Clostridium scindens metabolites trigger prostate cancer progression through androgen receptor signaling.

Prostate cancer (PCa) is one of the most common malignancies in men; recently, PCa-related mortality has increased worldwide. Although androgen deprivation therapy (ADT) is the standard treatment for PCa, patients often develop aggressive castration-resistant PCa (CRPC), indicating the presence of an alternative source of androgen. Clostridium scindens is a member of the gut microbiota and can convert cortisol to 11ß-hydroxyandrostenedione (11ß-OHA), which is a potent androgen precursor. However, the effect of C. scindens on PCa progression has not been determined. In this study, androgen-dependent PCa cells (LNCaP) were employed to investigate whether C. scindens-derived metabolites activate androgen receptor (AR), which is a pivotal step in the development of PCa. Results showed that cortisol metabolites derived from C. scindens-conditioned medium promoted proliferation and enhanced migration of PCa cells. Furthermore, cells treated with these metabolites presented activated AR and stimulated AR-regulated genes. These findings reveal that C. scindens has the potential to promote PCa progression via the activation of AR signaling. Further studies on the gut-prostate axis may help unravel an alternative source of androgen that triggers CRPC exacerbation.

Acupuncture for dyspnea and breathing physiology in chronic respiratory diseases: A protocol of a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Dyspnea is one of the most common symptoms of chronic respiratory disease (CRD) and is closely related to increased functional disability and mortality, resulting in substantial adverse outcomes on patients and imposing great social and economic burden. Although multiple clinical trials and systematic reviews have suggested that acupuncture could be effective in treating COPD and lung cancer, little is known about its effects on dyspnea relief in patients with CRD. The present study aimed to use a systematic review approach to evaluate the effectiveness and safety of acupuncture in the treatment of dyspnea in patients with CRD. METHODS: We will search the following 9 databases from inception to June 30, 2022, PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, WANFANG Database, Chinses Scientific and Technological Periodical Database, and Chinese Biomedical Database, and the Cochrane Library Database. Clinical randomized controlled trials in English or Chinese that evaluate invasive acupuncture versus control group in treatment of CRD with dyspnea will be included. The primary outcome will be dyspnea scores, breathing physiological function, and the secondary outcomes include exercise tolerance by six-minute walk distance quality of life, quality of life and adverse events. Two reviewers will independently conduct study selection, data extraction and quality assessment. The Review Manager software will be used for meta-analysis. This protocol will be carried out in accordance with the PRISMA-P guidance. CONCLUSION: This systematic review and meta-analysis will provide the evidence of whether acupuncture is an effective and safe intervention for CRD with dyspnea. The results will be disseminated through peer-reviewed publication.

Engineering high coenzyme Q10 tomato.

Coenzyme Q (CoQ) is vital for energy metabolism in living organisms. In humans, CoQ10 deficiency causes diseases and must be replenished via diet; however, CoQ content in plant foods is primarily low. Here, we report the breeding of high CoQ10 tomato lines by expressing four enzymes with a fruit-specific promoter, which modifies the chloroplast chorismate pathway, enhances cytosolic isoprenoid biosynthesis, and up-regulates the first two reactions in mitochondrion that construct the CoQ10 polyisoprenoid tail. We show that, while the level of the aromatic precursor could be markedly elevated, head group prenylation is the key to increasing the final CoQ10 yield. In the HUCD lines expressing all four transgenes, the highest CoQ10 content (0.15 mg/g dry weight) shows a seven-fold increase from the wild-type level and reaches an extraordinarily rich CoQ10 food grade. Overviewing the changes in other terpenoids by transcriptome and metabolic analyses reveals variable contents of carotenoids and α-tocopherol in the HUCD lines. In addition to the enigmatic relations among different terpenoid pathways, high CoQ10 plants maintaining substantial levels of either vitamin can be selected. Our investigation paves the way for the development of CoQ10-enriched crops as dietary supplements.

Campylobacter jejuni Cytolethal Distending Toxin C Exploits Lipid Rafts to Mitigate Helicobacter pylori-Induced Pathogenesis.

Helicobacter pylori infection is associated with several gastrointestinal diseases, including gastritis, peptic ulcer, and gastrointestinal adenocarcinoma. Two major cytotoxins, vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), interact closely with lipid rafts, contributing to H. pylori-associated disease progression. The Campylobacter jejuni cytolethal distending toxin consists of three subunits: CdtA, CdtB, and CdtC. Among them, CdtA and CdtC bind to membrane lipid rafts, which is crucial for CdtB entry into cells. In this study, we employed recombinant CdtC (rCdtC) to antagonize the functions of H. pylori cytotoxin in cells. Our results showed that rCdtC alleviates cell vacuolation induced by H. pylori VacA. Furthermore, rCdtC reduces H. pylori CagA translocation, which decreases nuclear factor kappa-B activation and interleukin-8 production, resulting in the mitigation of gastric epithelial cell inflammation. These results reveal that CdtC hijacks cholesterol to compete for H. pylori cytotoxin actions via lipid rafts, ameliorating H. pylori-induced pathogenesis.

[Correlation between CYP2C19 Gene Polymorphism and Elderly Cerebral Infarction].

Objective To investigate the correlation between CYP2C19 gene polymorphism and elderly cerebral infarction.Methods Two polymorphisms including rs4244285 and rs4986893 of the CYP2C19 gene were detected by gene chip technology in 72 elderly patients with acute cerebral infarction (stroke group) and 77 otherwise healthy controls. The clinical data and the polymorphism distribution of CYP2C19 were compared,and the potential association between genetic polymorphism and cerebral infarction was analyzed by Logistic regression.Results The frequencies of rs4244285 GG (45.83% vs. 63.64%,Χ 2=4.766,P=0.029) and rs4244285 A allele (34.03% vs. 22.73%,Χ 2=4.695,P=0.030) were significantly higher in stroke group than in control group. There were no significant differences in the distribution of the alleles of rs4986893 or the rs4244285 GA and AA between these two groups (all P>0.05). After the conventional cerebrovascular risk factors including gender,age,body mass index,smoking,and total cholesterol were adjusted,Logistic regression analysis showed that rs4244285 A allele significantly increased the stroke risk [the additive model AA vs. GG:OR=2.564,95%CI=1.181-5.566,P=0.017;the dominant model AA/AG vs. GG:OR=2.763,95%CI=1.343-5.685,P=0.006].Conclusion CYP2C19 genetic polymorphism may be associated with the increased risk of cerebral infarction in the elderly,although future well-designed studies with larger sample sizes are warranted.

Identification of a Novel (-)-5-Epieremophilene Synthase from Salvia miltiorrhiza via Transcriptome Mining.

Salvia miltiorrhiza, a medicinal plant in China, has been used for thousands of years to treat coronary heart diseases. Although biosynthesis of tanshinones, a group of diterpenoids in S. miltiorrhiza, has been extensively investigated, to date we know little about the formation of monoterpenes and sesquiterpenes in this medicinal plant. Here, we report the characterization of three sesquiterpene synthases, named SmSTPS1, SmSTPS2, and SmSTPS3, which catalyzed the formation of a new compound, (-)-5-epieremophilene. Additionally, the (-)-5-epieremophilene biosynthesis activity of SmSTPS1 was confirmed by transient expression in Nicotiana benthamiana. Despite the similar enzyme activities of SmSTPS1, SmSTPS2, and SmSTPS3, the three (-)-5-epieremophilene synthase genes displayed different spatial expression patterns and responded differently to hormone treatments, implicating their specific roles in plant-environment interactions. Our results provide valuable data to understanding the biosynthesis and composition of terpenes in plant.

OMOM capsule endoscopy in diagnosis of small bowel disease.

OBJECTIVE: To assess the diagnostic efficiency of OMOM capsule endoscopy (CE) in a group of patients with different indications. METHODS: Data from 89 consecutive patients (49 males, 40 females) with suspected small bowel disease who underwent OMOM CE (Jinshan Science and Technology Company, Chongqing, China) examination were obtained by retrospective review. The patients' indications of the disease consisted of the following: obscure gastrointestinal bleeding (OGIB), abdominal pain or diarrhea, partial intestinal obstruction, suspected inflammatory bowel disease, tumor of unknown origin, hypoproteinemia, constipation, weight loss, and elevated tumor markers. RESULTS: CE failed in one patient. Visualization of the entire small bowel was achieved in 75.0%. Capsules were naturally excreted by all patients. The detection rate of abnormalities was 70.5% for patients with suspected small bowel disease, and the diagnostic yield for patients with OGIB was higher than that for patients with abdominal pain or diarrhea (85.7% vs 53.3%, P<0.005). Angiodysplasia was the most common small bowel finding. Active bleeding sites were noted in the small intestine in 11 cases. CONCLUSION: OMOM CE is a useful diagnostic tool for the diagnosis of variably suspected small bowel disease, whose diagnostic efficiency is similar to that of the Pillcam SB (small bowel) CE (Given Imaging, Yoqneam, Israel).