The effects of vitamin E supplementation on sperm parameters, chromatin integrity, and gene expression before and after freezing in aged mice.

Objective: Some age-related testicular changes, such as Sertoli cell vacuolization and blood-testis barrier breakdown, reduce total sperm production and male fertility. Therefore, this study investigated the effect of vitamin E on restoring testicular function in aged mice. Sperm cryo-resistance was also assessed. Methods: Twenty-eight 48-week-old male Naval Medical Research Institute mice were divided into four groups for a daily gavage of vitamin E: the control group received distilled water, while the three treatment groups were administered 100, 200, and 400 mg/kg, respectively, for 4 weeks. Subsequently, semen analyses, DNA fragmentation index (DFI), and protamine deficiency tests were conducted. Testicular histology, tissue antioxidant enzyme activity, and gene expression levels were also assessed. Results: The two higher dosages of vitamin E were associated with a higher sperm count, greater progressive motility, and improved sperm morphology (p<0.05). These benefits were also evident after sperm freezing (p<0.05). Although chromatin abnormalities increased following vitrification, the treatment groups showed better outcomes (p<0.05). The tubular diameter, epithelium height, and luminal diameters remained unchanged with age. The tissue antioxidant capacity was greater in the groups receiving the high doses of vitamin E. Additionally, significant increases in inhibitor of DNA binding protein-4 (Id4) and GDNF family receptor alpha-1 (Gfra1) expression were observed in the higher vitamin E dosage groups, and promyelocytic leukemia zinc finger protein (Plzf) expression was notably present in the 400 mg/kg treatment group compared to the control group (p<0.05). Conclusion: Antioxidant supplementation might enhance reproductive outcomes in aging males. The observed effects included improved sperm cryo-resistance, which is advantageous for future applications such as sperm freezing or fertility preservation.

Comparison of serum levels of IL-10 and IL-11 and mRNA expression of IL-10, IL-11, COX-2, BCL6, and ZEB Family in peripheral blood mononuclear cells (PBMC) of women with polycystic ovary syndrome and healthy individuals.

BACKGROUND: The roles of IL-10, IL-11, COX-2, BCL6, ZEB1, and ZEB2 genes in the potential correlation between polycystic ovary syndrome (PCOS), inflammation, and cancer remain controversial. AIMS: This study aimed to compare serum levels of IL-10 and IL-11 and gene expression of IL-10, IL-11, COX-2, BCL6, ZEB1, and ZEB2 in PBMCs of women with PCOS and healthy controls. METHODS: A case-control study included 40 women with PCOS as the case group and 40 healthy women as controls. Group matching for age and BMI was performed. Serum levels of IL-10 and IL-11 were assessed using ELISA, while gene expression was measured using real-time PCR. Parameters were compared between groups, and correlations among gene expression and serum levels were explored. RESULTS: In comparison to healthy women, women with PCOS exhibited a significant decrease in the expression of COX-2 and IL-10 genes (p<0.001), alongside a significant increase in ZEB2 gene expression (p<0.001). There were no significant differences observed in the expression of IL-11, BCL6, and ZEB1 genes. Furthermore, the serum level of IL-10 was significantly lower in women with PCOS compared to the control group (p<0.001), while no significant difference was found in IL-11 levels. Additionally, no significant correlations were identified between gene expression and serum levels. CONCLUSION: In women with PCOS, reduced IL-10 gene expression may indicate inflammation and serve as a diagnostic biomarker. However, conflicting findings on COX-2 expression complicate understanding. Elevated ZEB2 expression in PCOS women may lead to infertility, epithelial-mesenchymal transition, and aggressive phenotypes.

Molecular-Phylogenetic Characterization of Xanthomonas hortorum pv. pelargonii Strains Causing Leaf Spot of Geraniums in Iran.

Bacterial blight and leaf spot of geraniums is a destructive disease of cultivated Pelargonium species around the world. During 2020-2021, surveys were conducted in seven geranium-growing provinces of Iran to monitor the status of bacterial blight and leaf spot disease. The disease was observed in six surveyed provinces varying in the extent of occurrence and severity. Twenty-two Gram-negative pale-yellow bacterial strains resembling members of Xanthomonas were isolated from symptomatic leaves and stems. Pathogenicity and host range assays showed that the bacterial strains were pathogenic on Pelargonium grandiflorum, P. graveolens, P. peltatum, and P. zonale. All strains were positive for PCR test using the primer pair XcpM1/XcpM2 which is specific for Xanthomonas hortorum pv. pelargonii. Phylogenetic analysis using the sequences of gyrB and lepA genes showed that the 22 strains clustered in a clade among the sequences of X. hortorum pv. pelargonii strains retrieved from the GenBank, while distinct from the other pathovars of X. hortorum. BOX-PCR-based fingerprinting using BOX-A1R primer revealed that the strains isolated in this study were grouped into two clusters while no distinct correlation was observed between the host/area of isolation and BOX-PCR fingerprinting. None of the strains obtained in this study nor reference strain of the pathogen did produce bacteriocin against each other. Results obtained in this study shed light on the geographic distribution, taxonomic status and host range of the bacterial blight and leaf spot pathogen of geraniums in Iran, paving the path of further research on disease management.

Evaluation of epigenetic-related gene expression (DNMT, HDAC1) in Iranian patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease in which the immune system abnormally reacts against cells and tissues leading to inflammation. Epigenetic alterations, including DNA methylation and histone modification, have critical effects on autoimmune disease and SLE pathogenesis via dysregulation of critical genes. AIMS: The purpose of this study was to evaluate the epigenetic-related gene expression of DNA methyltransferase (DNMT) and histone deacetylase 1 (HDAC1) in Iranian patients with SLE. METHODS: This matched case-control study included 16 people with SLE and 16 healthy people who were referred to the Rafsanjani rheumatology clinic, in southeast Iran. The expression of DNMT and HDAC1 genes was measured through a real-time PCR assay of blood samples. RESULTS: DNMT gene expression did not differ significantly between SLE and healthy groups (P=0.21). In contrast, HDAC1 gene expression was enhanced in the SLE group, but this enhancement failed to reach statistical significance (P=0.94). CONCLUSION: The results of this study suggest that overexpression of HDAC1 could serve as a diagnostic for SLE disease. Additional studies with larger sample sizes are required to confirm our findings. Evaluation of other genes related to SLE disease is essential and may help to make an accurate diagnosis of the disease.

Xanthomonas bonasiae sp. nov. and Xanthomonas youngii sp. nov., isolated from crown gall tissues.

The genus Xanthomonas contains a set of diverse bacterial strains, most of which are known for their pathogenicity on annual crops and fruit trees causing economically important plant diseases. Recently, five Xanthomonas strains were isolated from Agrobacterium-induced crown gall tissues of amaranth (Amaranthus sp.) and weeping fig (Ficus benjamina) plants in Iran. Phenotypic characteristics (i.e. biochemical tests and pathogenicity features) and whole genome sequence-based core-genome phylogeny followed by average nucleotide identity and digital DNA-DNA hybridization calculations suggested that these gall-associated strains belong to two new species within the genus Xanthomonas. In this study, we provide a formal species description for these new species where Xanthomonas bonasiae sp. nov. is proposed for the strains isolated from weeping fig with FX4T (=CFBP 8703T=DSM 112530T) as type strain. The name Xanthomonas youngii sp. nov. is proposed for the strains isolated from amaranth with AmX2T (=CFBP 8902T=DSM 112529T) as type strain.

Phenotypic and Molecular-Phylogenetic Analyses Reveal Distinct Features of Crown Gall-Associated Xanthomonas Strains.

In summer 2019, widespread occurrence of crown gall disease caused by Agrobacterium spp. was observed on commercially grown ornamental plants in southern Iran. Beside agrobacteria, pale yellow-pigmented Gram-negative strains resembling the members of Xanthomonas were also associated with crown gall tissues on weeping fig (Ficus benjamina) and Amaranthus sp. plants. The purpose of the present study was to characterize the crown gall-associated Xanthomonas strains using plant inoculation assays, molecular-phylogenetic analyses, and comparative genomics approaches. Pathogenicity tests showed that the Xanthomonas strains did not induce disease symptoms on their host of isolation. However, the strains induced hypersensitive reaction on tobacco, geranium, melon, squash, and tomato leaves via leaf infiltration. Multilocus sequence analysis suggested that the strains belong to clade IA of Xanthomonas, phylogenetically close to Xanthomonas translucens, X. theicola, and X. hyacinthi. Average nucleotide identity and digital DNA-DNA hybridization values between the whole-genome sequences of the strains isolated in this study and reference Xanthomonas strains are far below the accepted thresholds for the definition of prokaryotic species, signifying that these strains could be defined as two new species within clade IA of Xanthomonas. Comparative genomics showed that the strains isolated from crown gall tissues are genetically distinct from X. translucens, as almost all the type III secretion system genes and type III effectors are lacking in the former group. The data obtained in this study provide novel insight into the breadth of genetic diversity of crown gall-associated bacteria and pave the way for research on gall-associated Xanthomonas-plant interactions. IMPORTANCE Tumorigenic agrobacteria-members of the bacterial family Rhizobiaceae-cause crown gall and hairy root diseases on a broad range of plant species. These bacteria are responsible for economic losses in nurseries of important fruit trees and ornamental plants. The microclimate of crown gall and their accompanying microorganisms has rarely been studied for the microbial diversity and population dynamics of gall-associated bacteria. Here, we employed a series of biochemical tests, pathogenicity assays, and molecular-phylogenetic analyses, supplemented with comparative genomics, to elucidate the biological features, taxonomic position, and genomic repertories of five crown gall-associated Xanthomonas strains isolated from weeping fig and Amaranthus sp. plants in Iran. The strains investigated in this study induced hypersensitive reactions (HR) on geranium, melon, squash, tobacco, and tomato leaves, while they were nonpathogenic on their host of isolation. Phylogenetic analyses and whole-genome-sequence-based average nucleotide identity (ANI)/digital DNA-DNA hybridization (dDDH) calculations suggested that the Xanthomonas strains isolated from crown gall tissues belong to two taxonomically unique clades closely related to the clade IA species of the genus, i.e., X. translucens, X. hyacinthi, and X. theicola.

Validity and Reproducibility of a Semiquantitative Multiple-Choice Food Frequency Questionnaire in Iranian Adults.

Previous multiple-choice food-based food frequency questionnaires (FFQs) were not validated against weighed dietary records (WDRs) in Iran. This study investigated the validity and reproducibility of a multiple-choice semi-quantitative food frequency questionnaire (SQ-FFQ) in adults living in central Iran. Patients with diabetes and their spouses were asked to complete 3 SQ-FFQs by interview, and nine 3-day WDRs, over 9 months. They provided 2 blood samples to assess serum calcium, magnesium, zinc, and vitamin C levels. The Pearson and intraclass correlation coefficients were calculated to assess reproducibility and validity. The degree of misclassification was explored using a contingency table of quartiles which compare the information between third FFQ and WDRs. The method of triads was incorporated to assess validity coefficients between estimated intakes using third FFQ, WDRs, and biochemical markers and assumed true intakes. A total of 180 participants aged 48.9 ± 8.4 years completed the study. Compared to WDRs, FFQs overestimated all nutrient intakes except for iron. The median intraclass correlation between FFQs was 0.56. The median de-attenuated, age, sex, and education adjusted partial correlation coefficients for validity were 0.17 and 0.26 for FFQ1-WDRs and FFQ3-WDRs, respectively. The FFQ3 validity coefficients for vitamin C, calcium, magnesium, and zinc were 0.13, 0.62, 0.89, and 0.66, respectively, using the triads method. The median exact agreement and complete disagreement between FFQ3 and WDRs were 33% and 6%, respectively. The SQ-FFQ seems to be an acceptable tool to assess the long-term dietary intake for future large-scale studies in this population.

Taxonomic Refinement of Xanthomonas arboricola.

Xanthomonas arboricola comprises a number of economically important fruit tree pathogens classified within different pathovars. Dozens of nonpathogenic and taxonomically unvalidated strains are also designated as X. arboricola, leading to a complicated taxonomic status in the species. In this study, we have evaluated the whole-genome resources of all available Xanthomonas spp. strains designated as X. arboricola in the public databases to refine the members of the species based on DNA similarity indexes and core genome-based phylogeny. Our results show that, of the nine validly described pathovars within X. arboricola, pathotype strains of seven pathovars are taxonomically genuine, belonging to the core clade of the species regardless of their pathogenicity on the host of isolation (thus the validity of pathovar status). However, strains of X. arboricola pv. guizotiae and X. arboricola pv. populi do not belong to X. arboricola because of the low DNA similarities between the type strain of the species and the pathotype strains of these two pathovars. Thus, we propose to elevate the two pathovars to the rank of a species as X. guizotiae sp. nov. with the type strain CFBP 7408T and X. populina sp. nov. with the type strain CFBP 3123T. In addition, other mislabeled strains of X. arboricola were scattered within Xanthomonas spp. that belong to previously described species or represent novel species that await formal description.

Occurrence of Crown Gall Disease on Japanese Spindle (Euonymus japonicas var. Green Rocket) Caused by Agrobacterium rosae in Iran.

Crown gall disease caused by diverse Agrobacterium species is one of the main biotic constraints in the ornamental plants industry in Iran (Mafakheri et al. 2017). In August 2019, Japanese spindle (Euonymus japonicus var. Green Rocket) plants showing crown gall symptoms were observed in a commercial greenhouse in Tehran, Iran. Infected plants were characterized by a visible overgrowth on their stems and crown. Bacterial isolation from the gall tissues was performed on nutrient agar (NA) and 1A media as described by Moore et al. (2001). The six resulted bacterial strains (A.E1 to A.E6) were evaluated using PCR primer pair F8360/F8361 amplifying a 453 bp DNA fragment in recA gene and confirmed as Agrobacterium sp. (Shams et al. 2013). Pathogenicity of the strains was evaluated in two independent assays on Japanese spindle plantlets as well as 10-15 day old tomato (Solanum lycopersicum cv. Sunseed 6189) and sunflower (Helianthus annuus cv. Armavirski) plants in greenhouse conditions using the needle prick method as described previously (Mafakheri et al. 2019). The reference strain A. radiobacter ICMP 5856 and sterile distilled water were used as positive and negative controls, respectively. Crown gall symptoms appeared 20-25 days post inoculation on the Japanese spindle plantlets as well as tomato and sunflower plants inoculated with the strains isolated in this study, while the negative control plants remained asymptomatic. Koch's postulates were accomplished by re-isolating on NA medium and PCR-based identification of the inoculated strains from the symptomatic plants. The representative strain A.E1 was subjected to multilocus sequence analysis (MLSA) using the sequences of four housekeeping genes (i.e. atpD, gyrB, recA, and rpoB) as described previously (Mafakheri et al. 2019). MLSA results revealed that the strain A.E1 is phylogenetically closely related to A. rosae. The sequences were deposited into GenBank under the accession numbers MT007962 to MT007965 for atpD, gyrB, recA, and rpoB, respectively. Further, the strain A.E1 was subjected to whole genome sequencing using Illumina HiSeq X platform. DNA extraction was performed using NucleoSpin Microbial DNA kit (Macherey-Nagel, Germany), DNA libraries were obtained with Nextera XT DNA Library Prep Kit (Illumina, USA), and de novo sequence assembly was performed using SPAdes genome assembler. The resulting whole genome sequence was deposited into the GenBank database under the accession number JAFJZW000000000. Average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values were calculated among all the type strains of Agrobacterium species/genomospecies using standard criteria as detailed previously (Osdaghi et al. 2020; Chen et al. 2021). The strain A.E1 had 97% ANI and 72% dDDH values with A. rosae strain NCPPB 1650, suggesting that the bacterial strains isolated from Japanese spindle in Iran belong to A. rosae. This is the first report of A. rosae causing crown gall disease on Japanese spindle in Iran. The new crown gall disease could negatively affect the ornamental shrub production industry in central Iran unless strict sanitary measures are taken into the account in the nurseries in these areas. Further nationwide surveys and samplings are warranted to elucidate the economic impact of the pathogen on ornamental plant industry in the country.

Canola oil compared with sesame and sesame-canola oil on glycaemic control and liver function in patients with type 2 diabetes: A three-way randomized triple-blind cross-over trial.

BACKGROUND: This study aimed to compare the effects of sesame (SO), canola (CO), and sesame-canola (SCO: a blend) oils on glycaemic control markers and liver function enzymes in adults with type 2 diabetes. METHODS: In this randomized, triple-blind, three-way, cross-over clinical trial, participants replaced their usual oil with the intervention oils for 9 weeks. Serum fasting blood sugar, fasting serum insulin (FSI), insulin resistance (HOMA2-IR), beta-cell function (HOMA2-%B), insulin sensitivity (HOMA2-%S), quantitative insulin sensitivity check index (QUICKI), as well as serum liver function enzymes were measured at baseline and end of intervention periods. RESULTS: Ninety-two participants completed all treatment periods. After adjusting for confounders, all treatment oils resulted in significant improvements in FSI and HOMA2-%S (p < 0.05). SO and SCO led to favourable changes in HOMA2-IR and QUICKI (p < 0.05). Following CO and SCO, there was a significant decrease in HOMA2-%B (p < 0.05). The sex-stratified analysis revealed that FSI and HOMA2-IR were decreased after SO compared to CO in males (p = 0.024). Serum gamma-glutamyltransferase (GGT) was significantly lower following SO compared to CO in females (p = 0.02), however, the difference in change values was not significant (p = 0.058). CONCLUSIONS: SO consumption appears to improve glycaemic control markers in males and serum GGT in females compared with CO in patients with type 2 diabetes (registration code: IRCT2016091312571N6).

Comparative Genomics and Phylogenetic Analyses Suggest Several Novel Species within the Genus Clavibacter, Including Nonpathogenic Tomato-Associated Strains.

Members of the genus Clavibacter are economically important bacterial plant pathogens infecting a set of diverse agricultural crops (e.g., alfalfa, corn, potato, tomato, and wheat). Tomato-associated Clavibacter sp. strains account for a great portion of the genetic diversity of the genus, and C. michiganensissensu stricto (formerly C. michiganensis subsp. michiganensis), causing bacterial canker disease, is considered one of the most destructive seed-borne agents for the crop worldwide. However, current taxonomic descriptions of the genus do not reflect the existing diversity of the strains, resulting in unsatisfactory results in quarantine surveys for the pathogens. In this study, we used all the available genome sequences of Clavibacter sp. strains, including the type strains of newly described subspecies, to provide precise insight into the diversity of tomato-associated members of the genus and further clarify the taxonomic status of the strains using genotypic and phenotypic features. The results of phylogenetic analyses revealed the existence of nine hypothetical new species among the investigated strains. None of the three new subspecies (i.e., C. michiganensis subsp. californiensis, C. michiganensis subsp. chilensis, and C. michiganensis subsp. phaseoli) is included within the tomato-pathogenic C. michiganensissensu stricto lineage. Although comparative genomics revealed the lack of chp and tomA pathogenicity determinant gene clusters in the nonpathogenic strains, a number of pathogenicity-related genes were noted to be present in all the strains regardless of their pathogenicity characteristics. Altogether, our results indicate a need for a formal taxonomic reconsideration of tomato-associated Clavibacter sp. strains to facilitate differentiation of the lineages in quarantine inspections.IMPORTANCEClavibacter spp. are economically important bacterial plant pathogens infecting a set of diverse agricultural crops, such as alfalfa, corn, pepper, potato, tomato, and wheat. A number of plant-pathogenic members of the genus (e.g., C. michiganensissensu stricto and C. sepedonicus, infecting tomato and potato plants, respectively) are included in the A2 (high-risk) list of quarantine pathogens by the European and Mediterranean Plant Protection Organization (EPPO). Although tomato-associated members of Clavibacter spp. account for a significant portion of the genetic diversity in the genus, only the strains belonging to C. michiganensissensu stricto (formerly C. michiganensis subsp. michiganensis) cause bacterial canker disease of tomato and are subjected to the quarantine inspections. Hence, discrimination between the pathogenic and nonpathogenic Clavibacter sp. strains associated with tomato seeds and transplants plays a pivotal role in the accurate detection and cost-efficient management of the disease. On the other hand, detailed information on the genetic contents of different lineages of the genus would lead to the development of genome-informed specific detection techniques. In this study, we have provided an overview of the phylogenetic and genomic differences between the pathogenic and nonpathogenic tomato-associated Clavibacter sp. strains. We also noted that the taxonomic status of newly introduced subspecies of C. michiganensis (i.e., C. michiganensis subsp. californiensis, C. michiganensis subsp. chilensis, and C. michiganensis subsp. phaseoli) should be reconsidered.

Hesperidin supplementation has no effect on blood glucose control: A systematic review and meta-analysis of randomized controlled clinical trials.

AIMS: To the best of our knowledge, no study has tried to quantitatively summarize the published evidence regarding the effect of hesperidin supplementation on blood glucose control. The present systematic review and meta-analysis of randomized controlled trials aimed to determine the effectiveness of hesperidin supplementation in improving blood glucose control in adults. METHODS: Electronic databases including PubMed, ISI Web of Science, Scopus, and Google Scholar were searched up to February 2019. The risk of bias in individual studies was assessed using the Cochrane collaboration's tool. The overall estimates and their 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Six trials with 318 participants were reviewed in the present systematic review. The results showed that hesperidin had no significant effect on serum fasting blood glucose (weighted mean difference [WMD] = -1.10 mg/dL, 95% CI: -3.79, 1.57), plasma insulin (WMD = -0.01 µU/mL, 95% CI: -1.20, 1.19), glycated haemoglobin A1c (WMD = -0.04%, 95% CI: -0.14, 0.04), homeostasis model assessment for insulin resistance (WMD = 0.117, 95% CI: -0.06, 0.29) and quantitative insulin sensitivity check index (WMD = 0.135; 95% CI: -0.13, 0.39), with no significant between-study heterogeneity. Subgroup analyses also indicated that the effects were not different based on the studies' design and duration, or the health status of the participants. CONCLUSION: Although several animal studies have proposed that hesperidin supplementation might improve blood glucose control, the present study could not confirm this benefit in humans.

Phenotypically and Genotypically Heterogeneous Strains of Pseudomonas syringae Associated With Alfalfa Leaf Spot Disease in Iran.

In this study, we provide a polyphasic characterization of 18 Pseudomonas spp. strains associated with alfalfa leaf spot symptoms in Iran. All of the strains were pathogenic on alfalfa, although the aggressiveness and symptomology varied among the strains. All strains but one were pathogenic on broad bean, cucumber, honeydew, and zucchini, whereas only a fraction of the strains were pathogenic on sugar beet, tomato, and wheat. Syringomycin biosynthesis genes (syrB1 and syrP) were detected using the corresponding PCR primers in all of the strains isolated from alfalfa. Phylogenetic analyses using the sequences of four housekeeping genes (gapA, gltA, gyrB, and rpoD) revealed that all of the strains except one (Als34) belong to phylogroup 2b of P. syringae sensu lato, whereas strain Als34 placed within phylogroup 1 close to the type strain of P. syringae pv. apii. Among the phylogroup 2b strains, nine strains were phylogenetically close to the P. syringae pv. aptata clade, whereas the remainder were scattered among P. syringae pv. atrofaciens and P. syringae pv. syringae strains. Pathogenicity and host range assays of the bacterial strains evaluated in this study on a set of taxonomically diverse plant species did not allow us to assign a "pathovar" status to the alfalfa strains. However, these results provide novel insight into the host range and phylogenetic position of the alfalfa-pathogenic members of P. syringae sensu lato, and they reveal that phenotypically and genotypically heterogeneous strains of the pathogen cause bacterial leaf spot of alfalfa.

Induction of apoptosis and modulation of homologous recombination DNA repair pathway in prostate cancer cells by the combination of AZD2461 and valproic acid.

Cancer therapies using defects in homologous recombination (HR) DNA repair pathway of tumor cells are not yet approved to be applicable in patients with malignancies other than BRCA1/2-mutated tumors. This study was designed to determine the efficacy of combination therapy of a histone deacetylase inhibitor, valproic acid (VPA) and a novel PARP inhibitor AZD2461 in both PC-3 (PTEN-mutated) and DU145 (PTEN-unmutated) prostate cancer cell lines. The Trypan blue dye exclusion assay and the tetrazolium-based colorimetric (MTT) assay were performed to measure the cytotoxicity while combination effects were assessed based on Chou-Talalay's principles. Flow-cytometric assay determined the type of cell death. The real-time PCR analysis was used to evaluate the alterations in mRNA levels of HR-related genes while their protein levels were measured using the ELISA method. γ-H2AX levels were determined as a marker of DNA damage. We observed a synergistic relationship between VPA and AZD2461 in all affected fractions of PC-3 cells (CI<0.9), but not in DU145 cells (CI>1.1). Annexin-V staining analysis revealed a significant induction of apoptosis when PC-3 cells were treated with VPA+AZD2461 (p<0.05). Both mRNA and protein levels of Rad51 and Mre11 were significantly decreased in PC-3 cells co-treated with VPA+AZD2461 while enhanced H2AX phosphorylation was found in PC-3 cells after 12 and 24 hours of co-treatment (p<0.05). Our findings established a preclinical rationale for selective targeting of HR repair pathways by a combination of VPA and AZD2461 as a mechanism for reducing the HR pathway sufficiency in PTEN-mutated prostate cancer cells.

Effect of resveratrol on SNARE proteins expression and insulin resistance in skeletal muscle of diabetic rats.

OBJECTIVES: Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex proteins are involved in membrane trafficking. The expression of isoforms of SNAP-23, syntaxin-4, and VAMP-2 is significantly done in skeletal muscles; they control GLUT4 trafficking. It is believed that type 2 diabetes could be caused by the modifications in the expression of SNARE complex proteins. The purpose of this study was to evaluate the effect of resveratrol on the expression of these proteins in type 2 diabetes. MATERIALS AND METHODS: Forty male Wistar rats were selected. Streptozotocin and nicotinamide were applied for the induction of type 2 diabetes. The animals were divided into five groups. Healthy and diabetic groups were set as control; resveratrol (1, 5, and 10 mg/kg body weight) was applied to treat the three groups of diabetic rats for 30 days. Real-time qRT-PCR was applied to evaluate the expression of SNARE complex proteins. RESULTS: There is a link between diabetes and insulin resistance and up-regulation of SNARE proteins expression. Resveratrol improved hyperglycemia and insulin resistance along with a non-significant reduction in the expression of SNARE proteins. CONCLUSION: Increased expression of SNARE proteins was possibly a compensatory mechanism in response to insulin resistance in the skeletal muscles of diabetic rats. Resveratrol non-significantly reduced the expression of SNARE proteins by enhancing insulin sensitivity, where this effect was dose-dependent. Thus, higher doses of resveratrol and longer intervention periods could probably be more effective. Another molecular mechanism of the anti-diabetic properties of resveratrol was identified with an effect on the expression of SNARE proteins.

Evaluation of attenuative effect of tert-butylhydroquinone against diazinon-induced oxidative stress on hematological indices in male Wistar rats.

Diazinon is an organophosphate toxicant that has been identified to induce oxidative stress within biological systems through altering biochemical and hematological indices, by generating free radicals while deteriorating the cellular antioxidant defense system. The present study was designed to evaluate the effectiveness of tert-butylhydroquinone (TBHQ), a synthetic food additive, in serving as an antioxidant against sub-lethal diazinon-induced oxidative stress in male Wistar rats. Animals were randomly divided into 4 groups: Control (treated with corn oil as a vehicle), diazinon (10 mg/kg/day), TBHQ (0.028 g/kg of diet) and a combination group of TBHQ (0.028 g/kg of diet) plus diazinon (10 mg/kg/day). All animals were treated orally once a day by gastric tube and treatments were continued for 7 weeks. Hematological indices, including red blood cell (RBC) indices and white blood cell (WBC) and platelet counts, were measured at the end of the treatment schedule. On comparison of the treatment groups with the untreated control group, RBC count, hemoglobin (Hb), hematocrit (Hct), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were significantly decreased in the diazinon and TBHQ+diazinon groups, while MCHC in the TBHQ group and MCV in the diazinon and TBHQ+diazinon groups were significantly increased. When the diazinon and TBHQ+diazinon groups were compared with the TBHQ group, RBC, Hb, Hct, and MCHC were significantly decreased whereas MCV was increased in both groups. Additionally, when comparing the TBHQ+diazinon group with the diazinon group, MCHC was determined to be significantly decreased. The results of the current experiments suggested that TBHQ could not efficiently protect blood cells against diazinon toxicity.

The effect of n-3 PUFAs on circulating adiponectin and leptin in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

AIM: N-3 PUFAs can potentially influence levels of inflammatory and non-inflammatory adipokines. Given the contradictory effects of n-3 PUFAs on serum levels of adipokines in type 2 diabetes, we conducted a systematic review and meta-analysis study of randomized placebo-controlled clinical trials that examined the effects of n-3 PUFAs on serum levels of leptin and adiponectin in patients with type 2 diabetes. METHODS: The electronic databases, without regard to language restrictions including PubMed/Medline, Google Scholar, SCOPUS and ISI Web of Science until August 2017, were used to identify randomized controlled trials that assessed the effect of n-3 PUFAs on serum leptin and adiponectin concentrations in type 2 diabetes. Outcomes were extracted based on the mean ± SD as effect size at baseline and end of the intervention. Between-study heterogeneity was evaluated by the I2 estimates and their 95% CIs. Funnel plot asymmetry was used to investigate the existence of publication bias. Stata software and Review Manager were used for statistical data analysis. RESULTS: Data from 10 eligible articles involved 494 subjects with type 2 diabetes mellitus (intervention groups = 254 and control groups = 240), with age between 44 and 70 years, treated with doses of 0.52-7.4 g/day n-3 PUFAs. Adiponectin concentration nonsignificantly increased by a MD = 0.17 µg/mL (95% CI - 0.11, 0.44). Also, leptin concentration nonsignificantly reduced by a MD = - 0.31 ng/mL (95% CI - 0.69, 0.07). CONCLUSION: Plant and marine sources of n-3 PUFAs can modify serum leptin and adiponectin levels by increasing adiponectin and decreasing leptin levels in patients with type 2 diabetes. Due to some limitations in this study, further studies are needed to reach a definitive conclusion about the effect of n-3 PUFAs on the levels of leptin and adiponectin in T2DM.

Effect of resveratrol on resistin and apelin gene expressions in adipose tissue of diabetic rats.

BACKGROUND/AIM: Adipose tissue plays a major role in glucose homeostasis. Dietary antioxidants such as resveratrol (RSV) may offer some protection against the early stage of diabetes mellitus and the development of complications. The present study investigated the effects of RSV on biochemical parameters and resistin and apelin gene expressions in adipose tissue of rats with type 2 diabetes. MATERIALS AND METHODS: Diabetes was induced using a single dose of streptozotocin + nicotinamide. Three groups of diabetic rats were treated with different doses of RSV (1, 5, and 10 mg/kg body weight per day). Oxidative status, serum biochemical parameters, insulin, and HOMA index were measured. Finally, resistin and apelin gene expressions were determined in rats' adipose tissue using RT- PCR (qRT-PCR). RESULTS: A significant reduction in serum glucose level was observed in rats treated with 5 and 10 mg/kg per day RSV compared with the diabetic control. Resistin expression in adipose tissue was reduced in RSV-treated groups, while no significant changes were observed in apelin expression. CONCLUSION: The results showed that RSV improves insulin sensitivity due to a simultaneous decrease in blood glucose and an increase in insulin. We concluded that RSV has potential hypoglycemic effect, probably by increasing insulin levels and changing the expression of resistin.

Toxicity of zinc oxide nanoparticles on adult male Wistar rats.

The purpose of this study was to investigate the effects of zinc oxide nanoparticles (nZnO) on adult male Wistar rats. Thirty male Wistar rats divided into five groups of six animals each were used for this study. For ten days, Groups one to four continuously received 50, 100, 150 and 200 mg/kg nZnO, respectively. Group five served as the control group. At the end of the study, the rats were sacrificed and histopathological study of the liver and renal tissue, sperm analysis, serum oxidative stress parameters and some liver enzymes were done. The results of this study showed that nZnO at concentration more than 50 mg/kg lead to significant changes in liver enzymes, oxidative stress, liver and renal tissue and sperm quality and quantity. In conclusion, the toxicity of nZnO is more significant when the concentration is increased; however, the use of low doses requires further investigation.