Gastric cancer (GC) ranks the second prevalent cancer type and the second cancer-related death in China. However, the precise mechanisms of GC development remain poorly understood. Chronic infection with Helicobacter pylori is the strongest identified risk factor for GC. Toll-like receptor (TLR) genes, which play critical roles in Helicobacter pylori induced chronic inflammation, may also be implicated in GC susceptibility. TLR5 signaling deficiency could deregulate a cascade of inflammatory events. In current study, we systematically evaluated genetic variations of TLR5, and their interaction with Helicobacter pylori infection among carcinogenesis of gastric cancer, using a large case-controls study among Chinese population. Minor alleles of three SNPS, including rs5744174 (P = 0.001), rs1640827 (P = 0.005), and rs17163737 (P = 0.004), were significantly associated with increased GC risk (OR ranged from 1.20–1.24). Significant interactions with Helicobacter pylori infection were also identified for rs1640827 (P for interaction = 0.009) and rs17163737 (P for interaction = 0.006). These findings suggest that genetic variants in TLR5 may modify the role of Helicobacter pylori infection in the process of causing GC.
BackgroundYes-associated protein (YAP), a key player of the Hippo pathway, has been identified to have more and more important roles in tumorigenesis and may be an important biomarker for cancer therapy. YAP is important for bladder cancer cell migration, metastasis, and drug resistance; however, its function in bladder cancer stem cells remains unknown.PurposeThe aim of this work was to examine the expression and role of YAP in bladder cancer stem cells.Materials and methods:We identified that the expression level of YAP was significantly enriched in bladder cancer stem cells compared to noncancer stem cell population. Moreover, the effect of YAP on stem cell self-renewal was examined in bladder cancer cells by siRNA silencing approach. In addition, we showed that YAP is required for aldehyde dehydrogenase activity in bladder cancer cells.ResultsRNAseq analysis and quantitative real-time PCR results showed that silencing of YAP inhibited the expression of ALDH1A1 gene.ConclusionCollectively, our findings for the first time elucidated that YAP serves as a cancer stem cell regulator in bladder cancer, which provided a promising therapy strategy for patients with bladder cancer.
Esophageal squamous cell carcinoma (ESCC) has a high morbidity in China, accounting for 90% of all esophageal carcinoma cases. Hence, identifying drug targets for prevention and treatment of ESCC is essential. Due to its critical role in the regulation of cell apoptosis, Mcl-1 holds great potential as a target for treatment against ESCC. In current study, we used a 4-nitroquinoline-1-oxide (4-NQO)-induced ESCC mouse model of test whether A-1210477, a Mcl-1 small molecular inhibitor, could repress ESCC development. We showed that A-1210477 treatment decreased ESCC formation and animal weight loss in a dose dependent manner. We detected decreased cellular proliferation in A-1210477-treated ESCC tissue by Ki67 expression. Moreover, A-1210477 treatment increased the number of apoptotic cells in ESCC tissues. Our study clearly demonstrates the contribution of Mcl-1 to ESCC development through promoting cell proliferation and inhibition of apoptosis, and provides a strong evidence for further evaluation of A-1210477 for treating ESCC.
A green, biomimetic, phosphate-mediated
Pictet–Spengler
reaction was used in the synthesis of three catecholic tetrahydroisoquinolines, 1, 2, and 12, present in the medicinal
plant Portulaca oleracea, as well as their analogues 3–11, 13, and 14, with dopamine hydrochloride and aldehydes as the substrates. AB-8
macroporous resin column chromatography was applied for purification
of the products from the one-step high-efficacy synthesis. It eliminated
the difficulties in the isolation of catecholic tetrahydroisoquinolines
from the aqueous reaction system and unreacted dopamine hydrochloride.
Activity screening in CHO-K1/Gα15 cell models consistently expressing
α1B-, β1-, or β2-adrenergic receptors indicated that 12 and 2, compounds that are present in P. oleracea, possessed
the most potent β2-adrenergic receptor agonist activity
and 2 was a selective β2-adrenergic
receptor agonist at the concentration of 100 μM. Both 12 and 2 exhibited dose-dependent bronchodilator
effects on the histamine-induced contraction of isolated guinea-pig
tracheal smooth muscle, with EC50 values of 0.8 and 2.8
μM, respectively. These findings explain the scientific rationale
of P. oleracea use as an antiasthmatic herb in folk
medicine and provide the basis for the discovery of novel antiasthma
drugs.
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