Aims: Chlorogenic acid (CGA) is a phenolic acid that has a wide range of pharmacological effects. However, the protective effects and mechanisms of CGA on liver fibrosis are not clear. This study explored the effects of CGA on miR-21-regulated TGF-β1/Smad7 liver fibrosis in the hepatic stellate LX2 cell line and in CCl4-induced liver fibrosis in Sprague-Dawley rats.Methods: The mRNA expression of miR-21, Smad7, connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase 1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), and transforming growth factor-β1 (TGF-β1) and the protein levels of Smad2, p-Smad2, Smad3, p-Smad3, Smad2/3, p-Smad2/3, Smad7, CTGF, α-SMA, TIMP-1, MMP-9 and TGF-β1 were assayed in LX2 cells and liver tissue. The effects of CGA after miR-21 knockdown or overexpression were analyzed in LX2 cells. The liver tissue and serum were collected for histopathological examination, immunohistochemistry (IHC) and ELISA.Results: The mRNA expression of miR-21, CTGF, α-SMA, TIMP-1, and TGF-β1 and the protein expression of p-Smad2, p-Smad3, p-Smad2/3, CTGF, α-SMA, TIMP-1, and TGF-β1 were inhibited by CGA both in vitro and in vivo. Meanwhile, CGA elevated the mRNA and protein expression of Smad7 and MMP-9. After miR-21 knockdown and overexpression, the downstream molecules also changed accordingly. CGA also lessened the degree of liver fibrosis in the pathological manifestation and reduced α-SMA and collagen I expression in liver tissue and TGF-β1 in serum. Conclusion: CGA might relieve liver fibrosis through the miR-21-regulated TGF-β1/Smad7 signaling pathway, which suggests that CGA might be a new anti-fibrosis agent that improves liver fibrosis.

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Heart failure is one of the major public health problems in the world. In recent years, more and more attention has been paid to the relationship between heart failure and mitochondrial function. In the past 2 decades, a growing number of research papers in this field have been published. This study conducted a bibliometric analysis of the published literature on the relationship between MF and HF in the past 20 years by utilizing Microsoft Excel 2019, Biblio metric analysis platform, WoSCC database, VosViewer and Citespace. The results show that the papers have increased year by year and China and the United States are the leading countries in this field, as well as the countries with the most cooperation and exchanges. University of california system is the research institution with the greatest impacts on research results, and Yip H.K. is the author with more papers. The American Journal of Physiology-heart and Circulatory Physiology is probably the most popular magazine. At present, most of the published articles on mitochondria and HF are cited from internationally influential journals. The research focus includes oxidative stress, metabolic dysfunction, mitochondrial Ca2+ homeostasis imbalance, mitochondrial quality control and mitochondrial dysfunction mediated by inflammation in the pathogenesis of HF. Targeted regulating of mitochondria will be the keynote of future research on prevention and treatment of HF.

The dynamic regulation of mitochondrial morphology is key for eukaryotic cells to manage physiological challenges. Therefore, it is important to understand the molecular basis of mitochondrial dynamic regulation. The aim of the present study was to explore the role of HIG1 hypoxia inducible domain family member 1B (HIGD-1B) in hypoxia-induced mitochondrial fragmentation. Protein expression was determined via western blotting. Immunofluorescence assays were performed to detect the subcellular location of HIGD-1B. Cell Counting Kit-8 assays and flow cytometry were carried out to measure cell viability and apoptosis, respectively. Protein interactions were evaluated by co-immunoprecipitation. In the present study, it was found that HIGD-1B serves a role in cell survival by maintaining the integrity of the mitochondria under hypoxic conditions. Knockdown of HIGD-1B promoted mitochondrial fragmentation, while overexpression of HIGD-1B increased survival by preventing activation of caspase-3 and -9. HIGD-1B expression was associated with cell viability and apoptosis in cardiomyocytes. Furthermore, HIGD-1B delayed the cleavage process of optic atrophy 1 (OPA1) and stabilized mitochondrial morphology by interacting with OPA1. Collectively, the results from the present study identified a role for HIGD-1B as an inhibitor of the mitochondrial fission in cardiomyocytes.