Project description:Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology, mainly manifested by persistent abnormal proliferation of fibroblast-like synoviocytes (FLSs), inflammation, synovial hyperplasia and cartilage erosion, accompanied by joint swelling and joint destruction. Abnormal expression or function of long noncoding RNAs (lncRNAs) are closely related to human diseases, including cancers, mental diseases, autoimmune diseases and others. The abnormal sequence and spatial structure of lncRNAs, the disorder expression and the abnormal interaction with the binding protein will lead to the change of gene expression in the way of epigenetic modification. Increasing evidence demonstrated that lncRNAs were involved in the activation of FLSs, which played a key role in the pathogenesis of RA. In this review, the research progress of lncRNAs in the pathogenesis of RA was systematically summarized, including the role of lncRNAs in the diagnosis of RA, the regulatory mechanism of lncRNAs in the pathogenesis of RA, and the intervention role of lncRNAs in the treatment of RA. Furthermore, the activated signal pathways, the role of DNA methylation and other mechanism have also been overview in this review.
Project description:The AlkB family consists of Fe(II)- and α-ketoglutarate-dependent dioxygenases that can catalyze demethylation on a variety of substrates, such as RNA and DNA, subsequently affecting tumor progression and prognosis. However, their detailed functional roles in lung adenocarcinoma (LUAD) have not been clarified in a comprehensive manner. In this study, several bioinformatics databases, such as ONCOMINE, TIMER, and DiseaseMeth, were used to evaluate the expression profiles and prognostic significance of the AlkB family (ALKBH1-8 and FTO) in LUAD. The expression levels of ALKBH1/2/4/5/7/8 were significantly increased in LUAD tissues, while the expression levels of ALKBH3/6 and FTO were decreased. The main functions of differentially expressed AlkB homologs are related to the hematopoietic system and cell adhesion molecules. We also found that the expression profiles of the AlkB family are highly correlated with infiltrating immune cells (i.e., B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils and dendritic cells). In addition, DNA methylation analysis indicated that the global methylation levels of ALKBH1/2/4/5/6/8 and FTO were decreased, while the global methylation levels of ALKBH3/7 were increased. In addition, the patients with upregulated ALKBH2 have significantly poor overall survival (OS) and post-progressive survival (PPS). Taken together, our work could provide insightful information about aberrant AlkB family members as potential biomarkers for the diagnostic and prognostic evaluation of LUAD. Especially, ALKBH2 could be served as a therapeutic candidate for treating LUAD.
Project description:BackgroundThe ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as the latest threat to global health, causes overwhelming effects for the public healthcare systems worldwide. Of note, in addition to the respiratory complications, some patients with coronavirus disease 2019 (COVID-19) also develop serious cardiovascular injuries. Vasoactive peptides play an important role in a wide range of physiological and pathological conditions.AimWith the urgent need for exploring the specific therapeutic targets and biomarkers for the emerging COVID-19, the general aim of this review is to discuss the potentials of the vasoactive peptides including Angiotensin II (Ang II), vasoactive intestinal peptide (VIP), endothelin-1 (ET-1), calcitonin gene-related peptide (CGRP), natriuretic peptides, substance P (SP) and bradykinin (BK) as therapeutic targets and/or prognostic indicators for the COVID-19 pandemic.ConclusionBased on various observations some authors conclude that the assessment of vasoactive peptides shall be considered a routine part of COVID-19 patient monitoring, and they can serve as potential therapeutic targets for the disease management.
Project description:Aortic aneurysm is a chronic disease characterized by localized expansion of the aorta, including the ascending aorta, arch, descending aorta, and abdominal aorta. Although aortic aneurysms are generally asymptomatic, they can threaten human health by sudden death due to aortic rupture. Aortic aneurysms are estimated to lead to 150,000 ~ 200,000 deaths per year worldwide. Currently, there are no effective drugs to prevent the growth or rupture of aortic aneurysms; surgical repair or endovascular repair is the only option for treating this condition. The pathogenic mechanisms and therapeutic targets for aortic aneurysms have been examined over the past decade; however, there are unknown pathogenic mechanisms involved in cellular heterogeneity and plasticity, the complexity of the transforming growth factor-β signaling pathway, inflammation, cell death, intramural neovascularization, and intercellular communication. This review summarizes the latest research findings and current pathogenic mechanisms of aortic aneurysms, which may enhance our understanding of aortic aneurysms.
Project description:Patients harboring brain arteriovenous malformation (bAVM) are at life-threatening risk of rupture and intracranial hemorrhage (ICH). The pathogenesis of bAVM has not been completely understood. Current treatment options are invasive, and ? 20 % of patients are not offered interventional therapy because of excessive treatment risk. There are no specific medical therapies to treat bAVMs. The lack of validated animal models has been an obstacle for testing hypotheses of bAVM pathogenesis and testing new therapies. In this review, we summarize bAVM model development and bAVM pathogenesis and potential therapeutic targets that have been identified during model development.
Project description:Tuberculosis (TB) remains a significant public health concern in the 21st century, especially due to drug resistance, coinfection with diseases like immunodeficiency syndrome (AIDS) and coronavirus disease 2019, and the lengthy and costly treatment protocols. In this review, we summarize the pathogenesis of TB infection, therapeutic targets, and corresponding modulators, including first-line medications, current clinical trial drugs and molecules in preclinical assessment. Understanding the mechanisms of Mycobacterium tuberculosis (Mtb) infection and important biological targets can lead to innovative treatments. While most antitubercular agents target pathogen-related processes, host-directed therapy (HDT) modalities addressing immune defense, survival mechanisms, and immunopathology also hold promise. Mtb's adaptation to the human host involves manipulating host cellular mechanisms, and HDT aims to disrupt this manipulation to enhance treatment effectiveness. Our review provides valuable insights for future anti-TB drug development efforts.