Oxidative stress is the main cause of acute myocardial infarction (AMI), which is related to the disorder of the regulation of Bmal1 on the redox state. HSPB1 form homologous‐oxidized HSPB1 (homooxidized HSPB1) to resist oxidative damage via S‐thiolated modification. However, it is still unclarified whether there is an interaction between the circadian clock and HSPB1 in myocardial injury. A total of 118 AMI patients admitted and treated in our hospital from Sep. 2019 to Sep. 2020 were selected to detect the plasma HSPB1 expression and the redox state. We divided the AMI patients into three subgroups: morning‐onset AMI (5 : 00 am to 8 : 00 am; Am‐subgroup, n = 38), noon‐onset AMI (12 : 00 pm to 15 : 00; Pm‐subgroup, n = 45), and night‐onset AMI (20 : 00 pm to 23 : 00 pm; Eve‐subgroup, n = 35) according to the circadian rhythm of onset. The Am‐subgroup had remarkably higher cardiac troponin I (cTnI), creatine kinase MB (CK‐MB), and B‐type natriuretic peptide (BNP) but lower left ventricular ejection fraction (LVEF) than the Pm‐subgroup and Eve‐subgroup. Patients complicated with cardiogenic shock were significantly higher in the Am‐subgroup than in the other two groups. The homooxidized HSPB1 in plasma markedly decreased in the Am‐subgroup. The HSPB1C141S mutant accelerated H9c2 cell apoptosis, increased reactive oxygen species (ROS), and decreased reduced‐glutathione (GSH) and the ratio of reduced‐GSH and GSSG during oxidative stress. Importantly, we found that the redox state of HSPB1 was consistent with the oscillatory rhythm of Bmal1 expression in normal C57B/L mice. The circadian rhythm disorder contributed to decrease Bmal1 and homooxidized HSPB1 in cardiomyocytes of C57BL/6 mice. In addition, Bmal1 and homooxidized HSPB1 decreased in neonatal rat cardiomyocytes exposed to H₂O₂. Knockdown of Bmal1 led to significant attenuation in homooxidized HSPB1 expression, whereas overexpression of Bmal1 increased homooxidized HSPB1 expression in response to H₂O₂. Our findings indicated that the homooxidized HSPB1 reduced probably the AMI patients’ risk of shock and target organ damage, which was associated with Bmal1 regulating the redox state of HSPB1.

The clinical use of doxorubicin (DOX) is limited by its cardiotoxicity, which is closely associated with oxidative stress. Xinmailong (XML) is a bioactive peptide extracted from American cockroaches, which has been mainly applied to treat chronic heart failure in China. Our previous study showed that XML attenuates DOX‐induced oxidative stress. However, the mechanism of XML in DOX‐induced cardiotoxicity remains unclear. Heme oxygenase‐1 (HO‐1), an enzyme that is ubiquitously expressed in all cell types, has been found to take antioxidant effects in many cardiovascular diseases, and its expression is protectively upregulated under DOX treatment. Lysosome and autophagy are closely involved in oxidative stress as well. It is still unknown whether XML could attenuate doxorubicin‐induced lysosomal dysfunction and oxidative stress in H9c2 cells via HO‐1. Thus, this study was aimed at investigating the involvement of HO‐1‐mediated lysosomal function and autophagy flux in DOX‐induced oxidative stress and cardiotoxicity in H9c2 cells. Our results showed that XML treatment markedly increased cell proliferation and SOD activity, improved lysosomal function, and ameliorated autophagy flux block in DOX‐treated H9c2 cells. Furthermore, XML significantly increased HO‐1 expression following DOX treatment. Importantly, HO‐1‐specific inhibitor (Znpp) or HO‐1 siRNA could significantly attenuate the protective effects of XML against DOX‐induced cell injury, oxidative stress, lysosomal dysfunction, and autophagy flux block. These results suggest that XML protects against DOX‐induced cardiotoxicity through HO‐1‐mediated recovery of lysosomal function and autophagy flux and decreases oxidative stress, providing a novel mechanism responsible for the protection of XML against DOX‐induced cardiomyopathy.

The Hedyotis diffusa–Scutellaria officinalis pair (HD–SB) has therapeutic effects on a variety of cancers. Our study was to explore the mechanism of HD–SB in the treatment of hepatocellular carcinoma (HCC). A total of 217 active ingredients of HD–SB and 1196 HCC-related targets were reserved from the TCMSP and the SwissTarget Prediction database, and we got 63 intersection targets from GeneCards. We used a Venn diagram, and Cytoscape found that the three core ingredients were quercetin, luteolin, and baicalein. The PPI analysis showed that the core targets were TP53, CDK2, XPO1, and APP. Molecular docking results showed that these core ingredients had good binding potential with the core targets. HD–SB acts simultaneously on various HCC-related signaling pathways, including proteoglycans in cancer and the P53 signaling pathway. In vitro experiments confirmed that HD–SB can inhibit HepG2 cell proliferation by increasing TP53 and APP levels and decreasing XPO1 and CDK2 levels. This study analyzed active ingredients, core targets, and central mechanisms of HD–SB in the treatment of HCC. It reveals the role of HD–SB in targeting the P53 signaling pathway in the treatment of HCC. We hope that our research could provide a new perspective to the therapy of HCC and find new anticancer drugs.

Objective. Small heat shock protein-1 (HSPB1) is a small heat shock protein that participates in many cellular processes and alleviates stress-induced cell injury. Autophagy protects cells from many types of stress and plays a key role in preventing stress in arteriosclerosis obliterans (ASO). However, the roles of HSPB1 in autophagy and apoptosis in the context of ASO pathogenesis remain unclear. Methods. In vivo and in vitro studies were used to determine whether HSPB1 is associated with ASO progression. The expression of HSPB1 was measured in normal and sclerotic blood vessels. The role of HSPB1 and its potential downstream signaling pathway were determined in VSMCs by overexpressing and silencing HSPB1. Results. A total of 91 ASO patients admitted to and treated at our hospital from Sep. 2020 to Sep. 2021 were selected, and plasma HSPB1 expression was assessed. We divided the patients with ASO into the grade I ( ), II ( ), III ( ), and IV ( ) groups according to Fontaine’s classification. Plasma HSPB1 levels were markedly decreased in patients with grade III ( ) and IV ( ) ASO compared with patients with grade I ASO. Furthermore, HSPB1 expression was significantly decreased, and p62 and cleaved caspase-3 were increased in the sclerotic vasculature compared to the normal vasculature ( ). Overexpression of HSPB1 promoted apoptosis of VSMCs following ox-LDL treatment. Knockdown of HSPB1 led to a marked increase in the expression of LC3II and Beclin-1 in ox-LDL-stimulated VSMCs, whereas knockdown of HSPB1 attenuated these changes ( ). Importantly, overexpression of HSPB1 promoted the dephosphorylation of JNK in ox-LDL-stimulated VSMCs. Conversely, downregulation of HSPB1 induced the opposite change. Conclusion. Loss of HSPB1 promotes VSMC autophagy and inhibits VSMC apoptosis, which are associated with ASO. HSPB1 and its downstream signaling pathways could be potential therapeutic targets for ASO treatment.

Objective: Paraquat (PQ) is a toxic compound that selectively accumulates in the lungs, inducing severe pulmonary inflammation and fibrosis. However, data on the metabolomic changes induced by the PQ remain scant. This study aimed to determine the metabolic changes in Sprague–Dawley rats subjected to PQ using UPLC-Q-TOF-MS/MS. Methods: We established groups of PQ-induced pulmonary injury rats for 14 or 28 days. Results: Our data showed that PQ decreased the survival of the rats and induced pulmonary inflammation at day 14 or pulmonary fibrosis at day 28. There was upregulation of IL-1β expression in the inflammation group as well as upregulation of fibronectin, collagen and α-SMA in the pulmonary fibrosis group. OPLS-DA revealed differential expression of 26 metabotites between the normal and the inflammation groups; 31 plasma metabotites were also differently expressed between the normal and the fibrosis groups. There was high expression of lysoPc160-, hydroxybutyrylcarnitine, stearic acid, and imidazolelactic acid in the pulmonary injury group compared to the normal group. Conclusion: Metabolomics analysis confirmed that the PQ-induced lung injury was not only related to the aggravation of inflammation and apoptosis but also to mediated histidine, serine, glycerophospholipid, and lipid metabolism. This study gives insights into the mechanisms of PQ-induced lung injury and highlights the potential therapeutic targets. Nonstructured The effect of PQ on lung injury in rats was detected by metabonomics, and the possible metabolic mechanism was investigated by KEGG analysis. OPLS-DA revealed the differential expression of 26 metabotites and 31 plasma metabotites between the normal and the pulmonary injury groups. Metabolomics analysis confirmed that the PQ-induced lung injury was not only related to the aggravation of inflammation and apoptosis but also to mediated histidine, serine, glycerophospholipid, and lipid metabolism. Oleoylethanolamine, stearic acid, and imidazolelactic acid are potential molecular markers in PQ-induced pulmonary injury.