In this article, we review the origin and therapeutic perspectives of bladder cancer stem cells (BCSCs), which are integral to the initiation, high recurrence and chemoresistance of bladder cancer. BCSCs are heterogenous and originate from multiple cell types, including urothelial stem cells and differentiated cell types, including basal, intermediate stratum and umbrella cells. Cell surface markers, including CD44, CD67LR, EMA, ALDH1A1 and BCMab1, are used to identify and isolate BCSCs. The Hedgehog, Notch, Wnt and JAK-STAT signaling pathways play key roles in maintaining the stemness, self-renewal and proliferative potential of BCSCs. High expression of ABC transporters, acetaldehyde dehydrogenase, antioxidants and apoptosis resistance proteins in BCSCs play a critical role in chemoresistance. Consequently, a greater understanding of the biology of BCSCs will be important for identifying effective therapeutic targets to improve clinical outcomes for bladder cancer patients.
Objectives This study was designed to test whether serum vitamin D levels affected Helicobacter pylori (H. pylori) infection and eradication rates. Methods A multicenter observational prospective cohort study was conducted. A total of 496 H. pylori− positive (H. pylori+) and 257 H. pylori‐negative (H. pylori−) patients were enrolled from four hospitals in China. Baseline serum vitamin D levels were measured and a 13C‐urea breath test (UBT) was performed for all the participants. The H. pylori+ patients were divided into two subgroups based on their serum vitamin D levels (<10 or ≥10 ng/mL). A second 13C‐UBT was performed between 4 and 8 weeks after 14‐day bismuth‐containing quadruple eradication therapies. Factors potentially affecting H. pylori eradication were determined using a questionnaire survey. Results Serum vitamin D levels were significantly lower in the H. pylori+ group than in the H. pylori− group ([17.0 ± 6.9] ng/mL vs [19.2 ± 8.0] ng/mL, P = 0.000). H. pylori eradication rate significantly differed between patients with serum vitamin D levels of <10 ng/mL and ≥10 ng/mL (71.7% vs 87.3%, P = 0.005). A multivariate analysis showed that having serum vitamin D level ≥10 ng/mL was an independent risk factor for a successful H. pylori eradication (odds ratio 0.381, 95% confidence interval 0.183‐0.791, P = 0.010). Conclusions Serum vitamin D level may affect H. pylori infection and its eradication. Randomized controlled trials are needed to find out whether vitamin D supplements may increase the H. pylori eradication rate.
Cancer stem cells (CSCs) are considered one of the key contributors to chemoresistance and tumor recurrence. Therefore, the precise identification of reliable CSC markers and clarification of the intracellular signaling involved in CSCs remains a great challenge in fields relating to cancer biology. Here, we implemented a novel chemoresistant prostate cancer patient-derived xenograft (PDX) model in NOD/SCID mice and identified CD54 as a candidate gene among the most highly enriched gene expression profiles in prostate tumors exposed to chronic cisplatin administration. Additional in vitro and in vivo assays showed that CD54 played a critical role in the self-renewal and tumorigenesis of prostate CSCs. Moreover, silencing CD54 greatly reduced the tumorigenesis of prostate cancers both in vitro and in vivo and significantly extended the survival time of tumor-bearing mice in a prostate cancer xenograft model. Dissection of the molecular mechanism revealed that the p38-Notch1 axis was the main downstream signaling pathway in CD54-mediated regulation of CSCs in prostate cancers. Together, these results established that CD54 could be a novel reliable prostate CSC marker and provided a new potential therapeutic target in prostate cancer via CD54-Notch1 signaling.
Whole grain Qingke (WGQK) displays anti-obesity and lipid-lowering properties; however, the underlying mechanism remains elusive. This study investigated the alteration of gut microbiota composition and metabolite profile induced by WGQK intervention in mice through the integration of 16S ribosomal RNA (rRNA) sequencing and an untargeted metabolomics study. C57BL/6J male mice were fed a normal control diet (NC), high-fat diet (HFD), and HFD plus 30% WGQK (HFD+QK) for 16 weeks. The WGQK intervention decreased body weight gain, glucose tolerance, and serum lipid levels, and alleviated liver function damage induced by HFD. Moreover, WGQK changed gut microbiota composition and enriched specific genera such as Akkermansia, Bifidobacterium, and Lactobacillus. Fecal metabolomics analysis indicated that WGQK enhanced the abundance of tryptophan metabolism-related metabolites (indole, 3-indoleacetic acid, indole acetic acid (IAA), 5-hydroxyindole-3-acetic acid), histidine metabolism-related metabolites (histamine), and some unsaturated fatty acids (oleic acid, 9,10-dihydroxy-12Z-octadecenoic acid, and alpha-linolenic acid). Spearman correlation analysis revealed that these metabolites were negatively correlated with obesity-related parameters and positively correlated with the gut genera enriched by WGQK. Moreover, WGQK promoted the expression of Cholesterol 7α-hydroxylase (CYP7A1) responsible for primary bile acids production, accompanied by a decline in intestinal FXR-FGF15 expression levels. The transcript levels of two genes associated with lipogenesis, such as lipid fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) were also decreased in the HFD+QK group. Overall, our results suggest interactions between gut microbial shifts and host amino acid/lipid metabolism, and shed light on the mechanisms underlying the anti-obesity effect of WGQK.
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