Cardiovascular disease (CVD) is a significant cause of death worldwide. Because of its major individual differences in genetic background, pathogenesis, and disease progression pattern, the mortality risk rate remains high following conventional Western medicine diagnosis under current guidelines. Traditional Chinese medicine (TCM) has important multi-target, multi-pathway, and multi-layer benefits that can effectively address western medicine deficiencies. It was therefore commonly used in CVD diagnosis. Oxidative stress is also one of the main factors of CVD. Likewise, this main reaction regulator is the nuclear factor erythroid-2-related (Nrf2) factor. When activated, it can be transferred to the nucleus and initiated in the downstream pathway, thus playing an anti-oxidant stress role. As one of the most crucial endogenous protection systems in the body, Nrf2-related / heme oxygenase 1 (Nrf2/HO-1) signaling pathway is Nrf2's most classic approach to playing roles. Recently, various advances have been made to research and explain TCM by manipulating this pathway to treat CVD using modern molecular biology and other approaches. This analysis summarized the relationship between Nrf2/HO-1 signaling route, CVD and TCM. Further, Autodock calculation was also conducted to determine the binding amino acid on this TCM to Nrf2 and HO-1.

Cardiovascular diseases (CVD) are a significant cause of human health harm. In the past, stem cell therapy was reported to have functional defects, such as immune rejection, tumorigenicity, and infusion toxicity. Exosomes are extracellular vesicles with lipid bilayer membrane structure, containing proteins, lipids, mRNA, miRNA, DNA, and other molecules, which can mediate various biological functions such as immune response, inflammatory response, cell migration, and differentiation intercellular communication. Exosomal miRNAs have outstanding advantages in disease diagnosis and curative effect prediction. Likewise, paracrine factors could also mediate the main therapeutic effect of mesenchymal stem cells. Research has shown that mesenchymal stem cell-derived micro-exosomes, which may come from stem cells, accumulate in the ischemic tissue and regulate cell proliferation, apoptosis, inflammation, and angiogenesis sites of myocardial injury after being transplanted. This review reviewed the molecular mechanisms of exosomes and internal microRNAs derived from mesenchymal stem cells in cardiac ischemic injury repair.

Premature senescence of bone marrow-derived mesenchymal stem cells (BMSC) remains a major concern for their application clinically. Hedgehog signaling has been reported to regulate aging-associated markers and MSC skewed differentiation. Indian Hedgehog (IHH) is a ligand of Hedgehog intracellular pathway considered as an inducer in chondrogenesis of human BMSC. However, the role of IHH in the aging of BMSC is still unclear. This study explored the role IHH in the senescence of BMSC obtained from human samples and senescent mice. Isolated BMSC were transfected with IHH siRNA or incubated with exogenous IHH protein and the mechanisms of aging and differentiation investigated. Moreover, the interactions between IHH, and mammalian target of rapamycin (mTOR) and reactive oxygen species (ROS) were evaluated using the corresponding inhibitors and antioxidants. BMSC transfected with IHH siRNA showed characteristics of senescence-associated features including increased senescence-associated β-galactosidase activity (SA-β-gal), induction of cell cycle inhibitors (p53/p16), development of senescence-associated secretory phenotype (SASP), activation of ROS and mTOR pathways as well as the promotion of skewed differentiation. Interestingly, BMSC treatment with IHH protein reversed the senescence markers and corrected biased differentiation. Moreover, IHH shortage-induced senescence signs were compromised after mTOR and ROS inhibition. Our findings presented anti-aging activity for IHH in BMSC through down-regulation of ROS/mTOR pathways. This discovery might contribute to increasing the therapeutic, immunomodulatory and regenerative potency of BMSC and introduce a novel remedy in the management of aging-related diseases.

Rheumatoid arthritis (RA) is the major autoimmune destructive disease of joints with a complicated pathogenesis. The contribution of tumor necrosis factor‐like ligand 1A (TL1A) in RA pathogenesis, especially on fibroblast‐like synoviocytes (FLS), has been suggested clinically. The present study investigated the role of TL1A in mitochondrial dysfunction, induced oxidative stress in mitochondria, apoptosis resistance and the inflammatory response in FLS obtained from RA patients (RA‐FLS). RA‐FLS were incubated with TL1A and tumor necrosis factor receptor 2 (TNFR2) antagonist. Respiratory function, mitochondrial membrane potential and respiration associated genes of mitochondria were measured in both TL1A stimulated and non‐stimulated RA‐FLS. Additionally, the effects of TL1A on reactive oxygen species (ROS) production in mitochondria, apoptosis and the inflammatory response in RA‐FLS were also assessed. The role of TL1A in association between ROS generation, especially mitochondrial type and the inflammatory response, was evaluated by measuring inflammation‐related cytokines and signaling pathways using ROS inhibitors, diphenyleneiodonium chloride and Mito‐TEMPO (Sigma‐Aldrich, Miamisburg, OH, USA). We found that TL1A induced mitochondrial dysfunction by weakening mitochondrial respiration and membrane potential, which was blocked by a TNFR2 antagonist. Increased ROS synthesis in impaired mitochondria was observed with MitoSOX (Invitrogen, CA, USA) immunofluorescence staining in TL1A‐stimulated RA‐FLS but inhibited by a TNFR2 antagonist. TL1A influenced apoptosis resistance and inflammatory mediators via TNFR2. Inhibition of mitochondria‐derived ROS compromised the production of inflammatory factors in TL1A‐stimulated RA‐FLS, suggesting that mitochondrial dysfunction mediated by the TL1A/TNFR2 axis might amplify the inflammatory response via regulation of mitochondria‐derived ROS generation. Collectively, our results reveal that TL1A might be involved in making FLS more aggressive in RA pathogenesis via cell respiration interruption.