[Role of NLRP3 inflammasome in heart failure and traditional Chinese medicine intervention: a review].

Heart failure is characterized by high incidence and mortality rates, and the search for effective treatment strategies for heart failure and the improvement of clinical outcomes have always been important research directions. Imbalanced inflammation has been proven to be one of the critical pathological factors in heart failure, positively correlated with adverse events such as impaired cardiac function and myocardial fibrosis. In recent years, studies have confirmed that the activation of the NOD-like receptor thermal protein domain-associated protein 3(NLRP3) inflammasome plays a common regulatory role in the inflammation imbalance induced by various factors in heart failure. Moreover, certain traditional Chinese medicine(TCM) and active components can significantly inhibit the activation of the NLRP3 inflammasome, thereby improving heart failure. This article first overviewed the basic information about the NLRP3 inflammasome, summarized the regulatory mechanisms of the NLRP3 inflammasome in heart failure induced by various factors, introduced recent research progress on TCM and active components that inhibited the NLRP3 inflammasome to improve heart failure, aiming to provide references for innovative drug research in the field of integrated Chinese and western medicine for the prevention and treatment of heart failure.

[Mechanism of Jiming Powder in ameliorating heart failure with preserved ejection fraction based on metabolomics].

In this study, untargeted metabolomics was conducted using the liquid chromatography-tandem mass spectrometry(LC-MS/MS) technique to analyze the potential biomarkers in the plasma of mice with heart failure with preserved ejection fraction(HFpEF) induced by a high-fat diet(HFD) and nitric oxide synthase inhibitor(Nω-nitro-L-arginine methyl ester hydrochloride, L-NAME) and explore the pharmacological effects and mechanism of Jiming Powder in improving HFpEF. Male C57BL/6N mice aged eight weeks were randomly assigned to a control group, a model group, an empagliflozin(10 mg·kg~(-1)·d~(-1)) group, and high-and low-dose Jiming Powder(14.3 and 7.15 g·kg~(-1)·d~(-1)) groups. Mice in the control group were fed on a low-fat diet, and mice in the model group and groups with drug intervention were fed on a high-fat diet. All mice had free access to water, with water in the model group and Jiming Powder groups being supplemented with L-NAME(0.5 g·L~(-1)). Drugs were administered on the first day of modeling, and 15 weeks later, blood pressure and cardiac function of the mice in each group were measured. Heart tissues were collected for hematoxylin-eosin(HE) staining to observe pathological changes and Masson's staining to observe myocardial collagen deposition. Untargeted metabolomics analysis was performed on the plasma collected from mice in each group, and metabolic pathway analysis was conducted using MetaboAnalyst 5.0. The results showed that the blood pressure was significantly lower and the myocardial concentric hypertrophy and left ventricular diastolic dysfunction were significantly improved in both the high-dose and low-dose Jiming Powder groups as compared with those in the model group. HE and Masson staining showed that both high-dose and low-dose Jiming Powder significantly alleviated myocardial fibrosis. In the metabolomics experiment, 23 potential biomarkers were identified and eight strongly correlated metabolic pathways were enriched, including linoleic acid metabolism, histidine metabolism, alpha-linolenic acid metabolism, glycerophospholipid metabolism, purine metabolism, porphyrin and chlorophyll metabolism, arachidonic acid metabolism, and pyrimidine metabolism. The study confirmed the pharmacological effects of Jiming Powder in lowering blood pressure and ameliorating HFpEF and revealed the mechanism of Jiming Powder using the metabolomics technique, providing experimental evidence for the clinical application of Jiming Powder in treating HFpEF and a new perspective for advancing and developing TCM therapy for HFpEF.

[Effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction].

Jiming Powder is a traditional ancient prescription with good therapeutic effect in the treatment of heart failure, but its mechanism lacks further exploration. In this study, a mouse model of coronary artery ligation was used to evaluate the effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction. The study constructed a mouse model of heart failure after myocardial infarction using the method of left anterior descending coronary artery ligation. The efficacy of Jiming Powder was evaluated from multiple angles, including ultrasound imaging, hematoxylin-eosin(HE) staining, Masson staining, Sirius Red staining, and serum myocardial enzyme spectrum detection. Western blot analysis was performed to detect key proteins involved in ventricular remodeling, including transforming growth factor-ß1(TGF-ß1), α-smooth muscle actin(α-SMA), wingless-type MMTV integration site family member 3a(Wnt3a), ß-catenin, matrix metallopeptidase 2(MMP2), matrix metallopeptidase 3(MMP3), TIMP metallopeptidase inhibitor 1(TIMP1), and TIMP metallopeptidase inhibitor 2(TIMP2). The results showed that compared with the model group, the high and low-dose Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVID;s) and diastole(LVID;d), increased the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improved cardiac function in mice after myocardial infarction, and effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactic dehydrogenase(LDH), thus protecting ischemic myocardium. HE staining showed that Jiming Powder could attenuate myocardial inflammatory cell infiltration after myocardial infarction. Masson and Sirius Red staining demonstrated that Jiming Powder effectively inhibited myocardial fibrosis, reduced the collagen Ⅰ/Ⅲ ratio in myocardial tissues, and improved collagen remodeling after myocardial infarction. Western blot results showed that Jiming Powder reduced the expression of TGF-ß1, α-SMA, Wnt3a, and ß-catenin, decreased the levels of MMP2, MMP3, and TIMP2, and increased the level of TIMP1, suggesting its role in inhibiting cardiac fibroblast transformation, reducing extracellular matrix metabolism in myocardial cells, and lowering collagen Ⅰ and α-SMA content, thus exerting an anti-myocardial fibrosis effect after myocardial infarction. This study revealed the role of Jiming Powder in improving ventricular remodeling and treating myocardial infarction, laying the foundation for further research on the pharmacological effect of Jiming Powder.

Integrating network pharmacology and experimental evidence to decipher the cardioprotective mechanism of Yiqihuoxue decoction in rats after myocardial infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: "Qi deficiency and blood stasis" syndrome is one of the most common syndromes treated with Traditional Chinese Medicine among ischemic heart disease (IHD) patients in clinic. As a Chinese herbal formula with the function of tonifying Qi and activating blood, Yiqihuoxue Decoction (YQHX) has been frequently proven to be effective in the clinical treatment of IHD. AIM OF THE STUDY: The cardioprotective mechanisms of YQHX in treating ischemic heart disease were investigated, with emphasis on the key targets and pathways. MATERIALS AND METHODS: In the present study, the potential targets of compounds identified in YQHX were predicted using PharmMapper, Symmap, and STITCH databases, and a "herb-compound-target" network was constructed using Cytoscape. Subsequently, the GO and KEGG functional enrichment analyses were analyzed using the DAVID database. Furthermore, a protein-protein interaction network was constructed using STRING to obtain the key target information. Besides, we used a myocardial ischemia rat model to investigate the cardioprotective effects of YQHX. Transmission electron microscopy and Western blotting were used to observe apoptotic bodies and confirm protein expressions of key candidate targets, respectively. RESULTS: Network pharmacology showed that a total of 141 potential targets were obtained from these databases. The functional analysis results revealed that the targets of YQHX were largely associated with apoptosis, and the PI3K-AKT and MAPK pathways might represent key functional pathways. The hub genes of network include ALB, TP53, AKT1, TNF, VEGFA, EGFR, MAPK1, CASP3, JUN, FN1, MMP9, and MAPK8. In vivo, YQHX significantly improved cardiac function and suppressed apoptosis in ischemic rat myocardium. Furthermore, YQHX could significantly upregulate Nrf2 and HO-1 expression, and inhibit JNK phosphorylation. CONCLUSIONS: Based on network pharmacology and experimental evidence, this study proves that the cardioprotective effects and mechanisms of YQHX depend on multi-component, multi-target, and multi-pathway. In particular, YQHX exerts anti-apoptotic effects potentially by regulating the Nrf2/HO-1 and JNK-MAPK pathways.

Protective effect of Yi-Qi-Huo-Xue Decoction against ischemic heart disease by regulating cardiac lipid metabolism.

Yi-Qi-Huo-Xue Decoction (YQHX) is the recombination of Dang-Gui-Bu-Xue Decoction (DBD), which is one of the well-known traditional Chinese Medicine (TCM) prescription, and has long been shown to have significant protective effects against myocardial ischemic injury. In previous studies, we found that YQHX could regulate lipid and glucose metabolism, promote angiogenesis, attenuate inflammatory response, and ameliorate left ventricular function in myocardial ischemia rat models. However, the underlying mechanism of how YQHX involves in lipid metabolism remains unclear so far. In this study, the underlying mechanism of YQHX in lipid metabolism disorders was elucidated in a myocardial ischemia rat model and a hypoxia-induced H9c2 cell injury model. YQHX (8.2 g·kg-1) and positive-control drug trimetazidine (10 mg·kg-1) were administered daily on the second day after left anterior descending (LAD) operation. At 7 days and 28 days after surgery, changes of cardiac morphology, structure, and function were evaluated by H&E staining and echocardiography, respectively. The plasma lipid levels and mitochondrial ATP content were also evaluated. Western blot and RT-PCR were used to determine the protein and mRNA expressions of AMPK, PGC-1α, CPT-1α, and PPARα. YQHX improved cardiac function and ameliorated lipid metabolism disorders. Furthermore, YQHX increased the expression of p-AMPK, PGC-1α, and CPT-1α without changing PPARα in ischemic rat myocardium. In vitro, YQHX activated the protein and mRNA expression of PGC-1α, CPT-1α, and PPARα in hypoxia-induced H9c2 cells injury, whereas AMPK inhibitor Compound c blocked the effects of YQHX. Taken together, the results suggest that YQHX reduces lipid metabolism disorders in myocardial ischemia via the AMPK-dependent signaling pathway.

[Genetic variation of Thelazia callipaeda among isolates collected from patients in Zunyi City, Guizhou Province].

OBJECTIVE: To identify the genetic variation and possible sources of Thelazia callipaeda isolates collected from patients in Zunyi City, Guizhou Province. METHODS: Seven cases of T. callipaeda infection in Zunyi City, 2016 were verified, and DNA (s) were extracted from the T. callipaeda's body collected from the thelaziasis patients. A mitochondrial COX1 fragment was amplified and sequenced. The sequence alignment and phylogenetical analysis were performed to compare the genetic variation of the gene sequence with the homologous sequences downloaded from Genebank. RESULTS: COX1 genes of T. callipaeda were differed among the samples from the seven cases, which had low variation. CONCLUSIONS: Zunyi City is a new area with endemic of thelaziasis. The isolates from Zunyi City include either Asian origin or European origin of T. callipaeda. Moreover, at least four haplotypes are identified among the seven isolates.

[Preparation of anti HBs monoclonal antibody and its combination characterization to both wild-type HBsAg and immune escape mutant HBsAg].

AIM: To prepare monoclonal antibodies against HBsAg and estimate its binding capacity to both wild-type and varies of immune escape mutant-type HBsAg. METHODS: Using self-made the anti-HBs G6 mAb and HRP-labeled goat anti-HBs antibody, A sandwich ELISA for detection both wild-type and varies of immune escape mutant-type HBsAg has been developed. Applying this assay, to detect 17 species of whole gene wild-type and recombination expressed HBsAg which varied in "a" determinant. to evaluate its clinical application characteristic of this assay, we used the other commercial reagents to Comparing with it. RESULTS: One strain hybridoma cell lin secreted anti-HBs mAb (defined G6), was obtained. It grew stably and the titers of the culture supernatant and hydroperitoneum were 2 048 and 4 096x10(3). The sensitivity to the wild-type HBsAg of this assay was less than 0.125 microg/L. This anti-HBs mAb can bind with 12 in 15 species mutant HBsAg (P/N> or =2.5), and 2 of them were low absorbent value at 450 nm(A(450)) group which was 7.55 percent of the wild-type, 1 of them was middle A(450) value group which was 59.40 percent of the wild-type, 9 of them were high A(450) value group which was 92.1-109.4 percent of the wild-type. The low A(450) value group and the negative group were diversified in 120-124 basyl in I loop of the HBV "a" determinant. We also used other commercial reagents, which was widely used in clinic, to detect partial species mutant HBsAg, the average A(450) value was less than foregoing assay. CONCLUSION: The G6 anti-HBs mAb was able to bind most of the immune escape mutant HBsAg in the test. And there would be some special regulations between the mutant site and the recombination expressed HBsAg binding capability.