Search Results (5,757)

Background: Currently, the primary strategy for addressing polycystic ovarian syndrome (PCOS) involves lifestyle modifications, with a focus on weight loss. The purpose of this meta-analysis was to assess the impact of weight loss through dietary interventions on inflammatory status and hyperandrogenism in PCOS women. Methods: A comprehensive search was conducted to identify randomised controlled trials (RCTs) and cohort studies assessing the impact of diet-induced weight loss on circulating inflammatory markers (CRP, IL-6, IL-1β, TNF-α), androgens (testosterone, androstenedione), SHBG, and luteinising hormone (LH) in PCOS women. The quality and risk of bias of the included studies were assessed using the Cochrane Collaboration’s tool for RCTs and the Newcastle–Ottawa Scale for cohort studies. Data were entered into RevMan software v5.9 for the calculation of standard mean difference (SMD) and the 95% confidence interval (95%CI) of circulating inflammatory markers, androgens, and LH between baseline and post-weight loss values. Results: Eleven studies (n = 323) were eligible for the systematic review, of which nine (n = 286) were included in the meta-analysis. Pooled analysis of data revealed a statistically significant decrease in circulating CRP (SMD 0.39, 95%CI 0.22, 0.56; 9 studies, n = 286), IL-6 (SMD 0.37, 95%Cl, 0.12, 0.61; 3 Studies, n = 140), TNF-α (SMD 0.30, 95%Cl, 0.07, 0.53; 4 Studies, n = 162), androstenedione (SMD 0.36, 95%Cl, 0.13, 0.60; 4 studies, n = 147) and LH (SMD 0.30, 95% Cl, 0.09, 0.51; 5 studies, n = 197) after weight loss compared to baseline levels among PCOS women. A meta-analysis of five studies (n = 173) showed a statistically significant increase in circulating SHBG after weight loss compared to baseline levels (SMD −0.43, 95%Cl, −0.65, −0.21). Conclusions: These findings suggest that weight loss induced by dietary interventions seems to improve PCOS-related chronic inflammation and hyperandrogenism. The possible causative relationship between the improvement in inflammation and hyperandrogenism remains to be determined. Full article

Follicle development refers to the process in which the follicles in the ovary gradually develop from the primary stage to a mature state, and most primary follicles fail to develop normally, without forming a dense granular cell layer and cell wall, which is identified as atretic follicles. Granulosa cells assist follicle development by producing hormones and providing support, and interference in the interaction between granulosa cells and oocytes may lead to the formation of atretic follicles. Ferroptosis, as a non-apoptotic form of death, is caused by cells accumulating lethal levels of iron-dependent phospholipid peroxides. Healthy follicles ranging from 4 to 5 mm were randomly divided into two groups: a control group (DMSO) and treatment group (10 uM of ferroptosis inducer erastin). Each group was sequenced after three repeated cultures for 24 h. We found that ferroptosis was associated with atretic follicles and that the in vitro treatment of healthy follicles with the ferroptosis inducer erastin produced a phenotype similar to that of atretic follicles. Overall, our study elucidates that tRF-1:30-Gly-GCC-2 is involved in the apoptosis and ferroptosis of GCs. Mechanistically, tRF-1:30-Gly-GCC-2 inhibits granulosa cell proliferation and promotes ferroptosis by inhibiting Mitogen-activated protein kinase 1 (MAPK1). tRF-1:30-Gly-GCC-2 may be a novel molecular target for improving the development of atretic follicles in ovarian dysfunction. In conclusion, our study provides a new perspective on the pathogenesis of granulosa cell dysfunction and follicular atresia. Full article

Background/Objectives: The study aimed to evaluate the efficacy and safety of incorporating bevacizumab into the combination therapy of carboplatin and paclitaxel for epithelial ovarian cancer and other clinical applications. Methods: A systematic review was conducted following PRISMA guidelines using keyword searches in PubMed, Embase, Cochrane Library, CINAHL, ClinicalTrials.gov, and ICTRP until February 2024. Randomized controlled trials (RCTs) comparing carboplatin and paclitaxel with and without bevacizumab in ovarian cancer patients were included. Efficacy outcomes were overall survival (OS) and progression-free survival (PFS), as described by hazard ratios (HRs). Safety outcomes were analyzed with risk ratios (RRs) for 16 adverse events. Results: Seven RCTs (n = 5110) were included. The combination with bevacizumab significantly improved PFS (HR: 0.73; 95% confidence interval: 0.58, 0.92; p = 0.008). The chemotherapy group receiving bevacizumab with carboplatin and paclitaxel showed a significantly higher incidence of hypertension, non-CNS bleeding, thromboembolic events, GI perforation, pain, and proteinuria. Conclusions: The combination of carboplatin, paclitaxel, and bevacizumab improves PFS compared to the regimen without bevacizumab, but it raises significant safety concerns. Clinical management should consider adverse event prevention by vigilantly monitoring blood pressure, signs and symptoms of bleeding, thromboembolism, GI perforation, and pain to balance the therapeutic benefits with the potential risks of this combination therapy. Full article

Overexpression and aberrant activation of signal transducer and activator of transcription 3 (STAT3) contribute to tumorigenesis, drug resistance, and tumor-immune evasion, making it a potential cancer therapeutic target. BP1003 is a neutral liposome incorporated with a nuclease-resistant P-ethoxy antisense oligodeoxynucleotide (ASO) targeting the STAT3 mRNA. Its unique design enhances BP1003 stability, cellular uptake, and target affinity. BP1003 efficiently reduces STAT3 expression and enhances the sensitivity of breast cancer cells (HER2⁺, triple negative) and ovarian cancer cells (late stage, invasive ovarian cancer) to paclitaxel and 5-fluorouracil (5-FU) in both 2D and 3D cell cultures. Similarly, ex vivo and in vivo patient-derived models of pancreatic ductal adenocarcinoma (PDAC) show reduced tissue viability and tumor volume with BP1003 and gemcitabine combination treatments. In addition to directly affecting tumor cells, BP1003 can modulate the tumor microenvironment. Unlike M1 differentiation, monocyte differentiation into anti-inflammatory M2 macrophages is suppressed by BP1003, indicating its potential contribution to immunotherapy. The broad anti-tumor effect of BP1003 in numerous preclinical solid tumor models, such as breast, ovarian, and pancreatic cancer models shown in this work, makes it a promising cancer therapeutic. Full article

Centrosomal Protein 55 (CEP55) exhibits various oncogenic activities; it regulates the PI3K-Akt-pathway, midbody abscission, and chromosomal instability (CIN) in cancer cells. Here, we analyzed the mechanism of how CEP55 controls CIN in ovarian and breast cancer (OvCa) cells. Down-regulation of CEP55 reduced CIN in all cell lines analyzed, and CEP55 depletion decreased spindle microtubule (MT)-stability in OvCa cells. Moreover, recombinant CEP55 accelerated MT-polymerization and attenuated cold-induced MT-depolymerization. To analyze a potential relationship between CEP55-controlled CIN and its impact on MT-stability, we identified the CEP55 MT-binding peptides inside the CEP55 protein. Thereafter, a mutant with deficient MT-binding activity was re-expressed in CEP55-depleted OvCa cells and we could show that this mutant did not restore reduced CIN in CEP55-depleted cells. This finding strongly indicates that CEP55 regulates CIN by controlling MT dynamics. Full article

Feline calicivirus (FCV), an important model for studying the biology of the Caliciviridae family, encodes the leader of the capsid (LC) protein, a viral factor known to induce apoptosis when expressed in a virus-free system. Our research has shown that the FCV LC protein forms disulfide bond-dependent homo-oligomers and exhibits intrinsic toxicity; however, it lacked a polybasic region and a transmembrane domain (TMD); thus, it was initially classified as a non-classical viroporin. The unique nature of the FCV LC protein, with no similarity to other proteins beyond the Vesivirus genus, has posed challenges for bioinformatic analysis reliant on sequence similarity. In this study, we continued characterizing the LC protein using the AlphaFold 2 and the recently released AlphaFold 3 artificial intelligence tools to predict the LC protein tertiary structure. We compared it to other molecular modeling algorithms, such as I-Tasser’s QUARK, offering new insights into its putative TMD. Through exogenous interaction, we found that the recombinant LC protein associates with the CrFK plasmatic membrane and can permeate cell membranes in a disulfide bond-independent manner, suggesting that this interaction might occur through a TMD. Additionally, we examined its potential to activate the intrinsic apoptosis pathway in murine and human ovarian cancer cell lines, overexpressing survivin, an anti-apoptotic protein. All these results enhance our understanding of the LC protein’s mechanism of action and suggest its role as a class-I viroporin. Full article

Endometriosis, an inflammatory disease primarily affecting the pelvis and peritoneum, manifests with pelvic pain, dysmenorrhea, dyschezia, dyspareunia, and infertility. Despite its ubiquity, the management of endometriosis is challenging due to its heterogeneous presentation, limitations in diagnostic methods, variable therapeutic responses, and personal and socio-cultural impact on quality of life. This review attempts to consolidate the current literature on endometriosis occurring during and beyond menopause, and to present details regarding management strategies that take into account individual outcomes and goals when managing this condition. The topics included in this review are the clinical features and differential diagnosis of pelvic pain in postmenopausal patients, imaging considerations, serum and laboratory biomarkers, indications for surgery, the principles of hormone replacement therapy, the de novo development of endometriosis after menopause, and malignant transformation. Each topic includes a summary of the current literature, utilizing clinical research, case reports, and expert opinion. Despite a better understanding of the impact of endometriosis beyond menopause, there are many limitations to this condition, specifically with regard to cancer risk and indications for surgery. The existing evidence supports the use of shared decision making and the incorporation of patient preferences in guiding clinical management. Future research endeavors must shed light on the natural history of postmenopausal endometriosis through longitudinal studies in order to foster a deeper understanding of its complicated disease course across women’s lifespans. Full article

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)_n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)_n (n = 1–4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum stability at N/P ≥ 40. The synthesized conjugates, with a diameter of <100 nm, formed nano-complexes with siRNA and exhibited a stable range of zeta potential values (13–18 mV at N/P = 40). Confocal microscopy and flow cytometry analysis provided qualitative and quantitative evidence of a successful cellular internalization of siRNA. The peptides oleyl-(WRH)₃ and oleyl-(WRH)₄ showed ~60% and ~75% cellular uptake of siRNA, respectively, in both MDA-MB-231 and SK-OV-3 cells. Western blot analysis of oleyl-(WRH)₄ demonstrated effective silencing of the STAT-3 gene, with ~75% silencing in MDA-MB-231 cells and ~45% in SK-OV-3 cells. Full article

Background: RAD51C and RAD51D are crucial in homologous recombination (HR) DNA repair. The prevalence of the RAD51C and RAD51D mutations in breast cancer varies across ethnic groups. Associations of RAD51C and RAD51D germline pathogenic variants (GPVs) with breast and ovarian cancer predisposition have been recently reported and are of interest. Methods: We performed multi-gene panel sequencing to study the prevalence of RAD51C and RAD51D germline mutations among 3728 patients with hereditary breast and/or ovarian cancer (HBOC). Results: We identified 18 pathogenic RAD51C and RAD51D mutation carriers, with a mutation frequency of 0.13% (5/3728) and 0.35% (13/3728), respectively. The most common recurrent mutation was RAD51D c.270_271dupTA; p.(Lys91Ilefs*13), with a mutation frequency of 0.30% (11/3728), which was also commonly identified in Asians. Only four out of six cases (66.7%) of this common mutation tested positive for homologous recombination deficiency (HRD). Conclusions: Taking the family studies in our registry and tumor molecular pathology together, we concluded that this relatively common RAD51D variant showed incomplete penetrance in our local Chinese community. Personalized genetic counseling emphasizing family history for families with this variant, as suggested at the UK Cancer Genetics Group (UKCGG) Consensus meeting, would also be appropriate in Chinese families. Full article

(1) Background: Few studies focus on the development of obesity as a chronic disease as opposed to an acute condition. The “general purpose” C3H/HeJ (C3H) mouse strain is an alternative model for obesity development with regards to sex disparities and non-predisposed populations over time. (2) Methods: In this study, 64 female and 64 male C3H mice were separated into two groups (n = 32) and maintained on a control or high-fat diet (HFD) for up to 18 months. At 6-month intervals, a cross-sectional cohort (n = ~8) was censored for evaluation. The mice were monitored for change in total, lean and fat mass, survivability, and tumor incidence. (3) Results: Both sexes in the C3H mouse strain developed diet-induced obesity (DIO). An increase in total mass consistent with a HF diet was observed in both female and male C3H mice. Survivorship at 18 months was the highest in the HF-diet-fed males (~62%) and lowest in the males fed the control diet (~19%). Females showed survivability at ~40%, regardless of diet. Cancer development increased more notably in the males with the HF diet and showed sex bias for liver cancer (males) and ovarian cancer (females) incidence with age. (4) Conclusions: This study establishes a baseline for future use of C3H mice as a strong model for studying obesity as a chronic disease, in both sexes, and as long-term model for age-related diet-induced obesity and cancer development. Full article

The present study aims to evaluate the effect of Sepia pharaonis ink on insulin resistance in PCOS-induced mice. Treatment with sepia ink in dehydroepiandrosterone (DHEA)-induced PCOS mice at various doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg body weight mitigated the insulin resistance in the study groups with decreased concentration of testosterone and increased concentrations of estrogen and progesterone compared to the PCOS group tested by ELISA. The histopathological analysis and restoration of glucose analysis showed a significant reduction in treatment groups. Reduced expression of insulin resistance genes like androgen receptor (AR), insulin receptor substrate 1 (IRS-1), and insulin-like growth factor1 (IGF-1) by qRT-PCR indicate a positive impact of sepia ink in alleviating the symptoms associated with PCOS. Taken together, the results of this study indicate sepia ink as a promising therapeutic intervention and a possible drug target for insulin resistance in diabetes and gynecological disorders like PCOS. Full article

This study was designed to investigate the effects of vitamin D and mannitol in an experimental rat ovarian torsion model. Thirty-two female Wistar albino rats were randomly classified as group 1: (sham), group 2: (detorsion), group 3: (detorsion + mannitol), group 4: (detorsion + vitamin D) and group 5: (detorsion + mannitol + vitamin D) (for each group n = 8). All groups were subjected to bilateral adnexal torsion for 2 h except for group 1. Bilateral adnexal detorsion was performed in all groups except for group 1. Groups 3 and 5 intraperitoneally received the injection of mannitol at a dose of 0.3 mg/kg 30 min before detorsion. Also, the group’s 4 and 5 orally received vitamin D in a dose of 500 IU/kg/day for two weeks before torsion. Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and proliferating cell nuclear antigen (PCNA) levels were analyzed. According to the histopathological analyses, ovarian tissue damage and follicle counting were evaluated. TOS, OSI and histopathologic score values of ovarian tissue were significantly lower in group 5 than groups 2, 3 and 4 (p < 0.05). The PCNA level was significantly higher in group 5 than in groups 2, 3 and 4 (p < 0.05). A strong negative correlation was found between OSI and PCNA in groups 2, 3, 4 and 5 (r = −0.92, p = 0.01; r = −0.98, p < 0.0001; r = −0.98, p < 0.0001 and r = −0.96, p = 0.0002, respectively). The numbers of primordial follicles in group 5 (p < 0.001) and primary follicles in group 4 (p < 0.001) were significantly higher when compared to group 2. Based on the results of this study, it could be suggested that combination treatment of mannitol with vitamin D is more effective in reversing tissue damage induced by ischemia–reperfusion (I/R) injury in the ovarian torsion model than administration of only an agent. Full article

Chronic stress has become a major problem that endangers people’s physical and mental health. Studies have shown that chronic stress impairs female reproduction. However, the related mechanism is not fully understood. P2X7 receptor (P2X7R) is involved in a variety of pathological changes induced by chronic stress. Whether P2X7R is involved in the effect of chronic stress on female reproduction has not been studied. In this study, we established a chronic restraint stress mouse model and chronic cold stress mouse model. We found that the number of corpora lutea was significantly reduced in the two chronic stress models. The number of corpora lutea indirectly reflects the ovulation, suggesting that chronic stress influences ovulation. P2X7R expression was significantly increased in ovaries of the two chronic stress models. A superovulation experiment showed that P2X7R inhibitor A-438079 HCL partially rescued the ovulation rate of the two chronic stress models. Further studies showed that activation of P2X7R signaling inhibited the cumulus expansion and promoted the expression of NPPC in granulosa cells, one key negative factor of cumulus expansion. Moreover, sirius red staining showed that the ovarian fibrosis was increased in the two chronic stress models. For the fibrosis-related factors, TGF-β1 was increased and MMP2 was decreased. In vitro studies also showed that activation of P2X7R signaling upregulated the expression of TGF-β1 and downregulated the expression of MMP2 in granulosa cells. In conclusion, P2X7R expression was increased in the ovaries of the chronic restraint-stress and chronic cold-stress mouse models. Activation of P2X7R signaling promoted NPPC expression and cumulus expansion disorder, which contributed to the abnormal ovulation of the chronic stress model. Activation of P2X7R signaling is also associated with the ovarian fibrosis changes in the chronic stress model. Full article

ADIPOQ plays a crucial role in regulating the reproductive system, but there are few reports on the effects of ADIPOQ on ovarian in dairy cows. Previous studies have verified the presence of a 67-bp mutation in the promoter region of the ADIPOQ gene. Hence, we employed ovarian tissues (n = 2111) and blood samples (n = 108) from Chinese Holstein cows as experimental samples to examine the association between ADIPOQ promoter variants and ovarian traits. We extracted DNA from these samples and conducted genetic typing identification on each sample using advanced techniques like PCR and agarose gel electrophoresis. Consequently, the DD, ID, and II genotypes were discovered. and it has been observed that the mutation frequency of this locus is low in the Chinese Holstein cow. Importantly, the correlational analysis unveiled a significant relationship (p < 0.05) between the weight of ovaries in late estrus and the width of ovaries during the estrus interval with the mutation. Result of the RT-PCR revealed that the ID genotype partially diminished the expression of the ADIPOQ gene. The results of this study suggest that the identified variable duplication could serve as a potential genetic marker for enhancing the ovarian traits of Chinese Holstein cows. Full article

The present study evaluates the effect of including microencapsulated hot chili pepper (MHCP) in the diet of crossbred dairy cows on the volume and quality of milk and on ovarian morphofunctionality. Twenty-four crossbred females in their lactating period were used. The cows were divided into two experimental groups, a control (CT) and an MHCP -supplemented group (CP) given 1 g a day per animal of microencapsulated hot chili in concentrate for 42 days. Over seven weeks of daily milk production was measured, and sample milk was collected weekly for composition analysis. Animals were subject to an ovulation synchronization protocol on day 0 (D0), and an intravaginal progesterone (P4) implant, estradiol benzoate, and prostaglandin (PGF2α) were administered. On D8, the P4 implant was removed and PGF2α, equine chorionic gonadotropin, and estradiol cypionate were administered to the animals. The ovarian dynamics were evaluated in B mode and color Doppler. There were significant differences (p < 0.05) in the group X time interaction, the volume of milk produced, and the amount in kg/day of milk components. There was a higher percentage of vascularization in the preovulatory follicle in the CP group (p ≥ 0.10). The findings show that the inclusion of MHCP in the diet of dairy cows does influence their milk production and reproduction. Full article