ObjectivesToll-like receptors (TLRs) are important initiators in native immune responses to microbial infections. TLR4 is up-regulated in response to H.pylori infection in gastric epithelial cells. However, the regulatory mechanisms for the expression of TLR4 in H.pylori infection have not been clearly defined. The aims of this study are to present the evidence that microRNA let-7b directly regulates TLR4 expression in human gastric epithelial cells, and subsequently influences the activation of NF-κB and the expression of the downstream genes in H.pylori infection.MethodsThe expression of let-7b was determined in gastric mucosa specimens and in two gastric epithelial cell lines using quantitative RT-PCR. The expression of TLR4 was determined by immunohistochemistry staining and RT-PCR. The potential target of let-7b was identified by luciferase reporter assay and Western blot. Let-7b mimics and inhibitors were used to examine the effects of let-7b on NF-κB activity. The expression of the downstream genes of NF-κB was also determined in cells infected with H.pylori 26695.ResultsLet-7b was significantly decreased in gastric mucosa specimens and in gastric epithelial cell lines (AGS, GES-1) infected with H.pylori 26695 (cagA+). Let-7b was complementary to the 3′-UTR of TLR4 mRNA and regulated TLR4 expression via post-transcriptional suppression in gastric epithelium. Infection of H.pylori induced the expression of TLR4 and activated NF-κB in AGS and GES-1 cells. Overexpression of let-7b by mimics downregulated TLR4, and subsequently attenuated NF-κB, MyD88, NF-κB1/p50, RelA/p65. The expression of IL-8, COX-2 and CyclinD1 was inhibited in H.pylori infected cells with let-7b overexpression. Both TAK-242 (TLR4 inhibitor) and SN50 (NF-κB inhibitor) significantly inhibited the H.pylori induced downregulation of let-7b.ConclusionsLet-7b targets at TLR4 mRNA, and regulates the activation of NF-κB and the expression of the downstream genes related to the inflammation and immune responses in H.pylori infection.

Ten new saponins designated as certonardosides A-J (1-5, 7-11) and the known halityloside D (6) were isolated from the brine shrimp active fraction of the MeOH extract of the starfish Certonardoa semiregularis. The structures were determined on the basis of spectral analysis and chemical manipulation. The compounds were evaluated for antiviral activity against HIV, HSV, CoxB, EMCV, and VSV and displayed insignificant activity within the range of noncytotoxic concentrations.

Two unprecedented phosphorus-containing iodinated polyacetylenes, phosphoiodyns A and B (1-2), were isolated from a Korean marine sponge Placospongia sp. Their structures were elucidated by spectroscopic data analysis. Phosphoiodyn A exhibited potent agonistic activity on human peroxisome proliferator-activated receptor delta (hPPARδ) with an EC(50) of 23.7 nM.

Pancreatic cancer is estimated to be the fourth most common cancer in men and fifth in women in the world and has poor prognosis. In recent years, more and more effort has been put on the relationship between pancreatic cancer and apoptosis. As a newly discovered inhibitor of apoptosis, survivin has drawn more attention. Strong evidence has shown that survivin is expressed in pancreatic cancer cells on frozen sections. Survivin increases in the development of pancreatic ductal adenocarcinoma and its expression can be a marker in evaluating the prognosis of pancreatic cancer patients. Survivin itself may be a new target in the treatment of pancreatic cancer and a survivin DNA vaccine could generate specific antitumor effects in pancreatic carcinoma models.

When H. pylori infect in stomach, it may reduce the severity of inflammation. However, when colonizes in esophagus, H. pylori increases the severity of esophageal inflammation and the incidence of BE and EA. Celecoxib administration attenuates the incidence of EA by inhibiting COX-2 expression.

Two new benzophenones, acredinones A (1) and B (2), were isolated from a marine-sponge-associated Acremonium sp. fungus. Their chemical structures were elucidated on the interpretation of spectroscopic data. The structure of 1 was confirmed by palladium-catalyzed hydrogenation, followed by spectroscopic data analysis. Acredinones A (1) and B (2) inhibited the outward K(+) currents of the insulin secreting cell line INS-1 with IC50 values of 0.59 and 1.0 μM, respectively.

Eleven new polyhydroxysterols (1-11) and eight new saponins (12-19) were isolated from the brine shrimp active fraction of the starfish Certonardoa semiregularis. The structures were determined on the basis of spectral analysis and chemical derivatization. The structural variations of these compounds are due to the hydroxylation pattern of the sterol nucleus, the functionalization of the side chain, or the nature and location of the saccharide moiety. These compounds displayed considerable cytotoxicity against a small panel of human solid tumor cell lines.

Background: Antibiotic resistance is the main cause of Helicobacter pylori (H. pylori) treatment failure. This study aimed to explore the characteristics of antibiotic resistance of H. pylori isolates in Beijing in the last 8 years and to estimate the impact of previous eradication failure on resistance patterns. Materials and methods:This retrospective study included data from a single center in Beijing from 2013 to 2020. Antibiotic susceptibility of 365 clinical H. pylori isolates was tested for amoxicillin, clarithromycin, metronidazole, levofloxacin, moxifloxacin, and tetracycline. The characteristics of the included patients and their previous eradication history were collected. Primary and secondary resistance rates of H. pylori to the six antibiotics and the impact of previous eradication failure on antibiotic resistance patterns were analyzed. Results:The overall primary resistance rates of amoxicillin, clarithromycin, metronidazole, levofloxacin, moxifloxacin, and tetracycline were 0.7%, 55.2%, 68.0%, 49.7%, 64.5%, and 0%, with no significant increase during the observed period; while the secondary resistance rates were 3.2%, 96.7%, 90.7%, 93.1%, 80.0%, and 0%, respectively. The secondary resistance rate of clarithromycin (p < .001), metronidazole (p = .001), and levofloxacin (p < .001) significantly increased to 100% as the number of previous eradication therapies increased and exhibited a linear association. For strains naive to eradication, only 6.8% were susceptible to all the antibiotics, while 32.4% were single resistant, and 60.8% dual or multiple resistant. Clarithromycin+ metronidazole+fluoroquinolone multiple resistance was the predominant pattern (0 course: 21.6%, 1 course: 37.5%, 2 courses: 56.1%, ≥3 courses: 71.1%; p < .001) for patients with treatment failure. The prevalence of dual or multiple-resistance patterns increased significantly as the number of previous therapies increased. Conclusions:The prevalence of primary and secondary resistance rates of clarithromycin, metronidazole, moxifloxacin, and levofloxacin were high in Beijing. Multipleresistance patterns were common after treatment failure. Resistance rates of amoxicillin and tetracycline remained low and stable.