The relationship between immune cells and prostate cancer, and the mediating role of metabolites: a Mendelian randomization study.

Research has demonstrated the significant involvement of immune cells in the development and progression of prostate cancer (PCa). However, the precise causal relationship between immune cells and PCa remains unclear. This study utilized bidirectional Mendelian randomization (MR) analysis to investigate the causal link between immune cells and PCa. Additionally, employed mediation MR design to ascertain the potential mediating role of metabolites in the connection between immune cells and PCa outcomes. Unswitched memory B cell % lymphocyte and CD24 + CD27 + B cell % lymphocyte were positively related to PCa risk, while CD62L - monocyte absolute count and CD62L - monocyte % monocyte were negatively associated with PCa risk. Sensitivity analysis was conducted to validate these results. The mediation MR results indicate that 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) levels may be an independent risk factor for PCa, while the succinate to acetoacetate ratio (SA ratio) was found to be a mediator for the effect of CD62L - monocyte % monocyte on PCa, with a mediation proportion of 16.6% (mediation percentage: 16.6%, 95%CI - 163% - 196%). The research validates the genetic causality between particular immune cells and PCa, and has emphasized the potential intermediary function of SA ratio. These noteworthy discoveries provide fresh perspectives for the clinical management of PCa.

Sequential embryo transfer combined with intrauterine perfusion improved pregnancy outcomes in patients with recurrent implantation failure.

OBJECTIVE: To compare the application of sequential embryo transfer, cleavage embryo transfer, and blastocyst transfer combined with intrauterine perfusion in frozen-thawed embryo transfer cycles in patients with recurrent implantation failure to provide a reference for reproductive clinicians. METHODS: The 166 patients who underwent frozen-thawed embryo transfer due to recurrent implantation failure in the reproductive center from January 2021 to March 2022 were retrospectively analyzed. According to the different embryos transferred, they were divided into cleavage embryo transfer groups (72 cases in Group A), blastocyst transfer group (29 cases in Group B), and sequential transfer group (65 cases in Group C). All three groups were treated with intrauterine perfusion 5 days before embryo transfer. The general data and clinical pregnancy outcome indicators, such as embryo implantation rate, clinical pregnancy rate, ongoing pregnancy rate, live birth rate, twin rate, were compared among the three groups. RESULTS: The embryo implantation rate (53.1%), clinical pregnancy rate (76.9%), ongoing pregnancy rate (67.7%) and live birth rate(66.15%) in the sequential transfer group were significantly higher than those in the other two groups (P < 0.05), and the ectopic pregnancy rate was lower in the sequential transfer group. CONCLUSION: Sequential transfer combined with intrauterine perfusion partially improves clinical pregnancy outcomes and reduces the risk of ectopic pregnancy in frozen embryo cycle transfers in patients with recurrent implantation failure, which may be a favourable transfer reference strategy for patients with recurrent implantation failure.

ANGPTL4 accelerates ovarian serous cystadenocarcinoma carcinogenesis and angiogenesis in the tumor microenvironment by activating the JAK2/STAT3 pathway and interacting with ESM1.

BACKGROUND: Ovarian cancer (OC) is a malignant neoplasm that displays increased vascularization. Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that functions as a regulator of cell metabolism and angiogenesis and plays a critical role in tumorigenesis. However, the precise role of ANGPTL4 in the OC microenvironment, particularly its involvement in angiogenesis, has not been fully elucidated. METHODS: The expression of ANGPTL4 was confirmed by bioinformatics and IHC in OC. The potential molecular mechanism of ANGPTL4 was measured by RNA-sequence. We used a series of molecular biological experiments to measure the ANGPTL4-JAK2-STAT3 and ANGPTL4-ESM1 axis in OC progression, including MTT, EdU, wound healing, transwell, xenograft model, oil red O staining, chick chorioallantoic membrane assay and zebrafish model. Moreover, the molecular mechanisms were confirmed by Western blot, Co-IP and molecular docking. RESULTS: Our study demonstrates a significant upregulation of ANGPTL4 in OC specimens and its strong association with unfavorable prognosis. RNA-seq analysis affirms that ANGPTL4 facilitates OC development by driving JAK2-STAT3 signaling pathway activation. The interaction between ANGPTL4 and ESM1 promotes ANGPTL4 binding to lipoprotein lipase (LPL), thereby resulting in reprogrammed lipid metabolism and the promotion of OC cell proliferation, migration, and invasion. In the OC microenvironment, ESM1 may interfere with the binding of ANGPTL4 to integrin and vascular-endothelial cadherin (VE-Cad), which leads to stabilization of vascular integrity and ultimately promotes angiogenesis. CONCLUSION: Our findings underscore that ANGPTL4 promotes OC development via JAK signaling and induces angiogenesis in the tumor microenvironment through its interaction with ESM1.

Comprehensive Analyses and Experiments Confirmed IGFBP5 as a Prognostic Predictor Based on an Aging-genomic Landscape Analysis of Ovarian Cancer.

BACKGROUND: Ovarian cancer (OC) is one of the malignant diseases of the reproductive system in elderly women. Aging-related genes (ARGs) were involved in tumor malignancy and cellular senescence, but the specifics of these mechanisms in OC remain unknown. METHODS: ARGs expression and survival data of OC patients were collected from TCGA and CPTAC databases. Subtype classification was used to identify the roles of hub ARGs in OC progression, including function enrichment, immune infiltration, and drug sensitivity. LASSO regression was utilized to confirm the prognosis significance for these hub ARGs. MTT, EdU, Transwell, and wounding healing analysis confirmed the effect of IGFBP5 on the proliferation and migration ability of OC cells. RESULTS: ARGs were ectopically expressed in OC tissues compared to normal ovary tissues. Three molecular subtypes were divided by ARGs for OC patients. There were significant differences in ferroptosis, m6A methylation, prognosis, immune infiltration, angiogenesis, differentiation level, and drug sensitivity among the three groups. LASSO regression indicated that 4 signatures, FOXO4, IGFBP5, OGG1 and TYMS, had important prognosis significance. Moreover, IGFBP5 was significantly correlated with immune infiltration. The hub ARG, IGFBP5, expression was significantly decreased in OC patients compared to normal women. IGFBP5 could also reduce the migration and proliferation ability of OC cells compared to vector and NC groups. CONCLUSION: IGFBP5 was correlated with OC prognosis and associated with OC migration and proliferation. This gene may serve as potential prognostic biomarkers and therapeutic targets for OC patients.

Identification of bromodomain-containing proteins prognostic value and expression significance based on a genomic landscape analysis of ovarian serous cystadenocarcinoma.

Background: Ovarian serous cystadenocarcinoma (OSC), a common gynecologic tumor, is characterized by high mortality worldwide. Bromodomain (BRD)-containing proteins are a series of evolutionarily conserved proteins that bind to acetylated Lys residues of histones to regulate the transcription of multiple genes. The ectopic expression of BRDs is often observed in multiple cancer types, but the role of BRDs in OSC is still unclear. Methods: We performed the differential expression, GO enrichment, GSEA, immune infiltration, risk model, subtype classification, stemness feature, DNA alteration, and epigenetic modification analysis for these BRDs based on multiple public databases. Results: Most BRDs were dysregulated in OSC tissues compared to normal ovary tissues. These BRDs were positively correlated with each other in OSC patients. Gene alteration and epigenetic modification were significant for the dysregulation of BRDs in OSC patients. GO enrichment suggested that BRDs played key roles in histone acetylation, viral carcinogenesis, and transcription coactivator activity. Two molecular subtypes were classified by BRDs for OSC, which were significantly correlated with stemness features, m6A methylation, ferroptosis, drug sensitivity, and immune infiltration. The risk model constructed by LASSO regression with BRDs performed moderately well in prognostic predictions for OSC patients. Moreover, BRPF1 plays a significant role in these BRDs for the development and progression of OSC patients. Conclusion: BRDs are potential targets and biomarkers for OSC patients, especially BRPF1.

Comprehensive analysis of the glutathione S-transferase Mu (GSTM) gene family in ovarian cancer identifies prognostic and expression significance.

Background: Ovarian cancer (OC) is one of the most common types of gynecologic tumor over the world. The Glutathione S-transferase Mu (GSTM) has five members, including GSTM1-5. These GSTMs is involved in cell metabolism and detoxification, but their role in OC remains unknown. Methods: Data from multiple public databases associated with OC and GSTMs were collected. Expression, prognosis, function enrichment, immune infiltration, stemness index, and drug sensitivity analysis was utilized to identify the roles of GSTMs in OC progression. RT-qPCR analysis confirmed the effect of AICAR, AT-7519, PHA-793887 and PI-103 on the mRNA levels of GSTM3/4. Results: GSTM1-5 were decreased in OC samples compared to normal ovary samples. GSTM1/5 were positively correlated with OC prognosis, but GSTM3 was negatively correlated with OC prognosis. Function enrichment analysis indicated GSTMs were involved in glutathione metabolism, drug metabolism, and drug resistance. Immune infiltration analysis indicated GSTM2/3/4 promoted immune escape in OC. GSTM5 was significantly correlated with OC stemness index. GSTM3/4 were remarkedly associated with OC chemoresistance, especially in AICAR, AT-7519, PHA-793887 and PI-103. Conclusion: GSTM3 was negatively correlated with OC prognosis, and associated with OC chemoresistance and immune escape. This gene may serve as potential prognostic biomarkers and therapeutic target for OC patients.

Antimicrobial susceptibility profiles of Mycobacterium abscessus complex isolates from respiratory specimens in Shanghai, China.

OBJECTIVES: The aim of this study was to compare the antibiotic susceptibility profiles of Mycobacterium abscessus complex (MABC) isolates and to investigate the relationship between susceptibility profiles and genetic mechanisms of macrolide resistance. METHODS: More than 200 isolates collected from respiratory specimens between 2014 and 2018 were randomly analysed in this study. Minimum inhibitory concentrations (Mics) of ten potential antimicrobial agents were determined by the microplate alamarBlue assay. RESULTS: We identified 43 MABC isolates, including 32 M. abscessus subsp. abscessus (M. abscessus) (6 from immunocompromised patients) and 11 M. abscessus subsp. massiliense (M. massiliense). The majority of MABC isolates were susceptible to amikacin (96.9% and 100.0% for M. abscessus and M. massiliense, respectively), linezolid (96.9% and 100.0%, respectively), cefoxitin (100.0% and 100.0%, respectively), imipenem (90.6% and 72.7%, respectively) and tobramycin (90.6% and 72.7%, respectively). The resistance rates to clarithromycin and doxycycline in isolates of M. abscessus (68.8% and 100.0%) were significantly higher than those in isolates of M. massiliense (18.2% and 63.6%) (P < 0.05), whereas the percentage of tobramycin-resistant isolates among M. abscessus (9.4%) was significantly lower than among M. massiliense (27.3%) (P = 0.007). Sequencing analyses showed significant differences between erm(41) of M. abscessus and M. massiliense. CONCLUSION: Mycobacterium abscessus is the dominant pathogen of pulmonary MABC infections in our hospital. Aminoglycosides (amikacin and tobramycin), ß-lactams (cefoxitin and imipenem) and linezolid exhibited potent inhibitory activity against MABC in vitro. The erm(41) gene may be a promising marker to predict macrolide susceptibility for M. abscessus.

Fibrosarcoma of the corpus cavernosum: case report and literature review.

BACKGROUND: Fibrosarcoma is a very rare tumor that arises from fibrous tissue. Less than 5% of fibrosarcoma originate from the urogenital tract. Penile fibrosarcoma, even more rare, is characterized by pain, enlargement, penile erection and urinary tract obstruction. To our knowledge, this is the second reported case named "fibrosarcoma of the corpus cavernosum". CASE PRESENTATION: A 51-year-old male presented with a 1-month history of penis pain during erection. CT scan showed a soft tissue mass arising from the proximal part of the penis. We diagnosed it as penile sarcoma, performing local excision. The postoperative pathological result was moderately differentiated fibrosarcoma. 3 months later, CT scan showed the recurrence of the tumor, and multiple metastases. Although he received chemotherapy, he died 10 months after surgery. CONCLUSIONS: Fibrosarcoma of the corpus cavernosum is rare and have poor prognosis. Total penile amputation may be the best treatment. The effects of chemotherapy are limited. No more effective treatment has been found for a disseminated disease to date.

Knockdown of vascular cell adhesion molecule 1 impedes transforming growth factor beta 1-mediated proliferation, migration, and invasion of endometriotic cyst stromal cells.

PURPOSE: Endometriosis is one of the most common, difficult, and complicated gynecological disorders. Vascular cell adhesion molecule 1 (VCAM-1) has been reported to be aberrantly expressed in patients with endometriosis. However, the exact role and mechanism of VCAM-1 in endometriosis remains unclear. METHODS: The expression of transforming growth factor beta 1 (TGF-ß1) and VCAM-1 was determined by quantitative real-time polymerase chain reaction and western blotting. Human endometriotic cells were cultured and their responsiveness to TGF-ß1 was evaluated by Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, and transwell migration and invasion assays. RESULTS: The levels of TGF-ß1 and VCAM-1 mRNA were upregulated in the endometriotic tissues. Knockdown of TGF-ß1 in endometriotic cyst stromal cells caused a marked inhibition of cell proliferation, migration, and invasion. Treatment of endometriotic cyst stromal cells with TGF-ß1 resulted in an obvious promotion of cell proliferation, migration, and invasion, and strikingly increased the protein expression of VCAM-1. Silencing of Smad3 abated TGF-ß1-stimulated VCAM-1 expression. Furthermore, the promoting effects of TGF-ß1 on the proliferation, migration, and invasion of endometriotic cyst stromal cells were blocked by silencing of VCAM-1. CONCLUSION: Knockdown of VCAM-1 impedes TGF-ß1-mediated proliferation, migration, and invasion of endometrial cells, thereby indicating that VCAM-1 may serve as a therapeutic target for endometriosis.