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.

Does laparoscopic treatment of deep endometriosis improve sexual dysfunction.

Background: Endometriosis is one of the common gynecological problems during the reproductive years, affecting the quality of life, fertility, and sexual function of women. It is known that sexual dysfunction and quality of life are interrelated. Therefore, this study aimed to evaluate the effect of resection of endometriosis lesions via laparoscopic surgery on the improvement of sexual dysfunction in women with endometriosis. Methods: This clinical trial was performed on 30 patients with endometriosis. The Female Sexual Function Index, Endometriosis Health Profile-30, and Visual Analog Scale were completed for the patients before laparoscopic surgery and three, six, and 12 months after surgery. The results were examined and compared before and after the intervention using the ANOVA test. Results: The present results showed that the mean pain score of the patients (dysmenorrhea, dyspareunia, and pelvic pain) was significant after laparoscopic surgery (P<0.005). The female sexual function improved after laparoscopic surgery compared to the preoperative phase, and changes in the domains of psychological stimulation, humidity, and sexual orgasm were significant (P<0.005). Moreover, the female quality of life scores increased in all dimensions compared to the preoperative phase, although these improvements were not statistically significant. Conclusion: The present results revealed that laparoscopic surgery is an effective treatment, leading to a considerable improvement in female sexual function.

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.

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.

Leukemia inhibitory factor's effect on the growth and survival of sheep's follicles of ovarian tissue during vitrification.

One of the experimental programs for fertility protection in women includes protective cryopreservation. Vitroficasion of ovarian tissue is one of the protective cryopreservation methods that use high concentrations of antifreeze and faster cooling. To reduce its complications, LIF (Leukemia inhibitory factor) was used as a pretreatment in this study. In this study, the ovaries were randomly divided into 8 groups. In NCN (without pretreatment and LIF in culture media), NCP (without pretreatment and with LIF in culture media), PCP (with pretreatment and LIF in culture media), and PCN (with pretreatment and without LIF in culture media) groups, vitrification and reversal were not performed. In the groups NVN (without pretreatment and LIF in culture media), NVP (without pretreatment and with LIF in culture media) PV, PVP (with pretreatment and LIF in culture media), and PVN (with pretreatment and without LIF in culture medium) groups, vitrification and tissue reversal were performed. All groups were cultured and histological, cellular, and molecular evaluations were performed. The results of the present study showed that LIF in the culture medium reduced the number of abnormal, primordial, primary, and secondary follicles, and DNA breakage compared to the group without LIF (P < 0.05) and increases the growth of follicles and expression of GDF9, BMP, AMH, KITLG genes (P < 0.05). The use of LIF pretreatment before vitrification and melting of sheep ovary tissue in its culture medium reduces the damage caused by it and increases the growth and development of ovarian follicles while maintaining their function.

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.

Molecular signature of immunological mechanism behind impaired endometrial receptivity in polycystic ovarian syndrome

ABSTRACT Objective: Despite the treatment of anovulation, infertility is still one of the main complications in PCOS women during reproductive age, which appears to be mainly due to impaired uterine receptivity. This study investigated the transcriptome profiles of endometrium in PCOS patients and healthy fertile individuals as the control group. Material and methods: Total mRNA was extracted from endometrial tissues of PCOS patients (n = 12) and healthy fertile individuals (n = 10) during the luteal phase. After cDNA synthesis, PCR array was performed using Human Female Infertility RT² Profiler PCR Array kit (Qiagen, Cat. No: PAHS-164Z) for evaluating expression of 84 genes contributing to the female infertility. Results: PCR Array data analysis identified significantly greater expression of CSF, IL11, IL15, IL1r1, IL1b, TNF, LIF, TNFRSF10B, TGFβ, C3, ITGA4 (Cd49d), SPP1, and Calca in PCOS women than in controls (P < 0.05). However, the expression of LIFR, C2, CD55, CFD, CALCA, LAM1, LAMC2, MMP2, MMP7, MMP9, ESR, SELL, ITGB3, and VCAM1 was significantly lower in PCOS group than in controls (P < 0.05). The results revealed dysregulation of immune-inflammatory molecules, complement activation and downregulation of IGF-I as well as adhesion molecules in PCOS group. Conclusion: The findings of this study indicated some potential causes of reduced receptivity of endometrium thus compromising the fertility in PCOS patients.

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.

Toxicity of silver nanoparticles on endometrial receptivity in female mice.

Nanoparticles (NPs) have many toxic effects on fertility and can prevent successful implantation by affecting the maternal uterine tissue. Herein, by deploying 30 female NMRI mice, the effect of silver NPs on the endometrium and implantation has been investigated. Using spherical silver NPs of a diameter of 18-30 nm at doses of 2 and 4 mg/kg, mice in two groups were treated. Then, female mice mated with male mice. Endometrial tissue was extracted 4.5 days later. On the fourth day of pregnancy, the mice were anesthetized and blood samples were taken from the heart; furthermore, endometrial tissue was isolated and used for molecular tests, inductively coupled plasma, and examination of pinopods. The results revealed that the levels of interleukin 6 (IL-6) and IL-1ß and the accumulation of NPs in endometrial tissue in the group receiving NPs at a dose of 4 mg/kg had a major increase relative to the other two groups (p < 0.05); the group receiving a dose of 4 mg/kg exhibited a decrease in pinopods and microvillus compared with the other two groups. According to the results, NPs can reach the endometrium, suggesting that caution should be exercised due to serious exposure to NPs throughout pregnancy.

The role of sperm in inducing genomic changes in the implantation: An experimental study.

Endometrial receptivity and implantation are important topics in reproductive sciences. No evidence was found to support sperm involvement in endometrial receptivity and its associated factors. This study aimed to explore the effect of the normal human spermatozoa-endometrium cell interaction in regulating genes in the endometrial receptivity pathway. Semen samples were collected from a healthy and fertile man; then, they were incubated with endometrial cells for 24 hr and considered as the sperm group. A group was cultured without spermatozoa and considered as a control group. About 24 hr later, cells were collected from the bottom of the culture dish. The expressions of the VEGF, FGF2, HBEGF, LIFR, EGF, LIF, MUC1, HOXA10, CSF and PGR genes were evaluated in the two groups. Statistical analysis was performed using an independent sample test. Compared with the control group, in the sperm group, the mRNA levels of PGR (p = .0451), VEGF (p = .0101), HBEGF (p = .0163), EFG (p = .0339), FGF2 (p = .012), LIF (p = .0324), LIFR (p = .0321) and HOXA10 (p = .0098) were significantly upregulated. The results showed that there is a need for the interaction between spermatozoa and endometrium for implantation and can be used for preparing uterine in in vitro fertilisation cycles.

Design and evaluation of a novel nanodrug delivery system for reducing the side effects of clomiphene citrate on endometrium.

BACKGROUND: Stimulation of ovulation with clomiphene citrate can cause side effects on endometrial receptivity. Formulation with nano-size may be an alternative therapy for women with ovulatory disorders. In this study, we investigated sustained-release clomiphene citrate by using Phosal-based formulation (PBF) and evaluate its decreased side effect on the endometrial receptivity. METHODS: In the in-vitro study, CC loaded PBF was analyzed using Zetasizer, Fourier-transform infrared spectroscopy (FTIR), and Transmission electron microscopy (TEM). In the in-vivo study, 24 female mice were randomly divided into three groups: CC (5 mg/kg), CC/PBF (5 mg/kg) and SS (1 ml) daily administered and injected with 5 IU HCG and mated after two days. At day 4.5, pregnant mice were euthanized and endometrial tissue was extracted for quantitative polymerase chain reaction (Q-PCR) analysis. RESULTS: The optimized PBF contained Phosal 50PG/glycerol in a 2:8 ratios (w/w) and the particle size of optimum formulation was 67 ± 0.30551 nm and the release of CC from CC-containing PBF was slightly faster in the first 24 h; wherein, 29% of CC was released, and 76% of CC was released up to 120 h. The mRNA levels of leukemia inhibitory factor (LIF), leukemia inhibitory factor receptor alpha (LIFR), HOXA10, Heparin-binding epidermal growth factor (HB-EGF), and epidermal growth factor (EGF) were significantly upregulated and MUC1 and PGR mRNA levels were significantly downregulated in the CC-containing PBF-treated animals compared with only CC group (P < 0.05). CONCLUSION: Sustained release formulation of clomiphene citrate increased its targeting efficiency and improved the impact of the CC on implantation. Graphical abstract A new Phosal Based Formulation (PBF) was designed to decrease the side effects of Clomiphene citrate (CC) on endometrium. This drug formulation could react better during implantation by increasing the expression of genes involved in implantation. The in vivo study demonstrated that the CC-containing PBF in mice has a significantly higher endometrial receptivity, compared with the suspension.

The synergistic effect of Paeonia spp and Glycyrrhiza glabra on polycystic ovary induced in mice.

Paeonia spp and Glycyrrhiza glabra were traditionally used to treat female hormonal problems. This study was conducted to investigate the effect of root extract of these plants on ovarian follicles after induction of polycystic ovary syndrome (PCOS). 25-day-old NMRI mice were divided into 4 groups: control, dehydroepiandrosterone (DHEA), and DHEA plus 50mg/kg and 100mg/kg plant extract. Animals in the DHEA group received a daily dose of 6mg/100 g.b.w dissolved in 0.05ml sesame oil for 20 consecutive days through subcutaneous injection (0.2ml); the control group received sesame oil and saline only through i.p; and the other two groups received herbal extracts through i.p. At the end, blood samples were taken to examine hormonal changes and isolate ovarian tissue. There was a significant difference in the level of testosterone and fasting insulin between the polycystic group and treatment groups (50 and 100mg/kg doses). The results showed a significant difference between the control and DHEA treated groups in terms of the number of graph and primary follicles (P<0.05). The results of this study indicated that the mixture of paeonia spp and glycyrrhiza glabra extracts with the administered dosage had positive effects on the status of follicles in the ovaries in polycystic ovary syndrome.

Health Concerns of Various Nanoparticles: A Review of Their in Vitro and in Vivo Toxicity.

Nanoparticles (NPs) are currently used in diagnosis and treatment of many human diseases, including autoimmune diseases and cancer. However, cytotoxic effects of NPs on normal cells and living organs is a severe limiting factor that hinders their use in clinic. In addition, diversity of NPs and their physico-chemical properties, including particle size, shape, surface area, dispersity and protein corona effects are considered as key factors that have a crucial impact on their safe or toxicological behaviors. Current studies on toxic effects of NPs are aimed to identify the targets and mechanisms of their side effects, with a focus on elucidating the patterns of NP transport, accumulation, degradation, and elimination, in both in vitro and in vitro models. NPs can enter the body through inhalation, skin and digestive routes. Consequently, there is a need for reliable information about effects of NPs on various organs in order to reveal their efficacy and impact on health. This review covers the existing knowledge base on the subject that hopefully prepares us better to address these challenges.

Sub-chronic toxicity of gold nanoparticles in male mice.

BACKGROUND: Gold nanoparticles have many industrial applications; moreover, they are photothermic agents for clinical treatment of cancer. This study was provided to investigate the effects associated with different doses of applied gold nanoparticles by injection and contact procedures on the alterations of the serum levels and certain factors in male mice. MATERIALS AND METHODS: 72 male mice were randomly assigned into two protocols in terms of touching and injection. The injection protocol was included of five groups: Sham, control, 25, 50, and 100 ppm. They received gold nanoparticles at 25, 50, and 100 ppm concentrations administered in form of 0.3 ml/day for the period of 14 days and that of touching protocol were received 0.2 ml/day gold nanoparticles. Blood sample of which was taken to measure the serum level of creatine kinase phosphate, fasting blood, creatinine, albumin, blood urea nitrogen and eventually, the kidney was dissected for the intent of pathological analysis. RESULTS: The serum level of creatine kinase phosphate and fasting blood sugar at middle dose was significantly different (P ≤ 0.05) in touching protocol. In both protocols, the serum level of creatinine in high and medium doses showed a significant difference (P < 0.05) associated with the treated group. In the touching method, in high and medium doses administered to the treated group, the alteration was significant (P ≤ 0.05). In the both protocols, the serum level of albumin in high and medium doses of the treated group showed significant difference (P < 0.05). Thus, the gold nanoparticles could result in undesirable effects upon kidney tissue. CONCLUSION: The result of this study indicated that the administration of gold nanoparticles by touching method was more effective on the serum levels of these factors than that of injection method.