Sheng-Jie Huang, Tao Ai, Hui Hu, Juan Wang, Jin-Long Wang
{"title":"Immunotherapy for Sepsis Induced by Infections: Clinical Evidence and Potential Targets.","authors":"Sheng-Jie Huang, Tao Ai, Hui Hu, Juan Wang, Jin-Long Wang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Sepsis is a life-threatening organ dysfunction caused by the maladjustment of the body's response to infection. Abnormal immune response plays an important role in the progression of sepsis, and immunomodulatory therapy is a promising therapeutic strategy for sepsis. Great efforts have been made recently to elucidate the mechanism by which immune dysfunction contributes to sepsis, and identify potential biomarkers and targets for the diagnosis and therapy of sepsis induced by emerging pathogens, especially for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19. In this review, we summarize recent progress on the understanding of immune dysregulation involved in sepsis, and highlight potential biomarkers and targets to evaluate immune status of the patients with sepsis for individualized and precise immunotherapy.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"34 172","pages":"83-95"},"PeriodicalIF":1.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10404002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Clara Wang-Liang, Sarah Reid, Jacob Barkley, Prasoon Jain
{"title":"Methylprednisolone-induced Acute Pancreatitis, a Case Presentation.","authors":"Clara Wang-Liang, Sarah Reid, Jacob Barkley, Prasoon Jain","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Acute pancreatitis is one of the leading gastrointestinal causes of hospitalization in the United States, with drug-induced acute pancreatitis being rare which is only about 0.1-2% of all acute pancreatitis cases (Balani and Grendell, 2008). Based on current publications, there are about 100 medications that can potentially cause drug-induced acute pancreatitis. In this article, we present a case of a 74-year-old man who had been treated with high doses of methylprednisolone for three days prior to the presentation of symptoms in accordance with those of acute pancreatitis. A detailed evaluation of the patient's medical history and exclusion of other probable etiologies confirmed the diagnosis of methylprednisolone-induced pancreatitis. The treatment is supportive care and withdrawal of the offending agent. The diagnosis of drug-induced pancreatitis remains a challenge for clinicians. This case may add further evidence for the role of methylprednisolone in drug-induced acute pancreatitis. It also serves as a reminder to look closely at the patient's history and medications when a cause for acute pancreatitis is not immediately found.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":" ","pages":"79-81"},"PeriodicalIF":1.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40658023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of Proliferative Vitreoretinopathy Is Attenuated by Chicken Ovalbumin Upstream Promoter Transcriptional Factor 1 Via Inhibiting Epithelial-Mesenchymal Transition.","authors":"Huizi Jin, Wenting Cai, Donghui Yu, Jiaqi Fan, Qingyu Liu, Jing Yu","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Proliferative vitreoretinopathy (PVR) is an intractable condition after rhegmatogenous retinal detachment (RD), which is the primary cause of failure in retinal reattachment surgery. This study aimed to investigate the effects of chicken ovalbumin upstream promoter transcriptional factor 1 (COUP-TF1) in the development of proliferative vitreoretinopathy (PVR) both in vitro and in vivo. Adult retinal pigment epithelium cell line was used for in-vitro experiments. Immunocytochemistry assay, real-time quantitative polymerase chain reaction, and Western blot were used to measure the expression of COUP-TF1, alpha-smooth muscle actin (α-SMA), and E-cadherin. Epithelial-mesenchymal transition (EMT) was observed through cell counting kit-8 assay, wound healing tests, and the expression changes of related proteins. PVR rabbit models were established and evaluated by the images of fundus and vitreous cavity, pathological sections, and COUP-TF1 expression. As shown by our results, the proliferation and migration of the COUP-TF1 knockdown cells were reduced compared with the control cells with or without transforming growth factor-β1 (TGF-β1) treatment. After TGF-β1 treatment, α-SMA expression was upregulated in ARPE-19 cells but kept the same in COUP-TF1 knockdown cells. E-cadherin expression was down-regulated in all the groups but the extent of the decrease in COUP-TF1 knockdown cells was smaller. EMT was attenuated in ARPE-19 cells after COUP-TF1 was knocked down. In the in-vivo experiment, PVR severity was attenuated and the retinal detachment rate decreased on the 14th and 28th day in COUP-TF1 knockdown group. In conclusion, COUP-TF1 is related to the development of PVR, and COUP-TF1 knockdown attenuates the progression of PVR. This suggests that COUP-TF1 can be a promising candidate for the treatment of PVR.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":" ","pages":"103-113"},"PeriodicalIF":1.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40466928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jinghui Sun, Guodong Liu, Rui Chen, Jibin Zhou, Ting Chen, Yalan Cheng, Qiyang Lou, Hao Wang
{"title":"PARP1 Is Upregulated by Hyperglycemia Via N6-methyladenosine Modification and Promotes Diabetic Retinopathy.","authors":"Jinghui Sun, Guodong Liu, Rui Chen, Jibin Zhou, Ting Chen, Yalan Cheng, Qiyang Lou, Hao Wang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Poly (ADP-ribose) polymerase 1 (PARP1) plays an irreplaceable role in the progression of diabetic retinopathy (DR). The m6A methylation in mRNA controls gene expression under various physiological and pathological conditions. However, effects of m6A methylation on PARP1 expression and DR progression at molecular level have not been documented. This study shows that the levels of PARP1, inflammatory factors, and fibrosis markers were significantly upregulated via evaluation by real-time PCR, western blotting, and immunofluorescence in both in vivo and in vitro experiments. EdU, CCK8, and apoptosis assays demonstrate that knockdown of PARP1 not only significantly improved the vitality of hRMECs (human retinal microvascular endothelial cells) even under high glucose conditions but also prevented glucose-induced inflammation, fibrosis, and angiogenesis in vivo. Mechanistically, dot blot, RNA pull-down, and immunoblots were implemented to explore the mechanism of m6A-mediated PARP1 stability and function. PARP1 is identified as a target of YTHDF2-mediated m6A modification. Overexpression of YTHDF2 substantially suppressed PARP1 mRNA m6A modification and inhibited its mRNA expression. Collectively, it has been demonstrated that PARP1 is frequently upregulated in human retinas and contributes to DR progression, and that YTHDF2-mediated m6A modification epigenetically regulates diabetes-induced PARP1 expression. Findings from this work may engender therapeutic targets for treating diabetic retinopathy.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":" ","pages":"115-129"},"PeriodicalIF":1.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40466929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhizhi Wang, Huihui Zhou, Fei Cheng, Zhendong Zhang, Shunhua Long
{"title":"miR-21 Negatively Regulates the PTEN-PI3K-Akt-mTOR Signaling Pathway in Crohn's Disease by Altering Immune Tolerance and Epithelial-Mesenchymal Transition.","authors":"Zhizhi Wang, Huihui Zhou, Fei Cheng, Zhendong Zhang, Shunhua Long","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>miR-21 is involved in the mechanisms of inflammatory bowel disease (IBD). It negatively regulates PTEN, which is an upstream regulatory gene of the PI3K/Akt/mTOR signaling pathway. But the relationship between miR-21 and immune tolerance and intestinal epithelial injury, and the mechanism by which miR-21 participates in Crohn's disease (CD) have not been studied. We aimed to address these two questions. The results of the present study showed that the levels of miR-21 and PTEN respectively decreased and increased significantly in the intestinal mucosa from active CD compared with control ones. Transfection with miR-21-5p mimics significantly downregulated the expression of PTEN and upregulated PI3K-Akt-mTOR signaling and the downstream pathway in PBMCs, while transfection with a miR-21-5p inhibitor antagomiR-21had the opposite effect. Moreover, the ratio of Treg/Th1 cells differentiated from peripheral blood mononuclear cells (PBMCs) decreased after being transfected with mimics, and increased with the inhibitor. AntagomiR-21 significantly relieved the lesions in colons of mice with TNBS-induced colitis, accompanied by the upregulation of PTEN and downregulation of mTOR. Inhibition of miR-21 also effectively suppressed the process of epithelial-mesenchymal transition (EMT) in vivo. In conclusion, the level of miR-21 decreased in CD, resulting in an upregulated PI3K-Akt-mTOR signaling pathway, compromised immune tolerance, and elevated inflammation.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"34 171","pages":"45-58"},"PeriodicalIF":1.4,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10353547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MicroRNAs in Irritable Bowel Syndrome: a Systematic Review.","authors":"Katsunori Yanai, Kenichi Ishibashi, Yoshiyuki Morishita","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Irritable bowel syndrome (IBS), a common gastrointestinal disorder, was reported to contribute to abdominal pain, decrease the quality of life and work productivity of affected individuals, and lead to cachexia and frailty. However, molecules that regulate irritable bowel syndrome have not been fully clarified. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit the translation of target messenger RNAs. Previous studies have shown that miRNAs have critical roles in the regulation of the pathogenicity of irritable bowel syndrome. Therefore, this systematic review focused on miRNAs that regulate irritable bowel syndrome. PubMed and Web of Science were searched to retrieve reference lists of eligible articles and related reviews. Original articles and reviews that reported the utility of miRNAs as potential biomarkers or targets for specific therapies of IBS that were published in English from 2004 to 2021 were included. Among 78 identified studies, 22 eligible studies were included in this systematic review. These results suggest that miRNAs are potential biomarkers and targets of gene therapy for IBS. Further studies including clinical studies will be necessary to confirm the utility of miRNAs as biomarkers and targets for the gene therapy of IBS.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":" ","pages":"7-18"},"PeriodicalIF":1.4,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40580434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oxidative Stress-Responsive Small Extracellular Vesicles and MicroRNAs in Age-related Macular Degeneration: Biomarkers and Therapeutic Tools.","authors":"Zhongjing Lin, Ke Mao","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) is the main cause of blurred vision, and oxidative stress is a leading risk factor for AMD pathology. Small extracellular vesicles (EVs) are 50-90 nm membrane microvesicles (MVs) released by several cell types in a controlled fashion and they transfer from cell to cell to mediate disease progression. EVs encapsulate and transfer microRNAs (miRNA) to recipient cells. MiRNAs are small non-coding RNA molecules that inhibit expression and function of targeted mRNAs through miRNA/mRNA interactions in the conserved 3'UTR regions, and in this way they can modulate a variety of physiological and pathological processes. Dysregulation of EVs and their miRNAs cargo from retinal cells is believed to be correlated to a loss of cellular homeostasis and AMD pathology. This review investigates the association between oxidative stress, sEVs, miRNAs, and AMD pathogenesis, and the potential for discovering novel treatment targets for AMD.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":" ","pages":"33-43"},"PeriodicalIF":1.4,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40661034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Weiwei Wang, Xiaolei Liu, Jiaxi Huang, Shue Zeng, Jianjun Bao, Yi Lu, Zhong Zheng, Tianhao Bao
{"title":"The Connection of Early Life Adversity and Post Traumatic Stress Disorder: an Updated Review.","authors":"Weiwei Wang, Xiaolei Liu, Jiaxi Huang, Shue Zeng, Jianjun Bao, Yi Lu, Zhong Zheng, Tianhao Bao","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Human beings develop a highly coordinated and flexible system of social behavior and threat evaluation. In this review we focus on the unique role of early life adversity (ELA) in programming deficits in social behavior and threat processing, and provides guidance on future investigations in the areas of stress reactivity and mental health. We propose that neuroendocrine perturbations of hypothalamus-pituitary-adrenal (HPA) axis and gene activity by epigenetic mechanisms may explain how early adverse circumstances may lead to post traumatic stress disorder (PTSD). The detailed exploration of the interaction of stress as environmental factor and epigenetic and genetic regulation in HPA axis may improve targeted interventions among vulnerable individuals. We are convinced that further studies following these directions will contribute to effective prevention and treatment of PTSD in early traumatized patients.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":" ","pages":"25-32"},"PeriodicalIF":1.4,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40661033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Roles of Transepithelial Electrical Resistance in Mechanisms of Retinal Pigment Epithelial Barrier and Retinal Disorders.","authors":"Minli Wang, Hui Li, Fang Wang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Transepithelial/transendothelial electrical resistance (TEER) is a widely accepted quantitative technique to measure the integrity of tight junction dynamics in cell culture models of endothelial and epithelial monolayers. The value of TEER reflects the physical structure and characteristics of epithelial/endothelial cells. TEER value is a preferred physiological indicator reflecting transport rate of ions and macromolecules through the paracellular pathway, which is used to evaluate permeability of paracellular pathway. TEER value has a high specificity for the permeability of reactive tightly connected complex. TEER value is an effective indicator to evaluate the integrity of cell barrier. The cell barrier not only controls the diffusion penetration of various substances in adjacent intercellular spaces, but also regulates the transport of ions and macromolecules across. On one hand, the cell barrier protects the body from harmful substances; on the other hand, it restricts the entry of therapeutic drugs. Therefore, with the increase of permeability in paraepithelial pathway, the TEER value decreased, otherwise, it increased. In this review article, we compared the advantages and disadvantages of the existing methods for measuring TEER and summarized the factors affecting TEER accuracy, as well as the roles of TEER in mechanisms of retinal pigment epithelial barrier and retinal disorders such as proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD), diabetic retinopathy, and retinitis pigmentosa.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":" ","pages":"19-24"},"PeriodicalIF":1.4,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40580437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Application of Quantitative Flow Ratio via 3-dimensional Coronary Angiography in Clinical Cardiology: A Review.","authors":"Ying Li, Hui Chen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Fractional flow reserve (FFR) is a gold standard for the assessment of hemodynamic change during coronary stenosis, but it has several limitations such as high cost, the requirement of invasive pressure wire, and adverse drug reactions, which limit the wide application of FFR in clinical practice. In contrast, quantitative flow ratio (QFR) is a recently developed method for rapid calculation of FFR through 3-dimensional quantitative coronary angiography without the use of vasodilators and pressure wire. In this review we provide an updated summary of the principle of QFR, the correlation between QFR and FFR, and current applications of QFR in clinical cardiology. In conclusion, QFR provides a platform for functional evaluation of coronary stenoses based on angiographic data without invasive procedures; further development and optimization of QFR techniques will expand the application of QFR in clinical cardiology, ranging from diagnosis to coronary intervention to cardiac surgery, and benefit more patients.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"33 170","pages":"129-135"},"PeriodicalIF":1.4,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40652969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}