NLRP3 concentration, oxidants, and antioxidants in plasma of endometriosis patients undergoing treatment with dienogest.

OBJECTIVE: NOD-like receptor pyrin domain-containing 3 (NLRP3) is a cytosolic multi-protein complex that induces inflammation and is negatively regulated by progesterone. Previous researches have reported abnormal induction of reactive oxygen species (ROS) and progesterone resistance in endometriosis (EM). Since progesterone regulates ROS level and, consequently, inflammation, our objective is to investigate whether dienogest (DNG) regulates NLRP3 and whether the regulation of NLRP3 inflammasome by DNG in the blood plasma of patients with EM can affect oxidant and antioxidant markers. METHODS: Plasma samples were obtained from control and EM patients experiencing pain symptoms to measure the level of NLRP3, oxidants, and antioxidants. Subsequently, these patients were given oral DNG 2 mg/day for six months for drug treatment. After six months, plasma samples were collected from the patients for re-examination. RESULTS: The findings indicate that DNG reduced NLRP3 concentration and oxidant production while increasing antioxidant production in blood plasma. By reducing NLRP3, DNG was able to alleviate inflammation and pain caused by inflammation in EM patients. CONCLUSION: In conclusion, the use of DNG in EM patients resulted in a decrease in NLRP3 concentration in the patient's plasma. Furthermore, this effect was enhanced by balancing oxidant/antioxidant levels, which may contribute to reducing inflammation associated with EM.

Does transcutaneous electrical nerve stimulation reduce the laparoscopic related shoulder pain?

OBJECTIVE: Although laparoscopic surgery is a good substitute for laparotomy in reducing postsurgical pain, many patients complain of shoulder pain after laparoscopic surgery and require pain-relief. Post-operative pain management leads to increased patient satisfaction. Transcutaneous Electrical Nerve Stimulation (TENS) is a non-pharmacological, noninvasive modality that reduces pain by activating the descending inhibitory systems in the central nervous system. Given the importance of decreasing shoulder pain after gynecological laparoscopy, the current study aimed to investigate the management of shoulder pain in these patients using TENS. METHODS: This was a retrospective case-control study. A total of 112 women aged 18-45 years who experienced shoulder pain due to gynecologic laparoscopic surgery were included in the study. Patients were divided into TENS and control groups. In the TENS group, TENS was used twice for 20 minutes each, but in the control group, the patients received regular treatment. Patients were evaluated at intervals of 2, 4, 8, 24, 48, and 72 hours after laparoscopy for shoulder pain score. RESULTS: The results showed a significant decrease in visual analog scale scores at 2, 4, and 8-hour in the TENS group compared with the control group. At 24 hours evaluation, although the pain was reduced, the difference was not significant. At 48- and 72-hour assessment, all patients in each group reported zero score for severity of pain. CONCLUSION: The findings suggest that TENS significantly reduces postoperative shoulder pain.

Evaluation of expression of biomarkers of PLAGL1 (ZAC1), microRNA, and their non-coding RNAs in patients with endometriosis.

Since the PLAGL1 (ZAC1) gene is expressed in the human endometrium. It may be involved in the etiology of endometrial disorders by its abnormal regulation and expression. This study aimed to investigate the Zac1 gene and related microRNA and LncRNA and its alterations in patients with endometriosis. Blood plasma, ectopic (EC) and eutopic (EU) endometrial samples were gathered from 30 patients with endometriosis and 30 healthy fertile women, and the Q-PCR technique was used to determine the expression level of Zac1 mRNA and microRNAs (miR-1271-5p, hsa-miR-490-3pin) and LncRNAs (TONSL-AS1 TONSL, KCNQ1OT1 KCNQ1). According to the results, the Zac1 gene and KCNQ1OT1 KCNQ1, TONSL-AS1 TONSL LncRNA expression were significantly decreased in the endometriosis group versus the control group (P < 0.05). MiR-1271-5p and hsa-miR-490-3pin microRNA expression were significantly raised in the endometriosis group as opposed to the control group (P < 0.05). In summary, this research for the first time revealed that identifying Zac1 expression provides us with new indicators for evaluating endometriosis.

TLR-1, TLR-2, and TLR-6 MYD88-dependent signaling pathway: A potential factor in the interaction of high-DNA fragmentation human sperm with fallopian tube epithelial cells.

OBJECTIVE: The DNA integrity of spermatozoa that attach to fallopian tube (FT) cells is higher than spermatozoa that do not attach. FT epithelial cells can distinguish normal and abnormal sperm chromatin. This study investigated the effects of sperm with a high-DNA fragmentation index (DFI) from men with unexplained repeated implantation failure (RIF) on the Toll-like receptor (TLR) signaling pathway in human FT cells in vitro. METHODS: Ten men with a RIF history and high-DFI and 10 healthy donors with low-DFI comprised the high-DFI (>30%) and control (<30%) groups, respectively. After fresh semen preparation, sperm were co-cultured with a human FT epithelial cell line (OE-E6/E7) for 24 hours. RNA was extracted from the cell line and the human innate and adaptive immune responses were tested using an RT2 profiler polymerase chain reaction (PCR) array. RESULTS: The PCR array data showed significantly higher TLR-1, TLR-2, TLR-3, TLR-6, interleukin 1α (IL-1α), IL-1ß, IL-6, IL-12, interferon α (IFN-α), IFN-ß, tumor necrosis factor α (TNF-α), CXCL8, GM-CSF, G-CSF, CD14, ELK1, IRAK1, IRAK2, IRAK4, IRF1, IRF3, LY96, MAP2K3, MAP2K4, MAP3K7, MAP4K4, MAPK8, MAPK8IP3, MYD88, NFKB1, NFKB2, REL, TIRAP, and TRAF6 expression in the high-DFI group than in the control group. These factors are all involved in the TLR-MyD88 signaling pathway. CONCLUSION: The MyD88-dependent pathway through TLR-1, TLR-2, and TLR-6 activation may be one of the main inflammatory pathways activated by high-DFI sperm from men with RIF. Following activation of this pathway, epithelial cells produce inflammatory cytokines, resulting in neutrophil infiltration, activation, phagocytosis, neutrophil extracellular trap formation, and apoptosis.

Effects of Au@Ag core-shell nanostructure with alginate coating on male reproductive system in mice.

Despite the widespread use of silver nanoparticles (NPs), these NPs can accumulate and have toxic effects on various organs. However, the effects of silver nanostructures (Ag-NS) with alginate coating on the male reproductive system have not been studied. Therefore, this study aimed to investigate the impacts of this NS on sperm function and testicular structure. After the synthesis and characterization of Ag-NS, the animals were divided into five groups (n = 8), including one control group, two sham groups (received 1.5 mg/kg/day alginate solution for 14 and 35 days), and two treatment groups (received Ag-NS at the same dose and time). Following injections, sperm parameters, apoptosis, and autophagy were analyzed by the TUNEL assay and measurement of the mRNA expression of Bax, Bcl-2, caspase-3, LC3, and Beclin-1. Fertilization rate was assessed by in vitro fertilization (IVF), and testicular structure was analyzed using the TUNEL assay and hematoxylin and eosin (H&E) staining. The results showed that the NS was rod-shaped, had a size of about 60 nm, and could reduce sperm function and fertility. Gene expression results demonstrated an increase in the apoptotic markers and a decrease in autophagy markers, indicating apoptotic cell death. Moreover, Ag-NS invaded testicular tissues, especially in the chronic phase (35 days), resulting in tissue alteration and epithelium disintegration. The results suggest that sperm parameters and fertility were affected. In addition, NS has negative influences on testicular tissues, causing infertility in men exposed to these NS.

Does Gold-Silver Core-Shell Nanostructure with Alginate Coating Induce Apoptosis in Human Lymphoblastic Tumoral (Jurkat) Cell Line?

Background: T-cell acute lymphoblastic leukemia (T-ALL) is known as an aggressive malignant disease resulting from the neoplastic alteration of T precursor cells. Although treatment with stringent chemotherapy regimens has achieved an 80% cure rate in children, it has been associated with lower success rates in adult treatment. Silver nanoparticles (Ag-NPs) have a toxic effect on human breast cancer cells, human glioblastoma U251 cells, and chronic myeloid leukemia cells in vitro. This study aimed to investigate the effect of Ag nanostructures (Ag-NSs) on Jurkat cells' viability and apoptosis. Methods: The Jurkat cell line was acquired. Following the synthesis Ag-NSs and their characterization, they were incubated with Jurkat cells at different doses for 24, 48, and 72 hours to determine the optimal time and dose. Two groups were examined: a control group with Jurkat cells without nanostructure maintained in the same medium as the cells in the treatment group without changing the medium, and a treatment group with cells treated with the Ag nanostructure solution at a dose of 75 µg/ml for 48 hours according to the MTT results. After 48 hours, the cells from the two groups were used for the q RT-PCR of the apoptotic genes (BAX, BCL-2, and CASPASE-3). Results: According to our results, the rod-shaped silver nanostructures had a size of about 50 nm, increased apoptotic markers, including BAX and CASPASE-3, and induced cell death. Conclusions: Ag-NSs have anticancer properties and can induce apoptosis of cells; therefore, they may be a potential candidate for the treatment of T-cell acute lymphoblastic leukemia.

Treatment of Ovarian Hyperstimulation Syndrome in a Mouse Model by Cannabidiol, an Angiogenesis Pathway Inhibitor.

Studies suggest that ovarian hyperstimulation syndrome (OHSS) can be treated by reducing the level of vascular endothelial growth factor (VEGF). However, due to the side effects of commercially available VEGF-reducing drugs, they can be ruled out as a suitable treatment for OHSS; therefore, researchers are looking for new medications to treat OHSS. This study is aimed at investigating the effects of cannabidiol (CBD) in an OHSS model and to evaluate its efficacy in modulating the angiogenesis pathway and VEGF gene expression. For this purpose, 32 female mice were randomly divided into four groups (eight mice per group): control group, group 2 with OHSS induction, group 3 receiving 32 nmol of dimethyl sulfoxide after OHSS induction, and group 4 receiving 30 mg/kg of CBD after OHSS induction. The animals' body weight, ovarian weight, vascular permeability (VP), and ovarian follicle count were measured, and the levels of VEGF gene and protein expression in the peritoneal fluid were assessed. Based on the results, CBD decreased the body and ovarian weights, VP, and corpus luteum number compared to the OHSS group (p < 0.05). The peritoneal VEGF gene and protein expression levels reduced in the CBD group compared to the OHSS group (p < 0.05). Also, CBD caused OHSS alleviation by suppressing VEGF expression and VP. Overall, CBD downregulated VEGF gene expression and improved VP in OHSS.