Journal of Ovarian Research最新文献

{"title":"Identification of three subtypes of ovarian cancer and construction of prognostic models based on immune-related genes.","authors":"Wen Gao, Hui Yuan, Sheng Yin, Renfang Deng, Zhaodong Ji","doi":"10.1186/s13048-024-01526-w","DOIUrl":"10.1186/s13048-024-01526-w","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy has revolutionized the treatment of ovarian cancer (OC), but different immune microenvironments often constrain the efficacy of immunotherapeutic interventions. Therefore, there is an imperative to delineate novel immune subtypes for development of efficacious immunotherapeutic strategies.</p><p><strong>Methods: </strong>The immune subtypes of OC were identified by consensus cluster analysis. The differences in clinical features, genetic mutations, mRNA stemness (mRNAsi) and immune microenvironments were analyzed among subtypes. Subsequently, prognostic risk models were constructed based on differentially expressed genes (DEGs) of the immune subtypes using weighted correlation network analysis.</p><p><strong>Results: </strong>OC patients were classified into three immune subtypes with distinct survival rates and clinical features. Different subtypes exhibited varying tumor mutation burdens, homologous recombination deficiencies, and mRNAsi levels. Significant differences were observed among immune subtypes in terms of immune checkpoint expression and immunogenic cell death. Prognostic risk models were validated as independent prognostic factors demonstrated great predictive performance for survival of OC patients.</p><p><strong>Conclusion: </strong>In this study, three distinct immune subtypes were identified based on gene sets related to vaccine response, with the C2 subtype exhibiting significantly worse prognosis. While no statistically significant differences in tumor mutation burden (TMB) were observed across the three subtypes, the homologous recombination deficiency (HRD) score and mRNA stemness index (mRNAsi) were notably elevated in the C2 group compared to the others. Immune infiltration analysis indicated that the C2 subtype may have an increased presence of regulatory T (Treg) cells, potentially contributing to a more favorable response to combination therapies involving PARP inhibitors and immunotherapy. These findings offer a precision medicine approach for tailoring immunotherapy in ovarian cancer patients. Moreover, the C3 subtype demonstrated significantly lower expression levels of immune checkpoint genes, a pattern validated by independent datasets, and associated with a better prognosis. Further investigation revealed that the immune-related gene FCRL5 correlates with ovarian cancer prognosis, with in vitro experiments showing that it influences the proliferation and migration of the ovarian cancer cell line SKOV3.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"208"},"PeriodicalIF":3.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MECOM Locus classical transcript isoforms affect tumor immune microenvironment and different targets in ovarian cancer.","authors":"Ning Lan, Shuheng Bai, Min Chen, Xuan Wang, Zhaode Feng, Ying Gao, Beina Hui, Wen Ma, Xiangxiang Zhang, Fengyuan Hu, Wanyi Liu, Wenyang Li, Fang Wu, Juan Ren","doi":"10.1186/s13048-024-01522-0","DOIUrl":"10.1186/s13048-024-01522-0","url":null,"abstract":"<p><p>The MECOM locus is a gene frequently amplified in high-grade serous ovarian carcinoma (HGSOC). Nevertheless, the body of research examining the associations among MECOM transcripts, patient prognosis, and their role in modulating the tumor immune microenvironment (TIME) remains sparse, particularly in large cohorts. This study assessed the expression of MECOM transcripts in 352 HGSOC patients and 88 normal ovarian tissues from the combined GTEx/TCGA database. Using resources such as the UCSC Genome Browser, Ensembl, and NextProt, two transcripts corresponding to classical protein isoforms from MECOM were identified. Cox proportional hazards regression analysis, Kaplan-Meier survival curves, and a comprehensive TIME evaluation algorithm were employed to elucidate the connections between the expression levels of these transcripts and both patient prognosis and TIME status. Chromatin Immunoprecipitation sequencing (ChIP-seq) data for the two protein isoforms, as well as RNA sequencing data post-targeted silencing, were analyzed to identify potential regulatory targets of the different transcription factors. Elevated expression of the MECOM isoform transcripts was correlated with poorer survival in HGSOC patients, potentially through the modulation of cancer-associated fibroblasts (CAFs) and immunosuppressive cell populations. In contrast, higher levels of EVI1 isoform transcripts were linked to enhanced survival, possibly due to the regulation of CD8⁺ T cells, macrophages, and a reduction in the expression of JUN protein, or its DNA-binding activity on downstream genes. Diverse protein isoforms derived from MECOM were found to differentially affect the survival and tumor development in ovarian cancer patients through specific mechanisms. Investigating the molecular mechanisms underlying disease pathogenesis and identifying potential drug target proteins at the level of splice variant isoforms were deemed crucial.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"207"},"PeriodicalIF":3.8,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A preliminary study on the effects of Xiang Shao granules on reproductive endocrinology in drugged ovariectomised rats.","authors":"Qiucheng Jia, Huimin Tang, Xiangmei Zhong, Wanying Chen, Yihan Wu, Weiwei Wei, Hong Zheng, Jiming Chen","doi":"10.1186/s13048-024-01531-z","DOIUrl":"https://doi.org/10.1186/s13048-024-01531-z","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To establish a rat model of pharmacological ovariectomy by GnRH-a injection and to preliminarily investigate the reproductive endocrine effects of Xiangshao granules on pharmacologically ovariectomized rats.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A rat model of pharmacological ovariectomy was established by injecting female rats with Gonadotropin-releasing hormone agonist(GnRH-a).The rats were randomly divided into four groups: GnRH-a injected saline group (GnRH-a + NS); GnRH-a injected oestradiol group (GnRH-a + E2); GnRH-a injected Xiangshao granule group (GnRH-a + Xiangshao), and the control group of saline-injected rats (NS + NS). The number of rats per group was 6.According to observations of the rats' vaginal smears, modelling was determined as successful. Then corresponding drug gavage intervention was administered for 28 days, and rat body weight and anal temperature were measured every other day to adjust the drug intervention amount according to body weight changes. Plasma sex hormone levels (E2, FSH, LH), uterine weight, uterine index and endometrial histomorphological changes, ovarian weight, and ovarian index and ovarian histomorphological changes were measured in each group after the gavage.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;(1) Plasma sex hormone levels (E2, FSH, LH) of the GnRH-a + NS, GnRH-a + E2, and GnRH-a + Xiangshao granule groups were significantly lower than the NS + NS group (P &lt; 0.001), while the E2 level of the GnRH-a + E2 group was higher than that of the GnRH-a + Xiangshao granule group (P &lt; 0.05). The FSH level of the GnRH-a + E2 group was significantly lower than that of the GnRH-a + Xiangshao granule group (P &lt; 0.05). The LH level of the GnRH-a + E2 group was significantly lower than those in the GnRH-a + NS and GnRH-a + Xiangshao granule groups (P &lt; 0.001, P = 0.001). The LH and FSH levels of the GnRH-a + NS and GnRH-a + Xiangshao granule groups were not significantly different (P &gt; 0.05). (2) Compared with the NS + NS group, the uterine weight and uterine index, and ovarian weight and ovarian index of GnRH-a injected rats in each model all significantly decreased (P &lt; 0.001). Between the groups, the uterine weight and uterine index, and ovarian weight and ovarian index of GnRH-a + E2 and GnRH-a + Xiangshao granule groups were all significantly higher than those of the GnRH-a + NS group (P &lt; 0.001, P &lt; 0.05). The uterine weight and uterine index, and ovarian weight and ovarian index of the GnRH-a + E2 group increased compared with the GnRH-a + Xiangshao granule group (P &lt; 0.05). (3) Compared with the NS + NS group, the number of primordial follicles of the GnRH-a + NS, GnRH-a + E2, and GnRH-a + Xiangshao granule groups increased significantly and the number of growing follicles and mature follicles significantly decreased. (4) Rats' uterine wall of the NS + NS and various GnRH-a groups was significantly thinner, with the endothelial layer atrophied, while the uterine wall of the GnRH-a + E2 an","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"206"},"PeriodicalIF":3.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin increases superoxide dismutase 2 (SOD2) levels and improves rat ovarian graft function after transplantation.","authors":"Karla Krislane Alves Costa Monteiro, Luciana Lamarão Damous, Marcos Eiji Shiroma, Lara Termini, José Cipolla-Neto, Ricardo Dos Santos Simões, Rinaldo Florencio da Silva, José Antonio Turri, Edmund C Baracat, Jose Maria Soares-Junior","doi":"10.1186/s13048-024-01512-2","DOIUrl":"https://doi.org/10.1186/s13048-024-01512-2","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cryopreservation is a promising technique despite being hindered by damage from freezing and thawing. Melatonin can mitigate this outcome.</p><p><strong>Objective: </strong>This study aimed to evaluate the effect of melatonin on the follicular dynamics of ovarian tissue in a cryopreserved cell culture.</p><p><strong>Methods: </strong>Three-month-old adult female Wistar rats (n = 24) weighing approximately 250 g were oophorectomized and divided into two groups (n = 12): the control group (CG) and the melatonin group (MG). In the CG, slow cryopreservation was performed according to the standard protocol with Medium M2 and dimethyl sulfoxide (DMSO). In MG, melatonin diluted in ethyl alcohol vehicle at a concentration of 0.1 μm was added to the culture medium. In both groups, the ovaries were cryopreserved by slow freezing and kept in liquid nitrogen for 24 h. Subsequently, after thawing, the ovaries were reimplanted in the retroperitoneum, one on each side of the great vessels (inferior vena cava and aorta). After 30 days, the animals were euthanized during the diestrus phase; then, the grafts were removed and processed for histomorphometric and immunohistochemical analyses, whereas the blood was subjected to biochemical analysis. Student's t test was used to assess the difference between the groups.</p><p><strong>Results: </strong>The FSH levels in MG (83.79 ± 32.37) were lower than those in CG (120.52 ± 36.59), p = 0.03. The FSH/AMH ratios were also lower in MG (3.53 ± 1.13) than in CG (6.52 ± 2.85), p = 0.001. The SOD2 immunoexpression was higher in MG than in CG regarding all parameters except for the degenerated follicles (follicular cells and internal thecal cells): CG (16.80 ± 4.80 [13.36-20.24]) and MG (14.91 ± 4.04 [12.01-17.79]) p = 0.351. Statistically, the difference in intact follicles (theca + interstitium) between CG (6.60 ± 2.59 [4.75-8.45]) and MG (9.31 ± 3.09 [7.09-11.51]) was significant (p = 0.049), with a small difference in the expression of regular antral follicles.</p><p><strong>Conclusions: </strong>Melatonin can improve the quality of cryopreserved tissues, as evidenced in this study, and the evaluation of cryopreserved ovarian grafts, as shown in the melatonin group with better hormonal parameters and greater immunohistochemical expression of the SOD2 antioxidant. Thus, damage is reduced during cryopreservation and transplantation is improved.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"204"},"PeriodicalIF":3.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-acetylcysteine supplementation improves endocrine-metabolism profiles and ovulation induction efficacy in polycystic ovary syndrome.","authors":"Yu-Qing Fang, Hui Ding, Tao Li, Xiao-Jie Zhao, Dan Luo, Yi Liu, Yanhui Li","doi":"10.1186/s13048-024-01528-8","DOIUrl":"https://doi.org/10.1186/s13048-024-01528-8","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) affects 6-20% of women worldwide, with insulin resistance and hyperinsulinemia occurring in 50-70% of patients. Hyperinsulinemia exacerbates oxidative stress, contributing to PCOS pathogenesis. N-acetylcysteine (NAC) is an antioxidant and insulin sensitizer that shows promise as a therapeutic for PCOS. Our current study aimed to investigate the effects of NAC supplementation on endocrine-metabolic parameters in PCOS mice and its effect on ovulation induction (OI) efficacy in women with PCOS.</p><p><strong>Methods: </strong>Female C57BL/6 mice were orally administered letrozole (LE) to induce PCOS and then randomly divided into groups receiving daily oral administration of 160 mg/kg NAC (PCOS + NAC group), 200 mg/kg metformin (PCOS + Met group), or 0.5% carboxymethyl cellulose (drug solvent) (pure PCOS group) for 12 days. Healthy female mice served as pure controls. Estrous cycles were monitored during the intervention. Metabolic and hormone levels, ovarian phenotypes, antioxidant activity in ovarian tissues, and oxidative stress levels in oocytes were assessed post-intervention. Furthermore, a pragmatic, randomized, controlled clinical study was conducted with 230 PCOS women, randomly assigned to the NAC group (1.8 g/day oral NAC, n = 115) or the control group (n = 115). Patients in both groups underwent ≤ 3 cycles of OI with sequential LE and urinary follicle-stimulating hormone (uFSH). Cycle characteristics and pregnancy outcomes were compared between groups.</p><p><strong>Results: </strong>Similar to metformin, NAC supplementation significantly improved the estrous cycles and ovarian phenotypes of PCOS mice; reduced the LH concentration, LH/FSH ratio, and T level; and increased glucose clearance and insulin sensitivity. Notably, NAC significantly reduced oocyte ROS levels and increased the mitochondrial membrane potential in PCOS mice. Additionally, NAC significantly enhanced enzymatic and nonenzymatic antioxidant activities in PCOS mouse ovaries, whereas metformin had no such effect. In the clinical trial, compared to women in the control group, women receiving NAC had significantly lower average uFSH dosage and duration (p < 0.005) and significantly greater clinical pregnancy rates per OI cycle and cumulative clinical pregnancy rates per patient (p < 0.005).</p><p><strong>Conclusion: </strong>NAC supplementation improved endocrine-metabolic parameters in PCOS mice and significantly enhanced OI efficacy with sequential LE and uFSH in women with PCOS. Therefore, NAC could be a valuable adjuvant in OI for women with PCOS.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"205"},"PeriodicalIF":3.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nur77 ameliorates cyclophosphamide-induced ovarian insufficiency in mice by inhibiting oxidative damage and cell senescence.","authors":"Ying Yao, Bin Wang, Kaihua Yu, Ji Song, Liyan Wang, Xia Yang, Xuehong Zhang, Yulan Li, Xiaoling Ma","doi":"10.1186/s13048-024-01532-y","DOIUrl":"https://doi.org/10.1186/s13048-024-01532-y","url":null,"abstract":"<p><p>Premature ovarian failure (POF) is among the primary causes of ovarian dysfunction that severely affects women's physical and mental health. The main purpose of this study was to explore the expression level of Nerve growth factor-induced protein B (Nur77/NR4A1) in cyclophosphamide (CTX)-induced POF. We then tested whether Nur77 can exert a protective effect after CTX treatment and investigated the mechanism of Nur77's role during ovarian injury. CTX promotes follicular atresia by inducing redox imbalance, apoptosis, and senescence, thereby causing direct toxicity to gonads. Additionally, CTX decreases ovarian reserve consumption by stimulating the excessive activation of primordial follicles. Nur77 can be stimulated by oxidative stress, DNA damage, metabolism, inflammation, etc. However, its relationship with POF remains unelucidated. We here found that Nur77 is expressed at low levels in POF ovaries. Therefore, Nur77 was identified as a regulator of ovarian injury and follicular development. According to the results, Nur77 overexpression alleviated redox imbalances, reduced cell senescence and apoptosis, and improved follicular reserve. Nur77 protects ovarian function by restoring disordered sex hormone levels and estrus cycles and promoting follicle growth and development at all levels. Moreover, the rapamycin protein kinase (AKT)/mammalian target of the rapamycin (mTOR) is a crucial regulator of the primordial follicle pool and follicular development. A relationship was observed between Nur77 and AKT through string and molecular docking. Experiments confirmed the involvement of the AKT/mTOR signaling pathway in the regulatory role of Nur77 in ovarian function. Thus, Nur77 is a critical target for POF prevention and treatment.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"203"},"PeriodicalIF":3.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seasonal environmental fluctuations alter the transcriptome dynamics of oocytes and granulosa cells in beef cows.","authors":"Kamryn Joyce, Ahmed Gad, Nico G Menjivar, Samuel Gebremedhn, Daniella Heredia, Georgia Dubeux, Maria Camila Lopez-Duarte, Joao Bittar, Angela Gonella-Diaza, Dawit Tesfaye","doi":"10.1186/s13048-024-01530-0","DOIUrl":"https://doi.org/10.1186/s13048-024-01530-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Examining the mechanistic cellular responses to heat stress could aid in addressing the increasing prevalence of decreased fertility due to elevated ambient temperatures. Here, we aimed to study the differential responses of oocytes and granulosa cells to thermal fluctuations due to seasonal differences. Dry beef cows (n = 10) were housed together, synchronized and subjected to a stimulation protocol to induce follicular growth before ovum pick-up (OPU). Two OPU's were conducted (summer and winter) to collect cumulus-oocyte-complexes (COCs) and granulosa cells. In addition, rectal temperatures and circulating blood samples were collected during OPU. Oocytes were separated from the adherent cumulus cells, and granulosa cells were isolated from the collected OPU fluid. RNA was extracted from pools of oocytes and granulosa cells, followed by library preparation and RNA-sequencing. Blood samples were further processed for the isolation of plasma and leukocytes. The transcript abundance of HSP70 and HSP90 in leukocytes was evaluated using RT-qPCR, and plasma cortisol levels were evaluated by immunoassay. Environmental data were collected daily for three weeks before each OPU session. Data were analyzed using MIXED, Glimmix or GENMOD procedures of SAS, according to each variable distribution.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Air temperatures (27.5 °C vs. 11.5 °C), average max air temperatures (33.7 °C vs. 16.9 °C), and temperature-humidity indexes, THI (79.16 vs. 53.39) were shown to contrast significantly comparing both the summer and winter seasons, respectively. Rectal temperatures (Summer: 39.2 ± 0.2 °C; Winter: 38.8 ± 0.2 °C) and leukocyte HSP70 transcript abundance (Summer: 4.18 ± 0.47 arbitrary units; Winter: 2.69 ± 0.66 arbitrary units) were shown to increase in the summer compared to the winter. No visual differences persisted in HSP90 transcript abundance in leukocytes and plasma cortisol concentrations during seasonal changes. Additionally, during the summer, 446 and 940 transcripts were up and downregulated in oocytes, while 1083 and 1126 transcripts were up and downregulated in the corresponding granulosa cells, respectively (Fold Change ≤ -2 or ≥ 2 and FDR ≤ 0.05). Downregulated transcripts in the oocytes were found to be involved in ECM-receptor interaction and focal adhesion pathways, while the upregulated transcripts were involved in protein digestion and absorption, ABC transporters, and oocyte meiosis pathways. Downregulated transcripts in the granulosa cells were shown to be involved in cell adhesion molecules, chemokine signaling, and cytokine-cytokine receptor interaction pathways, while those upregulated transcripts were involved in protein processing and metabolic pathways.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In conclusion, seasonal changes dramatically alter the gene expression profiles of oocytes and granulosa cells in beef cows, which may in part explain the seasonal discrepancies in pregnancy su","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"201"},"PeriodicalIF":3.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stem cell-derived extracellular vesicles therapy for primary ovarian insufficiency: a systematic review and meta-analysis of pre-clinical studies.","authors":"Shahryar Rajai Firouzabadi, Ida Mohammadi, Kiana Ghafourian, Seyed Ali Mofidi, Shahrzad Rajaei Firouzabadi, Seyed Mahmoud Hashemi, Fahimeh Ramezani Tehrani, Kyana Jafarabady","doi":"10.1186/s13048-024-01513-1","DOIUrl":"10.1186/s13048-024-01513-1","url":null,"abstract":"<p><strong>Background: </strong>Primary ovarian insufficiency (POI) manifests with hormonal imbalances, menstrual irregularities, follicle loss, and infertility. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are emerging as a promising treatment for POI. This systematic review aims to assess the effects of MSC-EVs on follicle number, hormonal profile, and fertility in POI animal models.</p><p><strong>Methods: </strong>A systematic search of PubMed, Scopus, and Web of Science databases up to December 14th, 2023 was conducted. Two reviewers independently conducted screening, risk of bias assessment, and data extraction. Meta-analysis was performed to analyze treatment versus control outcomes using a random effects model. Publication bias was assessed using Egger's regression test and sensitivity analysis was assessed using the leave-one-out method. Subgroup analyses and meta-regressions were conducted based on EV source, induction model, type of animal, study quality, administration route, administration frequency and route, and dose.</p><p><strong>Results: </strong>a total of 29 studies were included. MSC-EVs treatment significantly increased total follicle count (SMD, (95CI), p-value; 3.56, (0.91, 6.21), < 0.001), including primordial (SMD, (95CI), p-value; 2.86, (1.60, 4.12), < 0.001), primary (SMD, (95CI), p-value; 3.17, (2.28, 4.06), < 0.001), mature (SMD, (95CI), p-value; 2.26, (1.02, 3.50), < 0.001), and antral follicles (SMD, (95CI), p-value; 2.44, (1.21, 3.67), < 0.001). Administration frequency and route did not affect this outcome, but EV source affected primordial, primary, secondary and antral follicle count. Additionally, MSC-EVs treatment elevated anti-müllerian hormone (SMD, (95CI); 3.36, (2.14, 4.58)) and estradiol (SMD, (95CI); 3.19, (2.20, 4.17)) levels while reducing follicle stimulating hormone levels (SMD, (95CI); -2.68, (-4.42, -0.94)). Unlike EV source, which had a significant impact on all three hormones, administration frequency, route, and EV dose did not affect this outcome. Moreover, treatment increased offspring number (SMD, (95CI); 3.70, (2.17, 5.23)) and pregnancy odds (OR, (95CI); 10.25, (4.29, 24.46)) compared to controls. Publication bias and a high level of heterogeneity was evident in all analyses, except for the analysis of the pregnancy odds. However, sensitivity analysis indicated that all of the analyses were stable.</p><p><strong>Conclusion: </strong>MSC-EVs therapy shows promise for POI treatment, potentially facilitating clinical translation. However, Further research is warranted to optimize methodology and assess side effects.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"200"},"PeriodicalIF":3.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanotechnology for boosting ovarian cancer immunotherapy.","authors":"Prabhjot Kaur, Santosh Kumar Singh, Manoj K Mishra, Shailesh Singh, Rajesh Singh","doi":"10.1186/s13048-024-01507-z","DOIUrl":"https://doi.org/10.1186/s13048-024-01507-z","url":null,"abstract":"<p><p>Ovarian cancer, often referred to as the \"silent killer,\" is notoriously difficult to detect in its early stages, leading to a poor prognosis for many patients. Diagnosis is often delayed until the cancer has advanced, primarily due to its ambiguous and frequently occurring clinical symptoms. Ovarian cancer leads to more deaths than any other cancer of the female reproductive system. The main reasons for the high mortality rates include delayed diagnosis and resistance to treatment. As a result, there is an urgent need for improved diagnostic and treatment options for ovarian cancer. The standard treatments typically involve debulking surgery along with platinum-based chemotherapies. Among patients with advanced-stage cancer who initially respond to current therapies, 50-75% experience a recurrence. Recently, immunotherapy-based approaches to enhance the body's immune response to combat tumor growth have shown promise. Immune checkpoint inhibitors have shown promising results in treating other types of tumors. However, in ovarian cancer, only a few of these inhibitors have been effective because the tumor's environment suppresses the immune system and creates barriers for treatment. This hampers the effectiveness of existing immunotherapies. Nonetheless, advanced immunotherapy techniques and delivery systems based on nanotechnology hold promise for overcoming these challenges.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"202"},"PeriodicalIF":3.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Withaferin A ameliorates ovarian cancer-induced renal damage through the regulation of expression of inflammatory cytokines.","authors":"Kusum Kumar, Katherine Bosch, Vasa Vemuri, Nicholas Kratholm, Madhavi Rane, Sham S Kakar","doi":"10.1186/s13048-024-01519-9","DOIUrl":"10.1186/s13048-024-01519-9","url":null,"abstract":"<p><strong>Background: </strong>Cachexia a multifactorial syndrome is a common sequala in patients with cancer. It varies from 42 to 80% depending upon the oncological stage and is directly responsible for 30% of deaths in these patients. Previous research from our laboratory demonstrated that peritoneal ovarian cancer generated in NSG mice resulted in skeletal and cardiac muscle atrophy - leading to loss of skeletal muscle mass and strength, and cardiac dysfunction (cachexia). Treatment of mice bearing i.p. tumors with withaferin A (WFA) showed reversal of skeletal muscle and cardiac cachexia. The present study is focused on determining effects of peritoneal ovarian tumors on kidney damage and effects of WFA treatment on ameliorating kidney damage.</p><p><strong>Methods: </strong>We generated intraperitoneal ovarian cancer by injecting female NSG mice with ovarian cancer cell line (A2780). After one week of injecting cancer cells, mice were treated with WFA (4 mg/kg) every third day, for three weeks. After 4 weeks of injection of cancer cells, the mice were sacrificed and various tissues including kidney and blood were collected, snap-frozen in liquid nitrogen, and stored at -80⁰C. The presence of kidney biomarker creatinine, was measured in the plasma by an ELISA. The mRNA was isolated from mouse kidneys and was used to examine the expression levels of signaling proteins, inflammatory cytokines, and genes responsible for inducing cachexia (IL-1β, IL-6, TNF-α, TGF-β, GDF-15, and MYD88).</p><p><strong>Results: </strong>Our results showed a significant increase in levels of expression of inflammatory cytokine IL-1 β (p < 0.01), IL-6 (p < 0.001), TNF-α (p < 0.001), and other related genes including TRAF6 (p < 0.01), MYD88 (p < 0.01), and GDF-15 (p = 0.005) in tumor-bearing mice compared to controls. Treatment of mice bearing tumors with WFA attenuated the increase in expression of each gene. In addition, our results showed a significant increase in creatinine levels in circulation in tumor-bearing mice compared to control mice. Treatment of tumor-bearing mice with WFA resulted in a significant decrease in plasma creatinine levels compared to tumor-bearing mice.</p><p><strong>Conclusions: </strong>Our results conclude that ovarian tumors in NSG mice caused kidney damage and renal dysfunction, which was effectively ameliorated by WFA treatment, suggesting a protective effect of WFA on kidney injury induced by ovarian cancer.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"199"},"PeriodicalIF":3.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}