Genetic insights into the gut microbiota, herpes zoster, and postherpetic neuralgia: a bidirectional two-sample Mendelian randomization study.

Background: An increasing amount of evidence suggests that gastrointestinal diseases are risk factors for herpes zoster (HZ) and postherpetic neuralgia (PHN). Among them, the gut microbiota may play a crucial role in this process. Therefore, this study aims to explore the potential causal association between the gut microbiota and HZ and PHN. Methods: Bidirectional two-sample Mendelian randomization (MR) analysis was used to detect the causal effect between HZ and PHN and the gut microbiota. Gut microbiota data were derived from the MiBioGen consortium, while HZ and PHN data were obtained from the FinnGen database. We selected single-nucleotide polymorphisms (SNPs) as instrumental variables with a threshold of p < 1 × 10⁻5 for the association with the gut microbiota in forward MR analysis and p < 5 × 10⁻8 for the association with HZ or PHN in reverse MR analysis and then removed SNPs in linkage disequilibrium (r 2 < 0.001) within a distance of 10,000 kb for both the gut microbiota and HZ and PHN. These SNPs were utilized to assess the causal effect between exposures and outcomes using inverse-variance weighting (IVW), MR-Egger, weighted mean, and weighted median tests. Results: The class Deltaproteobacteria, order Desulfovibrionales, family Desulfovibrionaceae, and genus Coprococcus 2 were found to reduce the risk of HZ, while the phylum Cyanobacteria, genus Eubacterium rectale group appeared to increase it. The class Coriobacteriia, order Coriobacteriales, family Coriobacteriaceae, genus Lachnospiraceae NK4A136 and genus Ruminococcaceae UCG011 were found to reduce the risk of PHN, while the genus Candidatus Soleaferrea, genus Eubacterium rectale group, and genus Methanobrevibacter appeared to increase it. Moreover, the onset of HZ was found to increase the level of the genus Eubacterium rectale group. These findings remained robust and unaffected by heterogeneity or horizontal pleiotropy among SNPs in both forward and reverse MR analysis. Conclusion: This MR study provided evidence supporting a potential causal relationship between the gut microbiota and HZ and PHN. Moreover, we found that the causal effect between the gut microbiota and HZ is bidirectional. Further studies are required to clarify the biological mechanisms linking the gut microbiota and these conditions.

Tumor immunity: A brief overview of tumor­infiltrating immune cells and research advances into tumor­infiltrating lymphocytes in gynecological malignancies (Review).

Tumor immunity is a promising topic in the area of cancer therapy. The 'soil' function of the tumor microenvironment (TME) for tumor growth has attracted wide attention from scientists. Tumor-infiltrating immune cells in the TME, especially the tumor-infiltrating lymphocytes (TILs), serve a key role in cancer. Firstly, relevant literature was searched in the PubMed and Web of Science databases with the following key words: 'Tumor microenvironment'; 'TME'; 'tumor-infiltrating immunity cells'; 'gynecologic malignancies'; 'the adoptive cell therapy (ACT) of TILs'; and 'TIL-ACT' (https://pubmed.ncbi.nlm.nih.gov/). According to the title and abstract of the articles, relevant items were screened out in the preliminary screening. The most relevant selected items were of two types: All kinds of tumor-infiltrating immune cells; and advanced research on TILs in gynecological malignancies. The results showed that the subsets of TILs were various and complex, while each subpopulation influenced each other and their effects on tumor prognosis were diverse. Moreover, the related research and clinical trials on TILs were mostly concentrated in melanoma and breast cancer, but relatively few focused on gynecological tumors. In conclusion, the present review summarized the biological classification of TILs and the mechanisms of their involvement in the regulation of the immune microenvironment, and subsequently analyzed the development of tumor immunotherapy for TILs. Collectively, the present review provides ideas for the current treatment dilemma of gynecological tumor immune checkpoints, such as adverse reactions, safety, personal specificity and efficacy.

Effects of esketamine on postoperative negative emotions and early cognitive disorders in patients undergoing non-cardiac thoracic surgery: A randomized controlled trial.

STUDY OBJECTIVE: To investigate whether a single dosage of esketamine injection in the anesthesia period could improve postoperative negative emotions and early cognitive function in patients undergoing non-cardiac thoracic surgery. DESIGN: A prospective single center double blinded randomized placebo-controlled trial. SETTING: Perioperative period; operating room, post anesthesia care unit and hospital ward. PATIENTS: 129 adult patients that underwent elective non-cardiac thoracic surgery under general anesthesia. INTERVENTIONS: During the operation, pharmacologic prevention of postoperative negative emotion and early cognitive disorder with 0.2 mg/kg (Low esketamine group) and 0.5 mg/kg esketamine (High esketamine group) vs. placebo. MEASUREMENTS: Emotion and early cognitive performance were assessed on the day before surgery (POD-1), postoperative day 1 (POD1) and day 3 (POD3) using HADS-A, HADS-D, Pain Visual Analogue Scale (VAS), Confusion Assessment Method (CAM), Mini-Mental State Examination (MMSE), and serum biomarkers (S100ß, BDNF, IL-6, acetylcholine, and norepinephrine). MAIN RESULTS: The high esketamine group showed significantly lower HADS-A and HADS-D scores than control group on POD1 and POD3. No significant differences were observed between the low esketamine group and the control group. The esketamine-treated groups showed lower pain VAS scores than the control group at 2 h and on the first day after operation. There were no significant differences among the three groups in CAM and MMSE scores. However, the high esketamine group had lower S100ß and IL-6 levels, and higher BDNF levels postoperatively, while serum acetylcholine and norepinephrine were not significantly different. CONCLUSIONS: A single intraoperative injection of 0.5 mg/kg esketamine can alleviate postoperative anxiety, depression, and pain to some extent. Although cognitive function behavioral evaluation did not show obvious benefits, it can also reduce the production of pro-inflammatory and brain injury-related factors while promoting the generation of brain-derived neurotrophic factor. Registration Trial registry: http://www.chictr.org.cn/; Identifier: ChiCTR2100047067.

Model construction and drug therapy of primary ovarian insufficiency by ultrasound-guided injection.

BACKGROUND: Clinically, hormone replacement therapy (HRT) is the main treatment for primary ovarian insufficiency (POI). However, HRT may increase the risk of both breast cancer and cardiovascular disease. Exosomes derived from human umbilical cord mesenchymal stem cell (hUC-MSC) have been gradually applied to the therapy of a variety of diseases through inflammation inhibition, immune regulation, and tissue repair functions. However, the application and study of hUC-MSC exosomes in POI remain limited. METHODS: Here, we first constructed four rat animal models: the POI-C model (the "cyclophosphamide-induced" POI model via intraperitoneal injection), the POI-B model (the "busulfan-induced" POI model), the POI-U model (the "cyclophosphamide-induced" POI model under ultrasonic guidance), and MS model (the "maternal separation model"). Second, we compared the body weight, ovarian index, status, Rat Grimace Scale, complications, and mortality rate of different POI rat models. Finally, a transabdominal ultrasound-guided injection of hUC-MSC exosomes was performed, and its therapeuticy effects on the POI animal models were evaluated, including changes in hormone levels, oestrous cycles, ovarian apoptosis levels, and fertility. In addition, we performed RNA-seq to explore the possible mechanism of hUC-MSC exosomes function. RESULTS: Compared with the POI-C, POI-B, and MS animal models, the POI-U model showed less fluctuation in weight, a lower ovarian index, fewer complications, a lower mortality rate, and a higher model success rate. Second, we successfully identified hUC-MSCs and their exosomes, and performed ultrasound-guided intraovarian hUC-MSCs exosomes injection. Finally, we confirmed that the ultrasound-guided exosome injection (termed POI-e) effectively improved ovarian hormone levels, the oestrous cycle, ovarian function, and fertility. Mechanically, hUC-MSCs may play a therapeutic role by regulating ovarian immune and metabolic functions. CONCLUSIONS: In our study, we innovatively constructed an ultrasound-guided ovarian drug injection method to construct POI-U animal models and hUC-MSC exosomes injection. And we confirmed the therapeutic efficacy of hUC-MSC exosomes on the POI-U animal models. Our study will offer a better choice for new animal models of POI in the future and provides certain guidance for the hUC-MSCs exosome therapy in POI patients.

Primary acinic cell carcinoma of the breast: A case report and literature review.

Acinic cell carcinoma (ACCA), a type of malignant epithelial neoplasm, tends to occur in the parotid gland, and is occasionally found within the breast. Published literature regarding primary ACCA of the breast is scarce, and the number of reports may be fewer than 100. At present, full clinical details have not been published. As an extremely rare disorder, ACCA cannot be definitively diagnosed depending on microscopic structure alone and often requires the assistance of immunohistochemistry. Currently, universal therapies are not available. Here, we present a 47-year-old patient with a history of a palpable mass in the outer upper quadrant of the left breast for more than 2 years, which had obviously increased in size in the last half year. This patient was definitively diagnosed with primary ACCA of the breast. Neoadjuvant chemotherapy was performed preoperatively, and drug sensitivity tests based on primary tumor cells were conducted after surgery and successfully screened chemotherapy schemes for the patient's greater benefit. The whole treatment course followed the guidelines for invasive breast cancer. The patient was free of symptoms for 14 months after surgery. Long-term follow-up is in progress. Altogether, to further broaden the understanding of primary ACCA of the breast, we detail the diagnosis and treatment of one patient and review the relevant literature.

Exploring a multi-objective optimization operation model of water projects for boosting synergies and water quality improvement in big river systems.

Due to excessive nutrient enrichment and rapidly increasing water demand, the occurrence of riverine environment deterioration events such as algal blooms in rivers of China has become more frequent and severe since the 1990s, which has imposed harmful consequences on riverine ecosystems. However, tackling river algal blooms as an important issue of restoring riverine environment is very challenging because the complex interaction mechanisms between the causes are impacted by multiple factors. The contributions of our study consist of: (1) optimizing joint operation of water projects for boosting synergies of water quality and quantity, and hydroelectricity; and (2) preventing algal bloom from perspectives of hydrological and water-quality conditions by regulating water releases of water projects. This study proposed a multi-objective optimization methodology grounded on the Non-dominated Sorting Genetic Algorithm to simultaneously minimize the excess values of algal bloom indicators (water quality, O1), minimize the used reservoir capacity for water supply (water quantity, O2), and maximize the hydropower generation (hydroelectricity, O3). The proposed methodology was applied to several catastrophic algal bloom events that took place between 2017 and 2021 and thirteen water projects in the Hanjiang River of China. The results indicated that the proposed methodology largely stimulated the synergistic benefits of the three objectives by reaching a 36.7% reduction in total nitrogen and phosphorus concentrations, a 33.1% improvement in the remaining reservoir capacity, and a 41.0% improvement in hydropower output, as compared with those of the standard operation policy (SOP). In addition, the optimal water release schemes of water projects would increase the minimum streamflow velocity of downstream algal bloom control stations by 8.6%-9.4%. This study provides a new perspective on water project operation in the environmental improvement in big river systems while boosting multi-objectives synergies to support environmentalists and decision-makers with scientific guidance on sustainable water resources management.

The impact of early pregnancy metabolic disorders on pregnancy outcome and the specific mechanism.

Miscarriage is the most common complication of pregnancy. The most common causes of early miscarriage are chromosomal abnormalities of the embryo, maternal endocrine abnormalities, organ malformations, and abnormal immune factors. Late miscarriages are mostly caused by factors such as cervical insufficiency. However, the causes of 50% of miscarriages remain unknown. Recently, increasing attention has been given to the role of metabolic abnormalities in miscarriage. In this review, we mainly discuss the roles of four major metabolic pathways (glucose, lipid, and amino acid metabolism, and oxidation‒reduction balance) in miscarriage and the metabolism-related genes that lead to metabolic disorders in miscarriage. Depending on aetiology, the current treatments for miscarriage include hormonal and immunological drugs, as well as surgery, while there are few therapies for metabolism. Therefore, we also summarize the drugs for metabolism-related targets. The study of altered metabolism underlying miscarriage not only helps us to understand the mechanisms involved in miscarriage but also provides an important basis for clinical research on new therapies.

Pan-cancer analysis of oncogenic role of insulin-like growth factor-binding proteins and validation in ovarian cancer.

BACKGROUND: Numerous studies have shown that the insulin-like growth factor (IGF) pathway is highly associated with tumor initial and progression in several tumors. However, compared with IGF1/1R and IGF2/2R, insufficient studies have focused on IGF-binding proteins (IGFBPs). METHODS: The GDC TCGA and GTEx data of 33 cancers, TCGA pan-cancer immune phenotypes, tumor mutation burdens, and the copy number alterations of IGFBPs were extracted. Next, the prognostic value of IGFBPs was analyzed based on a univariate Cox analysis. Additionally, the ESTIMATE algorithm was used to calculate stromal and immune scores and tumor purity, and the CIBERSORT algorithm was used to estimate tumor-infiltrating immunocyte levels. Ultimately, the correlation between IGFBP expression and cancer hallmark pathways was estimated with a Spearman analysis. RESULTS: The expression of IGFBPs was differentially expressed and correlated with prognosis in specific cancers. IGFBPs may operate as biological markers for carcinogenesis and progression and as prognostic biomarkers. Additionally, IGFBP5 has been proved that promotes the invasion and migration of ovarian cancer. CONCLUSIONS: In general, IGFBPs can serve as predictable biomarkers and potential therapeutic targets for specific tumors. Our results could provide underlying targets for the design of laboratory experiments to elucidate the mechanism of IGFBPs in cancers and identify IGFBP5 as a prognostic factor in ovarian cancers.

Comparison of the different animal modeling and therapy methods of premature ovarian failure in animal model.

Incidence of premature ovarian failure (POF) is higher with the increase of the pace of life. The etiology of POF is very complex, which is closely related to genes, immune diseases, drugs, surgery, and psychological factors. Ideal animal models and evaluation indexes are essential for drug development and mechanism research. In our review, we firstly summarize the modeling methods of different POF animal models and compare their advantages and disadvantages. Recently, stem cells are widely studied for tumor treatment and tissue repair with low immunogenicity, high homing ability, high ability to divide and self-renew. Hence, we secondly reviewed recently published data on transplantation of stem cells in the POF animal model and analyzed the possible mechanism of their function. With the further insights of immunological and gene therapy, the combination of stem cells with other therapies should be actively explored to promote the treatment of POF in the future. Our article may provide guidance and insight for POF animal model selection and new drug development.

Deletion of Insulin-like growth factor II mRNA-binding protein 3 participates in the pathogenesis of recurrent spontaneous abortion by inhibiting IL-10 secretion and inducing M1 polarization.

Insulin-like growth factor II mRNA-binding protein 3 (IGF2BP3) has been proved to affect trophoblast function and embryonic development, but its role and potential mechanism in recurrent spontaneous abortion (RSA) are not clear. RSA is a complex reproductive disease, causing physical and mental damage to patients. In recent years, many studies have found that immune microenvironment is vital to maintain successful pregnancy in the maternal fetal interface. Therefore, this study aims to explore the role of IGF2BP3 in affecting macrophage polarization and its possible mechanism. In this article, we found that IGF2BP3 expression was decreased in placental villous samples of human and RSA mouse model, and knockdown of IGF2BP3 in HTR8/SVneo cells promotes M1 Mφ polarization. Combining with RNA sequencing analysis, we found that IGF2BP3 may regulate the Mφ polarization by affecting the expression of trophoblast cytokines, especially IL-10 secretion. Further mechanistic studies showed that knockdown of IGF2BP3 decreased expression of IL-10 by activating NF-κB pathway. Moreover, we found that M2 Mφ promote trophoblast invasion not IGF2BP3 dependent. Our study reveals the interaction between trophoblast cells and macrophages at the maternal-fetal interface of RSA patients, and will provide theoretical guidance for its diagnosis and treatment of RSA patients.

Removal of an Aminopeptidase N From Midgut Brush Border Does Not Affect Susceptibility of Spodoptera litura (Lepidoptera: Noctuidae) Larvae to Four Insecticidal Proteins of Bacillus thuringiensis (Bacillales: Bacillaceae).

Spodoptera litura is one of the most destructive lepidopteran insects of cabbages and cauliflowers in the world. Cry1 and Vip3 toxins from Bacillus thuringiensis have been reported to show toxicity in multiple lepidopteran insects. Binding of toxic molecules to specific receptors on the midgut epithelial cells is known to be a key step in the action mode of Bt toxins. Aminopeptidase N (APN) -like proteins have been reported to be binding sites of multiple Cry toxins in the midgut of Cry susceptible insects. In the present study, we identified six midgut APNs by analysis of the genome and midgut transcriptome of S. litura. CRISPR/Cas9 mediated gene-knockout system was utilized to mutate the GPI-anchor signal peptide at the C terminus of SlAPN1. SlAPN1 was verified to be removed from the midgut brush border membrane vesicles of a homozygous knockout strain of S. litura (SlAPN1-KO). Bioassay results indicated that susceptibility of the SlAPN1-KO strain to Cry1Aa, Cry1Ac, Cry1Ca, and Vip3Aa toxins was close to that of the wild-type strain of S. litura. RT-qPCR results showed that the transcriptional level of SlAPN2-6 was not up-regulated after knockout of the SlAPN1. Results in this study indicated that the SlAPN1 did not play a critical role in the pathway of toxicity of Cry1Aa, Cry1Ac, Cry1Ca, and Vip3Aa toxins in S. litura.

Gene signature of m6A-related targets to predict prognosis and immunotherapy response in ovarian cancer.

PURPOSE: The aim of the study was to construct a risk score model based on m6A-related targets to predict overall survival and immunotherapy response in ovarian cancer. METHODS: The gene expression profiles of 24 m6A regulators were extracted. Survival analysis screened 9 prognostic m6A regulators. Next, consensus clustering analysis was applied to identify clusters of ovarian cancer patients. Furthermore, 47 phenotype-related differentially expressed genes, strongly correlated with 9 prognostic m6A regulators, were screened and subjected to univariate and the least absolute shrinkage and selection operator (LASSO) Cox regression. Ultimately, a nomogram was constructed which presented a strong ability to predict overall survival in ovarian cancer. RESULTS: CBLL1, FTO, HNRNPC, METTL3, METTL14, WTAP, ZC3H13, RBM15B and YTHDC2 were associated with worse overall survival (OS) in ovarian cancer. Three m6A clusters were identified, which were highly consistent with the three immune phenotypes. What is more, a risk model based on seven m6A-related targets was constructed with distinct prognosis. In addition, the low-risk group is the best candidate population for immunotherapy. CONCLUSION: We comprehensively analyzed the m6A modification landscape of ovarian cancer and detected seven m6A-related targets as an independent prognostic biomarker for predicting survival. Furthermore, we divided patients into high- and low-risk groups with distinct prognosis and select the optimum population which may benefit from immunotherapy and constructed a nomogram to precisely predict ovarian cancer patients' survival time and visualize the prediction results.

MiR-93-5p promotes granulosa cell apoptosis and ferroptosis by the NF-kB signaling pathway in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. miR-93-5p has been reported to be elevated in granulosa cells of PCOS patients. However, the mechanism by which miR-93-5p drives granulosa cell (GC) progression remains unclear. Thus, this study focuses on the roles and mechanisms of miR-93-5p in the GCs of PCOS. Methods: KGN cells have similar ovarian physiological characteristics and are used to study the function and regulatory mechanism of GCs. In this study, KGN cells were transfected with si-NC, si-miR93-5p, oe-NC and oe-miR93-5p. A cell counting kit-8 assay, flow cytometry and western blotting were performed to observe the proliferation and apoptosis of KGN in different groups. Subsequently, the levels of reactive oxygen species, malondialdehyde, GPX4, SLC7A11 and Nrf2, which are indicators of ferroptosis, were measured by a dihydroethidium fluorescent dye probe, biochemical kit, western blotting and reverse transcription quantitative polymerase chain reaction. Ultimately, bioinformatic analysis and experimental methods were used to examine the interaction between miR-93-5p and the NF-κB signaling pathway. Results: miR-93-5p was upregulated in the GCs of PCOS patients. Overexpression of miR-93-5p promoted apoptosis and ferroptosis in KGN cells, while knockdown of miR-93-5p showed the reverse effect. Biological analysis and subsequent experiments demonstrated that miR-93-5p negatively regulates the NF- κB signaling pathway. Conclusion: miR-93-5p promotes the apoptosis and ferroptosis in GC by regulating the NF-κB signaling pathway. Silencing of miR-93-5p protects against GC dysfunction. Our study identified miR-93-5p as a new molecular target for improving the function of GCs in PCOS patients.

Epigenetic and transcriptomic characterization of maternal-fetal interface in patients with recurrent miscarriage via an integrated multi-omics approach.

Recurrent miscarriage (RM) occurs in 2.5 % of women aiming at childbirth, with unknown etiology in half of the cases. To identify the molecular features, an integrative study combining bioinformatics and multi-omics from GEO database was performed in these patients. Two datasets (GSE43256 and GSE73025) were integrated to indicate 1657 differentially expressed genes (DE-genes) in villus of females with RM. DE-genes in villus of females with RM mainly focused on cell growth and development. On the other hand, 230 DE-genes in decidua of RM patients were retrieved from GSE113790, and the DE-genes were involved in diverse functions, including transport of nutrients, immune response, extracellular matrix remodeling, and angiogenesis. Additionally, the results of immunologic signatures indicated that immune regulation played roles in both decidua and villus of RM. Interestingly, C1q and TNF related 7 (C1QTNF7), acquired from the intersection of decidua and villus datasets, is crucial in maintaining immune homeostasis, so is its upstream miRNA (miR-149-3p). The enhanced expression of C1QTNF7 in macrophages might inhibit the proliferation and migration of trophoblasts, and further result in pregnancy loss. The present study suggests C1QTNF7 might be a new target for the diagnosis and treatment of RM, but more basic researches are further required to illustrate its mechanism in RM.

Integrated Bioinformatic Analysis of DNA Methylation and Immune Infiltration in Endometrial Cancer.

Background: Endometrial cancer greatly threatens the health of female. Emerging evidences have demonstrated that DNA methylation and immune infiltration are involved in the occurrence and development of endometrial cancer. However, the mechanism and prognostic biomarkers of endometrial cancer are still unclear. In this study, we assess DNA methylation and immune infiltration via bioinformatic analysis. Methods: The latest RNA-Seq, DNA methylation data, and clinical data related to endometrial cancer were downloaded from the UCSC Xena dataset. The methylation-driven genes were selected, and then the risk score was obtained using "MethylMix" and "corrplot" R packages. The connection between methylated genes and the expression of screened driven genes were explored using "survminer" and "beeswarm" packages, respectively. Finally, the role of VTCN1in immune infiltration was analyzed using "CIBERSORT" package. Results: In this study, 179 upregulated genes, and 311 downregulated genes were identified and found to be related to extracellular matrix organization, cell-cell junctions, and cell adhesion molecular binding. The methylation-driven gene VTCN1 was selected, and patients classified to the hypomethylation and high expression group displayed poor prognosis. The VTCN1 gene exhibited highest correlation coefficient between methylation and expression. More importantly, the hypomethylation of promoter of VTCN1 led to its high expression, thereby induce tumor development by inhibiting CD8+ T cell infiltration. Conclusions: Overall, our study was the first to reveal the mechanism of endometrial cancer by assessing DNA methylation and immune infiltration via integrated bioinformatic analysis. In addition, we found a pivotal prognostic biomarker for the disease. Our study provides potential targets for the diagnosis and prognosis of endometrial cancer in the future.

Ecological risk assessment and sources identification of heavy metals in surface sediments of a river-reservoir system.

Heavy metal contamination of river water and sediments is a global issue affecting ecological health. To reveal heavy metals' ecological risks and biological toxicity in the middle and lower Han River (MLHR), sediment samples collected in this area were analyzed based on a modified ecological risk assessment method (NIRI) and a biological toxicity assessment method. Also, Spearman correlation analysis and Positive Matrix Factorization (PMF) methods were applied to identify the potential sources of heavy metals. The results indicated that the heavy metal content significantly exceeded the background concentrations in Hubei Province. The average potential risk of heavy metals at sampling sites was: Cd > Hg > As > Pb > Cu > Zn. Consequently, high biological toxicity occurred along the MLHR due to the heavy metal enrichment. River damming and water diversion significantly enhanced the hydrologic regime variations and ecological risk in the MLHR. Moreover, two possible pollution sources of the MLHR were identified: one is a combined source of traffic pollution, agricultural pollution, and partial industrial pollution consisting of five heavy metals, Pb, Hg, Zn, Cu, and As, the other is an industrial pollution source dominated by Cd and As. This study provides insights into sediment heavy metal pollution management and ecological risk control in the MLHR and similar rivers worldwide.

The Mechanism of Insulin-Like Growth Factor II mRNA-Binging Protein 3 Induce Decidualization and Maternal-Fetal Interface Cross Talk by TGF-ß1 in Recurrent Spontaneous Abortion.

Recurrent spontaneous abortion (RSA) is defined as the loss of two or more consecutive intrauterine pregnancies that are clinically established early in pregnancy. To date, the etiology and underlying mechanisms of RSA remain unclear. It is widely thought that the impairment of decidualization is inclined to induce subsequent pregnancy failure and leads to the dysregulation of extra-villous trophoblast invasion and proliferation through maternal-fetal cross talk. However, the mechanism of decidualization in RSA has yet to be understood. In our study, we demonstrate that decidual samples from RSA patients have significantly higher insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and lower TGF-ß1 levels compared to healthy controls. In addition, the overexpression of IGF2BP3 in human endometrial stromal cells (hESCs) can lead to the impairment of decidualization in vitro-induced model and the abnormal cell cycle regulation. Furthermore, TGF-ß1 and MMP9 levels were greatly increased after decidualization, whereas IGF2BP3 overexpression inhibited endometrial mesenchymal decidualization by downregulating TGF-ß1, impeding maternal-fetal interface cytokine cross talk, and limiting the ability of trophoblast invasion. In conclusion, our investigation first demonstrates that abnormal elevation of IGF2BP3 in the pregnant endometrium leads to the impairment of decidualization and abnormal trophoblast invasion, thereby predisposing individuals to RSA.

The clinical value of miRNA-21 in cervical cancer: A comprehensive investigation based on microarray datasets.

Previous work has demonstrated that the expression of microRNA-21 (miR-21) is implicated in cervical cancer (CC). However, little is known regarding its associations with clinical parameters. We first conducted a meta-analysis using data from Gene Expression Omnibus (GEO) microarrays and The Cancer Genome Atlas (TCGA). Then, enrichment analysis and hub gene screening were performed by bioinformatic methods. Finally, the role of the screened target genes in CC was explored. According to the meta-analysis, the expression of miR-21 in cancer tissues was higher than in adjacent nontumor tissues (P < 0.05). In addition, 46 genes were predicted as potential targets of miR-21. After enrichment analyses, it was detected that these genes were enriched in various cancer pathways, including the phosphatidylinositol signaling system and mammalian target of rapamycin (mTOR) signaling pathway. In this study, bioinformatic tools and meta-analysis validated that miR-21 may function as a highly sensitive and specific marker for the diagnosis of CC, which may provide a novel approach to the diagnosis and treatment of CC.

Immune-Related Genes to Construct a Novel Prognostic Model of Breast Cancer: A Chemosensitivity-Based Study.

Chemotherapy combined with surgery is effective for patients with breast cancer (BC). However, chemoresistance restricts the effectiveness of BC treatment. Immune microenvironmental changes are of pivotal importance for chemotherapy responses. Thus, we sought to construct and validate an immune prognostic model based on chemosensitivity status in BC. Here, immune-related and chemosensitivity-related genes were obtained from GSE25055. Then, univariate analysis was employed to identify prognostic-related gene pairs from the intersection of the two parts of the genes, and modified least absolute shrinkage and selection operator (LASSO) analysis was performed to build a prognostic model. Furthermore, we investigated the efficiency of this model from various perspectives, and further validation was performed using the Cancer Genome Atlas (TCGA) cohorts. We identified seven immune and chemosensitivity-related gene pairs and incorporated them into the Cox regression model. After multilevel validation, the risk model was found to be closely related to the survival rate, various clinical characteristics, tumor mutation burden (TMB) score, immune checkpoints, and response to chemotherapeutic drugs. In addition, the model was verified to exhibit predictive capacity as an independent factor over other candidate clinical features. Notably, the constructed nomogram was more accurate than any single factor. Altogether, the risk score model and the nomogram have potential predictive value and may have important practical implications.

Landscape of Immune Microenvironment in Epithelial Ovarian Cancer and Establishing Risk Model by Machine Learning.

BACKGROUND: Epithelial ovarian cancer (EOC) is an extremely lethal gynecological malignancy and has the potential to benefit from the immune checkpoint blockade (ICB) therapy, whose efficacy highly depends on the complex tumor microenvironment (TME). METHOD AND RESULT: We comprehensively analyze the landscape of TME and its prognostic value through immune infiltration analysis, somatic mutation analysis, and survival analysis. The results showed that high infiltration of immune cells predicts favorable clinical outcomes in EOC. Then, the detailed TME landscape of the EOC had been investigated through "xCell" algorithm, Gene set variation analysis (GSVA), cytokines expression analysis, and correlation analysis. It is observed that EOC patients with high infiltrating immune cells have an antitumor phenotype and are highly correlated with immune checkpoints. We further found that dendritic cells (DCs) may play a dominant role in promoting the infiltration of immune cells into TME and forming an antitumor immune phenotype. Finally, we conducted machine-learning Lasso regression, support vector machines (SVMs), and random forest, identifying six DC-related prognostic genes (CXCL9, VSIG4, ALOX5AP, TGFBI, UBD, and CXCL11). And DC-related risk stratify model had been well established and validated. CONCLUSION: High infiltration of immune cells predicted a better outcome and an antitumor phenotype in EOC, and the DCs might play a dominant role in the initiation of antitumor immune cells. The well-established risk model can be used for prognostic prediction in EOC.