventable bacterial STI. C. trachomatis can affect both sperm and the male reproductive tract. Recently, mesenchymal stem cells (MSCs) derived exosomes have been considered as a new therapeutic medicine due to their immunomodulatory, anti-inflammatory, anti-oxidant, and regenerative effects without consequences through the stem cell transplantation based therapies. Inflammation of the genital tract and sperm dysfunction are the consequences of the microbial infections, especially Chlamydia trachomatis. Exosome therapy as a noninvasive approach has shown promising results on the ability to regenerate the damaged sperm and treating asthenozoospermia. Recent experimental methods may be helpful in the novel treatments of male infertility. Thus, it is demonstrated that exosomes play an important role in preventing the consequences of infection, and thereby preventing inflammation, reducing cell damage, inhibiting fibrogenesis, and reducing scar formation. This review aimed to overview the studies about the potential therapeutic roles of MSCs-derived exosomes on sperm abnormalities and male infertility caused by STIs.

Safety assessment of genetically modified rice expressing Cry1Ab protein in Sprague-Dawley rats.

Rice is considered one of the most important staple food crops. Genetically modified (GM) Bt rice, harbored cry1Ab gene expressing the insect-resistance protein has been developed to resistance to the insects. In this study, we assessed the safety of the GM Bt rice on Sprague-Dawley rats for 90 days. Totally, 120 rats in both sexes were used for three different diets, including 50% GM Bt rice, feeding with 50% rice, and standard feeding. Each 40 SD rats including 20 males and 20 females were considered as each diet. The clinical variables such as body weight and food consumption were measured and a range of clinical tests was examined, including hematology, serum chemistry parameters, urinalysis profile, thyroid, and sex hormone levels. Pathological assessments were also done. The results showed that the mean weekly feed utilization (%) had no significant difference among the studied groups. Also, blood biochemistry, hematological parameters, urine analysis, and hormonal levels had no significant differences among the groups. However, alanine aminotransferase was less in males versus female feeding with GM Bt rice. No histopathological changes were observed among the groups. In conclusion, this study demonstrated that GM Bt rice had no obvious adverse effects on rats' health.

Association of exon 9 but not intron 8 VDR polymorphisms with occult HBV infection in south-eastern Iranian patients.

BACKGROUND AND AIM: Occult hepatitis B infection (OBI) is characterized as a form of hepatitis in which, despite the absence of detectable hepatitis B surface antigen (HBsAg), hepatitis B virus DNA (HBV-DNA) is present in a patient's peripheral blood. Investigators believe that divergent genetics and immunological parameters vary between resistant individuals and patients with OBI. Vitamin D3 and its known receptor appear to be involved in antiviral immune responses. Therefore, because OBI is a form of viral infection, the aim of this study was to investigate the association between polymorphisms in intron 8 and exon 9 of the vitamin D receptor (VDR) with OBI. METHODS: In this experimental study, the plasma samples of 3700 blood donors were collected and tested for HBsAg and anti-HBs using ELISA. The HBsAg(-)/anti-HBc(+) samples were selected and screened for HBV-DNA using polymerase chain reaction (PCR). HBV-DNA-positive samples assigned as OBI cases and PCR-restricted fragment length polymorphism. RESULTS: The results of the current study demonstrated that 352 (9.5%) of 3700 blood samples were HbsAg(-)/anti-HBc(+). HBV-DNA was detected in 57/352 (16.1%) of HBsAg(-)/anti-HBc(+) samples. Our results showed a significant difference in the T/T allele of exon 9 of VDR, but any differences were also observed in the other examined alleles. CONCLUSION: The polymorphisms in the T/T allele of exon 9 of VDR is possibly associated with OBI, thus it can be concluded that VDR and its functional polymorphisms are likely to be related to sensitivity and resistance of the immune system to HBV in OBI patients.

17ß-Estradiol improves insulin signalling and insulin resistance in the aged female hearts: Role of inflammatory and anti-inflammatory cytokines.

Aging effects in energy balance in all tissues and organs, including the cardiovascular. The risk of cardiovascular disease is drastically higher in postmenopausal women than in premenopausal women. Estrogen plays an important role in the cardiac function and body's metabolism. The aim of this study was to determine whether 17ß-estradiol (E2) has beneficial effects on insulin resistance and some key stages of the insulin signalling pathway in the aged hearts. Young and aged female Wistar rats were ovariectomized and were randomly divided into three groups: young (YS) and aged (AS) sham, young (YV) and aged (AV) vehicle, and young (YE2) and aged (AE2) E2 treatment groups. E2 (1 mg/kg) was administrated every four days for four weeks. Results showed that ovariectomy increased fasting blood glucose, insulin, and HOMAIR in young, while none of these parameters was affected in aged animals. On the other hand, aging itself increased these variables. Furthermore, E2 therapy alleviated these changes in both young and aged animals. Moreover, aging also decreased the p-IRS1, p-Akt level, and translocation of GLUT4 to the plasma membrane. E2 reduced the negative impact of menopause and aging on insulin sensitivity by favoring increase in the level of IL-10 and decrease in the levels of TNF-α and IL-1ß. Our results indicated that the heart response to E2 depended on age, and E2 increased insulin sensitivity in the heart of both young and aged animals by altering inflammatory conditions. Determining the exact mechanism of this action is suggested in future studies.

Effect of endogenous sulfur dioxide on spatial learning and memory and hippocampal damages in the experimental model of chronic cerebral hypoperfusion.

Background The vascular changes due to cerebrovascular damage, especially on the capillaries, play a vital role in causing vascular dementia. Increasing oxidative stress can lead to tissue damage while reducing brain blood flow. The use of factors reducing the oxidative stress level can decrease the brain damages. Sulfur dioxide (SO2) is one of the most important air pollutants that lead to the development of severe brain damage in large quantities. However, studies have recently confirmed the protective effect of SO2 in cardiac ischemic injury, atherosclerosis and pulmonary infections. Methods The permanent bilateral common carotid artery occlusion (BCAO) method was used to induce chronic cerebral hypoperfusion (CCH). Two treatment groups of SO2 were studied. The animal cognitive performance was evaluated using the Morris water maze. Hippocampal tissue damage was examined after 2 months of BCAO. In the biochemical analysis, the activity of catalase and lipid peroxidation of the hippocampus was studied. Results Neuronal damage in hippocampus, as well as cognitive impairment in ischemia groups treated with SO2 showed a significant improvement. Catalase activity was also significantly increased in the hippocampus of treated groups. Conclusions According to the results, SO2 is likely to be effective in reducing the CCH-caused damages by increasing the antioxidant capacity of the hippocampus.

Carvacrol suppresses learning and memory dysfunction and hippocampal damages caused by chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion (CCH) is a common phenomenon in many neurological diseases such as vascular dementia and Alzheimer's disease. Several drugs have been investigated to prevent and treat the CCH. The carvacrol (CAR) has been shown to have beneficial effects on various neurodegenerative and neuropsychiatric disorders. Accordingly, the present study was designed to evaluate the effect of CAR on neuronal damages in hippocampus in a well-defined model for CCH. Forty-eight male Wistar rats were equally divided into four groups of sham (A), CCH (B), CCH+ CAR 25, and 50 mg/kg/daily (C and D). The animals were subjected to permanent bilateral occlusion of the carotid arteries (2-vessel occlusion, 2VO) to induce CCH model. Cognitive function was evaluated by Morris water maze test. Morphological changes of hippocampus were assessed using Nissl staining. Free radical scavenging activity was measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Moreover, catalase (CAT) and superoxide dismutase (SOD) activities and lipid peroxidation levels were measured using biochemical analysis. CAR significantly improved the spatial learning and memory deficits assessed using the Morris water maze test. CAR also significantly attenuated neuronal necrosis as well as malondialdehyde (MDA) and elevated the levels of SOD and CAT activity in the hippocampus. The results indicate that CAR produces significant neuroprotective effects on neuronal damages induced by CCH. Protective effect of CAR may be mediated by antioxidative effect of this drug.