Validation of mitochondrial biomarkers and immune dynamics in polycystic ovary syndrome.

PROBLEM: Polycystic ovary syndrome (PCOS), a prevalent endocrine-metabolic disorder, presents considerable therapeutic challenges due to its complex and elusive pathophysiology. METHOD OF STUDY: We employed three machine learning algorithms to identify potential biomarkers within a training dataset, comprising GSE138518, GSE155489, and GSE193123. The diagnostic accuracy of these biomarkers was rigorously evaluated using a validation dataset using area under the curve (AUC) metrics. Further validation in clinical samples was conducted using PCR and immunofluorescence techniques. Additionally, we investigate the complex interplay among immune cells in PCOS using CIBERSORT to uncover the relationships between the identified biomarkers and various immune cell types. RESULTS: Our analysis identified ACSS2, LPIN1, and NR4A1 as key mitochondria-related biomarkers associated with PCOS. A notable difference was observed in the immune microenvironment between PCOS patients and healthy controls. In particular, LPIN1 exhibited a positive correlation with resting mast cells, whereas NR4A1 demonstrated a negative correlation with monocytes in PCOS patients. CONCLUSION: ACSS2, LPIN1, and NR4A1 emerge as PCOS-related diagnostic biomarkers and potential intervention targets, opening new avenues for the diagnosis and management of PCOS.

Chitosan alleviates ovarian aging by enhancing macrophage phagocyte-mediated tissue homeostasis.

BACKGROUND: Age-related changes in the ovarian microenvironment are linked to impaired fertility in women. Macrophages play important roles in ovarian tissue homeostasis and immune surveillance. However, the impact of aging on ovarian macrophage function and ovarian homeostasis remains poorly understood. METHODS: Senescence-associated beta-galactosidase staining, immunohistochemistry, and TUNEL staining were used to assess senescence and apoptosis, respectively. Flow cytometry was employed to evaluate mitochondrial membrane potential (MMP) and apoptosis in granulosa cells lines (KGN), and macrophages phagocytosis. After a 2-month treatment with low molecular weight Chitosan (LMWC), ovarian tissues from mice were collected for comprehensive analysis. RESULTS: Compared with the liver and uterus, the ovary displayed accelerated aging in an age-dependent manner, which was accompanied by elevated levels of inflammatory factors and apoptotic cells, and impaired macrophage phagocytic activity. The aged KGN cells exhibited elevated reactive oxygen species (ROS) and apoptotic levels alongside decreased MMP. H2O2-induced aging macrophages showed reduced phagocytosis function. Moreover, there were excessive aging macrophages with impaired phagocytosis in the follicular fluid of patients with diminished ovarian reserve (DOR). Notably, LMWC administration alleviated ovarian aging by enhancing macrophage phagocytosis and promoting tissue homeostasis. CONCLUSIONS: Aging ovarian is characterized by an accumulation of aging and apoptotic granulosa cells, an inflammatory response and macrophage phagocytosis dysfunction. In turn, impaired phagocytosis of macrophage contributes to insufficient clearance of aging and apoptotic granulosa cells and the increased risk of DOR. Additionally, LMWC emerges as a potential therapeutic strategy for age-related ovarian dysfunction.

Meta-Analysis of Electroencephalographic Correlates and Cognitive Performance for Acute Exercise-Induced Modulation.

INTRODUCTION: Although abundant research delving into the acute exercise-induced modulation of cognitive performance and the P300-ERP component has been conducted, there is a lack of consensus regarding whether or not this type of intervention has a beneficial effect on cognition and how it relates to the P300-ERP. METHODS: To examine the possible sources of this discrepancy, we conducted a meta-analysis of ERP results together with cognitive performance that were systemically stratified by relevant demographic and methodological moderators. RESULTS: Our results indicate that while acute exercise exerted an overall stable effect on cognitive improvement, associated with enlarged P300 amplitudes, the effect size varied across factors of age, biological sex, exercise intensity, exercise type, control type, and experimental design. Future research taking into consideration modulating factors as to avoid misestimating the beneficial effects of acute exercise are encouraged. CONCLUSION: All in all, and to our knowledge, this is the first meta-analysis quantitatively summarizing the relevant literature on the associations between P300-ERP correlates, acute exercise, and its positive influence on attention and cognitive performance in healthy individuals.

The cytokine profiles in follicular fluid and reproductive outcomes in women with endometriosis.

PROBLEM: Endometriosis patients undergoing in vitro fertilization-embryo transfer (IVF-ET) treatment suffer from poor oocyte quality, a reduced likelihood of the fertilization rate, and low embryo quality. The dysregulation of immune cells and cytokine profiles in the follicular fluid (FF) may play an important role in the competence of the oocyte and the development of the embryo, but the mechanism remains largely unknown. METHOD OF STUDY: A total of 40 proved advanced staged endometriosis patients were enrolled in this study. The pregnancy results were followed until all the embryos collected by the first oocyte retrieval cycle were used up. The immune cells subtypes in FF and serum collected on the day of oocyte retrieval were detected by flow cytometry and 27 cytokines were determined using the Bio-Plex Pro Human Cytokine 27-Plex Immunoassay. The specific effect of cytokine on the gene expression of human granulosa cells was determined by RT-qPCR. RESULTS: The fertilization rate and the cumulative live birth rate were significantly lower in the endometriosis group. The ratio of CD4+ /CD8+ T cells in FF was significantly lower, while the level of IP-10, RANTES and G-CSF were statistically higher in the endometriosis group. The level of IP-10 correlated with the IVF outcome. Moreover, treated by IP-10, the mRNA level of FSHR and CYP19A1 the human granulosa cells were downregulated in vitro. CONCLUSION: These results suggest that alterations of the lymphocyte subsets and cytokines in women with advanced endometriosis may have an impact on the oocyte development and resulting in poorer IVF outcomes.

Changes of insulin resistance and ß-cell function in women with gestational diabetes mellitus and normal pregnant women during mid- and late pregnant period: a case-control study.

AIM: The aim of this study was to observe insulin resistance and ß-cell function changes among women diagnosed with gestational impaired glucose tolerance or gestational diabetes mellitus (GDM) in mid-pregnancy. MATERIAL AND METHODS: Sixty-four pregnant women receiving prenatal care underwent an oral glucose tolerance test at 20-24 weeks of gestation and an insulin release test. The GDM group included 34 pregnant women diagnosed with gestational impaired glucose tolerance or GDM, and the subjects with normal blood glucose were the control group. Insulin resistance and islet ß-cell function changes were observed with the oral glucose tolerance test and insulin release test. RESULTS: The homeostatic model assessment-ß levels in late pregnancy were higher than those in mid-pregnancy for both groups, and the primary time effect was statistically significant. The early insulin secretion index (ΔI(30)/ΔG(30)) values in mid- and late pregnancy were lower in the GDM group. The values of the area under the curve of blood glucose in mid- and late pregnancy were higher in the GDM group than those in the control group. Insulin resistance was higher in GDM patients than in normal pregnant women. CONCLUSIONS: Insulin resistance was aggravated, and ß-cell's ability to compensate for the increased insulin resistance by modulating insulin secretion was aggravated, as gestational week increased in women with gestational diabetes and normal pregnant women. Insulin resistance in women with GDM is higher than in pregnant women with normal metabolism of glucose.

Impact of the new lung cancer staging system for a predominantly advanced-disease patient population.

INTRODUCTION: To investigate the feasibility and clinical impact of the 7th edition of the "Tumor, Node, Metastasis" (TNM) classification scheme in lung cancer as proposed by the International Association for the Study of Lung Cancer (IASLC) for non-small cell lung cancer. METHODS: We evaluated the feasibility of the new staging system in our routine biweekly multidisciplinary lung cancer staging conference compared with the 6th TNM staging in a prospective manner from April 2008 to June 2009. The impact of IASLC staging versus the 6th TNM staging was observed at three levels: change in substaging, staging, and clinical management (based on the discussion within the staging conference). RESULTS: From 348 patients discussed during these conferences, 226 eligible non-small cell lung cancer patients newly diagnosed within the study period were reviewed and clinically staged. The majority were elderly (median age, 67 years) and men (58%). Of these, 23 patients had different staging, and four patients had different substaging in the IASLC staging compared with the 6th TNM staging. An impact on clinical management was seen in 2.7% (6 of 226) of these patients because of coding ipsilateral different-lobe metastasis as T4 instead of M1. CONCLUSIONS: The new staging system was clinically feasible and resulted in some (27 of 226, 12%) differences in staging. An impact on clinical decision making was occasionally seen within our institutional practice. Further studies are needed to investigate the comprehensive and long-term impact of the new staging system.