RESUMO
Objective: This meta-analysis comprehensively summarizes the current clinical research on compound glycyrrhizin (CG) treatment for liver cancer and protecting liver function to guide clinical treatment. Methods: Eighteen English-language articles were retrieved from PubMed, SinoMed, Cochrane, Embase, Web of Science, and three Chinese databases: The Wan Fang database, China National Knowledge Infrastructure (CNKI), and the VIP database. Results: CG treatment improved the patient's alanine aminotransferase (ALT) level (in the metastatic liver cancer group: mean deviation (MD) = -13.78, 95% confidence interval (CI) = [-17.29, 10.27]; in the primary liver cancer group: MD = -32.15, 95% CI = [-35.48, 28.81]); aspartate aminotransferase (AST) level (in the primary liver cancer group: MD = -21.63, 95% CI = [-24.29, 18.96]; in the metastatic liver cancer group: MD = -15.64, 95% CI = [-19.08, -12.20]); serum total bilirubin (TBIL) level (MD = -1.61, 95% CI = [-2.71, -0.51]); and serum albumin (ALB) level (MD = 2.80, 95% CI = [1.85, 3.74]). CG treatment was efficient than the control (relative risk [RR] = 1.66, 95% CI = [1.35, 2.04]). Although adverse reactions, including fever, were higher than in the control group (RR = 1.13, 95% CI = [0.89, 1.43]), they were controllable. Conclusion: CG affects liver preservation in treating liver cancer, which can reduce ALT, AST, and TBIL levels in patients; increase the ALB level; and protect liver cells. The CG-treated group showed improvement compared with the control group; although adverse reactions occurred in the treated group, the duration was shortened.
Assuntos
Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Medicamentos de Ervas Chinesas/uso terapêutico , Ácido Glicirrízico/uso terapêutico , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgiaRESUMO
The hypothalamus regulates metabolic homeostasis by influencing behavior and endocrine systems. Given its role governing key traits, such as body weight and reproductive timing, understanding the genetic regulation of hypothalamic development and function could yield insights into disease pathogenesis. However, given its inaccessibility, studying human hypothalamic gene regulation has proven challenging. To address this gap, we generate a high-resolution chromatin architecture atlas of an established embryonic stem cell derived hypothalamic-like neuron model across three stages of in vitro differentiation. We profile accessible chromatin and identify physical contacts between gene promoters and putative cis-regulatory elements to characterize global regulatory landscape changes during hypothalamic differentiation. Next, we integrate these data with GWAS loci for various complex traits, identifying multiple candidate effector genes. Our results reveal common target genes for these traits, potentially affecting core developmental pathways. Our atlas will enable future efforts to determine hypothalamic mechanisms influencing disease susceptibility.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Células-Tronco Embrionárias Humanas/fisiologia , Hipotálamo/embriologia , Neurônios/fisiologia , Diferenciação Celular/genética , Linhagem Celular , Mapeamento Cromossômico , Estudo de Associação Genômica Ampla , Humanos , Hipotálamo/citologia , Herança Multifatorial , RNA-Seq , Elementos Reguladores de Transcrição/genéticaRESUMO
BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is a polygenic disorder characterized principally by dysregulated inflammation impacting the gastrointestinal tract. However, there also is increasing evidence for a clinical association with stress and depression. Given the role of the hypothalamus in stress responses and in the pathogenesis of depression, useful insights could be gleaned from understanding its genetic role in IBD. METHODS: We conducted genetic correlation analyses on publicly available genome-wide association study summary statistics for depression and IBD traits to identify genetic commonalities. We used partitioned linkage disequilibrium score regression, leveraging our ATAC sequencing and promoter-focused Capture C data, to measure enrichment of IBD single-nucleotide polymorphisms within promoter-interacting open chromatin regions of human embryonic stem cell-derived hypothalamic-like neurons (HNs). Using the same data sets, we performed variant-to-gene mapping to implicate putative IBD effector genes in HNs. To contrast these results, we similarly analyzed 3-dimensional genomic data generated in epithelium-derived colonoids from rectal biopsy specimens from donors without pathologic disease noted at the time of colonoscopy. Finally, we conducted enrichment pathway analyses on the implicated genes to identify putative IBD dysfunctional pathways. RESULTS: We found significant genetic correlations (rg) of 0.122 with an adjusted P (Padj) = 1.4 × 10-4 for IBD: rg = 0.122; Padj = 2.5 × 10-3 for ulcerative colitis and genetic correlation (rg) = 0.094; Padj = 2.5 × 10-3 for Crohn's disease, and significant approximately 4-fold (P = .005) and approximately 7-fold (P = .03) enrichment of IBD single-nucleotide polymorphisms in HNs and colonoids, respectively. We implicated 25 associated genes in HNs, among which CREM, CNTF, and RHOA encode key regulators of stress. Seven genes also additionally were implicated in the colonoids. We observed an overall enrichment for immune and hormonal signaling pathways, and a colonoid-specific enrichment for microbiota-relevant terms. CONCLUSIONS: Our results suggest that the hypothalamus warrants further study in the context of IBD pathogenesis.