Background Fecal microbiota transplantation (FMT) is an emerging treatment approach for inflammatory bowel disease (IBD). The donor selection, the separation of fecal bacteria, the frequency of FMT, the way of infusion, the long-term safety, and efficacy are still uncertain. Aim To further study the efficacy and safety and protocol of FMT for IBD. Methods A systematic review and meta-analysis were conducted until February, 2018. Clinical remission was established as the primary outcome. Results A total of 596 paediatric and adult IBD patients were enrolled, and 459 patients received FMT therapy. 28.8% (132/459) patients achieved clinical remission during follow-up. 53% (241/459) patients achieved clinical response. The pooled estimated clinical remission for ulcerative colitis (UC) was 21% (95% CI: 8%-37%) and 30% (95% CI: 11%-52%) for Crohn's disease (CD), both with a risk of heterogeneity; 10% (95% CI: 0%-43%) for paediatric UC; 26% (95% CI: 10%-48%) for adult UC; 45% for paediatric CD (95% CI: 24%-66%); 22% (95% CI: 3%-52%) for adult CD. Meta-analysis of cohort studies showed that moderate-severe IBD patients could achieve more significant remission from FMT than mild-moderate patients (P=0.037). Delivery route has no impact on the efficacy of FMT in UC and CD. Based on current available evidence, a trend was observed towards higher clinical remission rate of frozen stool FMT than that of fresh stool for UC, while there was no significant difference between fresh and frozen FMT for CD. The optimal donor stool for FMT is still uncertain. Meta-analysis of RCTs showed that FMT treatment achieved significantly higher clinical remission rate than placebo for UC (28% versus 9%, P=0.0003). Conclusion FMT is an effective and safe therapy for both paediatric and adult IBD; fresh or frozen donor stool, delivery route, and antibiotic pretreatment or not have no impact on the efficacy of FMT in IBD. FMT might be a potential rescue therapy and even an initial standardized therapy for IBD. However, few data exist on long-term safety and efficacy and further validation is needed.
A clear understanding of physicochemical factors governing nanoparticle toxicity is still in its infancy. We used a systematic approach to delineate physicochemical properties of nanoparticles that govern cytotoxicity. The cytotoxicity of fourth period metal oxide nanoparticles (NPs): TiO2, Cr2O3, Mn2O3, Fe2O3, NiO, CuO, and ZnO increases with the atomic number of the transition metal oxide. This trend was not cell-type specific, as observed in non-transformed human lung cells (BEAS-2B) and human bronchoalveolar carcinoma-derived cells (A549). Addition of NPs to the cell culture medium did not significantly alter pH. Physiochemical properties were assessed to discover the determinants of cytotoxicity: (1) point-of-zero charge (PZC) (i.e., isoelectric point) described the surface charge of NPs in cytosolic and lysosomal compartments; (2) relative number of available binding sites on the NP surface quantified by X-ray photoelectron spectroscopy was used to estimate the probability of biomolecular interactions on the particle surface; (3) band-gap energy measurements to predict electron abstraction from NPs which might lead to oxidative stress and subsequent cell death; and (4) ion dissolution. Our results indicate that cytotoxicity is a function of particle surface charge, the relative number of available surface binding sites, and metal ion dissolution from NPs. These findings provide a physicochemical basis for both risk assessment and the design of safer nanomaterials.
Novel composites were synthesized from keratin (KER), cellulose (CEL) and chitosan (CS). The method is recyclable because majority (>88%) of [BMIm+Cl−], an ionic liquid (IL), used as the sole solvent, was recovered for reuse. Experimentally, it was confirmed that unique properties of each component remain intact in the composites, namely bactericide (from KER and CS) and anti-inflammatory property (from KER). Specifically, the composites were examined for their anti-inflammatory influence on macrophages. The cells were imaged and immunophenotyped to determine the quantity using the macrophage marker CD11b. The 75:25 [KER+CS] composite was found to have the least amount of CD11b macrophages compared to other composites. Bactericidal assays indicated that all composites, except the 25:75 [KER+CS], substantially reduce the growth of organisms such as vancomycin resistant Enterococcus (VRE) and Eschericia coli. The results clearly indicate that the composites possess all properties needed for effective use as a wound dressing.
Background To assess the long-term safety and efficacy of monotherapy with a single fresh fecal microbiota transplant (FMT) for recurrent ulcerative colitis (UC). Results Twenty-six eligible patients were enrolled, and 6 patients were excluded. Ultimately, 20 patients were randomized to the FMT group (n = 10) and the control group (n = 10); 80% were females (F/M = 16/4), the mean age was 48 ± 14 years, and the mean duration was 6.4 ± 8.2 years. The mean length of post-FMT follow-up was 19.1 ± 10.1 months (6–38). No statistically significant differences in baseline demographic or clinical characteristics were found between the groups. Ninety percent of patients in the FMT group and 50% of patients in the control group met the primary endpoint at week 8. The Mayo score was significantly decreased compared with that of the control group (n = 10) when reassessed at week 4 (P = 0.001) and week 8 (P = 0.019) after FMT; there was no significant difference 6 months after treatment. The median remission time was 24 months (95% CI 68.26–131.7%) in both the FMT (range 6–38 months) and control groups (range 7–35 months), with no significant difference (P = 0.895). Participants tolerated FMT treatment, and no adverse events occurred during long-term follow-up, with one treatment-related significant adverse event (EBV infection) occurring within 2 weeks after FMT. Stool microbiota composition analysis indicated improved gut microbiota diversity after FMT, with expansion of stool-donor taxa. Bacteroidetes, Firmicutes and Proteobacteria were the dominant bacterial phyla of the gut microbiota in active UC patients. The relative abundance of Bacteroidetes decreased and that of Proteobacteria increased significantly in active UC patients compared with donors, while Firmicutes showed no significant changes. A single fresh FMT could effectively reconstruct the gut microbiota composition in patients with active UC and maintain stability, with increased Bacteroidetes and decreased Proteobacteria abundance. FMT significantly reduced the relative abundance of Escherichia and increased the relative abundance of Prevotella at the genus level. Pyruvate metabolism, glyoxylate and dicarboxylate metabolism, and pantothenate and CoA biosynthesis showed significant differences after transplantation. Conclusions Monotherapy with a single fresh FMT is an effective and safe strategy to induce long-term remission without drugs in patients with active UC and may be an alternative induction therapy for recurrent UC or even primary UC.
Abstract. Cervical cancer is one of the most malignant types of tumor and the fourth leading cause of cancer-associated mortality in females worldwide. High expression of brain cytoplasmic RNA 1 (BCYRN1) has been detected in various tumors. The present study aimed to investigate the effect of BCYRN1 in the viability and motility of cervical cancer, and the relevant mechanism. The results demonstrated that BCYRN1 was upregulated in cervical cancer tissues compared with normal tissues. Elevated levels of BCYRN1 were also detected in three human cervical cancer cell lines (SiHa, HeLa and CaSki) compared with non-cancerous ectocervical epithelial cell line (Ect1/E6E7). The expression of BCYRN1 was suppressed following transfection with small interfering RNA (siRNA) in HeLa cells. The silence of BCYRN1 significantly reduced cell viability and motility. Furthermore, microRNA (miR)-138 was predicted as a direct target of BCYRN1 and the expression of miR-138 was elevated in HeLa cells transfected with BCYRN1 siRNA. Subsequently, elevated levels of miR-138 were suppressed by transfection with miR-138 inhibitor in HeLa cells pretreated with BCYRN1 siRNA. The targeting association between BCYRN1 and miR-138 was supported by luciferase reporter assays. Additionally, BCYRN1 siRNA partially counteracted the effect of miR-138 inhibitor on promoting cell viability and mobility in HeLa cells. Finally, the in vivo experiment verified that BCYRN1 siRNA was able to prevent tumor growth, and reduced the expression of migration marker proteins metalloproteinase 2 and vascular endothelial cell growth factor, with enhanced expression levels of miR-138. These results suggest that lncRNA BCYRN1 promotes the proliferation and invasion of cervical cancer via targeting miR-138.
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