Identification of a new splice-acceptor mutation in HFM1 and functional analysis through molecular docking in nonobstructive azoospermia.

PURPOSE: To investigate the genetic cause of nonobstructive azoospermia (NOA). METHODS: We performed whole exome sequencing (WES) on the proband who had three relatives suffering from NOA. We used a list of candidate genes which have high expression level in testis and their mutations have been reported in NOA. Sanger sequencing verified the identified variant and its structural and functional consequence was evaluated by protein three-dimensional (3D) structure prediction and protein-ligand docking. RESULTS: WES revealed a novel splice-acceptor mutation (c.1832-2A>T) in helicase for meiosis 1 (HFM1) gene, which co-segregated with the NOA in this family. 3D structural models were generated and verified. Molecular docking indicated that the c.1832-2A>T mutation affects not only the ADP binding residues but also the hydrogen bond interactions. The ADP binding site will be lost in the mutant protein, potentially causing defective crossover and synapsis. CONCLUSION: We report that the c.1832-2A>T mutation is the likely cause of NOA in the family studied. Regarding that many reported NOA genes are involved in the formation of crossovers and synapsis and have critical roles in the production of germ cells, we suggest that such genes should be considered for screening of infertility among large cohorts of infertile individuals.

Metabolic Syndrome and Body Composition Among People Aged 50 Years and Over: Results from The Neyshabur Longitudinal Study on Ageing (NeLSA).

There are few studies regarding body composition and metabolic syndrome (MetS) association in older adults. To evaluate the association between MetS and body composition indices in a large-scale population of subjects with an age of 50 and up. This study was based on the data from Neyshabur Longitudinal Study on Ageing (NeLSA) in a total of 7462 people of Neyshabur city in IRAN. The best cut-off scores and AUC value of body composition variables for having association with likelihood of MetS were determined by using a receiver operating curve analysis. Each unit increase in the Waist/Hip ratio, the odds of having MetS increase 3-6 times (OR: 4.937, 95%CI: 3.930, 6.203 in men; OR: 3.322, 95%CI: 2.259, 4.884 in women). In addition, in the case of BMI (OR: 1.256, 95% Cl: 1.226, 1.286 in men; OR: 1.104, 95% Cl: 1.086, 1.121 in women) and BFM (OR: 1.119, 95% Cl: 1.105, 1.133 in men; OR: 1.050, 95% Cl: 1.041, 1.060 in women), the chance of having MetS increases with increasing these variables. Totally, BMI and BFM showed the best AUC values. The optimal cut-off values for BMI in men was 26.45 and in women was 27.35 and for BFM in men was 23.35 and in women was 26.85. These results suggest that adiposity measures such as BMI and BFM are associated with likelihood of having MetS in subjects with an age of 50 and up, and that avoiding high adiposity is important to prevent MetS incidence.

Short-term Side Effects of COVID-19 Vaccines (Astrazeneca, Sputnik-V, and Sinopharm) in Health Care Workers: A Cross-Sectional Study in Iran.

Background: The occurrence of side effects of vaccines plays an important role in their acceptance by people. Therefore, the aim of this study was to evaluate the side effects of COVID-19 vaccines (Sputnik-V, AstraZeneca, and Sinopharm) in Neyshabur health care workers (HCWs). Methods: A cross-sectional study was performed to evaluate the side effects of COVID-19 vaccines among the HCWs of the Neyshabur University of Medical Sciences from July 31, 2021, to September 6, 2021, by using a self-report checklist. We sent our checklist via an internet link to collect data such as demographic data of participants, previous COVID-19 infection (PCR+), vaccine information and side effects of vaccines. Mean, median and standard deviation were used to determine descriptive statistics and a logistic regression model was also used to determine the relationship between the type of vaccine and its side effects. Results: 317 participants filled out the checklist; among them 47% (N= 149), 21.14% (N= 67), and 31.86% (N= 101) have been vaccinated with Sputnik-V, AstraZeneca, and Sinopharm, respectively. The percentage of side effects after the first dose was 62.15% (N= 197). The Percentage of local side effects was 76% (N= 241) and systemic side effects were 29.36% (N= 95). The most common side effects in all three vaccines were injection site pain (75.08%, N= 240), muscle pain (62.46%, N=198) and headache (52.05%, N=165). Also, the odds ratio of injection site pain, chill and sweating in those who received the AstraZeneca vaccine was 3.9(95% CI, 1.7-9.3), 3.7 (95% CI, 1.8-7.3), and 3.2 (95% CI, 1.7-63), of those who received the Sputnik V vaccine (p ≤ 0.001). Conclusion: The most common side effects among our participants were injection site pain, muscle pain, and headache. Most of the post-vaccination side effects are mild to moderate in severity and self-limited. Reported side effects were more common in recipients with AstraZeneca than in those with Sputnik-V and Sinopharm.

Lactobacillus bulgaricus and Lactobacillus plantarum improve diabetic wound healing through modulating inflammatory factors.

Probiotics are nonpathogenic bacterial strains that exert beneficial effects on the host. Previous studies have shown that topical use of some strains of probiotic bacteria have good effects on the healing of cutaneous wounds. In the current study, the wound healing potentials of bacterial probiotics on diabetic cutaneous wounds were evaluated. The effects of probiotics on migration, the viability of fibroblasts, and macrophage proliferation were measured through using wound healing assay, methylthiazol tetrazolium assay, and bromodeoxyuridine, respectively. In this regard, in vivo diabetic wound healing experiments in Wistar rats following treatment with nontoxic concentrations of Lactobacillus bulgaricus and Lactobacillus plantarum were conducted. The histopathological and gene expression analyses were performed following removal of wound sites 3, 7, and 14 days postwounding. Results showed that treatment with probiotics accelerated the healing process of diabetic wounds and modulated the inflammatory cells in wound sites during a 14-day period postwounding. The altered mRNA levels of inflammatory cytokines were observed in wound sites following treatment with probiotics. The findings of the current study reveal that L. bulgaricus and L. plantarum could improve the healing of diabetic wounds via regulation of inflammation.

A multi-centre survey on hospital malnutrition: result of PNSI study.

BACKGROUND: Disease-related malnutrition is associated with adverse outcomes such as increased rates of morbidity and mortality, prolonged hospital stay, and extra costs of health care. This study was conducted to assess nutritional status among patients and to determine the risk factors for malnutrition in Iran university f. METHODS: Persian Nutritional Survey In Hospitals (PNSI) was a cross-sectional study that conducted in 20 university hospitals across Iran. All the patients with age range of 18 to 65 years, who were admitted or discharged, were assessed by subjective global assessment (SGA). RESULTS: In total, 2109 patients were evaluated for malnutrition. Mean values of age and body mass index were 44.68 ± 14.65 years and 25.44 ± 6.25 kg/m2, respectively. Malnutrition (SGA-B & C) was identified in 23.92% of the patients, 26.23 and 21% of whom were among the admitted and discharged patients, respectively. The highest prevalence of malnutrition was in burns (77.70%) and heart surgery (57.84%) patients. Multivariate analysis presented male gender (OR = 1.02, P < 0.00), malignant disease (OR = 1.40, P < 0.00), length of hospital stay (OR = 1.20, P < 0.00), and polypharmacy (OR = 1.06, P < 0.00) as independent risk factors for malnutrition. Malnutrition was not associated with age (P = 0.10). CONCLUSION: This study provides an overall and comprehensive illustration of hospital malnutrition in Iran university hospitals, finding that one out of four patients were malnourished; thus, appropriate consideration and measures should be taken to this issue.

The Effect of Curcumin Phytosome on the Treatment of Patients with Non-alcoholic Fatty Liver Disease: A Double-Blind, Randomized, Placebo-Controlled Trial.

Non-alcoholic fatty liver disease (NAFLD) is a global health problem with increasing prevalence among overweight and obese patients. It is strongly associated with conditions of insulin resistance including type 2 diabetes mellitus (T2DM) and obesity. It has detrimental consequences ranged from simple steatosis to irreversible hepatic fibrosis and cirrhosis. Curcumin is a dietary polyphenol with potential effect in improving NAFLD. Therefore, the aim of this trial was to examine the effect of curcumin supplementation on various aspects of NAFLD. In this trial, a total number of 80 patients were randomised to receive either curcumin at 250 mg daily or placebo for 2 months. Lipid profiles, hepatic enzymes, anthropometric indices and hepatic fat mass were assessed at the baseline and the end of the trial, and compared within the groups. The grade of hepatic steatosis, and serum aspartate aminotransferase (AST) levels were significantly reduced in the curcumin group (p = 0.015 and p = 0.007, respectively) compared to the placebo. There was also a significant reduction in high density lipoprotein (HDL) levels and anthropometric indices in both groups with no significant differences between the two groups. Low dose phospholipid curcumin supplementation each day for 2 months showed significant reduction in hepatic steatosis and enzymes in patients with NAFLD compared to placebo. Further studies of longer duration and higher dosages are needed to assess its effect on other parameters of NAFLD including cardiovascular risk.

Roles of Nrf2 in Gastric Cancer: Targeting for Therapeutic Strategies.

Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) is a specific transcription factor with potent effects on the regulation of antioxidant gene expression that modulates cell hemostasis under various conditions in tissues. However, the effects of Nrf2 on gastric cancer (GC) are not fully elucidated and understood. Evidence suggests that uncontrolled Nrf2 expression and activation has been observed more frequently in malignant tumors, including GC cells, which is then associated with increased antioxidant capacity, chemoresistance, and poor clinical prognosis. Moreover, Nrf2 inhibitors and the associated modulation of tumor cell redox balance have shown that Nrf2 also has beneficial effects on the therapy of various cancers, including GC. Based on previous findings on the important role of Nrf2 in GC therapy, it is of great interest to scientists in basic and clinical tumor research that Nrf2 can be active as both an oncogene and a tumor suppressor depending on different background situations.

Women's Attempts Related to Complementary and Alternative Medicine Use in Infertility Causes and Diagnosis: A Narrative Inquiry.

In most cultures of the world, infertility is seen as a disaster and is associated with a myriad of emotional and psychological problems for women. Using Complementary and alternative medicine (CAM) can help treat infertility. The present qualitative study aimed to explore women's attempts related to CAM use in infertility causes and diagnosis. This qualitative study has been carried out through a purposive sampling technique on 78 women living in Neyshabur, Iran. An individual interview and focus group discussions (FGDs) was used to collect data. Purposive sampling was used based on the objective of the study and the characteristics of a population. The data collection was discontinued when saturation occurred, and no new themes or information were explored in the data. Data analysis was performed by content analysis and Atlas T software. This study revealed medical diagnosis and traditional medicine, custom activity, medicine causes, and nutrition issues influence women's view pints and attempt towards infertility and CAM use. Results suggested that infertility should be understood not only in biomedical terms but in light of cultural beliefs and the contingent need for culturally-appropriate supportive CAM. The application of CAM along with medical medicine is an essential element in assisting couples in infertility causes.

Association between serum cell adhesion molecules with hs-CRP, uric acid and VEGF genetic polymorphisms in subjects with metabolic syndrome.

Metabolic syndrome (MetS) is associated with a pro-inflammatory state and endothelial dysfunction that places subjects with MetS at a higher risk of atherosclerosis. Inflammatory biomarkers are raised in patients at risk of developing cardiovascular diseases. In the current study, we aimed to examine the possible association between MetS and serum soluble adhesion molecules, hs-CRP, uric acid, and the genetic variations related to vascular endothelial growth factor (VEGF) gene. In this cross-sectional study, participants were enrolled from the Mashhad stroke and heart atherosclerotic disorders (MASHAD) study. The International Diabetes Federation criteria were used to define the MetS. Cell adhesion molecules (CAM) and serum hs-CRP were measured by ELISA and PEG-enhanced immunoturbidimetry method, respectively. We used a logistic regression analysis to determine independent associations of CAMs with the VEGF polymorphisms and MetS. Two hundred and 59 participants with and without MetS were enrolled. Participants with MetS and DM had a significantly higher serum E-selectin level (p < 0.05). Participants with a high serum E-selectin level had higher levels of hs-CRP, FBG, TG, uric acid, BMI and lower levels of serum HDL-C (p < 0.05). Interestingly, individuals with MetS with a genetic variant of the VEGF gene (rs6921438) had higher level of serum ICAM-1 (p = 0.04). There were significant associations between serum E-selectin concentrations and the presence of MetS, and its risk factors. Moreover, we demonstrated that MetS subjects with the rs6921438 genetic variant had a higher serum level of ICAM-1 (p < 0.05).

Association of MTHFR C677T Polymorphism with Preeclampsia in North East of Iran (Khorasan Province).

Background: Preeclampsia (PE) is one of the main causes of fetal and maternal mortality. The analysis of candidate gene polymorphisms can improve our understanding of the mechanisms underlying pathogenesis of PE. Present study is aimed at investigating the association between MTRR c.66A > G, MTHFR c.677C > T, MTHFR c.1298A > C, and MTR c.2756A > G polymorphisms and PE in Iranian women. Methods: About 117 women with history of PE and 103 healthy women with a pregnancy not complicated by PE were selected. The genomic DNA was extracted from peripheral blood. Single-nucleotide polymorphisms were genotyped using Real-Time PCR. Results: There was a significant difference between MTHFR c.677C > T polymorphism with PE (p = 0.045). The frequency of C/T heterozygous genotypes were (58% vs. 36%) in the case and control groups, respectively. There were no statistically significant differences between other genetic polymorphisms. Conclusions: The results indicated that the MTHFR c.677C > T polymorphism may be associated with development of PE in Iranian women.

Thymoquinone-induced antitumor and apoptosis in human lung adenocarcinoma cells.

BACKGROUND: Lung cancer has been associated with the highest cancer-associated mortality rate in the world. Chemotherapeutic management of cancer necessitates introducing new promising agents. Plants represent a rich source of new antineoplastic and chemotherapeutic agents. Thymoquinone (TQ), the main constituent of Nigella sativa (black seed or black cumin), has shown potent antioxidant and anti-inflammatory activities so far. The purpose of the current study was to evaluate the antineoplastic potential of TQ and their underlying mechanisms in A549 cells (human lung cancer cell line). METHOD: The A549 cells were treated with the different concentrations of TQ for three following days. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Necrosis and apoptosis were assessed by fluorescence-activated cell sorter analysis through propidium iodide and annexin V staining and also by assessing caspase-3 and -9 activation. DNA fragmentation was monitored by gel electrophoresis. RESULTS: TQ decreased the viability and increased apoptotic cell death in A549 human lung tumor cells. TQ treatment significantly elevated the Bax/ Bcl-2 ratio in the lung cancer cells. TQ also upregulated p53 expression, another apoptotic modulator in A549 cancer cells. TQ also activated caspase-dependent apoptosis by the activation of caspases-3 and -9. CONCLUSION: Our results proposed that TQ may be a potential new therapeutic agent for the management of lung cancer. TQ promoted apoptosis in A546 lung cancer cells by the activation of p53 and caspase cascade dependent pathways.

The role of arsenic in obesity and diabetes.

As many individuals worlwide are exposed to arsenic, it is necessary to unravel the role of arsenic in the risk of obesity and diabetes. Therefore, the present study reviewed the effects of arsenic exposure on the risk and potential etiologic mechanisms of obesity and diabetes. It has been suggested that inflammation, oxidative stress, and apoptosis contribute to the pathogenesis of arsenic-induced diabetes and obesity. Though arsenic is known to cause diabetes through different mechanisms, the role of adipose tissue in diabetes is still unclear. This review exhibited the effects of arsenic on the metabolism and signaling pathways within adipose tissue (such as sirtuin 3 [SIRT3]- forkhead box O3 [FOXO3a], mitogen-activated protein kinase [MAPK], phosphoinositide-dependant kinase-1 [PDK-1], unfolded protein response, and C/EBP homologous protein [CHOP10]). Different types of adipokines involved in arsenic-induced diabetes are yet to be elucidated. Arsenic exerts negative effects on the white adipose tissue by decreasing adipogenesis and enhancing lipolysis. Some epidemiological studies have shown that arsenic can promote obesity. Nevertheless, few studies have indicated that arsenic may induce lipodystrophy. Arsenic multifactorial effects include accelerating birth and postnatal weight gains, elevated body fat content, glucose intolerance, insulin resistance, and increased serum lipid profile. Arsenic also elevated cord blood and placental, as well as postnatal serum leptin levels. The data from human studies indicate an association between inorganic arsenic exposure and the risk of diabetes and obesity. However, the currently available evidence is insufficient to conclude that low-moderate dose arsenic is associated with diabetes or obesity development. Therefore, more investigations are needed to determine biological mechanisms linking arsenic exposure to obesity and diabetes.

VEGF gene polymorphism interactions with dietary trace elements intake in determining the risk of metabolic syndrome.

There is a complex association among genetic, metabolic, and environmental factors in determining the risk of metabolic syndrome (MetS). The aim of this study was to investigate the role of the association between the dietary intake of iron, copper, zinc, manganese, selenium, and iodine (assessed by 24 recall) with vascular endothelial growth factor variants (rs6921438, rs4416670, rs6993770, and rs10738760), on the risk of MetS. Two-hundred and forty-eight individuals with MetS and 100 individuals without MetS were recruited. The dietary intake and the daily average of energy and nutrient intake were obtained by a questionnaire and quantified using Diet Plan 6 software. DNA was extracted from EDTA anticoagulated whole blood. The SNPs were assessed using using a Sequenom iPLEX Gold assay. Data analysis was undertaken using the Student t test, χ2 test and logistic regression using SPSS 11.5 software. There was a significant association between low dietary iron intake and rs6993770 (ß = .10, P < .05), and a low dietary zinc and a high manganese intake with rs6921438 in relation to the presence of MetS (ß = -.17, P < .05, ß = -.30, P < .05, respectively). Our data showed the association of rs6993770 with iron intake and rs6921438 with zinc and manganese intake, indicating further investigation in a larger population to evaluate their values.

Protective effects of carnosol against oxidative stress induced brain damage by chronic stress in rats.

BACKGROUND: Oxidative stress through chronic stress destroys the brain function. There are many documents have shown that carnosol may have a therapeutic effect versus free radical induced diseases. The current research focused the protective effect of carnosol against the brain injury induced by the restraint stress. METHODS: The restraint stress induced by keeping animals in restrainers for 21 consecutive days. Thereafter, the rats were injected carnosol or vehicle for 21 consecutive days. At the end of experiment, all the rats were subjected to his open field test and forced swimming test. Afterwards, the rats were sacrificed for measuring their oxidative stress parameters. To measure the modifications in the biochemical aspects after the experiment, the activities of malondialdehyde (MDA), reduced glutathione (GSH), as well as superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were evaluated in the whole brain. RESULTS: Our data showed that the animals received chronic stress had a raised immobility time versus the non-stressed animals (p < 0.01). Furthermore, chronic stress diminished the number of crossing in the animals that were subjected to the chronic stress versus the non-stressed rats (p < 0.01). Carnosol ameliorated this alteration versus the non-treated rats (p < 0.05). In the vehicle treated rats that submitted to the stress, the level of MDA levels was significantly increased (P < 0.001), and the levels of GSH and antioxidant enzymes were significantly decreased versus the non-stressed animals (P < 0.001). Carnosol treatment reduced the modifications in the stressed animals as compared with the control groups (P < 0.001). All of these carnosol effects were nearly similar to those observed with fluoxetine. CONCLUSION: The current research shows that the protective effects of carnosol may be accompanied with enhanced antioxidant defenses and decreased oxidative injury.

Preventive Effect of Carvacrol Against Oxidative Damage in Aged Rat Liver.

The present study was designed to investigate the changes in activities of antioxidant enzymes and lipid peroxidation level in the liver of 2, 10 and 20 months old rats, and to see whether these changes are restored to those of the two month old rats after carvacrol treatment. Male rats of 2, 10, and 20 months (n = 10 for each group) were used for all the experiments. The aged rats (10 and 20 months old) were given carvacrol (15 mg/day per body weight) for 30 days. Control animals received an equal volume of vehicle. After the treatment, livers were removed for estimation of superoxide dismutase-SOD, glutathione-S-transferase-GST, catalase-CAT activities and lipid peroxidation level. The present findings determined that normal aging was associated with a significant decrease in the activities of antioxidant enzymes (SOD; 11.87 ± 0.6 (2 months old) vs 7.56 ± 0.1 (20 months old); P < 0.001) in liver, as well as an increase in lipid peroxidation level (MDA; 0.15 ± 0.01 (2 months old) vs 0.41 ± 0.01 (20 months old); P < 0.001) in aged rats. Also, the results of this study indicated that carvacrol treatment increased the activities of the antioxidant enzymes in 20 months old animals versus the aged matched control group (SOD; 9.87 ± 0.4; P < 0.01). Furthermore, carvacrol decreased lipid peroxidation content in 10 and 20 months old animals compared with the aged matched control (MDA; 9.87 ± 0.4; P < 0.001). Our data shows that carvacrol could be a candidate to inhibit the development of age-induced liver damage through inhibition of oxidative stress and also increasing antioxidant defenses.

Crocin attenuate Tumor Necrosis Factor-alpha (TNF-α) and interleukin-6 (IL-6) in streptozotocin-induced diabetic rat aorta.

OBJECTIVE: Crocin, a bioactive component of saffron, has many biological effects such as antioxidant property. The present study investigated the anti-hyperglycemic, anti oxidant and immunomodulatory effects of crocin on streptozotocin-induced diabetic rats. METHOD: In this study, the rats were divided into the following groups of 9 animals each: control, untreated diabetic, three crocin (10, 20, 30mg/kg/day)-treated diabetic groups. Diabetes was induced by streptozotocin in rats. Streptozotocin was injected intraperitoneally at a single dose of 60mg/kg for diabetes induction. Crocin (intraperitoneal injection) was administered 3days after streptozotocin administration; these injections were continued to the end of the study (4weeks). At the end of the 4-week period, blood was drawn for biochemical assays and abdominal aorta was removed for detecting the inflammatory cytokines expression. RESULTS: Ours results showed that the crocin decreased blood glucose, malondialdehyde, nitric oxide, total lipids, triglycerides, cholesterol levels significantly (p<0.01) and increased glutathione level, catalase and superoxide dismutases activities in the crocin-treated diabetic groups compared with the untreated groups, in a dose dependent manner (p<0.05, p<0.01, p<0.001). On the other hand, crocin-treated diabetic rats inhibited the expression of inflammatory cytokines in abdominal aorta, with respect to the untreated diabetic rats. CONCLUSIONS: These results validate the use of crocin as a treatment against diabetes mellitus and its complications and suggest it is suitable to continue studies for its safe therapeutic use.

Chrysin treatment improves diabetes and its complications in liver, brain, and pancreas in streptozotocin-induced diabetic rats.

Chrysin (CH) is a natural flavonoid with pharmacological influences. The purpose of the current study was the assessment of possible protective effects of CH against oxidative damage in the serum, liver, brain, and pancreas of streptozotocin (STZ)- induced diabetic rats. In the present study, the rats were divided into the following groups of 8 animals each: control, untreated diabetic, 3 CH (20, 40, 80 mg/kg/day)-treated diabetic groups. To find out the modulations of cellular antioxidant defense systems, malondialdehyde (MDA) level and antioxidant enzymes including glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in the serum, liver, brain, and pancreas. STZ caused an elevation of glucose, MDA, TG, TC, LDL-C and with reduction of HDL-C, total protein, SOD, CAT, and GST in the serum, liver, brain, and pancreas (p < 0.01). The findings showed that the significant elevation in the glucose, MDA, TG, TC, LDL-C and reduction of HDL-C, total protein, SOD, CAT, and GST were ameliorated in the CH-treated diabetic groups versus to the untreated groups, in a dose dependent manner (p < 0.05). The current study offers that CH may be recovered diabetes and its complications by modification of oxidative stress.

Effect of crocin on aged rat kidney through inhibition of oxidative stress and proinflammatory state.

This study evaluated whether crocin, a bioactive component of saffron, has a protective effect on kidney through reducing the oxidative stress and inflammatory response in aged rats. In this study the changes in activities of antioxidant enzymes, lipid peroxidation, glutathione (GSH) levels and the expression of pro-inflammatory cytokines in the serum and renal tissue were evaluated by ELISA and RT-PCR, respectively. The middle and aged rats were given intraperitoneal injections of crocin (10, 20, 30 mg/kg/day) for 4 weeks. After 4 weeks, animals were anesthetized with diethyl ether. The kidney samples were taken for biochemical analysis. The results revealed the aging was associated with a significant decrease in the activities of antioxidant enzymes, and GSH content with increase in lipid peroxidation level in kidney of the aged rats (p < 0.001). The increased levels of serum renal functional parameter, oxidative parameters (p < 0.01) and also pro-inflammatory cytokine levels were significantly reduced by crocin administration (p < 0.05). The aged rats exhibited a dysregulation of the oxidative stress, and inflammation in the kidneys, but crocin treatment significantly reduced the expression of the inflammatory genes. These results provide pivotal documentation that crocin has a renoprotective effects against the development of oxidative stress and inflammation in the kidney of old rats. Copyright © 2016 John Wiley & Sons, Ltd.

Angiogenesis related genes NOS3, CD14, MMP3 and IL4R are associated to VEGF gene expression and circulating levels in healthy adults.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis. The aim was to assess the genetic connections between the angiogenesis-related NOS3, CD14, MMP3, IL4R, IL4 genes and VEGF expression and plasma levels. METHODS: The associations between VEGF plasma levels with the polymorphisms of NOS3, CD14, MMP3, IL4R, and IL4 were assessed in 403 healthy unrelated adults. The epistatic and environmental interactions were explored, including four VEGF-related polymorphisms previously identified. The VEGF expression in peripheral blood mononuclear cells was quantified (n = 65) for the VEGF121, VEGF145, VEGF165, and VEGF189 isoforms. RESULTS: The polymorphism rs1799983 of NOS3 was associated with the sum of all VEGF isoforms mRNA levels (P = 0.032) and VEGF145 (P = 0.033). Rs1800779 of NOS3 interacted with rs3918226 of the same gene and with the rs2569190 of CD14 (P = 0.022, P = 0.042, respectively) for VEGF plasma levels. Other epistatic interactions included the rs1801275 of IL4R with the rs6921438 (VEGF-related variant) and rs3025058 of MMP3 (P = 0.042, P = 0.010 respectively) and the rs2569190 of CD14 with the rs3025058 of MMP3 (P = 0.0119). We also identified an interaction of rs1800779 with obesity, high-density lipoprotein cholesterol and triglycerides (P = 0.018, P = 0.005, P = 0.043, respectively) as well as the interaction of rs6921438 with hypertension (P = 0.028). CONCLUSIONS: Our findings indicated that genetic variants of NOS3, CD14, MMP3 and IL4R are implicated in the determination of VEGF expression and plasma levels. Thus, they support the hypothesis that in physiological conditions there are complex biological relationships between pathways (such as angiogenesis and inflammation), which are involved in the development of chronic diseases.

Effects of buprenorphine on balance of oxidant/antioxidant system in the different ages of male rat liver.

Our knowledge about a link between buprenorphine and hepatotoxicity is controversial. This study evaluated the effects of buprenorphine on the liver of young, adult, and aged rats. For this reason, young, adult, and aged rats received intraperitoneally 0.25, 0.5, and 1 mg/kg buprenorphine for 30 days. The present results revealed that the normal aging was associated with a significant decrease in the activities of antioxidant enzymes, and an increase in the liver lipid peroxidation, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities in the aged rats. This study also demonstrated that buprenorphine led to a significant increase in the serum activities of ALT, AST, and LDH as well as liver lipid peroxidation content with a decrease in the antioxidant enzymes in the liver of buprenorphine-treated aged rat versus the aged matched control animals. In conclusion, the present results demonstrate that buprenorphine deteriorated oxidative damage in the aged livers.