This study aimed to investigate the relationship between follicular fluid Bisphenol A (BPA) concentrations with alterations in the expressions of NOTCH1-3, CASPASE 3/7, HLA-G, and ICAM-1 genes and the number of retrieved mature oocytes (MII oocyte) in the cumulus cells of infertile poor ovarian response stimulates women. In this prospective cohort study, 80 infertile unexpected poor ovarian response (POR) subjects were selected on the basis of subgroup 1a of the POSEIDON classification. They were divided into two groups: group 1 consisted of 40 women, each with a higher number of metaphase II (MII) oocytes (G1, 3-4 oocytes retrieved), while group 2 comprised of 40 women, each with a lower number of MII oocytes (G2, ≤2 oocytes retrieved). The expressions of the studied genes were evaluated by quantitative-real time polymerase chain reaction (PCR). The concentration of BPA in follicular fluid was measured with HPLC. The expression levels of NOTCH1-3, HLA-G, and ICAM-1 genes were significantly lower in G2 than G1 (P<0.05). Meanwhile, CASPASE 3/7 expression levels were higher in unexpected POR patients in G2 compared to G1 (P<0.05). There was a significant direct correlation between the levels of NOTCH1-3, HLA-G and ICAM-1 gene expressions and there was also a significant inverse correlation (P<0.05) between the levels of CASPASE 3/7, with the number of MII oocytes and embryo development between the two groups. The concentration of BPA in the follicular fluids of G2 was higher compared to G1 (P<0.05). A higher concentration of BPA was associated with a lower number of mature oocytes and oocyte quality in these patients. Also, alterations of NOTCH1-3, CASPASE 3/7, HLA-G, and ICAM-1 transcript levels in unexpected POR women were associated with BPA concentration.

In this article published in Cell J, Vol 19, No 4, Jan-Mar (Winter) 2018, on pages 654-659, the authors found that Figures 2 and 3 had some errors that accidentally happened during organizing figures. Because of mislabeling of some images and saving them in an incorrect folder, the following figures' legends are corrected. The authors would like to apologies for any inconvenience.

There is interest in using cytotoxic T lymphocyte antigen-4 (CTLA-4) immunotherapy to treat blood cancers. Unfortunately, patients with acute lymphoblastic leukaemia (ALL) frequently exhibit resistance to treatment and natural killer (NK) cell exhaustion. This study aims to increase the cytotoxic potency of natural killer cells by using CTLA-4 to block the Nalm-6 leukaemia cell line. In this experimental study, NK cells were purified from the peripheral blood mononuclear cells (PBMCs) of 10 healthy people and assessed by flow cytometry for purity and viability. The purified cells were activated overnight at 37°C and 5% CO2 with interleukin-15 (IL-15, 10 ng/ml) followed by evaluation of expressions of CTLA-4, activating and inhibitory receptors, and the release of interferon gamma (IFN-γ) and granzyme B (GZM B). CTLA-4 expression on NK cells from recurrent ALL patients was also evaluated. Finally, the cytotoxic activity of NK cells was assessed after the CTLA-4 blockade. The purity of the isolated cells was 96.58 ± 2.57%. Isolated NK cells activated with IL-15 resulted in significantly higher CTLA-4 expression (8.75%, P<0.05). Similarly, CTLA-4 expression on the surface of NK cells from patients with ALL was higher (7.46%) compared to healthy individuals (1.46%, P<0.05). IL-15 reduced NKG2A expression (P<0.01), and increased expressions of NKP30 (P<0.05) and NKP46 (P<0.01). The activated NK cells released more IFN-γ (P<0.5) and GZM B (P<0.01) compared to unactivated NK cells. Blockade of CTLA-4 enhanced the NK cell killing potential against Nalm-6 cells (56.3%, P<0.05); however, IFN-γ and GZM B levels were not statistically different between the blocked and non-blocked groups. Our findings suggest that CTLA-4 blockage of Nalm-6 cells causes an increase in antitumour activity of NK cells against these cells. Our study also provides evidence for the potential of cancer immunotherapy treatment using blocking anti-CTLA-4 mAbs.

The aim of this study was to synthesize chitosan nanoparticles (Cs NPs) for resveratrol (RSV) delivery and assess their effectiveness in inducing autophagy in MDA-MB 231 cells. In this experimental study, Pure and RSV-loaded Cs NPs (RSV. Cs NPs) were prepared via the ionic gelation method, and their physicochemical properties were characterized using standard techniques, and RSV release was measured in vitro. MDA-MB 231 cells were incubated with RSV, Cs NPs, and RSV. Cs NPs and Half-maximal inhibitory concentration (IC50) values were calculated following the MTT test. Cell viability was assessed by lactate dehydrogenase (LDH) assay, and autophagy was evaluated using the real-time polymerase chain reaction (PCR). NP formation was confirmed with the analysis of FTIR spectra. Pure and RSV. Cs NPs had 36.7 and 94.07 nm sizes with 18.3 and 27 mV zeta potentials, respectively. Above 60% of RSV entrapped within NPs was released in an initial burst manner followed by a gradual release till 72 hours. Cs and RSV. Cs NPs restrained cell proliferation at lower concentrations. RSV. Cs NPs showed the highest anticancer effect and stimulated autophagy, indicated by increased Beclin-1 ATG5, ATG7, LC3A, and P62 expression. RSV. Cs NPs show promising effects in inhibiting invasive breast cancer (BC) cells in vitro by inducing autophagy.

Genetic aspects can play an essential role in the occurrence and development of ischemic stroke (IS). Rs1894720 polymorphism is one of the eight single nucleotide polymorphisms (SNPs) in the long non-coding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) locus. The aim of study is the lncRNA MIAT rs1894720 polymorphism decreases IS risk by reducing lncRNA MIAT expression. In this case-control study, we studied 232 Iranian patients and 232 controls. The blood samples were collected from patients admitted at different times after stroke symptoms. We enrolled 80, 78, and 74 patients who arrived at the hospital between 0-24, 24-48, and 48-72 hours after the first appearance of symptoms, respectively. DNA genotyping was done by the tetra-primer ARMS-PCR method. Circulating MIAT levels were evaluated by real-time polymerase chain reaction (PCR). The GT genotype of MIAT rs1894720 showed a significant association with the risk of IS (OR=3.53, 95% CI=2.13-5.84, P<0.001). MIAT expression was higher relative to the control within the first hours after IS. The MIAT levels in IS patients with rs1894720 (GT) were significantly lower relative to patients who had the GG and TT genotypes. Linear regression model indicated a significant correlation between MIAT expression with atherosclerotic risk factors and types of stroke in IS patients. Receiver operating characteristic (ROC) curve analysis showed that the level of lncRNA MIAT after IS could be diagnostic with an area under the curve (AUC) of 0.82. The sensitivity and specificity were 80.17 and 67.24%, respectively (P<0.001). Our study demonstrated that the MIAT rs1894720 polymorphism (GT) might increase the risk of IS in the Iranian population. MIAT expression was up-regulated in our IS patients. Hence, it could be a diagnostic biomarker for IS.

Epigenetic modifications such as DNA methylation play a key role in male infertility etiology. This study aimed to explore the global DNA methylation status in testicular spermatogenic cells of varicocele-induced rats and consider their semen quality, with a focus on key epigenetic marks, namely 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC), as well as the mRNA and proteins of ten-eleven translocation (TET) methylcytosine dioxygenases 1-3. In this experimental study, 24 mature male Wistar rats (8 in each group) were assigned amongst the control, sham, and varicocele groups. Sperm quality was assessed, and DNA methylation patterns of testicular spermatogenic cells were investigated using reverse transcription-polymerase chain reaction (RT-PCR), western blot, and immunofluorescence techniques. Sperm parameters, chromatin and DNA integrity were significantly lower, and sperm lipid peroxidation significantly increased in varicocele-induced rats in comparison with control rats. During spermatogenesis in rat testis, 5-mC and 5-hmC epigenetic marks, and TET1-3 mRNA and proteins were expressed. In contrast to the 5-mC fluorescent signal which was presented in all testicular cells, the 5-hmC fluorescent signal was presented exclusively in spermatogonia and a few spermatids. In varicocele-induced rats, the 5-mC signal decreased in all cells within the tubules, whereas a strong signal of 5-hmC was detected in seminiferous tubules compared to the control group. As well, the levels of TET2 mRNA and protein expression were significantly upregulated in varicocele-induced rats in comparison with the control group. Also, our results showed that the varicocele-induced animals exhibited strong fluorescent signals of TET1-3 in testicular cells, whereas weak fluorescent signals were identified in the seminiferous tubules of the control animals. Consequently, we showed TET2 upregulation and the 5-hmC gain at testicular levels are associated with varicocele and sperm quality decline, and therefore they can be exploited as potential biomarkers of spermatogenesis.

Vaccinium arctostaphylos has traditionally been employed in Iranian folk medicine to treat diabetes. However, the precise molecular mechanisms underlying its antidiabetic properties remain incompletely understood. The current experiment intended to explore the modulatory effects of V. arctostaphylos fruit ethanolic extract (VAE) on biochemical and molecular events in the livers of diabetic rats. In this experimental study, male Wistar rats were randomly assigned to four groups: normal control, normal rats with VAE treatment, diabetic control, and diabetic rats with VAE treatment. Following 42 days of treatment, the impact of VAE on diabetes-induced rats was assessed by measuring various serum biochemical parameters, including insulin, free fatty acids (FFA), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS), and adiponectin levels. The activities of hepatic carbohydrate metabolic enzymes and glycogen content were determined. Additionally, expression levels of selected genes implicated in carbohydrate/lipid metabolism and miR-27b expression were evaluated. H and E-stained liver sections were prepared for light microscopy examination. Treatment with VAE elevated levels of insulin and adiponectin that reduced levels of FFA, ROS, and TNF-α in the serum of diabetic rats. VAE-treated rats exhibited increased activities of hepatic glucokinase (GK), glucose-6-phosphate dehydrogenase (G6PD), and glycogen concentrations, in conjunction with decreased activities of glucose-6-phosphatase (G6Pase) and fructose-1,6-bisphosphatase (FBPase). Furthermore, VAE significantly upregulated the transcription levels of hepatic insulin receptor substrate 1 (Irs1) and glucose transporter 2 (Glut2), while considerably downregulated the expression of peroxisome proliferator-activated receptor gamma (Pparg) and sterol regulatory element-binding protein 1c (Srebp1c). VAE remarkably enhanced the expression of miR27-b in the hepatic tissues of diabetic rats. Abnormal histological signs were dramatically normalized in diabetic rats receiving VAE compared to those in the diabetic control group. Our findings underscore the hypoglycemic and hypolipidemic activities of V. arctostaphylos and assist in better comprehension of its antidiabetic properties.

The use of biocompatible scaffolds with appropriate characteristics to treat large bone defects has attracted significant attention. The main objective of the current study is to fabricate a 3D nanocomposite structure that contains green synthesized magnesium oxide nanoparticles (MgONPs) and bacterial cellulose (BC) nanofibres, as a bioscaffold for bone regeneration. In this experimental study, Camellia sinensis extract was used as the green method to synthesize MgONPs. The synthesized hydrogels were evaluated for their porosity, morphology, degradation rate, mechanical features, cell attachment, and cytocompatibility. Osteogenic differentiation was assessed by alkaline phosphatase (ALP) activity, real-time reverse transcription-polymerase chain reaction (RT-PCR), and alizarin red staining. MgONPs significantly increased both mechanical strength (P=0.009) and porosity (P=0.01) of the BC hydrogels. Human MG-63 osteoblast proliferation significantly increased in the MgONP-BC group compared to the pure BC group (P=0.003). Expression rates of both the ALP (P=0.001) and osteocalcin (OCN) genes were significantly enhanced in cells seeded on the MgONP-incorporated BC. MG-63 cells had significantly greater calcium deposition and ALP activity (P=0.002) on the MgONP-BC scaffold compared to the BC at day 21. The MgONP-BC scaffold can promote the osteogenic activity of osteoblast-like cells, which indicates its therapeutic potential for bone tissue regeneration.

Surgery and chemotherapy are the most common therapeutic strategies proposed for oral squamous cell carcinoma (OSCC). However, some of the disadvantages associated with the current methods like unwanted side effects and poor drug response lead the scientist to seek for novel modalities and delivery approaches to enhance the efficacy of treatments. The study aimed to assess the effectiveness of disulfiram (DSF)-loaded Niosomes on cancerous phenotypes of the OSCC cells. In this experimental study, an optimum formulation of DSF-loaded Niosomes was developed for the treatment of OSCC cells to reduce drug doses and improve the poor stability of DSF in the OSCC environment. The design expert software was utilized to optimize the particles in terms of size, polydispersity index (PDI), and entrapment efficacy (EE). Acidic pH increased the release rate of DSF from these formulations. The size, PDI, and EE of Niosomes were more stable at 4°C compared to 25°C. The results indicated that DSF-loaded Niosomes could induce apoptosis (P=0.019) in the OSCC cells compared to the control group. Moreover, it could reduce colony formation ability (P=0.0046) and also migration capacity of OSCC cells (P=0.0015). Our findings indicated that the application of proper dose of DSF-loaded Niosomes (12.5 μg/ml) increases apoptosis, decreases colony formation capacity and declines the migration ability of OSCC cells.

Traumatic optic neuropathy (TON) causes partial or complete blindness because death of irreplaceable retinal ganglion cells (RGCs). Neuroprotective functions of erythropoietin (EPO) in the nervous system have been considered by many studies investigating effectiveness of this cytokine in various retinal disease models. It has been found that changes in retinal neurons under conditions of glial cells are effective in vision loss, therefore, the present study hypothesized that EPO neuroprotective effect could be mediated through glial cells in TON model. In this experiment study, 72 rats were assessed in the following groups: intact and optic nerve crush which received either the 4000 IU EPO or saline. Visual evoked potential and optomotor response and RGC number were assessed and regenerated axons evaluated by anterograde test. Cytokines gene expression changes were compared by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Density of astrocytes cells, assessed by fluorescence intensity, in addition, possible cytotoxic effect of EPO was measured on mouse astrocyte culture in vitro. in vitro data showed that EPO was not toxic for mouse astrocytes. Intravenous injection of EPO improved vision, in terms of visual behavioral tests. RGCs protection was more than two times in EPO, compared to the vehicle group. More regenerated axons were determined by anterograde tracing in the EPO group compared to the vehicle. Moreover, GFAP immunostaining showed while the intensity of reactive astrocytes was increased in injured retina, systemic EPO decreased it. In the treatment group, expression of GFAP was down-regulated, while CNTF was upregulated as assessed by qRT-PCR in the 60th day post-crush. Our study showed that systemic administration of EPO can protect degenerating RGCs. Indeed, exogenous EPO exerted neuroprotective and neurotrophic functions by reducing reactive astrocytic gliosis. Therefore, reduction of gliosis by EPO may be considered as therapeutic targets for TON.