Dysbiotic microbiota contributes to the pathogenesis of Crohn's disease (CD) by regulating the immune system. Although pro-inflammatory microbes are probably enriched in the small intestinal (SI) mucosa, most studies have focused on fecal microbiota. This study aimed to examine jejunal and ileal mucosal specimens from patients with CD via double-balloon enteroscopy. Comparative microbiome analysis revealed that the microbiota composition of CD SI mucosa differs from that of non-CD controls, with an increased population of several families, including Enterobacteriaceae, Ruminococcaceae, and Bacteroidaceae. Upon anaerobic culturing of the CD SI mucosa, 80 bacterial strains were isolated, from which 9 strains representing 9 distinct species (Escherichia coli, Ruminococcus gnavus, Klebsiella pneumoniae, Erysipelatoclostridium ramosum, Bacteroides dorei, B. fragilis, B. uniformis, Parabacteroides distasonis, and Streptococcus pasteurianus) were selected on the basis of their significant association with CD. The colonization of germ-free (GF) mice with the 9 strains enhanced the accumulation of TH1 cells and, to a lesser extent, TH17 cells in the intestine, among which an E. coli strain displayed high potential to induce TH1 cells and intestinal inflammation in a strain-specific manner. The present results indicate that the CD SI mucosa harbors unique pro-inflammatory microbiota, including TH1 cell-inducing E. coli, which could be a potential therapeutic target.

The aim of this study is to investigate the role of microRNA-499 (miR-499) in hepatocellular carcinoma tumor growth and the underlying molecular mechanisms. The expression of miR-499 was significantly decreased in hepatocellular carcinoma tissues compared with that in adjacent normal tissues. Furthermore, miR-499 overexpression in HEPG2 cell was related to the tumor growth in nude mice xenograft models. Likewise, miR-499 mimic or inhibitor decreased or accelerated cell proliferation, respectively. Mechanistically, miR-499 directly targeted the 3'- untranslated region of astrocyte elevated gene-1 and downregulate astrocyte elevated gene-1 expression. Restoration of astrocyte elevated gene-1 expression in hepatocellular carcinoma cells reversed the inhibitory effect of miR-499 on cell growth. In addition, astrocyte elevated gene-1 and miR-499 expression were inversely correlated in human and mice hepatocellular carcinoma tissues. Our study identified miR-499 as a tumor-suppressive miR in hepatocellular carcinoma, thus providing a candidate therapeutic target for the future diagnosis or treatment of hepatocellular carcinoma.

The world is witnessing an unprecedented crisis with Coronavirus disease 2019 (COVID-19). It is important to accurately analyze the available evidence to provide correct clinical guidance for optimal patient care. We aim to discuss current clinical evidence regarding chloroquine, hydroxychloroquine, azithromycin, remdesivir, and the cardiovascular burden of COVID-19.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could recur as seasonal outbreaks, a circulating pattern observed among other preexisting human seasonal coronaviruses (sCoVs). However, little is known about seasonality of sCoVs on a global scale.

Dysregulation of long non-coding RNAs (lncRNAs) has been implicated in many cancer developments. Previous studies showed that lncRNA LINC00941 was aberrantly expressed in oral squamous cell carcinoma (OSCC). However, its role in OSCC development remains elusive. In this study, we demonstrated that in OSCC cells, EP300 activates LINC00941 transcription through up-regulating its promoter H3K27ac modification. Up-regulated LINC00941 in turn activates CAPRIN2 expression by looping to CAPRIN2 promoter. Functional assays suggest that both LINC00941 and CAPRIN2 play pivotal roles in promoting OSCC cell proliferation and colony formation. In vivo assay further confirmed the role of LINC00941 in promoting OSCC cell tumour formation. Lastly, we showed that the role of LINC00941 and CAPRIN2 in OSCC progression was mediated through activating the canonical WNT/β-catenin signaling pathway. Thus, LINC00941/CAPRIN2/ WNT/β-catenin signaling pathway provides new therapeutic targets for OSCC treatment.

Bile at strongly acidic pH exerts a carcinogenic effect on the hypopharynx, based upon recent pre-clinical studies that support its role as an independent risk factor. We recently demonstrated in vitro that curcumin can prevent oncogenic profile of bile in human hypopharyngeal cells, by inhibiting NF-κB. We hypothesize that topically applied curcumin to the hypopharynx can similarly block early oncogenic molecular events of bile, by inhibiting NF-κB and consequently altering the expression of genes with oncogenic function. Using Mus musculus (C57Bl/6J), we topically applied curcumin (250 μmol/L; three times per day; 10 days) to the hypopharynx, 15 minutes before, 15 minutes after or in combination with bile acids (pH 3.0). Immunohistochemical analysis and qPCR revealed that topically applied curcumin either before, after or in combination with acidic bile exposure significantly suppressed its induced NF-κB activation in regenerating epithelial cells, and overexpression of Rela, Bcl2, Egfr, Stat3, Wnt5a, Tnf, Il6, Ptgs2. Akt1 was particularly inhibited by curcumin when applied simultaneously with bile. We provide novel evidence into the preventive and therapeutic properties of topically applied curcumin in acidic bile-induced early oncogenic molecular events in hypopharyngeal mucosa, by inhibiting NF-κB, and shaping future translational development of effective targeted therapies using topical non-pharmacologic inhibitors of NF-κB.

Baicalein, a flavonoid phytochemical, has been shown to be effective as an anti-metastatic agent for various cancers, especially for non-small-cell lung cancer (NSCLC). However, the underlying mechanism of how baicalein targets cellular processes during NSCLC cell invasion and metastasis remains elusive. In this study, we found that non-cytotoxic concentrations of baicalein still retained anti-dissemination activity both in vitro and in vivo. Using a genetic encoding tension probe based on Förster resonance energy transfer (FRET) theory, baicalein was shown to significantly decrease ezrin tension by downregulating cellular ezrin S-nitrosylation (SNO) levels in NSCLC cells in the inflammatory microenvironment. Decreased ezrin tension inhibited the formation of an aggressive phenotype of NSCLC cell and leader cell in collective migration, and subsequently suppressed NSCLC dissemination. Baicalein restrained SNO-mediated ezrin tension by decreasing iNOS expression levels. Overall this study demonstrates the novel mechanism used by baicalein to suppress NSCLC invasion and metastasis from a mechanopharmacology perspective and illustrates a new direction for drug development.

The mammalian Notch family ligands delta-like 3 (DLL3) is reported to be a potential therapeutic target for large cell neuroendocrine carcinomas (LCNEC). The effect of DLL3 expression on LCNEC prognosis has not yet been elucidated.

To investigate the relation between AAPR and OS in patients with advanced non-small cell lung cancer (NSCLC).

HIV testing and pre-exposure prophylaxis (PrEP) are effective HIV prevention strategies often underused by transgender people.

To investigate the association of body mass index (BMI) with multivessel coronary artery disease in patients with myocardial infarction.

Cardiovascular autonomic neuropathy is highly prevalent in patients with end-stage renal disease (ESRD), and it has a high fatality rate. This study aimed to determine whether peritoneal dialysis (PD) improves cardiovascular autonomic function (CAF) and decreases protein-bound uremic toxin (indoxyl sulfate [IS], p-cresyl sulfate [PCS]) levels.

Nucleocytoplasmic transport is tightly regulated by the nuclear pore complex (NPC). Among the thousands of molecules that cross the NPC, even very large (>15 nm) cargoes such as pathogens, mRNAs and pre-ribosomes can pass the NPC intact. For these cargoes, there is little quantitative understanding of the requirements for their nuclear import, especially the role of multivalent binding to transport receptors via nuclear localisation sequences (NLSs) and the effect of size on import efficiency. Here, we assayed nuclear import kinetics of 30 large cargo models based on four capsid-like particles in the size range of 17-36 nm, with tuneable numbers of up to 240 NLSs. We show that the requirements for nuclear transport can be recapitulated by a simple two-parameter biophysical model that correlates the import flux with the energetics of large cargo transport through the NPC. Together, our results reveal key molecular determinants of large cargo import in cells.

Multiplexed assays allow functional testing of large synthetic libraries of genetic elements, but are limited by the designability, length, fidelity and scale of the input DNA. Here, we improve DropSynth, a low-cost, multiplexed method that builds gene libraries by compartmentalizing and assembling microarray-derived oligonucleotides in vortexed emulsions. By optimizing enzyme choice, adding enzymatic error correction and increasing scale, we show that DropSynth can build thousands of gene-length fragments at >20% fidelity.

To explore the effects of FAM83D on the proliferation, invasion and radiosensitivity of human esophageal cancer cells and to elucidate the mechanism involved in the regulation of the growth and metastasis of esophageal cancer cells.

The specific function of pre-mRNA processing factors (Prps) in human malignancies has not been yet investigated. The aim of the present study was to determine the impacts of Prp8 in a common human malignancy, hepatocellular carcinoma (HCC).

miR-877-5p has been reported as a tumor suppressor in multiple cancers. Its role in gastric cancer, however, remains unclear. Hence, the purpose of this study was to elucidate the function, and underlying molecular mechanism, of miR-877-5p in the development of gastric cancer.

Urinary tract infection is one of the most common health problems during pregnancy. It is most commonly reported among pregnant women and is a known reason of morbidity during pregnancy worldwide, predominantly in developing countries. The etiological agents include Escherichia coli, Klebsiella species, Staphylococcus aureus, coagulase negative Staphylococci, Proteus mirabilis, Enterococcus species, Pseudomonas aeruginosa, Enterobacter species, non-hemolytic streptococci, Citrobacter species and others. Different risk factors expose pregnant women to urinary tract infection. Drug resistance by uropathogenic bacteria is a current problem of the world. This study was aimed at reviewing the prevalence of bacterial uropathogens and their antimicrobial resistance patterns among pregnant women in developing countries in Asia and Africa, during the past decade.

To compare the clinical efficacy between peramivir and oseltamivir in hospitalized patients with influenza.

The study investigates the molecular epidemiology of multi-drug resistant (MDR) Bacteroides spp. isolates and the clinical characteristics of the patients.