Cell Journal (Yakhteh)
Volume:25 Issue: 7, Jul 2023

Role of Endoplasmic Reticulum Stress in The Male Reproductive SystemTesticular dysfunction, whether linked to varicocele, obesity, diabetes, aging, inflammation, or lifestyle or environmental issues, is frequently accompanied by an accumulation of unfolded or misfolded proteins, indicating impaired endoplasmic reticulum (ER) function. In this review, we examined the Google Scholar, Scopus and PubMed databases (from 2011 to 2022) to support the association of ER stress with defective spermatogenesis in animal models and humans. ER stress, whether in its pro-survival or pro-apoptotic aspect, appears to be closely linked to each studied situation. Several studies have demonstrated a significant increase in oxidative stress (OS) levels in infertile men compared to fertile individuals, which is associated with poor spermatogenesis quality. OS is likely the result of the interplay between ER stress and spermatogenesis defects. These findings suggest that therapeutic strategies aimed at mitigating both ER stress and OS could be of interest in restoring male reproductive function.

Previous reports showed that mouse embryonic fibroblasts (MEFs) could support pluripotent stem cell selfrenewal and maintain their pluripotency. The goal of this study was to reveal whether the decellularized extracellular matrix derived from MEFs (MEF-ECM) is beneficial to promote the proliferation of inner ear-derived cells.

In this experimental study, we prepared a cell-free MEF-ECM through decellularization. Scanning electron microscope (SEM) and immunofluorescent staining were conducted for phenotype characterization. Organs of Corti were dissected from postnatal day 2 and the inner ear-derived cells were obtained. The identification of inner ear-derived cells was conducted by using reverse transcription-polymerase chain reaction (RT-PCR). Cell counting kit-8 (CCK-8) was used to evaluate the proliferation capability of inner ear-derived cells cultured on the MEFECM and tissue culture plate (TCP).

The MEF-ECM was clearly observed after decellularization via SEM, and the immunofluorescence staining results revealed that MEF-ECM was composed of three proteins, including collagen I, fibronectin and laminin. Most importantly, the results of CCK-8 showed that compared with TCP, MEF-ECM could effectively facilitate the proliferation of inner ear-derived cells.

The discovery of the potential of MEF-ECM in promoting inner ear-derived cell proliferation indicates that the decellularized matrix microenvironment may play a vital role in keeping proliferation ability of these cells. Our findings indicate that the use of MEF-ECM may serve as a novel approach for expanding inner ear-derived cells and potentially facilitating the clinical application of inner ear-derived cells for hearing loss in the future.

Some reports have indicated that conditioned medium from growing mouse embryonic stem cells (ESCs) provides a supportive condition for small follicles growing, oocyte maturation, and following embryo growth. The aim of this study is assessing in vitro maturation (IVM) and consequent in vitro fertilization (IVF) outcome of immature mouse oocytes using human embryonic stem cells conditioned medium (HESCM).

In this experimental study, 240 germinal vesicle (GV) oocytes were took from NMRI female mice, aged 4-6 weeks, 48 hours before injection of 5 IU pregnant mare serum gonadotropin (PMSG). 120 GV oocytes without cumulus cells were cultured in each of the groups. 120 GV were cultured in HESCM as test groups and also 120 GV cultured in human embryonic stem cells medium (HESM) as control groups. After evaluating the metaphase II (MII) oocyte maturation rate at 8, 16 and 24 hours, the MII oocytes subsequently were fertilized in vitro and the two-cell embryo development rate was recorded at days 1, 2, and 3. Statistical analysis was performed by using the generalized estimating equations (GEE) method that calculated their rate ratio.

Our data indicated there are significant differences between the maturation rates in HESCM and HESM (P=0.004), also the two-cell embryo development was significant between two culture media (P=0.00).

Similar to some other studies, the secretome of the HESCM showed a significant impact on the IVM outcomes in mice.

This study aimed to compare the effect of different physical training on the mechanism of ceramidedependent insulin resistance in the flexor hallucis longus (FHL) muscle of diabetic rats.

In this experimental study, 7 healthy as a healthy control (HC) group, and 21 diabetics (55 mg/ kg Streptozotocin) Wistar rats (200-220 g; 8-10 weeks old) divided into the diabetic control (DC), moderate continuous training (MCT), and moderate intensity interval training (MIIT) groups. Both MCT (55-70% of maximal oxygen uptake (VO2max), and MIIT (85% VO2max) groups trained for 10-25 minutes at a speed of 10-20 m/minutes. The changes in the expression of blood glucose, insulin, insulin resistance, lipid profile and total ceramide were measured as well as ceramide synthase-1, Glucose transporter type 4 (GLUT4), Protein kinase B known as Akt, phosphorylated protein kinase B known as pAkt, protein kinase C (PKC), and tumour necrosis factor α (TNFα).

Blood glucose, triglyceride (TG) and ceramide synthase-1 (CS1) expression levels in the MCT group decreased in comparison with the DC group. FHL protein expression of GLUT4 in the MCT group was higher than the DC group. FHL expression of GLUT4, pAKT, AKT/pAKT, PKC, CS1 and total ceramide in the MIIT group were higher than the DC group. Cholesterol, low-density lipoprotein (LDL), TG, and TNF-α protein expression in the MIIT group were lower than the DC group. GLUT4, PKC, pAKT, AKT/pAKT in the MIIT group were higher, and total ceramide and TNF-α were lower in the MIIT group than the MCT group.

It seems that both training plan MIIT and MCT have favorable effects on the metabolism of glucose, insulin, lipids, and the decrease of TNFα level in the diabetes, but in connection with the improvement of the ceramides mechanism, it seems that the MIIT training plan is more optimal than MCT training plan.

Endoplasmic reticulum-metallopeptidase 1 (ERMP1) is involved in cellular response to oxidative stress. However, its functional role in proliferation and progression of cancer cells remains unknown. The focus of this study was to investigate the molecular-mechanisms in which ERMP1 modulates the proliferation and progression of colorectal cancer (CRC) cells under normal and environment stress conditions.

In this experimental study, ERMP1 expression was evaluated using reverse transcriptionquantitative polymerase chain reaction (RT-qPCR) in CRC cells. ERMP1 was knocked down using lentiviral transduction of ERMP1-specific shRNA into HCT116 cells. ERMP1 was also upregulated using lipofectamine transfection of ERMP1-overexpressing vector into SW48 cells. To evaluate the role of ERMP1 in the cellular and environmental stress conditions, ERMP1-downregulated cells were exposed to stressful conditions including starvation, serum free medium, and treatment with redox or chemotherapy agents for 72 hours. The expression of AKT, p-AKT, phospho-mammalian target of rapamycin (p-mTOR), β-catenin, p-β-catenin, E-cadherin, and Glucose-regulating protein 78 (GRP78) proteins was evaluated by western blotting. The expression of ERMP1, CYCLIN D, and c-MYC was evaluated by RT-qPCR. The cell surface localization of GRP78, cell cycle distribution, and apoptosis were determined by Flow cytometry.

ERMP1 knock-down reduced the cellular proliferation, inactivated the PI3K/AKT pathway, prompted the G1 arrest, and attenuated the free β-catenin and CYCLIN D expression. Opposite results were obtained in ERMP1- overexpressed cells. Knock-down of ERMP1 also reduced the GRP78 localization at the cell surface. Various environmental stress conditions differently affected the ERMP1-downregulated cells.

ERMP1 functioned as an oncogene in CRC cells by promoting malignant characteristics. The phosphoinositide 3-kinases (PI3K)/AKT/β-catenin pathway and localization of GRP78 were closely related to the effects of ERMP1. Consequently, ERMP1 might be regarded as a promising target in therapeutic strategies related to CRC.

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.

Premature ovarian failure (POF) is a heterogeneous disorder. POF is defined as hypergonadotropic hypoestrogenism in women under 40 years. There is no effective treatment to cure POF patients. Antioxidants prevent ovarian damage by reducing the lipid peroxidation cascades affecting folliculogenesis, meiosis and ovulation. Hence; the aim of present study was to investigate the effects of Capsaicin (CAP) and Quercetin (QUR) on cyclophosphamide (CYC)-induced POF in rat model.

In this experimental study, POF was induced by intraperitoneal injection of 200 mg/kg CYC on first day and then 8 mg/kg/day for the following 3 days. After 4 days of CYC administration, rats were randomly divided into five groups (n=6/group) as follows: POF, dimethyl sulfoxide (DMSO), CAP (0.5 mg/kg/day), QUR (100 mg/kg/day) and CAP+QUR. Biochemical, hormonal, gene expression, and histological evaluations were performed on blood serum and tissue samples after 14 days of treatment with the CAP and QUR.

CAP, QUR and CAP+QUR groups showed signs of restored ovarian function in the form of a significant increase in serum total antioxidant capacity (TAC), estrogen, progesterone and anti-mullerian hormone (AMH) levels versus POF and DMSO groups and a significant improvement in histological parameters and follicle numbers in treatment groups compared to POF and DMSO groups. Polymerase chain reaction (PCR) analysis demonstrated that CAP and QUR upregulate the expression of BAX gene and decreased the expression of apoptosis inducing genes (BCL-2 and P53).

CAP and QUR treatment of CYC-induced POF rats showed a positive effect on reducing ovarian damage by improving TAC levels, expression of apoptotic genes, levels of ovarian reserve markers, and histological parameters. Our results suggest that treatment with CAP or QUR may be a conservative treatment approach for CYC -induced POF.

Rheumatoid arthritis (RA) is a common progressive autoimmune disorder that causes chronic inflammation of the joints and damage to other organs. Previous studies have reported the important role of miRNA-146a in the pathogenesis of RA. In addition, the anti-inflammatory and modulatory effects of oleuropein (OLEU) on the expression pattern of microRNAs (miRNAs) have been shown in different diseases. Therefore, this study aimed to evaluate both the sensitivity and specificity of miRNA-146a and determine the potential effects of OLEU on the expression levels of miRNA-146a and tumour necrosis factor-alpha (TNF-α) in RA patients.

The participants in this experimental study were divided into 2 groups: RA (n=45) and healthy controls (n=30). The isolated peripheral blood mononuclear cells (PBMCs) were treated with different concentrations of OLEU; and the level of TNF-α expression, anti-citrullinated protein, and miRNA-146a were determined using enzyme-linked immunoassay and real-time polymerase chain reaction, respectively. In addition, the receiver operating characteristic (ROC) curve analysis evaluated the sensitivity and specificity of miRNA-146a in RA patients.

Results revealed a positive correlation between the levels of miRNA-146a expression with the serum levels of C-reactive protein (CRP) and rheumatoid factor (RF) in RA patients. In addition, OLEU treatment decreased the levels of TNF-α and miRNA-146a expression in treated PBMCs samples compared with untreated cells. The ROC curve analysis showed an 85% sensitivity and 100% specificity of miRNA-146a in RA patients.

Therefore, miRNA-146a can be used as a useful biomarker for RA diagnosis, particularly for early detection. In addition, OLEU could suppress inflammation in RA patients through the regulation of miRNA-146a.