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Human Reproduction Update Jul 2023Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal cell turnover during adulthood, as... (Review)
Review
BACKGROUND
Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal cell turnover during adulthood, as well as the elimination of infected or damaged cells throughout life. Quality control through regulation of cell death pathways is particularly important in the germline, which is responsible for the generation of offspring. Women are born with their entire supply of germ cells, housed in functional units known as follicles. Follicles contain an oocyte, as well as specialized somatic granulosa cells essential for oocyte survival. Follicle loss-via regulated cell death-occurs throughout follicle development and life, and can be accelerated following exposure to various environmental and lifestyle factors. It is thought that the elimination of damaged follicles is necessary to ensure that only the best quality oocytes are available for reproduction.
OBJECTIVE AND RATIONALE
Understanding the precise factors involved in triggering and executing follicle death is crucial to uncovering how follicle endowment is initially determined, as well as how follicle number is maintained throughout puberty, reproductive life, and ovarian ageing in women. Apoptosis is established as essential for ovarian homeostasis at all stages of development and life. However, involvement of other cell death pathways in the ovary is less established. This review aims to summarize the most recent literature on cell death regulators in the ovary, with a particular focus on non-apoptotic pathways and their functions throughout the discrete stages of ovarian development and reproductive life.
SEARCH METHODS
Comprehensive literature searches were carried out using PubMed and Google Scholar for human, animal, and cellular studies published until August 2022 using the following search terms: oogenesis, follicle formation, follicle atresia, oocyte loss, oocyte apoptosis, regulated cell death in the ovary, non-apoptotic cell death in the ovary, premature ovarian insufficiency, primordial follicles, oocyte quality control, granulosa cell death, autophagy in the ovary, autophagy in oocytes, necroptosis in the ovary, necroptosis in oocytes, pyroptosis in the ovary, pyroptosis in oocytes, parthanatos in the ovary, and parthanatos in oocytes.
OUTCOMES
Numerous regulated cell death pathways operate in mammalian cells, including apoptosis, autophagic cell death, necroptosis, and pyroptosis. However, our understanding of the distinct cell death mediators in each ovarian cell type and follicle class across the different stages of life remains the source of ongoing investigation. Here, we highlight recent evidence for the contribution of non-apoptotic pathways to ovarian development and function. In particular, we discuss the involvement of autophagy during follicle formation and the role of autophagic cell death, necroptosis, pyroptosis, and parthanatos during follicle atresia, particularly in response to physiological stressors (e.g. oxidative stress).
WIDER IMPLICATIONS
Improved knowledge of the roles of each regulated cell death pathway in the ovary is vital for understanding ovarian development, as well as maintenance of ovarian function throughout the lifespan. This information is pertinent not only to our understanding of endocrine health, reproductive health, and fertility in women but also to enable identification of novel fertility preservation targets.
Topics: Adult; Animals; Female; Humans; Apoptosis; Granulosa Cells; Mammals; Oocytes; Ovarian Follicle; Ovary; Regulated Cell Death; Homeostasis
PubMed: 36857094
DOI: 10.1093/humupd/dmad005 -
Frontiers in Immunology 2023Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of immunosuppressive regimens in adults with LN.
METHODS
We systematically searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases, including conference proceedings, trial registries, and reference lists, from inception until July 10, 2022. The effects of treatment were compared and ranked using the surface under the cumulative ranking curve (SUCRA). The primary endpoint was total remission. The secondary endpoints were complete remission, systemic lupus erythematosus disease activity index (SLEDAI), relapse, all-cause mortality, end-stage renal disease (ESRD), infection, herpes zoster, ovarian failure, myelosuppression, and cancer.
RESULTS
Sixty-two trials reported in 172 studies involving 6,936 patients were included in the network meta-analysis. The combination of tacrolimus (TAC), mycophenolate mofetil (MMF), and glucocorticoid (GC) provided the best result for the total remission rate (SUCRA, 86.63%) and SLEDAI (SUCRA, 91.00%), while the combination of voclosporin (VCS) , MMF and GC gave the best improvement in the complete remission rate (SUCRA, 90.71%). The combination of cyclophosphamide (CYC), MMF and GC was associated with the lowest risk of relapse (SUCRA, 85.57%) and cancer (SUCRA, 85.14%), while the combination of obinutuzumab (OTB), MMF and GC was associated with the lowest risk of all-cause mortality (SUCRA, 84.07%). Rituximab (RTX) plus MMF plus GC was associated with the lowest risk of ESRD (SUCRA, 83.11%), while the risk of infection was lowest in patients treated with azathioprine (AZA) plus CYC plus GC (SUCRA, 68.59%). TAC plus GC was associated with the lowest risk of herpes zoster (SUCRA, 87.67%) and ovarian failure (SUCRA, 73.60%). Cyclosporine (CsA) plus GC was associated with the lowest risk of myelosuppression (SUCRA, 79.50%), while AZA plus GC was associated with the highest risk of myelosuppression (SUCRA, 16.25%).
DISCUSSION
This study showed that a combination of TAC, MMF and GC was the best regimen for improving the total remission rate. The optimal regimen for specific outcomes should be highlighted for high-risk patients.
Topics: Humans; Adult; Immunosuppressive Agents; Lupus Nephritis; Network Meta-Analysis; Treatment Outcome; Cyclophosphamide; Tacrolimus; Azathioprine; Mycophenolic Acid; Glucocorticoids; Bone Marrow Diseases; Kidney Failure, Chronic; Recurrence; Herpes Zoster; Neoplasms
PubMed: 37901212
DOI: 10.3389/fimmu.2023.1232244 -
European Journal of Surgical Oncology :... Sep 2023Patients with ovarian metastasis of colorectal cancer (CROM) usually have poor prognosis. Metastasectomy is controversial in patients with CROM. This study aims to... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Patients with ovarian metastasis of colorectal cancer (CROM) usually have poor prognosis. Metastasectomy is controversial in patients with CROM. This study aims to evaluate the prognostic value of ovarian metastasectomy and other factors in CROM patients.
METHODS
We searched literature up to November 1, 2021 in MEDLINE (PubMed), Embase, Cochrane Library, and Clinicaltrials.gov. Retrospective studies were assessed if survival outcome of CROM patients was reported. Results were pooled in a random-effects model and reported as hazard ratios (HRs) with 95% confidence intervals (CI). Sensitivity was analyzed.
RESULTS
Among 2497 studies screened, 15 studies with 997 patients, published between 2000 and 2021, were included. Longer overall survival (OS) was correlated with ovarian metastasectomy (pooled HR = 0.44, 95% CI: 0.34-0.58, P < 0.05) and R0 resection (pooled HR = 0.26, 95% CI: 0.16-0.41, P < 0.05). Longer disease-specific survival (DSS) was associated with systematic chemotherapy (pooled HR = 0.26, 95% CI: 0.15-0.45, P < 0.0001). Shorter OS was associated with extraovarian metastases (pooled HR = 3.00, 95% CI 1.68-5.36, P < 0.05) and bilateral OM (pooled HR = 1.66, 95% CI: 1.09-2.51, P < 0.05). No significant difference in OS was observed among patients with systematic chemotherapy (pooled HR = 0.68, 95% CI: 0.35-1.31, P > 0.05).
CONCLUSION
Metastasectomy achieving R0 resection can significantly prolong OS and DSS of CROM patients as a reasonable treatment modality. Primary tumor resection and systematic chemotherapy can improve patients' outcomes.
REGISTRATION NUMBER
CRD42022299185 (http://www.crd.york.ac.uk/PROSPERO).
Topics: Humans; Female; Metastasectomy; Retrospective Studies; Prognosis; Ovarian Neoplasms; Colorectal Neoplasms
PubMed: 37355393
DOI: 10.1016/j.ejso.2023.06.013 -
Indian Journal of Pathology &... 2024Ovarian tuberculosis is a rare entity with non-specific clinical manifestations, difficult diagnosis, and specific medical management. Ovarian involvement in...
Ovarian tuberculosis is a rare entity with non-specific clinical manifestations, difficult diagnosis, and specific medical management. Ovarian involvement in tuberculosis (TB) may occur in two forms, namely, perioophoritis and oophoritis. The constitutional symptoms of tuberculosis such as anorexia, weight loss, night sweats, and evening rise in temperature have been reported in up to 45% of patients. Misdiagnosis and delayed diagnosis are common. A direct histopathological demonstration is the best diagnostic modality. Fine needle aspiration cytology (FNAC) is the study of choice and polymerase chain reaction (PCR) assay increases its sensitivity. The standard short-course antituberculous for 6 months is recommended for isolated ovarian tuberculosis and for widespread disease, 12 months of therapy is recommended. Surgery is reserved for failure of medical therapy and abscess formation. There are many studies on genito-urinary tuberculosis but a detailed study defining diagnostic studies and management guidelines is still lacking. This article aims to present and share a review of the English-language literature on ovarian tuberculosis to gain a better understanding of etiopathogenesis and diagnostic methods and to provide guidelines for its management.
Topics: Female; Humans; Tuberculosis; Biopsy, Fine-Needle; Cytodiagnosis; Polymerase Chain Reaction
PubMed: 38358181
DOI: 10.4103/ijpm.ijpm_6_23 -
Translational Psychiatry Mar 2024The global impact of SARS-CoV-2 infection has raised concerns about secondary diseases beyond acute illness. This review explores the significance and potential... (Meta-Analysis)
Meta-Analysis
The global impact of SARS-CoV-2 infection has raised concerns about secondary diseases beyond acute illness. This review explores the significance and potential underlying mechanisms of how SARS-CoV-2 infection might elicit an immune response targeting N-methyl-D-aspartate (NMDA) receptors, and its implications for autoimmune-driven neuropsychiatric manifestations. We identified 19 published case reports of NMDA receptor encephalitis associated with SARS-CoV-2 infection or vaccination by a systematic literature search. The significance of these reports was limited since it is not clear if a coincidental or causal relationship exists between SARS-CoV-2 infection or vaccination and manifestation of NMDA receptor encephalitis. The included studies were hampered by difficulties in establishing if these patients had pre-existing NMDA receptor antibodies which entered the brain by infection- or vaccination-associated transient blood-brain barrier leakage. In addition, four cases had comorbid ovarian teratoma, which is a known trigger for development of NMDA receptor encephalitis. Considering that billions of people have contracted COVID-19 or have been vaccinated against this virus, the publication of only 19 case reports with a possible link to NMDA receptor encephalitis, indicates that it is rare. In conclusion, these findings do not support the case that SARS-CoV-2 infection or vaccination led to an increase of existing or de novo encephalitis mediated by an autoimmune response targeting NMDA receptor function. Nevertheless, this work underscores the importance of ongoing vigilance in monitoring viral outbreaks and their potential impact on the central nervous system through basic, epidemiological and translational research.
Topics: Humans; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antibodies; COVID-19; Receptors, N-Methyl-D-Aspartate; SARS-CoV-2
PubMed: 38459000
DOI: 10.1038/s41398-024-02831-0 -
Journal of Personalized Medicine Mar 2024Ovarian cancer (OC) remains a significant health challenge globally, with high mortality rates despite advancements in treatment. Emerging research suggests a potential... (Review)
Review
Ovarian cancer (OC) remains a significant health challenge globally, with high mortality rates despite advancements in treatment. Emerging research suggests a potential link between OC development and genital dysbiosis, implicating alterations in the microbiome composition as a contributing factor. To investigate this correlation, a meta-analysis was conducted following PRISMA and MOOSE guidelines, involving eight studies encompassing 3504 patients. Studies investigating the role of upper and inferior genital tract dysbiosis were included, with particular reference to HPV infection and/or history of pelvic inflammatory disease. The analysis revealed no significant difference in genital dysbiosis prevalence between OC patients and healthy controls. Although previous literature suggests associations between dysbiosis and gynecologic cancers, such as cervical and endometrial cancers, the findings regarding OC are inconclusive. Methodological variations and environmental factors may contribute to these discrepancies, underscoring the need for standardized methodologies and larger-scale studies. Despite the limitations, understanding the microbiome's role in OC development holds promise for informing preventive and therapeutic strategies. A holistic approach to patient care, incorporating microbiome monitoring and personalized interventions, may offer insights into mitigating OC risk and improving treatment outcomes. Further research with robust methodologies is warranted to elucidate the complex interplay between dysbiosis and OC, potentially paving the way for novel preventive and therapeutic approaches.
PubMed: 38672978
DOI: 10.3390/jpm14040351 -
Journal of Personalized Medicine Aug 2023Coronavirus disease (COVID-19) is a pandemic causing respiratory symptoms, taste alterations, olfactory disturbances, and cutaneous, cardiovascular, and neurological... (Review)
Review
Coronavirus disease (COVID-19) is a pandemic causing respiratory symptoms, taste alterations, olfactory disturbances, and cutaneous, cardiovascular, and neurological manifestations. Recently, research interest has shifted to reproductive health to understand the factors predisposing to COVID-19 infection in pregnancy, the consequences of the infection on the fetus and on the mother, and possible vertical transmission through the placenta. Pregnancy does not increase the risk of SARS-CoV-2 infection, according to studies. However, contrary to non-pregnant women, pregnancy worsens the clinical outcome of COVID-19. Studies investigating the effects of COVID-19 on pregnancy women are heterogeneous, and the results are often conflicting. The goal of the current work was to offer a thorough and up-to-date systematic review of, and meta-analysis on, the impact of COVID-19 on ovarian function, pregnancy, and fetal outcomes. This meta-analysis (PROSPERO n. CRD42023456904) was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. The search for relevant material was conducted using PubMed, Scopus, Cochrane, and Embase databases, through to 15 December 2022. Original articles on fertile pregnant women or women attempting to become pregnant, with an active case of, or history of, SARS-CoV-2 infection were included, and reproductive function was compared to that of uninfected women. The effects of COVID-19 on female reproductive function, particularly ovarian function, the profile of female sex hormones, pregnancy outcomes and fetal outcomes were the focus of our search. Quantitative analysis was performed with Comprehensive Meta-Analysis Software. The standard difference of the mean was calculated for the statistical comparison between cases and controls. Cochran's Q test and heterogeneity (I) indexes were used to assess statistical heterogeneity. Sensitivity analysis and publication bias tests were also performed. Twenty-eight articles met our inclusion criteria, for a total of 27,383 patients pregnant or looking to have offspring, with active or anamnestic COVID-19, and 1,583,772 uninfected control women. Our study revealed that there was no significant difference between COVID-19 patients and the control group in terms of maternal characteristics such as age, body mass index (BMI) and comorbidities that could affect pregnancy and fetal outcomes. The risk of a miscarriage or Cesarean delivery was significantly lower, while the risk of fetal death or premature delivery was significantly higher in COVID-19 patients than in the controls. None of the included studies evaluated hormonal profiles or investigated the presence of infertility. Maternal comorbidities, age, and BMI do not raise the risk of COVID-19. However, pregnant women with COVID-19 had a lower risk of miscarriage and Cesarean delivery, possibly because of better prenatal care and high levels of observation during labor. COVID-19 during pregnancy increases the risk of fetal death and premature delivery.
PubMed: 37763105
DOI: 10.3390/jpm13091337 -
Immunity, Inflammation and Disease Jan 2024The current study aims to evaluate the impact of COVID-19 infection and vaccination on ovarian reserve by detecting the anti-Mullerian hormone (AMH) level. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The current study aims to evaluate the impact of COVID-19 infection and vaccination on ovarian reserve by detecting the anti-Mullerian hormone (AMH) level.
METHOD
PubMed, Embase, Web of Science, and Scopus has been searched for studies assessing the effect of COVID-19 infection and/or vaccination on AMH levels up to February 27, 2023. Based on PRISMA 2020 statement criteria, a systematic review and meta-analysis of included studies were performed. The studies' quality was assessed by the National Institute of Health (NIH) quality assessment tool. The standardized mean difference (MD) of the AMH level was used and the quantitative values of each study were pooled separately by using a random effect model.
RESULTS
Out of 246 studies screened, 18 were included in the systematic review and 14 in the meta-analysis. Included studies were published between 2021 and 2022 and were conducted in different countries, including the USA (n = 3), China (n = 2), Russia (n = 2), Turkey (n = 5), Israel (n = 3), Czech (n = 2), and Spain (n = 1). Eight studies investigated the effect of SARS-CoV-2 infection on AMH levels, and ten studies investigated the possible effect of COVID-19 vaccination on AMH levels. The pooled analysis showed a statistically significant decrease in AMH levels after COVID-19 infection (SMD: -0.24; 95% CI: -0.36 to -0.11; I2 = 0%; p = .0003). Vaccination analysis showed a nonstatistically significant change in AMH levels after COVID-19 vaccination (SMD: -0.11; 95% CI: -0.25 to 0.04; I2 = 35%; p = .14).
CONCLUSION
COVID-19 infection can result in ovarian reserve injury by reducing the AMH level but getting vaccinated against COVID-19 has no impact on the AMH level.
Topics: Humans; Anti-Mullerian Hormone; COVID-19; COVID-19 Vaccines; SARS-CoV-2; Vaccination; Transforming Growth Factor beta
PubMed: 38270314
DOI: 10.1002/iid3.1136 -
Frontiers in Pharmacology 2024Poly (ADP-ribose) polymerase (PARP) inhibitor and antiangiogenic agent monotherapy have shown to be effective as maintenance treatment in patients with ovarian cancer...
Efficacy and safety of PARP inhibitors combined with antiangiogenic agents in the maintenance treatment of ovarian cancer: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.
Poly (ADP-ribose) polymerase (PARP) inhibitor and antiangiogenic agent monotherapy have shown to be effective as maintenance treatment in patients with ovarian cancer (OC). However, there is currently a lack of evidence-based study to directly compare the effects of combination therapy with these two drugs. Therefore, this study aimed to compare the efficacy and safety of combination therapy with PARP inhibitors and antiangiogenic agents in women with OC using a meta-analysis. An exhaustive search of literature was undertaken using multiple databases, including PubMed, Web of Science, Embase, and the Cochrane Library to identify pertinent randomized controlled trials (RCTs) published up until 17 December 2023. The data on progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were pooled. We computed the pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) for PFS and OS, along with the relative risks (RRs) and 95% CIs for AEs. Trial sequential analysis, heterogeneity test, sensitivity analysis, and publication bias assessment were performed. Stata 12.0 and Software R 4.3.1 were utilized for all analyses. This meta-analysis included 7 RCTs with a total of 3,388 participants. The overall analysis revealed that combination therapy of PARP inhibitors and antiangiogenic agents significantly improved PFS (HR = 0.615, 95% CI = 0.517-0.731; 95% PI = 0.379-0.999), but also increased the risk of AEs, including urinary tract infection (RR = 1.500, 95% CI = 1.114-2.021; 95% PI = 0.218-10.346), fatigue (RR = 1.264, 95% CI = 1.141-1.400; 95% PI = 1.012-1.552), headache (RR = 1.868, 95% CI = 1.036-3.369; 95% PI = 0.154-22.642), anorexia (RR = 1.718, 95% CI = 1.320-2.235; 95% PI = 0.050-65.480), and hypertension (RR = 5.009, 95% CI = 1.103-22.744; 95% PI = 0.016-1580.021) compared with PARP inhibitor or antiangiogenic agent monotherapy. Our study has not yet confirmed the benefit of combination therapy on OS in OC patients (HR = 0.885, 95% CI = 0.737-1.063). Additionally, subgroup analyses further showed that combination therapy resulted in an increased risk of AEs, encompassing thrombocytopenia, vomiting, abdominal pain, proteinuria, fatigue, headache, anorexia, and hypertension (all < 0.05). Our study demonstrated the PFS benefit of combination therapy with PARP inhibitors and antiangiogenic agents in patients with OC. The OS result need to be updated after the original trial data is mature. Clinicians should be vigilant of AEs when administering the combination therapy in clinical practice. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023494482.
PubMed: 38584601
DOI: 10.3389/fphar.2024.1372077 -
Cureus Apr 2024The oncogenic potential of human papillomavirus (HPV) has been widely acknowledged in relation to multiple types of cancer. The objective of this investigation was to... (Review)
Review
The oncogenic potential of human papillomavirus (HPV) has been widely acknowledged in relation to multiple types of cancer. The objective of this investigation was to conduct a comprehensive assessment of the available evidence pertaining to the correlation between HPV and various types of cancer, such as cervical, colon, ovarian, and head and neck cancers, in the Kingdom of Saudi Arabia (KSA). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were complied with to conduct a systematic literature search aimed at identifying studies that explore the correlation between HPV and the specified cancers. Databases such as Web of Science, Embase, PubMed, and the Cochrane Library were queried up until May of 2023. Relevant literature was obtained, information was extracted, and the methodological rigor was evaluated. The high-risk HPV, namely HPV-16 and HPV-18, were detected as the most prevalent variants in KSA. A significant proportion of cervical cancer cases in the region were found to be associated HPV infection. The molecular tests have furnished evidence that establishes a connection between HPV infection and colonic polyps as well as colorectal cancer. This finding suggests that HPV may have a plausible role in the etiology of these medical conditions. The results of genotyping and integration analyses suggest a probable correlation between HPV and the development of ovarian cancer. Additionally, the prevalence of head and neck squamous cell cancer related to HPV was notably reduced in this particular geographical area. This study presents persuasive findings that establish a connection between HPV and cervical cancer and proposes plausible correlations with squamous cell carcinomas in the colon, ovaries, and head and neck. The aforementioned results emphasize the necessity for additional inquiry into the function of HPV in the onset and advancement of said malignancies. Further investigations are necessary to augment our comprehension of the role of HPV in these neoplasms.
PubMed: 38721199
DOI: 10.7759/cureus.57851