Cell Journal最新文献

Objective: The relationship between oxidative stress (OS), insulin resistance (IR), and polycystic ovary syndrome (PCOS) is an important medical issue in human reproduction. Some of the oxidative phosphorylation (OXPHOS) genes have been previously studied in granulosa and muscle cells of PCOS patients. Cumulus cells (CCs) remain close to the oocyte even after ovulation. This research has been designed to compare the expression of OXPHOS genes in CCs of PCOS, with or without insulin resistance.

Materials and methods: In this experimental study, patients were included in PCOS insulin-resistant, PCOS insulinsensitive (IS), and control (fertile women with male infertility history) groups. The expression of NCF2, TXNIP, UCP2, NDUFB6, ATP5H, COX7C, NDUFA3, SDHA, and SDHB was studied by real-time polymerase chain reaction (PCR), and normalization was performed considering HPRT1 and CYC1 as reference genes. One-way ANOVA and Tukey test were used for data analysis.

Results: The results showed that the expression of NCF2, TXNIP, UCP2, and ATP5H was significantly higher in the IR group than IS and control groups (P<0.01). NDUFB6 showed the highest expression in the IS group, which was significantly different from other groups (P<0.01). The other genes of interest, except COX7C, were observed with the most transcriptional levels in the IS group, although there was no significant difference for those genes.

Conclusion: Altered expression of genes involved in mitochondrial function compared to the control group in CCs of both IR and IS categories of the PCOS patients suggests that alteration in OXPHOS genes can contribute to the pathophysiology of PCOS.

Objective: Ovarian hyperstimulation syndrome (OHSS) is one female reproductive disorder that can occur after administration of injectable hormonal drugs to stimulate ovulation. Betaine (BET) is an intracellular biomolecule with anti-inflammatory and tissue protective effects. There is no information about its effects in an experimental model of OHSS. The current study aims to investigate the possible effects of BET on abnormal expressions of vasoconstrictor proteins and ovarian histological changes in an experimental OHSS rat model.

Materials and methods: In this experimental study, 30 adult female rats (two months old) were randomly divided into six groups (n=5 per group): i. Control, ii. OHSS [10 IU sc equine chorionic gonadotropin (eCG) for 4 days followed by 30 IU sc human chorionic gonadotropin (hCG) on the fifth day], iii. OHSS+BET (200 mg/kg/day, orally for seven days), iv. OHSS+Cabergoline (CAB, 100 mg/kg/day, orally for six days), v. BET, and vi. CAB. Expression levels of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and blood levels of oestradiol (E2) and progesterone (P4) were measured at the end of the experiment. The ovaries were studied for histomorphological changes.

Results: Induction of OHSS altered tissue histology, including an increase in the number of corpora lutea and atretic follicles, and decreased the number of follicular reserves. In this group, we observed increased expressions of the VEGF and COX-2 proteins, and increased serum E2 and P4 levels. Administration of CAB and BET significantly attenuated all molecular and histological alterations observed in the OHSS animals.

Conclusion: Our findings, for first time, indicate the beneficial effects of BET to reduce OHSS complications in patients by reducing the expressions of vasoactive proteins and improving changes to the ovarian tissues. The findings are similar to CAB and can be a new avenue for future research on BET.

Objective: Celiac disease is a common chronic inflammatory condition of the small intestine caused by permanent intolerance to gluten/gliadin. It has been demonstrated that oxidative stress is one of the mechanisms that is involved in gliadin toxicity, and there is a correlation between oxidative damage with this disease. Similarly, increased oxidative stress was repeatedly reported in infertile men which led to low-quality of sperm function. Therefore, we aimed to assess sperm parameters and chromatin status in men with Celiac disease.

Materials and methods: In this case-control study, semen samples were collected from 11 fertile men without Celiac and 10 men with diagnostic Celiac disease. Basic semen analyses were performed according to the World Health Organization (WHO) 2010 protocol. The percentage of sperm with persistence histones, protamine deficiency, DNA fragmentation, malondialdehyde (MDA), and intracellular reactive oxygen species (ROS) were assessed using aniline blue, chromomycin A3, sperm chromatin structure assay, thiobarbituric acid reactive substances (TBARS) assay, and diacetyldichlorofluorescein staining, respectively.

Results: Unlike the sperm parameters, which did not show significant differences between men with Celiac disease and fertile individuals, sperm chromatin maturation (persistence histones and protamine deficiency) and sperm DNA damage in men with Celiac disease were significantly higher compared to fertile individuals (P<0.05). In addition, the percentage of sperm viability in these individuals was significantly lower than that in the fertile individuals (P<0.05). We did not observe any significant differences in sperm lipid peroxidation and intracellular ROS levels between the two study groups (P>0.05).

Conclusion: Celiac disease affects sperm chromatin maturation and DNA fragmentation, emphasizing its impact on reproductive health.

In this article published in Cell J, Vol 18, No 2, Jul-Sep (Summer) 2016, on pages 179-188, the authors found that Figure 2A was the same as the one that has already been published and it was confusing. The following figure's legend is corrected in reference 9. The authors would like to apologies for any inconvenience caused.

Objective: Multiple sclerosis (MS) has a multi-factorial etiology involving genetic factors. Fingolimod (Gilenya ®, FTY720) modulates the G-protein-coupled sphingosine 1-phosphate (S1P) receptors, S1PR1, 2, 3, 4 and 5. Variation in the human S1PR1 coding sequence results in heterogeneity in the function of the receptor. Interleukin-17, producing CD4+ T cells, tends to be increased after treatment with Fingolimod. The aim of the study was to investigate singlenucleotide polymorphisms (SNPs) in the S1PR1 gene or interleukin-17 (IL-17) levels in a small group of Iranian relapsing-remitting MS patients treated with Fingolimod.

Materials and methods: In this case-control study, the genomic DNA of 94 MS patients treated with Fingolimod was extracted and Sanger sequencing was performed on polymerase chain reaction (PCR) products to detect variants in the S1PR1 gene. Quantification of IL-17 from the serum of the patients was performed using a commercially available enzyme-linked immunosorbent assay (ELISA).

Results: Among 94 relapsing-remitting MS patients treated with Fingolimod, 69 (73.4%) were responders and 25 (26.6%) were non-responders. There were four novel and five common SNPs in the S1PR1 gene and no significant association between SNP genotype and drug response was detected. In a subset of 34 patients, there was no significant difference in IL-17 serum concentrations before or after treatment and no association with S1PR1 polymorphisms was determined.

Conclusion: This study is the first in Iran to investigate association between SNPs of the S1PR1 gene or IL-17 levels with fingolimod response in a small group of Iranian relapsing remitting MS patients. There was no association with S1PR1 gene SNPs or IL-17 levels before or after treatment.

Objective: Schwann cells are the main cells for myelination and regeneration of peripheral nerves. Idebenone is a synthetic antioxidant used to treat central nervous system diseases. The aim of the study is to determine whether idebenone can protect Schwann cells and increase cell activity under conditions of oxidative stress caused by hydrogen peroxide (H₂O₂) in vitro.

Materials and methods: In this experimental study, Schwann cells were pre-treated with various concentrations of idebenone and H₂O₂; after determining the appropriate doses, the cells were treated with 10 μM idebenone for 48 hours and 1000 μM H₂O₂ for the last two hours. The malondialdehyde (MDA) level, and activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were assessed by ELISA. Cell viability was assessed by the MTT assay. Western blot analysis was conducted to determine the expressions of myelin protein zero (MPZ) and peripheral myelin protein 22 (PMP22), and expression ratio of the Bax/Bcl-2 proteins. The percentage of cell apoptosis was evaluated by annexin V staining using flow cytometry.

Results: Schwann cells under oxidative stress conditions caused by H₂O₂ and treated with idebenone had increased cell viability; increased SOD, CAT, and GPx activity; and increased expressions of the MPZ and PMP22 proteins. There was a decreased level of MDA, decreased expression ratio of Bax/Bcl-2 proteins, and a decrease in the percentage of apoptotic cells stained with Annexin V.

Conclusion: The appropriate dose of idebenone may improve both survival and function of Schwann cells exposed to H₂O₂ by reducing oxidative stress and apoptosis.

The rapid development of knowledge on healthy nutrition, and hygiene practices, as well as the advent of antibiotics and vaccines, has led to increased life expectancy in the recent century. The extended lifespan has brought new challenges for healthcare professionals, including the management of chronic degenerative diseases, malignancies, and autoimmune disorders. Advanced therapeutic medicinal products (ATMPs) have emerged as a promising frontier alongside conventional therapeutic modalities, offering innovative solutions through cell-based therapies, gene therapy, and tissue engineering. Recent years have witnessed remarkable advancements in regenerative medicine and the launching of innovative ATMPs. Numerous ATMPs have been registered and approved by regulatory agencies for the management of different diseases in 2023. The approval of groundbreaking therapies around the world has made 2023 an exceptional year. Novel ATMPs and the development of artificial intelligence (AI) in 2023 will pave the way for the integration of ATMPs and advanced technologies in personalized medicine, early diagnosis and targeted treatments.

Infertility is a common clinical condition and about half of the major causes are due to male-related infertility. Pathogenesis of this abnormality is generally undefined; so establishing a proper treatment option is relatively uncertain. In recent years, several evidences demonstrated that mesenchymal stem cells (MSCs) can be a hope for innovative and efficient treatment of male infertility. This study reviews possible applications of MSCs in the restoration of spermatogenesis in male infertility of both humans and animals to suggest new avenues for future clinical practices. Articles published in "PubMed" and "Google Scholar" from January 1, 2000, to August 1, 2023, were investigated by searching items of "mesenchymal stem cells", "cell therapy", "cell transplantation", and, "regenerative medicine" keywords, in addition to the "urology", "andrology", "reproductive medicine", "male infertility", "azoospermia", and "spermatogenesis". The results obtained from the transplantation of MSCs in the treatment of male infertility seemed encouraging and they revealed the safety and efficacy of these cells to recover spermatogenesis; eventhough further stem cell research is still required before recruiting clinical application of MSCs in the treatment of human male infertility. Undertaking more well-defined, standardized, and reproducible protocols and enrolling larger sample sizes during a longer follow-up period can benefit the relevance of MSC transplantation in the restoration of spermatogenesis and treatment of male infertility. It seems that developing and utilizing stem cell transplantations, exosomes, scaffold delivery systems, and three dimensional (3D) culture methods may open a new window to getting more benefits from cell therapy in the treatment of men infertility.

Objective: According to the response-to-retention hypothesis, the inception of atherosclerosis is attributed to the deposition and retention of lipoprotein in the arterial intima, facilitated by altered proteoglycans with hyperelongated glycosaminoglycan (GAG) chains. Recent studies have elucidated a signaling pathway whereby transforming growth factor-β (TGF-β) promotes the expression of genes linked to proteoglycan GAG chain elongation (CHSY1 and CHST11) via reactive oxygen species (ROS) and the downstream phosphorylation of ERK1/2 and Smad2L. Atorvastatin is known to exhibit pleiotropic effects, including antioxidant and anti-inflammatory. The purpose of the present research was to ascertain the influence of atorvastatin on TGF-β-stimulated expression of CHSY1 and CHST11 and associated signaling pathways using an in vitro model.

Materials and methods: In this experimental study, vascular smooth muscle cells (VSMCs) were pre-incubated with atorvastatin (0.1-10 μM) prior to being stimulated with TGF-β (2 ng/ml). The experiment aimed to evaluate the phosphorylation levels of Smad2C, Smad2L, ERK1/2, the NOX p47phox subunit, ROS production, and the mRNA expression of CHST11 and CHSY1.

Results: Our research results indicated that atorvastatin inhibited TGF-β-stimulated CHSY1 and CHST11 mRNA expression. Further experiments showed that atorvastatin diminished TGF-β-stimulated ROS production and weakened TGF-β-stimulated phosphorylation of p47phox, ERK1/2, and Smad2L; however, we observed no effect on the TGF-β- Smad2C pathway.

Conclusion: These data suggest that atorvastatin demonstrates anti-atherogenic properties through the modulation of the ROS-ERK1/2-Smad2L signaling pathway. This provides valuable insight into the potential mechanisms by which atorvastatin exerts its pleiotropic effects against atherosclerosis.

Exposure to phosgene, a colourless poisonous gas, can lead to various health issues including eye irritation, a dry and burning throat, vomiting, coughing, the production of foamy sputum, difficulty in breathing, and chest pain. This systematic review aims to provide a comprehensive overview of the clinical manifestations and treatment of phosgene toxicity by systematically analyzing available literature. The search was carried out on various scientific online databases to include related studies based on inclusion and exclusion criteria with the use of PRISMA guidelines. The quality of the studies was assessed using the Mixed Methods Appraisal Tool (MMAT). Thirteen articles were included in this study after the screening process. Inhalation was found to be the primary health problem of phosgene exposure with respiratory symptoms such as coughing and dyspnea. Chest pain and pulmonary oedema were also observed in some cases. Furthermore, pulmonary crackle was the most common reported physical examination. Beyond respiratory tract health issues, other organs involvements such as cardiac, skin, eye, and renal were also reported in some studies. The symptoms can occur within minutes to hours after exposure, and the severity of symptoms depends on the amount of inhaled phosgene. The findings showed that bronchodilators can alleviate symptoms of bronchoconstriction caused by phosgene. Oxygen therapy is essential for restoring oxygen levels and improving respiratory function in cases of hypoxemia. In severe cases, endotracheal intubation and invasive mechanical ventilation are used for artificial respiration, along with the removal of tracheal secretions and pulmonary oedema fluid through suctioning as crucial components of supportive therapy.