Pub Date : 2020-01-01Epub Date: 2019-10-09DOI: 10.1152/ajpcell.00175.2019
Natasha Chernis, Peter Masschelin, Aaron R Cox, Sean M Hartig
Endocrine-disrupting chemicals interact with transcription factors essential for adipocyte differentiation. Exposure to endocrine-disrupting chemicals corresponds with elevated risks of obesity, but the effects of these compounds on human cells remain largely undefined. Widespread use of bisphenol AF (BPAF) as a bisphenol A (BPA) alternative in the plastics industry presents unknown health risks. To this end, we discovered that BPAF interferes with the metabolic function of mature human adipocytes. Although 4-day exposures to BPAF accelerated adipocyte differentiation, we observed no effect on mature fat cell marker genes. Additional gene and protein expression analysis showed that BPAF treatment during human adipocyte differentiation failed to suppress the proinflammatory transcription factor STAT1. Microscopy and respirometry experiments demonstrated that BPAF impaired mitochondrial function and structure. To test the hypothesis that BPAF fosters vulnerabilities to STAT1 activation, we treated mature adipocytes previously exposed to BPAF with interferon-γ (IFNγ). BPAF increased IFNγ activation of STAT1 and exposed mitochondrial vulnerabilities that disrupt adipocyte lipid and carbohydrate metabolism. Collectively, our data establish that BPAF activates inflammatory signaling pathways that degrade metabolic activity in human adipocytes. These findings suggest how the BPA alternative BPAF contributes to metabolic changes that correspond with obesity.
干扰内分泌的化学物质与脂肪细胞分化所必需的转录因子相互作用。暴露于干扰内分泌的化学物质会导致肥胖风险升高，但这些化合物对人体细胞的影响在很大程度上仍未确定。塑料工业广泛使用双酚 AF（BPAF）作为双酚 A（BPA）的替代品，其健康风险尚不可知。为此，我们发现双酚 AF 会干扰成熟人类脂肪细胞的代谢功能。虽然暴露于双酚 AF 4 天会加速脂肪细胞的分化，但我们观察到它对成熟脂肪细胞的标记基因没有影响。其他基因和蛋白质表达分析表明，在人类脂肪细胞分化过程中，双酚 AF 处理未能抑制促炎转录因子 STAT1。显微镜和呼吸测定实验表明，双酚 AF 会损害线粒体的功能和结构。为了验证双酚 AF 易导致 STAT1 激活的假说，我们用干扰素-γ（IFNγ）处理先前暴露于双酚 AF 的成熟脂肪细胞。双酚 AF 增加了 IFNγ 对 STAT1 的激活，暴露了线粒体的脆弱性，从而破坏了脂肪细胞的脂质和碳水化合物代谢。总之，我们的数据证实双酚 AF 激活了炎症信号通路，从而降低了人类脂肪细胞的代谢活性。这些发现表明，双酚 A 替代物 BPAF 是如何导致与肥胖相应的代谢变化的。
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Pub Date : 2020-01-01DOI: 10.1093/med/9780198746690.003.0307
M. Irving
Ulcerative colitis is a chronic relapsing and remitting disease in which chronic inflammation affects the rectum and extends proximally to a variable extent. The precise aetiology remains unknown but involves an interplay between reduced diversity in the gut microbiota and a genetically dysregulated gut immune system and epithelial barrier. Typical presentation of mild or moderate disease is with a gradual onset of symptoms including diarrhoea, rectal bleeding, and the passage of mucus. Severe disease is characterized by anorexia, nausea, weight loss, and severe diarrhoea, with the patient likely to look unwell with fever, tachycardia, and other signs of volume depletion, and the abdomen may be distended and tympanitic, with reduced bowel sounds and marked colonic tenderness. Diagnosis is usually made on the basis of exclusion of infective colitis by stool culture and the finding of typical diffuse inflammation in the rectum and above at sigmoidoscopy. Management requires rapid control of symptoms with induction therapy followed by maintenance of remission. Mild disease is typically treated with 5-aminosalicyclic acid delivered both orally and by enema, and moderate disease by 5-aminosalicyclic acid and steroids. Patients with severe disease require hospital admission, intravenous steroids, and daily review by both a physician and a surgeon experienced in the management of ulcerative colitis. Ciclosporin or infliximab are used as rescue therapies for steroid-resistant acute severe ulcerative colitis, but colectomy should not be delayed when this is required. Maintenance therapy with immunomodulators and biological therapies are both effective at maintaining remission, and several new biologicals are in clinical trials.
{"title":"Ulcerative colitis.","authors":"M. Irving","doi":"10.1093/med/9780198746690.003.0307","DOIUrl":"https://doi.org/10.1093/med/9780198746690.003.0307","url":null,"abstract":"Ulcerative colitis is a chronic relapsing and remitting disease in which chronic inflammation affects the rectum and extends proximally to a variable extent. The precise aetiology remains unknown but involves an interplay between reduced diversity in the gut microbiota and a genetically dysregulated gut immune system and epithelial barrier.\u0000 Typical presentation of mild or moderate disease is with a gradual onset of symptoms including diarrhoea, rectal bleeding, and the passage of mucus. Severe disease is characterized by anorexia, nausea, weight loss, and severe diarrhoea, with the patient likely to look unwell with fever, tachycardia, and other signs of volume depletion, and the abdomen may be distended and tympanitic, with reduced bowel sounds and marked colonic tenderness. Diagnosis is usually made on the basis of exclusion of infective colitis by stool culture and the finding of typical diffuse inflammation in the rectum and above at sigmoidoscopy. Management requires rapid control of symptoms with induction therapy followed by maintenance of remission. Mild disease is typically treated with 5-aminosalicyclic acid delivered both orally and by enema, and moderate disease by 5-aminosalicyclic acid and steroids. Patients with severe disease require hospital admission, intravenous steroids, and daily review by both a physician and a surgeon experienced in the management of ulcerative colitis. Ciclosporin or infliximab are used as rescue therapies for steroid-resistant acute severe ulcerative colitis, but colectomy should not be delayed when this is required. Maintenance therapy with immunomodulators and biological therapies are both effective at maintaining remission, and several new biologicals are in clinical trials.","PeriodicalId":74327,"journal":{"name":"Nursing times","volume":"73 38 1","pages":"1466-9"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49568323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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