Translational research : the journal of laboratory and clinical medicine
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The complement system plays crucial roles in homeostasis and host defense against microbes. Deficiency of early complement cascade components has been associated with increased susceptibility to systemic lupus erythematosus (SLE), whereas excessive complement consumption is a hallmark of this disease. ⋯ Therapeutic agents targeting complement activation have been used in LN patients and clinical trials are ongoing. We review the mechanisms by which complement system dysregulation contributes to renal injury in SLE and summarize the latest evidence on the use of anticomplement agents to manage this condition.
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Hand-foot skin reaction (HFSR) is the most debilitating and prevalent side effect caused by multikinase inhibitors (MKIs) that share vascular endothelial growth factor receptor (VEGFR) as the common inhibition target, such as sorafenib, regorafenib, axitinib, etc. Though not life-threatening, HFSR can significantly deteriorate patients' quality of life and jeopardize the continuity of cancer therapy. Despite years of efforts, there are no FDA-approved treatments for HFSR and the understanding of the precise pathogenic mechanism is still limited. ⋯ Local application of GTN mitigated tissue damage in a rat model, while not impacting the anti-tumor effect of the MKI in HepG2 tumor-bearing mice. Finally, GTN ointment alleviated cutaneous damages and improved quality of life in 6 HFSR patients. Our study proposed and validated the mechanism to counteract VEGFR inhibition, providing GTN as the potential treatment to MKI-induced HFSR, which may further improve the therapeutic window of various MKI based cancer therapies.
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Long noncoding RNAs (lncRNAs) and miRNAs have been reported to participate in intervertebral disc degeneration (IDD) progression. However, the key lncRNA-miRNA axis and its corresponding affected hub genes in IDD remain unknown. In this study, weighted gene coexpression network analysis (WGCNA) was first used to determine the key gene cluster and hub genes implicated in IDD progression. ⋯ Furthermore, miR-214-3p overexpression partially reversed the effects of ADIRF-AS1 overexpression. Collectively, these data suggest that ADIRF-AS1 overexpression could mitigate IDD by binding to miR-214-3p to upregulate SERPINA1. Additional studies (especially those using an axial loading-induced IDD animal model) will be needed to further validate the role of the ADIRF-AS1/miR-214-3p/SERPINA1 signaling axis in IDD progression.