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Objectives: Fecal microbiota transplantation (FMT) has been recommended for the treatment of recurrent Clostridioides difficile infection (CDI). We aimed to evaluate the therapeutic efficacy and safety of washed microbiota transplantation (WMT), a new method of FMT, for CDI across various medical settings. Methods: This multicenter real‐world cohort study included CDI patients undergoing WMT. The primary outcome was the clinical cure rate of CDI within 8 weeks after WMT. Secondary outcomes included the CDI recurrence rate and reduction in total abdominal symptom score (TASS) during the follow‐up period. Adverse events related to WMT were recorded. Results: Altogether 90.7% (49/54) of CDI patients achieved clinical cure after treated with WMT. The cure rate was 83.3% for cases with severe and complicated CDI (ScCDI) (n = 30) and 100% for non‐ScCDI cases (n = 24) (P = 0.059). No difference was observed in the clinical cure rate between patients with first and recurrent CDI (91.9% vs 88.2%, P = 0.645). One week post‐WMT, TASS showed a remarkable decrease compared to that at baseline (P < 0.001). Totally, 8.2% (4/49) of patients suffered CDI recurrence during the follow‐up period. A WHO performance score of 4, age ≥65 years, higher TASS score, and higher Charlson comorbidity index score were potential risk factors for efficacy (P = 0.018, 0.03, 0.01, 0.034, respectively). Four (3.8%) transient adverse events related to WMT were observed. Conclusions: This study emphasizes the attractive value of WMT for CDI. Early WMT may be recommended for CDI, especially for those in serious condition or with complex comorbidities. Trial registration: ClinicalTrials.gov, no. NCT03895593 (registered on 27 March 2019). [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the short‐term efficacy and safety of fecal microbiota transplantation (FMT) by washed preparation for moderate to severely active UC. Methods: An open‐label prospective trial was conducted in an inflammatory bowel disease (IBD) tertiary referral center from April 2016 to March 2018. Patients with moderate to severely active UC were randomly assigned to undergo FMT thrice on day 1, 3 and 5 by nasojejunal tube (NJT) or transendoscopic enteral tubing (TET). The primary end‐point was a clinical response at week 2 post‐FMT. The secondary end‐points were clinical and endoscopic remission at week 12 post‐FMT, safety and disease progression. Results: Of the nine patients included, 77.8% (7/9) achieved a clinical response at week 2. And 55.6% (5/9) and 33.3% (3/9), respectively, achieved clinical remission and endoscopic remission at week 12. In two patients who had no response to FMT, one switched to anti‐tumor necrosis factor‐α therapy, and the other underwent a colectomy. FMT was delivered through NJT in 44.4% (4/9) of the patients, while TET was used in 55.6% (5/9). The clinical outcomes did not differ significantly based on the delivery route (P > 0.05). Adverse events, all mild and self‐limiting, were observed in 33.3% (3/9) of the patients. Conclusions: FMT by washed preparation appears to be a safe and effective adjunct therapy for moderate to severely active UC during a short‐term follow‐up. The efficacy did not differ significantly between the NJT or TET delivery routes. Further randomized controlled studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Dysregulation of epidermal growth factor receptor (EGFR) signaling is responsible for the resistance to EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, and is thereby associated with the progression of tumors in non-small cell lung cancers (NSCLCs). Immunoblotting results revealed that geranylgeranyl transferase 1 inhibitor (GGTI)-298, a geranylgeranyl transferase 1 inhibitor with potential antitumor effects, effectively inhibited the phosphorylation of EGFR and its downstream target protein kinase B (AKT). A combination of gefitinib and GGTI-298 amplified the inhibition of the EGFR-AKT signaling pathway. In addition, GGTI-298 treatment produced a synergistic effect on the inhibition of proliferation as indicated by the combination index values of <1 when combined with gefitinib in the NSCLC cell lines HCC827 and A549. These synergistic effects were also observed to induce apoptosis and migration inhibition. Further mechanistic studies demonstrated that GGTI-298 inhibited the activity of Ras homolog family member A (RhoA), and downregulation of RhoA with small interfering RNA impaired the phosphorylation of EGFR, which suggested that EGFR inhibition by GGTI-298 may be exerted mainly through RhoA mediation. These results presented a novel, promising therapeutic strategy involving a combination of two drugs for targeting EGFR signaling in lung cancer. [ABSTRACT FROM AUTHOR]

The transcription factor Forkhead box protein M1 (FOXM1) plays critical roles in cancer development and progression, including human hepatocellular carcinoma (HCC). However, the regulatory role and underlying mechanisms of FOXM1 is still limited. Here, we found that the high level expression of FOXM1 and CCNB1 is closely associated with poor prognosis in HCC patients. And FOXM1 and CCNB1 were overexpressed concomitantly in liver tumor tissues. Knockdown of FOXM1 significantly inhibited the expression levels of CCNB1 in HCC cell lines at both the mRNA and protein levels. Mechanistic studies revealed that FOXM1 binds directly to the promoter region of CCNB1 and regulates the expression levels of the CCNB1 gene in the transcriptional level. Furthermore, the loss of functional and rescue experiments showed that CCNB1 is essential for FOXM1-driven proliferation in HCC cells. In the present study, our results partially explained the dysregulated expression of FOXM1 play an important role in proliferation of human hepatocellular carcinoma cells via transcriptional activation of CCNB1 expression. And it also highlights a FOXM1/CCNB1 axis could be a potential target for the treatment of HCCs. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is caused by aberrant immune responses to the gut microbiota. Among the gut microbiota, adherent-invasive Escherichia Coli (AIEC) is thought to be the pathogen through invading the intestinal epithelial cells and causing inflammation. IL-17 secretion increase, induced by enhanced bacterial adhesion to the intestine epithelium, could on one hand protect the mucosa, but on the other hand, over amount of IL-17 initializes inflammation reactions that in turn damages the mucosa. The relationship between IL-17 and AIEC is still unclear. In this study, we tried to elucidate the function of IL-17 in AIEC-mediated colitis. Wild type (WT) and IL-17 knockout (IL-17 KO) mice were inoculated with AIEC strain E. coli LF82 and treated with dextran sodium sulphate (DSS). Histological examination of the colon was performed. Mucosa damage was assessed and scored. IL-22 and IL-17 in colon tissues were detected by ELISA, qPCR and immunohistochemistry methods. Transient AIEC colonization in IL-17 KO mice resulted in increased intestinal epithelial damage, systemic bacterial burden and mortality compared with WT controls. Moreover, IL-17 is required for the induction of IL-22 in the experimental animal models during AIEC strain E. coli LF82 colonization. These results indicate IL-17 plays a protective role in AIEC strain E. coli LF82 induced colitis by promoting IL-22 secretion. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the cytotoxicity of silk fibroin/gelatin (SF/G) composite scaffolds in vitro as well as their biocompatibility and degradation in vivo. METHODS: The proliferation and relative growth rate of human hepatic QZG cells grown on different blends of two-dimensional (2-D) SF/G scaffolds were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry was used to evaluate apoptotic rate of QZG cells on different blends of 2-D SF/G scaffolds. The effect of silk protein materials on cell growth was observed by scanning electron microscopy. Three-dimensional (3-D) SF/G scaffolds of three different ratios (diameter 10 mm, thickness 1 mm) were implanted into subcutaneous pockets on male Sprague-Dawley (SD) rats. On the 7th, 14th and 30th day post-implantation, the rats were sacrificed. The scaffold area including the surrounding tissues was retrieved. Hematoxylin and eosin staining was performed for observation under a light microscope. RESULTS: Significant cell attachment and proliferation on the SF/G scaffolds were observed. As the increased gelatin concentration, SF/G scaffolds became more amenable to cell adhesion. After the subcutaneous implantation of the SF/G scaffolds in SD rats, immunological rejection tests showed only slight inflammation, measured by the presence of inflamed cells on day 7 and 14. By day 30, each scaffold had been completely infiltrated and organized by fibroblasts and inflamed cells. The greater the gelatin concentration in the scaffold, the faster the degradation rate. CONCLUSION: Composite SF/G scaffolds are a promising candidate matrix for implantable bio-artificial livers. [ABSTRACT FROM AUTHOR]

Previous studies have highlighted the role of genetic predispositions in disease, and several genes had been identified as important in Crohn's disease (CD). However, many of these genes are likely rare and not associated with susceptibility in Chinese CD patients. We found 294 shared identical variants in the CD patients of which 26 were validated by Sanger sequencing. Two heterozygous IFN variants (IFNA10 c.60 T > A; IFNA4 c.60 A > T) were identified as significantly associated with CD susceptibility. The single-nucleotide changes alter a cysteine situated before the signal peptide cleavage site to a stop code (TGA) in IFNA10 result in the serum levels of IFNA10 were significantly decreased in the CD patients compared to the controls. Furthermore, the IFNA10 and IFNA4 mutants resulted in an impairment of the suppression of HCV RNA replication in HuH7 cells, and the administration of the recombinant IFN subtypes restored DSS-induced colonic inflammation through the upregulation of CD4+ Treg cells. We identified heterozygous IFNA10 and IFNA4 variants as a cause of impaired function and CD susceptibility genes in Chinese patients from multiple center based study. These findings might provide clues in the understanding of the genetic heterogeneity of CD and lead to better screening and improved treatment. [ABSTRACT FROM AUTHOR]