Alzheimer's disease increases the risk of erectile dysfunction independent of cardiovascular diseases: A mendelian randomization study.

BACKGROUND: Previous research has underscored the correlation between Alzheimer's disease (AD) and erectile dysfunction (ED). However, due to inherent limitations of observational studies, the causative relationship remains inconclusive. METHODS: Utilizing publicly available data from genome-wide association studies (GWAS) summary statistics, this study probed the potential causal association between AD and ED using univariate Mendelian randomization (MR). Further, the multivariable MR assessed the confounding effects of six cardiovascular diseases (CVDs). The primary approach employed was inverse variance weighted (IVW), supplemented by three additional methods. A series of sensitivity analyses were conducted to ensure the robustness of the results. RESULTS: In the forward MR analysis, the IVW method revealed causal evidence of genetically predicted AD being a risk factor for ED (OR = 1.077, 95% CI 1.007∼1.152, P = 0.031). Reverse analysis did not demonstrate any causal evidence linking ED to AD (OR = 1.018, 95% CI 0.974∼1.063, P = 0.430). Multivariable MR analysis showed that after adjusting for coronary heart disease (OR = 1.082, 95% CI 0.009∼1.160, P = 0.027), myocardial infarction (OR = 1.085, 95% CI 1.012∼1.163, P = 0.022), atrial fibrillation (OR = 1.076, 95% CI 1.002∼1.154, P = 0.043), heart failure (OR = 1.103, 95% CI 1.024∼1.188, P = 0.010), ischemic stroke (OR = 1.079, 95% CI 1.009∼1.154, P = 0.027), hypertension (OR = 1.092, 95% CI 1.011∼1.180, P = 0.025), and all models (OR = 1.115, 95% CI 1.024∼1.214, P = 0.012), the causal association between AD and ED persisted. Sensitivity analyses confirmed the absence of pleiotropy, heterogeneity, and outliers, validating the robustness of our results (P > 0.05). CONCLUSIONS: This MR study consistently evidences a causal effect of genetically predicted AD on the risk of ED, independent of certain CVDs, yet offers no evidence for a reverse effect from ED.

[Exploring the mechanisms of Jujing pill on varicocele-associated male infertility via network pharmacology and molecular docking technology].

OBJECTIVE: To investigate the potential mechanism of treating varicocele-associated male infertility with Jujing pill using network pharmacology and molecular docking technology. METHODS: The TCMSP and BATMAN databases were used to search for the Chinese medicine components of the Jujing pill and obtain the corresponding targets. The databases GeneCards, DISGENET, OMIM, and HPO were searched for 'varicocele' and 'male infertility' to identify the potential targets of varicocele-associated male infertility. Wayne diagrams were drawn using the jvenn tool to determine the intersection targets of the Chinese medicine targets and disease targets. The intersecting targets were further analyzed to identify the components and Chinese medicine corresponding to them. A Chinese medicine-active ingredient-target network map was constructed in Cytoscape 3.8.2. The protein-protein interaction (PPI) network of the intersecting targets was constructed using the STRING platform. The intersecting targets were imported into the DAVID database for GO enrichment analysis and KEGG-based pathway enrichment analysis. The KEGG database was used to select the most relevant pathway to the topic, and a KEGG pathway map was constructed using the mapper tool. The top 15 pathways with FDR values and their related targets and components were used to draw a core ingredient-target-pathway map. Finally, molecular docking was performed to verify the protein receptors and small molecule ligands of the core genes, and the results were visualized using AutoDock and PyMol software. RESULTS: A total of 207 ingredients and 1103 predicted targets of Jujing pill were screened. Additionally, 285 targets of varicocele were also identified. By using a Venn diagram, 86 common targets were obtained. The analysis of Gene Ontology (GO) results revealed significant enrichment in various biological processes (BP) such as positive regulation of gene expression, positive regulation of transcription, positive and negative regulation of apoptotic processes, response to hypoxia, response to estradiol, and positive regulation of nitric oxide biosynthesis processes. Furthermore, significant enrichment in cellular components (CC) was observed in macromolecules, cytoplasm, nucleus, and phosphatidylinositol 3-kinase complex. In terms of molecular function (MF), enrichment was found in enzyme binding, identical protein binding, transcriptional co-activator binding, and others. KEGG analysis demonstrated enrichment in pathways related to cancer, AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, FoxO signaling pathway, and more. Molecular docking results indicated that the core ingredients exhibited a strong binding capacity with the key targets. Conclusion： The effective active ingredients of Jujing pill exert their therapeutic effects on varicocele-associated male infertility through multiple targets and pathways. These findings provide a theoretical basis for future cell and animal experiments to verify the mechanism of action of Jujing pill in treating varicocele-associated male infertility.

Synthetic Biology-Driven Microbial Production of Resveratrol: Advances and Perspectives.

Resveratrol, a bioactive natural product found in many plants, is a secondary metabolite and has attracted much attention in the medicine and health care products fields due to its remarkable biological activities including anti-cancer, anti-oxidation, anti-aging, anti-inflammation, neuroprotection and anti-glycation. However, traditional chemical synthesis and plant extraction methods are impractical for industrial resveratrol production because of low yield, toxic chemical solvents and environmental pollution during the production process. Recently, the biosynthesis of resveratrol by constructing microbial cell factories has attracted much attention, because it provides a safe and efficient route for the resveratrol production. This review discusses the physiological functions and market applications of resveratrol. In addition, recent significant biotechnology advances in resveratrol biosynthesis are systematically summarized. Furthermore, we discuss the current challenges and future prospects for strain development for large-scale resveratrol production at an industrial level.

[Relationship of pathogenic microorganisms and chronic inflammation with prostate cancer].

Prostate cancer is a common malignant tumor in elderly men, which seriously affects the physical and mental health of the patients. The pathogenesis of prostate cancer is still unclear though thought of to be possibly associated with age, race, diet, infection and inflammation. In recent years, more and more studies have found a close correlation of prostate cancer to pathogenic microorganisms and chronic inflammation, and that pathogenic microorganisms cause increase genome damage and instability of the cells, and induce mutations with the involvement of cytokines and oxidative stress molecular mechanisms. This review summarizes the advances in the studies of the correlation of pathogenic microorganisms and chronic inflammation with prostate cancer.

Long noncoding RNA H19 promotes the apoptosis of corpus cavernsum smooth muscle cells after cavernosal nerve injury via JNK signalling pathway.

JNK/ Bcl-2/ Bax pathway participates in corpus cavernosal smooth muscle cells apoptosis during early period after cavernosal nerve (CN) crush injury (CNCI). Nevertheless, the regulation mechanisms of long noncoding RNA H19 in apoptosis during early stage after CN injury are still poorly understood. The rats in sham group were not direct injury to the CNs. The rats in CNCI group were performed to bilateral CN crush injury. The ICP/MAP rate and smooth muscle content were significantly lower than that in the sham group. Primary CCSMCs were prepared from the tissues samples after completing erectile function detection. Phosphorylated-JNK level was increased significantly, and the expression of Bax and Bcl-2 was elevated and declined in CNCI group respectively. Except for Bcl-2, the mRNA levels of H19, JNK and Bax were significantly increased in CNCI group. After H19 siRNA transfection, for the mRNA and protein levels, JNK and Bax were declined, while Bcl-2 was enhanced. LncRNA H19 might be involved in regulation of Bcl-2, Bax via JNK signalling pathway in CCSMCs apoptosis after CN injury.

CENPE promotes glioblastomas proliferation by directly binding to WEE1.

BACKGROUND: Glioblastoma (GBM) is one of the most lethal tumors. Even though radiotherapy and chemotherapy have been greatly developed, the survival of patients with GBM is still only about 16 months. METHODS: In this assay, centromere protein E (CENPE) expression levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) assays. 5-ethynyl-2'-deoxyuridine (EDU) assay was used to assess the effect of CENPE on cell proliferation. The propidium iodide (PI) method was used to detect the cell cycle. RESULTS: CENPE expression was increased in GBM tissues and was associated with clinical stage and unfavorable overall survival in glioma patients. Inhibition of CENPE expression resulted in proliferation inhibition of U251 and U87 cell. Cell cycle assay showed that CENPE mainly regulates the G0-G1 and G2/M phase transitions. Then, we found that CENPE regulated the proliferation of GBM mainly through WEE1 G2 checkpoint kinase (WEE1) pathway and can bind to WEE1. CONCLUSIONS: CENPE promotes GBM proliferation through WEE1 pathway and binding to WEE1.

MicroRNA-1291 mediates cell proliferation and tumorigenesis by downregulating MED1 in prostate cancer.

miRNAs are important factors involved in the regulation of tumor development. miR-1291 was found to have regulatory effects in many tumors, but its role in prostate cancer (PCa) still remains unclear. We explored the expression of miR-1291 in PCa to reveal its role in regulating the progression of PCa as well as its underlying mechanism. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-1291 in PCa tissues and cell lines compared to normal tissues and cell lines. miR-1291 mimics and inhibitors were applied to overexpress or inhibit the level of miR-1291 in PCa cells. The ability of cell proliferation was measured using MTT assay, and cell cycle distribution was determined by flow cytometry. The potential target of miR-1291 was identified via western blot analysis and luciferase assays. Then a xenograft model was established to explore the function of miR-1291 in PCa in vivo. The results revealed that the expression level of miR-1291 was significantly lower in the PCa tissues than that in the normal adjacent tissues. In PCa-derived cells, there was also a downregulated expression level of miR-1291. Overexpression of miR-1291 obviously inhibited DU-145 cell proliferation and induced cell cycle transition from G0/G1 to S phase. However, inhibition of miR-1291 promoted the growth of LNCaP cells, and promoted the cell cycle transition to S phase and G2/M phase. MED1 was proven to be a potential target gene of miR-1291, and miR-1291 significantly inhibited its expression. At the in vivo level, overexpression of miR-1291 inhibited the growth of xenograft tumors and significantly inhibited the expression of MED1 protein. Our study demonstrated that miR-1291 inhibits cell proliferation and tumorigenesis of PCa via MED1, which might provide a novel target for PCa diagnosis and biological therapy.

Characterization of the roles of suppressor of cytokine signaling-3 in prostate cancer development and progression.

As negative feedback regulators of cytokine signaling, suppressor of cytokine signaling proteins are induced by interleukins and various peptide hormones and may prevent sustained activation of signaling pathways. In particular, suppressor of cytokine signaling-3 (SOCS-3) plays pivotal roles in the development and progression of various cancers and exerts pleiotropic effects on cell proliferation and apoptosis. In recent years, abnormal expression of SOCS-3 and its multiple functions have been extensively investigated in human carcinomas, particularly in prostate cancer. SOCS-3 can act as an oncogene or a tumor suppressor depending on the cellular context. In this review, we focus on the role of SOCS-3 in prostate cancer development and prognosis, as well as the potential of SOCS-3 as a therapeutic target and diagnostic marker.