Background and aims: Renal damage in severe coronavirus disease 2019 (COVID-19) is highly associated with mortality. Finding relevant therapeutic candidates that can alleviate it is crucial. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) have been shown to be harmless to COVID-19 patients, but it remains elusive whether ACEIs/ARBs have protective benefits to them. We wished to determine if ACEIs/ARBs had a protective effect on the renal damage associated with COVID-19, and to investigate the mechanism.Methods: We used the envelope (E) protein of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) to induce COVID-19-like multiple organ damage and observed renal fibrosis. We induced the epithelial–mesenchymal transformation of HK-2 cells with E protein, and found that olmesartan could alleviate it significantly. The protective effects of olmesartan on E protein-induced renal fibrosis were evaluated by renal-function assessment, pathologic alterations, inflammation, and the TGF-β1/Smad2/3 signaling pathway. The distribution of high-mobility group box (HMGB)1 was examined after stimulation with E protein and olmesartan administration.Results: E protein stimulated HMGB1 release, which triggered the immune response and promoted activation of TGF-β1/Smad2/3 signaling: both could lead to renal fibrosis. Olmesartan regulated the distribution of HMGB1 under E protein stimulation. Olmesartan inhibited the release of HMGB1, and reduced the inflammatory response and activation of TGF-β1/Smad2/3 signaling. Olmesartan increased the cytoplasmic level of HMGB1 to promote the autophagic degradation of TGF-β1, thereby alleviating fibrosis further.Conclusion: Olmesartan alleviates E protein-induced renal fibrosis by regulating the release of HMGB1 and its mediated autophagic degradation of TGF-β1.
Heterogeneous human periodontal ligament cells (hPDLCs)
are the
key seed cells to address the regeneration of periodontal bone defects,
and nanomaterials b ring strategies for periodontal bone regeneration.
Herein, we synthesized cerium-based nanoparticles by a convenient,
green, and efficient bovine serum albumin (BSA) culture strategy.
The results of in vitro experiments showed that CeO2@BSA
had a significant ability to promote osteogenesis in hPDLCs at lower
concentrations, which was mediated through TGF-β signaling pathway.
However, this ability was diminished at high concentrations, which
may be caused by excessive activation of autophagy. Notably, the osteogenic
potential of hPDLCs was inhibited after autophagy was blocked. The
construction of tissue-engineered membranes confirmed that CeO2@BSA facilitated reconstruction of periodontal bone defects
in Sprague–Dawley (SD) rats. Our work demonstrated that CeO2@BSA exhibited efficient therapeutic effects in osteogenic
differentiation and periodontal bone defect repair, while greatly
expanding the application of CeO2@BSA in disease treatment.
Cancer is a genetic disease caused by alterations in genome and epigenome and is one of the leading causes for death worldwide. The exploration of disease development and therapeutic strategies at the genetic level have become the key to the treatment of cancer and other genetic diseases. The functional analysis of genes and mutations has been slow and laborious. Therefore, there is an urgent need for alternative approaches to improve the current status of cancer research. Gene editing technologies provide technical support for efficient gene disruption and modification in vivo and in vitro, in particular the use of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems. Currently, the applications of CRISPR-Cas systems in cancer rely on different Cas effector proteins and the design of guide RNAs. Furthermore, effective vector delivery must be met for the CRISPR-Cas systems to enter human clinical trials. In this review article, we describe the mechanism of the CRISPR-Cas systems and highlight the applications of class II Cas effector proteins. We also propose a synthetic biology approach to modify the CRISPR-Cas systems, and summarize various delivery approaches facilitating the clinical application of the CRISPR-Cas systems. By modifying the CRISPR-Cas system and optimizing its
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