Increasing study have found that stem cell transplantation have a therapeutical effect to diabetes mellitus (DM)-induced erectile dysfunction (ED). So, the aim of this study was to evaluate the beneficial effect of corin from adipose-derived stem cells (ADSCs) on DM-induced ED. Exosomes were isolated from ADSCs (ADSC-EXOs) or from ADSCs in which corin gene expression was silenced by siRNA (siCorin). For in vivo studies, rats with streptozotocin-induced DM were intravenously injected with ADSC-EXOs or siCorin-ADSC-EXOs. Two weeks later, intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured to assess erectile function, and penile tissues were harvested for further evaluation of levels of inflammatory factors and expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and neuronal nitric oxide synthase (nNOS). We also evaluated the recovery of neurovascular function in penile tissues by immunofluorescence analysis. The results showed that ADSC-EXOs restored erectile function in diabetic rats, as determined by the ICP/MAP ratio. Exosomes from ADSCs also promoted neurovascular function and suppressed expression of inflammatory factors. In contrast, the decreased content of corin in exosomes after silencing corin in ADSCs reduced the therapeutic effect of exosomes on ED. These findings demonstrated the therapeutic mechanism underlying the use of ADSC-EXOs for treating ED and the beneficial effect of corin.

The prognosis and overall survival of castration-resistant prostate cancer (CRPC) patients are poor. The search for novel and efficient anti-CRPC agents is therefore extremely important. WM-3835 is a cell-permeable, potent and first-in-class HBO1 (KAT7 or MYST2) inhibitor. Here in primary human prostate cancer cells-derived from CRPC patients, WM-3835 potently inhibited cell viability, proliferation, cell cycle progression and in vitro cell migration. The HBO1 inhibitor provoked apoptosis in the prostate cancer cells. It failed to induce significant cytotoxicity and apoptosis in primary human prostate epithelial cells. shRNA-induced silencing of HBO1 resulted in robust anti-prostate cancer cell activity as well, and adding WM-3835 failed to induce further cytotoxicity in the primary prostate cancer cells. Conversely, ectopic overexpression of HBO1 further augmented primary prostate cancer cell proliferation and migration. WM-3835 inhibited H3-H4 acetylation and downregulated several pro-cancerous genes (CCR2, MYLK, VEGFR2, and OCIAD2) in primary CRPC cells. Importantly, HBO1 mRNA and protein levels are significantly elevated in CRPC tissues and cells. In vivo, daily intraperitoneal injection of WM-3835 potently inhibited pPC-1 xenograft growth in nude mice, and no apparent toxicities detected. Moreover, intratumoral injection of HBO1 shRNA adeno-associated virus (AAV) suppressed the growth of primary prostate cancer xenografts in nude mice. H3-H4 histone acetylation and HBO1-dependent genes (CCR2, MYLK, VEGFR2, and OCIAD2) were remarkably decreased in WM-3835-treated or HBO1-silenced xenograft tissues. Together, targeting HBO1 by WM-3835 robustly inhibits CRPC cell growth.

The Coatomer protein complex subunit beta 2 (COPB2) is involved in the formation of the COPI coatomer protein complex and is responsible for the transport of vesicles between the Golgi apparatus and the endoplasmic reticulum. It plays an important role in maintaining the integrity of these cellular organelles, as well as in maintaining cell homeostasis. More importantly, COPB2 plays key roles in embryonic development and tumor progression. COPB2 is regarded as a vital oncogene in several cancer types and has been implicated in tumor cell proliferation, survival, invasion, and metastasis. Here, we summarize the current knowledge on the roles of COPB2 in cancer development and progression in the context of the hallmarks of cancer.

The correlation between G388R or V10I polymorphisms of fibroblast growth factor receptor (FGFR) 4 gene and the risk of carcinoma has been investigated previously, but the results are contradictory. Odds ratios (ORs) with 95% confidence intervals (95%CIs), in silico tools, and immunohistochemical staining (IHS) were adopted to assess the association. In total, 13,793 cancer patients and 16,179 controls were evaluated in our pooled analysis. Summarization of all the studies showed that G388R polymorphism is associated with elevated susceptibility to cancer under homozygous comparison (OR = 1.21, 95%CI = 1.03–1.43, P = 0.020) and a recessive genetic model (OR = 1.21, 95%CI = 1.04–1.41, P = 0.012). In the stratification analysis by cancer type and ethnicity, similar findings were indicated for prostate cancer, breast cancer, and individuals of Asian descendant. Polyphen2 bioinformatics analysis showed that the G388R mutation is predicted to damage the protein function of FGFR4. IHS analysis indicated that FGFR4 expression is increased in advanced prostate cancer. These findings may guide personalized treatment of certain types of cancers. Up-regulation of FGFR4 may be related to a poor prognosis in prostate cancer.

Background: Over the past two decades, several studies have focused on the association between a common polymorphism (rs1800795) from interleukin-6 (IL-6) gene and Diabetes Mellitus (DM) risk. However, the results remain ambiguous and indefinite. Methods: A comprehensive analysis was performed to explore this relationship. A search was conducted in the PubMed, Embase, Chinese (CNKI and Wanfang), and GWAS Catalog databases, covering all publications until February 10, 2022. Odds ratios (OR) with 95% confidence intervals (CI) were used to evaluate the strength of the association. Publication bias was assessed using both Begg and Egger tests. Results: Overall, 34 case–control studies with 7257 T2DM patients and 15,598 controls, and 12 case–control studies (10,264 T1DM patients and 9031 health controls) were included in the analysis. A significantly lower association was observed between the rs1800795 polymorphism and T2DM risk in Asians, mixed population, and hospital-based (HB) subgroups (C-allele vs. G-allele: OR = 0.76, 95% CI 0.58–0.99, P = 0.039 for Asians; CG vs. GG: OR = 0.74, 95% CI 0.58–0.94, P = 0.014 for mixed population; CC vs. GG: OR = 0.61, 95% CI 0.41–0.90, P = 0.014 for HB). However, increased associations were found from total, mixed population, and HB subgroups between rs1800795 polymorphism and T1DM susceptibility (CG vs. GG: OR = 1.32, 95% CI 1.01–1.74, P = 0.043 for total population, CC vs. GG: OR = 2.45, 95% CI 1.18–5.07, P = 0.016 for mixed individuals; C-allele vs. G-allele: OR = 1.29, 95% CI 1.07–1.56, P = 0.0009 for HB subgroup). Conclusions: In summary, there is definite evidence to confirm that IL-6 rs1800795 polymorphism is associated with susceptibility to decreased T2DM and increased T1DM.