RESUMO
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent hepatic pathology worldwide. However, the precise molecular mechanisms for NAFLD are still not sufficiently explained. Recently, a new mode of cell death (cuproptosis) is found. However, the relationship between NAFLD and cuproptosis remains unclear. We analyzed three public datasets (GSE89632, GSE130970, and GSE135251) to identify cuproptosis-related genes stably expressed in NAFLD. Then, we performed a series of bioinformatics analyses to explore the relationship between NAFLD and cuproptosis-related genes. Finally, 6 high-fat diet- (HFD-) induced NAFLD C57BL/6J mouse models were established to carry out transcriptome analysis. The results of gene set variation analysis (GSVA) revealed that the cuproptosis pathway was abnormally activated to a certain degree (p = 0.035 in GSE89632, p = 0.016 in GSE130970, p = 0.22 in GSE135251), and the principal component analysis (PCA) of the cuproptosis-related genes showed that the NAFLD group separated from the control group, with the first two principal components accounting for 58.63%-74.88% of the variation. Among three datasets, two cuproptosis-related genes (DLD and PDHB, p < 0.01 or 0.001) were stably upregulated in NAFLD. Additionally, both DLD (AUC = 0.786-0.856) and PDHB (AUC = 0.771-0.836) had favorable diagnostic properties, and the multivariate logistics regression model further improved the diagnostic properties (AUC = 0.839-0.889). NADH, flavin adenine dinucleotide, and glycine targeted DLD, and pyruvic acid and NADH targeted PDHB in the DrugBank database. The DLD and PDHB were also associated with clinical pathology, especially with steatosis (DLD, p = 0.0013-0.025; PDHB, p = 0.002-0.0026) and NAFLD activity score (DLD, p = 0.004-0.02; PDHB, p = 0.003-0.031). What is more, DLD and PDHB were correlated with stromal score (DLD, R = 0.38, p < 0.001; PDHB, R = 0.31, p < 0.001) and immune score (DLD, R = 0.26, p < 0.001; PDHB, R = 0.27, p < 0.001) in NAFLD. Furthermore, Dld and Pdhb were also significantly upregulated in the NAFLD mouse model. In conclusion, cuproptosis pathways, especially DLD and PDHB, could be potential candidate genes for NAFLD diagnostic and therapeutic options.
Assuntos
Apoptose , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Morte Celular , Biologia Computacional , Camundongos Endogâmicos C57BL , NAD , Hepatopatia Gordurosa não Alcoólica/genética , Cobre , Apoptose/genéticaRESUMO
BACKGROUND: It is disputed about optimal bowel preparation for small bowel capsule endoscopy (SBCE). This meta-analysis aimed to investigate the role of simethicone in intestinal preparation for SBCE. METHODS: We searched four databases (PubMed, web of science, Embase, and Scopus databases) for relevant studies. Studies evaluating the effect of simethicone as an adjunct to SBCE bowel preparation were included. The random-effects model was applied to calculate the risk estimates. Primary outcomes include the degree of gas bubbles and small bowel visualization quality (SBVQ). Secondary outcomes include diagnostic yield (DY), gastric transit time (GTT), small bowel transit time (SBTT), and completion rate (CR). RESULTS: A total of 10 studies were included (8 RCTs, 1 prospective, and 1 retrospective study). Compared with the control group, the simethicone group showed significant improvements in the degree of gas bubbling (RR = 2.05, 95%CI:1.56-2.71, P < 0.001, I2 = 62%) and SBVQ (RR = 1.41, 95%CI: 1.20-1.65, P < 0.001, I2 = 16%). Subgroup analysis showed that the SBVQ of simethicone group was better than fasting (RR = 2.62, 95% CI:1.49-4.59, P < 0.001, I2 = 0%), mannitol (RR = 1.35, 95% CI: 1.14-1.59, P < 0.001, I2 = 0%) and PEG group (RR = 1.32, 95%CI:1.06-1.65, P = 0.01, I2 = 0%). No significant associations were found for DY, GTT, SBTT, and CR. CONCLUSIONS: Simethicone for bowel preparation is useful to improve visualization and reduce the gas bubbling of SBCE.
Assuntos
Endoscopia por Cápsula , Humanos , Simeticone/farmacologia , Estudos Retrospectivos , Estudos Prospectivos , Intestino DelgadoRESUMO
Purpose: Based on a large number of systematic reviews and meta-analyses exploring the relationship between psoriasis and various health outcomes, we conducted an comprehensive analysis to assess the strength and evidence for the association between psoriasis and medical end-point ramifications in patients. Methods: We searched related meta-analyses, investigating the links between psoriasis and medical ramifications from three databases. All summary effect sizes, 95% CIs, heterogeneity, and small-study effects in the included meta-analyses were recalculated. We assessed the methodological quality of included articles with the AMSTAR 2 tool and graded the epidemiological evidence. Subgroup analysis based on the severity of psoriasis and study design were also performed. Results: A total of 38 articles comprising 85 unique meta-analyses were included in this study. Although 69 outcomes were statistically significant, only 8 outcomes (nonvascular dementia, ulcerative colitis, pediatric dyslipidemia, gestational diabetes, gestational hypertension, fracture, multiple sclerosis, and schizophrenia) showed a high quality of epidemiological evidence. Conclusion: We found that psoriasis increased the risk of 69 health outcomes, and 8 outcomes were graded as high-quality evidence. No evidence was found that psoriasis was beneficial for any medical end point. However, to verify our results, more large-sample, multi-center prospective cohort studies are needed.
RESUMO
The objective of this paper was to explore the role and molecular mechanism of miR-193a in membranous nephropathy (MN). Experimental rats and podocytes were randomly divided into four groups: control, MN, miR-NC, and miR-193a inhibitor groups. The relative mRNA level of miR-193a was determined. The mRNA level and protein expression of PODXL, NPHS1, and Notch1 were determined by real-time polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. The mRNA level and protein expression of WT1 in podocytes were also determined by RT-PCR and Western blot analysis. The relative mRNA level of miR-193a in the MN group was significantly higher than that in the control group, and inhibition of miR-193a inhibited the increase successfully. Inhibition of miR-193a inhibited renal injury, podocyte injury, and tissue cell apoptosis resulting from MN. The expression of PODXL, NPHS1, and Notch1 was decreased in the MN group, while the expression was increased in the miR-193a inhibitor group. WT1 was verified as a target gene of miR-193a and the expression of WT1 increased after inhibition of miR-193a. Inhibition of miR-193a by targeting WT1 could inhibit renal function injury, renal tissue cell apoptosis, and podocytosis.
Assuntos
Regulação Neoplásica da Expressão Gênica , Glomerulonefrite Membranosa/patologia , MicroRNAs/genética , Podócitos/patologia , Proteínas WT1/metabolismo , Animais , Apoptose , Proliferação de Células , Glomerulonefrite Membranosa/genética , Glomerulonefrite Membranosa/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Podócitos/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor Notch1/genética , Receptor Notch1/metabolismo , Sialoglicoproteínas/genética , Sialoglicoproteínas/metabolismo , Transdução de Sinais , Proteínas WT1/genéticaRESUMO
Renal interstitial fibrosis is characterized by inflammation and an excessive accumulation of extracellular matrix, which leads to end-stage renal failure. Our previous studies have shown that a natural product from Cordyceps cicadae can ameliorate chronic kidney diseases. N6-(2-Hydroxyethyl) adenosine (HEA), a physiologically active compound in C. cicadae, has been identified as a Ca2+ antagonist and an anti-inflammatory agent in pharmacological tests. However, its role in renal interstitial fibrosis and the underlying mechanism remains unclear. Here, unilateral ureteral obstruction (UUO) was used to induce renal interstitial fibrosis in male C57BL/6 mice. Different doses of HEA (2.5, 5, and 7.5 mg/kg) were given by intraperitoneal injection 24 h before UUO, and the treatment was continued for 14 days post-operatively. Histologic changes were examined by hematoxylin & eosin, Masson's trichrome, and picrosirius red stain. Quantitative real-time PCR analysis, enzyme-linked immunosorbent assays, immunohistochemistry, and western blot analysis were used to evaluate proteins levels. And the results showed that HEA significantly decreased UUO-induced renal tubular injury and fibrosis. In vivo, HEA apparently decreased UUO-induced inflammation and renal fibroblast activation by suppression of the NF-κB and TGF-ß1/Smad signaling pathway. In vitro, HEA also obviously decreased lipopolysaccharide-induced inflammatory cytokine level in RAW 264.7 cells and TGF-ß1-induced fibroblast activation in NRK-49F cells by modulating NF-κB and TGF-ß1/Smad signaling. In general, our findings indicate that HEA has a beneficial effect on UUO-induced tubulointerstitial fibrosis by suppression of inflammatory and renal fibroblast activation, which may be a potential therapy in chronic conditions such as renal interstitial fibrosis.