Mild Therapeutic Hypothermia Alleviated Myocardial Ischemia/Reperfusion Injury via Targeting SLC25A10 to Suppress Mitochondrial Apoptosis.

Myocardial ischemia/reperfusion injury (MI/RI) is identified as a severe vascular emergency, and the treatment strategy of MI/RI still needs further improvement. The present study aimed to investigate the potential effects of mild therapeutic hypothermia (MTH) on MI/RI and underlying mechanisms. In ischemia/reperfusion (I/R) rats, MTH treatment significantly improved myocardial injury, attenuated myocardial infarction, and inhibited the mitochondrial apoptosis pathway. The results of proteomics identified SLC25A10 as the main target of MTH treatment. Consistently, SLC25A10 expressions in I/R rat myocardium and hypoxia and reoxygenation (H/R) cardiomyocytes were significantly suppressed, which was effectively reversed by MTH treatment. In H/R cardiomyocytes, MTH treatment significantly improved cell injury, mitochondrial dysfunction, and inhibited the mitochondrial apoptosis pathway, which were partially reversed by SLC25A10 deletion. These findings suggested that MTH treatment could protect against MI/RI by modulating SLC25A10 expression to suppress mitochondrial apoptosis pathway, providing new theoretical basis for clinical application of MTH treatment for MI/RI.

Effects of curcumin on non-alcoholic fatty liver disease: A scientific metrogy study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases encountered in clinical practice. Curcumin can alleviate insulin resistance, inhibit oxidative stress response, reduce inflammation, reduce liver fat deposition, and effectively improve NAFLD through various modalities, inhibiting the progression into cirrhosis and fibrosis. PURPOSE: To explore the current status, hot spots, and developing trends of curcumin in NAFLD treatment through quantitative scientific analysis to serve as a reference for subsequent studies. STUDY DESIGN: A comprehensive analysis of the mechanism of action of curcumin in the treatment of NAFLD and methods to increase curcumin bioavailability using bibliometric analysis and literature review. METHODS: This study used VOSviewer software to analyze the literature related to curcumin treatment of NAFLD in the Web of Science (WOS) core set database. A comprehensive and in-depth review was conducted based on the results of scientific econometric research and literature review. RESULTS: The review observed that curcumin can activate various signaling pathways such as AMPK and NF-κB to inhibit oxidative stress and apoptosis, thereby reflecting its pharmacological effects: lowering lipid, anti-inflammatory, reducing insulin resistance, and anti-fibrosis. These mechanisms improve or even reverse the complex pathological features of lipid metabolism disorders associated with NAFLD. Curcumin also can potentially serve as a primary regulatory target for treating hepatic steatosis using gut microbiota. However, these pharmacological effects of curcumin were limited owing to its low bioavailability. CONCLUSION: This review discusses NAFLD treatment with curcumin, analyzes the reasons for its low bioavailability, and introduces models for studying and methods for improving curcumin bioavailability. As research on NAFLD grows, future research should capture the trend of basic research, pay attention to clinical research, and continuously explore the therapeutic potential of curcumin.

UPLC-Q-TOF-MS based investigation into the bioactive compounds and molecular mechanisms of Lamiophlomis Herba against hepatic fibrosis.

BACKGROUND: Lamiophlomis Herba (LH) is a valuable traditional medicinal plant found on the Qinghai-Tibetan Plateau that promotes blood circulation, removes blood stasis, and has antibacterial and anti-inflammatory properties. The main components of LH are iridoid glycosides, phenethyl alcohol glycosides, flavonoids, and polysaccharides. PURPOSE: To investigate the mechanism of the anti-liver fibrosis effects of LH and screen for its bioactive compounds. STUDY DESIGN: Screening LH marker components and validating the LH anti-liver fibrosis mechanism. METHODS: The active ingredients of LH were identified using UPLC-Q-TOF-MS, and HotMap combined with principal components analysis (PCA) was used to screen for marker components. Network pharmacology and molecular docking techniques were used to predict the potential anti-fibrotic targets of LH. Immunofluorescence, enzyme-linked immunosorbent assay (ELISA), real-time PCR (RT-PCR), and western blotting were used for experimental validation and mechanistic studies. RESULTS: Fifteen compounds that actively contributed to the cluster were identified as marker compounds. Acteoside, 8-O-acetyl shanzhiside methyl ester (8-O-ASME), Luteolin, Shanzhiside Methyl ester (SME), Loganin, Loganate were the main active components. Network pharmacology and molecular docking studies have shown that LH might improve liver fibrosis, inflammation, and oxidative stress, which might be related to key targets such as PTGS2, MAPK, EGFR, AKT1, SRC, Fn1, Col3a1, Col1a1, and PC-III. The results of ELISA, RT-PCR and western blot experiments showed that Acteoside, 8-O-ASME, Luteolin, SME, Loganin, Loganate, and the LH group could reduce the levels of fibronectin, Col1a1, Col3a1, α-SMA, Col-Ⅳ, LN, and PC-Ⅲ. CONCLUSION: LH improves liver fibrosis induced by HSC-T6 cells and inhibits the deposition of extracellular matrix (ECM) in hepatocytes, resulting in a decrease in the degree of liver fibrosis and a good anti-liver fibrosis effect.

Schisandrol A, a bioactive constituent from Schisandrae Chinensis Fructus, alleviates drug-induced liver injury by autophagy activation via exosomes.

OBJECTIVE: To investigate the bioactive compounds of Schisandrae Chinensis Fructus (SCF) and their mechanisms of action in the treatment of drug-induced liver injury (DILI), specifically Acetaminophen (APAP)-induced DILI. METHOD: Chemical components in SCF were identified using the UPLC-Q-TOF-MS method. Active components were then screened using HotMap, combined with SCF efficacy results concerning the prevention and treatment of drug-induced liver injury. Its direct target was elucidated using a comprehensive chemical-pharmacodynamic-exosome approach. RESULT: We identified Schisandrol A, is a lignan component, as a key active compound that improved the symptoms DILI in mouse liver tissue; specifically, reducing oxidative stress and thereby the inflammatory response. To further understand the biological function of miRNAs in mouse liver exosomes, we used TargetScan (v5.0) and Miranda (v3.3a) to predict the target genes of MicroRNAs (miRNAs), where changes in the expression of mmu-let-7 family miRNAs were closely related to autophagy. This revealed differential miRNA target genes that were involved in 20 Kyoto Encyclopedia of Genes and Genomes pathways, including glycerol phosphate metabolism, inositol phosphate metabolism, phospholipase D signaling pathway, Rap1 signaling pathway, and Ras signaling pathway. CONCLUSION: Schisandrol A alleviated the symptoms of DILI in mice by inhibiting oxidative stress and inflammation, whereas, it alleviated DILI by activating autophagy in the exosomes.

Effect of Dan-Lou tablets on coronary heart disease revealed by microarray analysis integrated with molecular mechanism studies.

Dan-Lou tablets (DLT) effectively treat coronary heart disease (CHD). However, its pharmacological mechanism in CHD treatment requires further investigation. This study aimed to elucidate the underlying pharmacological mechanisms of DLT in the treatment of CHD through clinical trials, microarray research, bioinformatics analysis, and molecular mechanism research. In this study, DLT improved coagulation function, endothelial injury, and levels of lipids, metalloproteases, adhesion molecules, inflammatory mediators, and homocysteine. The results of molecular biology research demonstrated that DLT can increase the gene and protein expressions of meningioma expressed antigen 5 (MGEA5) and mouse doubleminute 2 (MDM2) and inhibited the gene and protein expressions of signal transcription and transcription activator 5 B (STAT5B), tropomyosin-1 (TPM1), and aromatic hydrocarbon receptor nuclear transpose (ARNT). The results indicate that DLT reduced the extent of vascular endothelial damage in CHD rats by reducing the expressions of STAT5B, TPM1, and MDM2; inhibiting the inflammatory reaction; and increasing the expressions of ARNT and MGEA5.

Mechanisms of theaflavins against gout and strategies for improving the bioavailability.

BACKGROUND: Gout is a crystal related arthropathy caused by monosodium urate deposition. At present, the identification of appropriate treatments and new drugs to reduce serum uric acid levels and gout risk is a major research area. PURPOSE: Theaflavins are naturally occurring compounds characterized by a benzodiazepine skeleton. The significant benefits of theaflavins have been well documented. A large number of studies have been carried out and excellent anti-gout results have been achieved in recent years. STUDY DESIGN: A comprehensive analysis of the mechanism of the anti-gout effect of theaflavins is presented through a literature review and network pharmacology prediction, and strategies for increasing the bioavailability of theaflavins are summarized. METHODS: In this review, the active components and pharmacological mechanisms of theaflavins in the treatment of gout were summarized, and the relationship between theaflavins and gout, the relevant components, and the potential mechanisms of anti-gout action were clarified by reviewing the literature on the anti-gout effects of theaflavins and network pharmacology. RESULTS: Theaflavins exert anti-gout effects by down regulating the gene and protein expression of glucose transporter 9 (GLUT9) and uric acid transporter 1 (URAT1), while upregulating the mRNA expression levels of organic anion transporter 1 (OAT1), organic cation transporter N1 (OCTN1), organic cation transporters 1/2 (Oct1/2), and organic anion transporter 2 (OAT2). Network pharmacology prediction indicate that theaflavins can regulate the AGE-RAGE and cancer signaling pathways through ATP-binding cassette subfamily B member 1 (ABCB1), recombinant mitogen activated protein kinase 14 (MAPK14), telomerase reverse tranase (TERT), signal transducer and activator of transcription 1 (STAT1), matrix metalloproteinase 2 (MMP2), B-cell lymphoma-2 (BCL2), and matrix metalloproteinase 14 (MMP14) targets for anti-gout effects. CONCLUSION: This review presents the mechanisms of anti-gout action of theaflavins and strategies for improving the bioavailability of theaflavins, as well as providing research strategies for anti-gout treatment measures and the development of novel anti-gout drugs.

Relation Between New York Heart Association Functional Class and Remnant Cholesterol, and Non-high Density Lipoprotein Cholesterol in Coronary Heart Disease Patients With Type 2 Diabetes Mellitus.

Remnant cholesterol (RC) and non-high-density lipoprotein cholesterol (non-HDL-C) are associated with coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). However, the association between RC, non-HDL-C, and CHD patients with T2DM has not been comprehensively investigated. We analyzed the association between RC, non-HDL-C, and cardiac function in CHD patients with T2DM. Of the 22 022 CHD patients from six hospitals in Tianjin, 5373 (24.4%) patients with T2DM had higher levels of RC and non-HDL-C (P < .001) than those without T2DM. Among CHD patients with T2DM, RC and non-HDL-C were positively associated with New York Heart Association (NYHA) class Ⅱ [RC: odds ratio (OR), 1.74; 95% confidence interval (CI), 1.50-2.01; P < .01; non-HDL-C: OR, 1.23; 95% CI, 1.15-1.31; P < .01]. After adjusting for confounding factors, this association remained (RC: OR, 1.22; 95% CI, 1.03-1.45; P < .05; non-HDL-C: OR, 1.09; 95% CI, 1.02-1.17; P < .05). These findings provide evidence of an independent positive association between RC, non-HDL-C, and NYHA functional classes. More research is warranted to confirm these findings and determine the mechanisms involved.

Schisandrin B ameliorates acute liver injury by regulating EGFR-mediated activation of autophagy.

OBJECTIVE: To investigate the role and possible molecular mechanism of Schisandrin B-induced cell autophagy in the prevention and treatment of APAP-induced liver injury. METHODS: Molecular docking method was used to predict the interaction between Schisandrin B and the EGFR protein. HepG2 cells were treated with different concentrations of Schisandrin B for 24 h. Schisandrin B-induced autophagy of HepG2 cells was determined using real-time label-free cell analysis (RTCA), flow cytometry, immunofluorescence, PCR, and western blot. Flow cytometry and western blot were used to explore whether Schisandrin B-induced autophagy plays a role in the prevention and treatment of liver injury via the EGFR/TFEB signaling pathway. RESULTS: Schisandrin B treatment of APAP-induced HepG2 cells inhibited the production of TNF-α and IL-1ß. Further, Schisandrin B downregulated EGFR protein expression and activated the EGFR/TFEB signaling pathway. Autophagy inhibition promoted APAP-induced apoptosis of HepG2 cells. Moreover, the protein expression levels of TFEB, LC3 and Beclin-1 were upregulated, whereas those of ATG3 and EGFR were downregulated. CONCLUSION: Schisandrin B can induce autophagy in HepG2 cells. Autophagy may play a role in the prevention and treatment of liver injury via the EGFR/TFEB signaling pathway. Activation of autophagy enhances the effect of Schisandrin B on APAP-induced liver injury.

Association of Serum γ-Glutamyltransferase With C-Reactive Protein Levels in Patients With Coronary Heart Disease.

Serum γ-glutamyltransferase (GGT) levels have been shown to be associated with C-reactive protein (CRP) levels. Nevertheless, studies on this relationship in coronary heart disease (CHD) populations are limited. This study retrospectively assessed 17 523 patients with CHD undergoing GGT and CRP testing. They were divided into 3 groups according to GGT tertiles. The critical points for high CRP levels was 10.0 mg/L, which corresponded to the 75th percentile. Logistic regression analysis was used to analyze the association between GGT and CRP levels in CHD patients. The baseline analysis showed significant differences in related parameters among patients with CHD. Compared with GGT tertile 1 (T1), the odds ratio (OR) of T3 for GGT in CHD patients was 2.15 (95% confidence interval [CI]: 1.96-2.36). The association between GGT and CRP was higher in males (OR: 2.23; 95% CI: 1.98-2.52) than in females (OR: 2.18; 95% CI: 1.89-2.51). This study showed an association between serum GGT and CRP levels in patients with CHD. GGT may be an inflammatory marker and an additional measure for assessing cardiovascular risk.

Potential therapeutic effects and applications of Eucommiae Folium in secondary hypertension.

Eucommiae Folium (EF), a traditional Chinese medicine, has been used to treat secondary hypertension, including renal hypertension and salt-sensitive hypertension, as well as hypertension caused by thoracic aortic endothelial dysfunction, a high-fat diet, and oxidized low-density lipoprotein. The antihypertensive components of EF are divided into four categories: flavonoids, iridoids, lignans, and phenylpropanoids, such as chlorogenic acid, geniposide acid and pinoresinol diglucoside. EF regulates the occurrence and development of hypertension by regulating biological processes, such as inhibiting inflammation, regulating the nitric oxide synthase pathway, reducing oxidative stress levels, regulating endothelial vasoactive factors, and lowering blood pressure. However, its molecular antihypertensive mechanisms are still unclear and require further investigation. In this review, by consulting the relevant literature on the antihypertensive effects of EF and using network pharmacology, we summarized the active ingredients and pharmacological mechanisms of EF in the treatment of hypertension to clarify how EF is associated with secondary hypertension, the related components, and underlying mechanisms. The results of the network pharmacology analysis indicated that EF treats hypertension through a multi-component, multi-target and multi-pathway mechanism. In particular, we discussed the role of EF targets in the treatment of hypertension, including epithelial sodium channel, heat shock protein70, rho-associated protein kinase 1, catalase, and superoxide dismutase. The relevant signal transduction pathways, the ras homolog family member A (RhoA)/Rho-associated protein kinase (ROCK) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase/eNOS/NO/Ca2+ pathways, are also discussed.

Impaired Sensitivity to Thyroid Hormones Is Associated With Elevated Blood Glucose in Coronary Heart Disease.

Context: Thyroid hormones influence glucose homeostasis through central and peripheral regulation. To date, the association between thyroid hormone sensitivity and elevated blood glucose (EBG) in patients with coronary heart disease (CHD) remains unknown. The purpose of this study was to investigate the association between thyroid hormone sensitivity and risk of EBG in patients with CHD, and to further explore their association in different sexes and ages. Methods: This large multicenter retrospective study included 30,244 patients with CHD (aged 30-80 years) between 1 January 2014 and 30 September 2020. Parameters representing central and peripheral sensitivity to thyroid hormones were calculated. Central sensitivity to thyroid hormones was assessed by calculating the Thyroid Feedback Quantile-based Index (TFQI), Thyroid-stimulating Hormone Index (TSHI), and Thyrotropin Thyroxine Resistance Index (TT4RI), and Parametric Thyroid Feedback Quantile-based Index (PTFQI); peripheral sensitivity to thyroid hormones was evaluated using the ratio of free triiodothyronine (FT3) /free thyroxine (FT4). Taking normal glucose tolerance (NGT) as a reference, logistic regression was used to analyse the relationship between central and peripheral thyroid hormone sensitivity and EBG in patients with CHD. Results: Among the 30,244 participants, 15,493 (51.23%) had EBG. The risk of EBG was negatively correlated with TSHI (OR: 0.91; 95%CI: 0.91 to 0.92; P < 0.001), TT4RI (OR: 0.99; 95% CI: 0.99 to 0.99; P<0.001), TFQI (OR: 0.82; 95%CI: 0.80 to 0.84; P <0.001) and PTFQI (OR: 0.76; 95%CI: 0.74 to 0.78; P<0.001). Compared to males and patients aged 60 and below, the OR value for EBG was lower in females and in patients aged over 60 years old. Conversely, EBG risk was positively associated with FT3/FT4 (OR: 1.08; 95% CI: 1.07 to 1.09; P <0.001) and in the sex-categorized subgroups, males had higher OR values than females. Conclusions: This study showed that thyroid hormone sensitivity is significantly associated with EBG in patients with CHD. This association is higher in females than in males, and the association in those aged over 60 years old is higher than that in patients aged 60 years and below.

Clinical metabolomic analysis of Danlou tablets with antioxidant effects for treating stable angina pectoris.

The Danlou tablets (DLT) is a patented Chinese medicine that can effectively ameliorate coronary heart disease- and angina pectoris-related chest congestion and pain. However, the mechanism underlying the therapeutic effects of DLT in the context of stable angina pectoris (SAP) has not been clearly elucidated. In this study, ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to analyze serum samples from patients with SAP before and after DLT administration. The results of metabolomic analyses were verified biologically, and the mechanisms of action of DLT with respect to treating SAP were elucidated. Nineteen biomarkers were identified. Among these biomarkers, the levels of 15 reverted to those corresponding to a healthy state following DLT treatment. The main metabolic pathways associated with the functions of DLT in SAP were energy metabolism, purine metabolism, glycerophospholipid metabolism and amino acid metabolism, all of which are related to oxidative stress. Biological verification revealed that DLT decreased the expression of the oxidative stress indicators, xanthine oxidase (XOD) and malondialdehyde (MDA), and increased heme oxygenase-1 (HO-1) expression and superoxide dismutase (SOD) activity. Taken together, we revealed that DLT effectively ameliorates SAP by adjusting the oxidative stress status. This study provided an objective index for evaluating the efficacy of DLT for treating SAP.

Correlation between the triglyceride-to-high-density lipoprotein cholesterol ratio and other unconventional lipid parameters with the risk of prediabetes and Type 2 diabetes in patients with coronary heart disease: a RCSCD-TCM study in China.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is often accompanied by undiagnosed dyslipidemia. Research on the association of unconventional lipid markers with prediabetes (pre-DM) and T2DM simultaneously is limited in coronary heart disease (CHD) patients. METHODS: This study included 28,476 patients diagnosed with CHD. Their lipid levels, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were measured, and non-traditional lipid parameters were calculated. The patients were divided into three groups based on the diabetic status including normoglycemic (NG), pre-DM, and T2DM. Multiple logistic regression was used to compare the association of TG/HDL-C and other non-traditional lipid parameters with pre-DM and T2DM. The tertiles of TG/HDL-C included T1 (TG/HDL-C < 1.10), T2 (1.10 ≤ TG/HDL-C ≤ 1.89) and T3 (TG/HDL-C > 1.89). Low and high TG/HDL-C was defined with sex-specific cutoff points. RESULTS: Multiple logistic regression results showed that the non-traditional lipid parameters, including non-HDL-C, LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C and TG/HDL-C, were all correlated with the risk of pre-DM and T2DM. Meanwhile TG/HDL-C showed the strongest correlation (odds ratio [OR]: 1.19; 95% confidence interval [CI] 1.16-1.23), (OR: 1.36; 95% CI 1.33-1.39). When dividing TG/HDL-C into tertiles, using T1 as a reference, T3 was observed to have the highest association with both pre-DM and T2DM (OR: 1.60; 95% CI 1.48-1.74), (OR: 2.79; 95% CI 2.60-3.00). High TG/HDL-C was significantly associated with pre-DM and T2DM (OR: 1.69; 95% CI 1.52-1.88), (OR: 2.85; 95% CI 2.60-3.12). The association of TG/HDL-C with T2DM and pre-DM existed across different sex, age, smoking, and drinking statuses. CONCLUSION: Elevated non-traditional lipid parameters were significantly associated with pre-DM and T2DM in CHD patients, especially TG/HDL-C. High TG/HDL-C was the risk factor with a strong correlation with the risk of pre-DM and T2DM.

UPLC-MS analysis and network pharmacology-based investigation into the active ingredients and molecular mechanisms of anti-fatigue of male flowers with Eucommia ulmoides Oliv.

The male flowers of Eucommia ulmoides Oliv. (MFEU) was a natural product that could alleviate fatigue and accelerate fatigue alleviation. Nonetheless, the active ingredients and underlying pharmacological mechanisms remain unknown. This study aimed to decode the active ingredients and potential action mechanisms of MFEU in the therapy of anti-fatigue using an integrated UPLC-MS analysis, network pharmacology approach, and cell experiments. Characterizations of chemical constituents of MFEU extract were identified by UPLC-Q-TOF-MS. The corresponding drug targets were retrieved from the drug target database and used to construct the "composite-target-pathway" network. The Cytoscape was used to identify potential protein targets of these MFEU components, indicating that 24 anti-fatigue compounds in MFEU regulate 18 anti-fatigue-related targets in 10 signaling pathways. The 16 components of MFEU were verified at the cellular level. The results of cell experiments showed that MFEU extract (0.361 µg/ml), Caffeic acid, Deacetylasperulosidic acid, Naringenin, Acanthoside B, Geniposidic acid, Rutin, and Quercetin could promote testosterone secretion on Leydig cells at 50 µM. The MFEU extract and seven compounds in MFEU might play a role in anti-fatigue by participating in the regulation of testosterone secretion. Finally, the results of PCR analysis showed that MFEU promotes the secretion of testosterone, which is related to CYPIIa1 and 17ß-HSD, STAR in the signal pathway of testosterone synthesis. This study provides a basis for further exploring the anti-fatigue mechanism of MFEU, adopting the method of multi-compound and multi-target.

Association between triglyceride glucose index and carotid artery plaque in different glucose metabolic states in patients with coronary heart disease: a RCSCD-TCM study in China.

BACKGROUND: The triglyceride glucose (TyG) index serves as a surrogate indicator of insulin resistance. However, there is limited evidence on the association between the TyG index and carotid artery plaque (CAP) in patients with coronary heart disease (CHD). METHODS: The 10,535 CHD patients were divided according to TyG index quartiles (Q1: TyG index < 8.52; Q2: 8.52 ≤ TyG index < 8.93; Q3: 8.93 ≤ TyG index ≤ 9.40; Q4: TyG index > 9.40). The presence or absence of CAP was determined by carotid ultrasonography. Logistic regression was used to analyze the relationship between the TyG index and CAP in CHD patients. The relationship between the TyG index and CAP in according to sex, age groups, and glucose metabolism states were also assessed. RESULTS: The baseline analysis showed that there were significant differences in related parameters among CHD patients divided into four groups according to the quartile of the TyG index. In the multi-adjusted modles, compared to Q1 of the TyG index, the odds ratios (OR) for Q4 of the TyG index for CAP were 1.37 (95% confidence interval [CI] 1.28-1.47) in CHD patients. The association between the TyG index and CAP in female (OR: 1.35; 95% CI 1.29-1.43) was higher than that in male (OR: 1.20; 95% CI 1.13-1.27). The OR value of middle-aged (≤ 60 years old) patients (OR: 1.34; 95% CI 1.26-1.42) was higher than that in elderly (> 60 years old) patients (OR: 1.16; 95% CI 1.11-1.22). In different glucose metabolism states, the TyG index of CHD patients was significantly related to the risk of CAP, with the highest OR value observed for diabetes (OR: 1.36; 95% CI 1.26-1.46). CONCLUSIONS: The TyG index and CAP showed a significant association in CHD patients. This association between TyG index and CAP in CHD patients is higher in female than in male, and the association in middle-aged and elderly patients is higher than that in elderly patients. In the condition of DM, the association between TyG index and carotid artery plaque in CHD patients is higher.

Network pharmacology, molecular docking technology integrated with pharmacodynamic study to reveal the potential targets of Schisandrol A in drug-induced liver injury by acetaminophen.

Schisandrae Chinensis Fructus (SCF) was a Traditional Chinese Medicine for protecting liver. However, underlying therapeutic mechanisms of these bioactive lignans from SCF similar hepatoprotective effects against drug-induced liver injury (DILI) by acetaminophen (APAP) are still unclear. This study aims to discover the potential regulation mechanisms of Schisandrol A in the treatment of DILI by APAP. The integrated UPLC-Q-TOF/MS, pharmacodynamic study, histopathological combination with network pharmacology and molecular docking technology were used to explore the potential mechanisms. The results showed that Schisandrol A reduced the level of AST, ALT, MDA, PNP, TNF-α and IL-1ß, increased the levels of the GSH against acute liver failure. Additionally, Schisandrol A could improve the morphological characteristics of DILI by APAP in mice with liver tissue. Molecular docking results had showed that Schisandrol A with high scores when docking with COX-2, ALOX5, CYP2E1, CYP2C9, CYP2C19, EGFR SRC, Nrf2, MAPK14 and MAPK8. The study demonstrated that Schisandrol A could play critical roles in DILI by APAP via regulating TNF signaling pathway, inhibiting oxidative stress, inflammation and inhibiting the activities of cytochrome P450 enzymes, which contributed to searching for leading compounds and the development of new drugs for DILI by APAP.

Low-/high-density lipoprotein cholesterol ratio and carotid plaques in patients with coronary heart disease: a Chinese cohort study.

BACKGROUND: Evidence on the relationship between the low-/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C) and carotid plaques remains limited. This study aimed to examine the association between LDL-C/HDL-C and carotid plaques in participants with coronary heart disease (CHD) and to further explore the extent to which a healthy lifestyle reduces the risk of LDL-C/HDL-C-related carotid plaques. METHODS: This large-scale and multi-centre retrospective study included 9426 CHD patients (aged 35-75 years) between January 1, 2014 and September 30, 2020. The LDL-C/HDL-C values were converted to the following tertiles: lowest (< 2.15), middle (2.15-3), and highest (> 3). Healthy lifestyle-related factors referred to whether or not the participant was a non-smoker and non-drinker. Participants were divided into an unfavourable group (those who did not adhere to healthy lifestyle factors), intermediate (only one unhealthy factor), and favourable (neither of the two unhealthy factors). Logistic regression was used for statistical analyses. RESULTS: Of the 9426 participants, 6989 (74.15%) CHD patients had carotid plaques. After adjustment for confounders, each unit increase in the LDL-C/HDL-C was significantly associated with carotid plaques (OR: 1.61; 95%CI: 1.43-1.84; P <  0.001). Multivariate logistic regression revealed that carotid plaques risk for the highest tertile (> 3) was 1.18 times that of the lowest quartile (< 2.15). Compared with an unfavourable lifestyle, an intermediate or a favourable lifestyle was associated with a significant 30% (OR: 0.70; 95%CI: 0.64-0.78; P <  0.001) or 67% (OR: 0.33; 95%CI: 0.29-0.37; P <  0.001) reduction in carotid plaques risk, respectively, among CHD patients with high LDL-C/HDL-C. There were significantly additive and multiplicative interactions between lifestyle and LDL-C/HDL-C with regards to carotid plaques. CONCLUSION: A high LDL-C/HDL-C is associated with a risk of carotid plaques developing in CHD patients. Adhering to a healthy lifestyle has additive beneficial effects on reducing the risk of carotid plaques, especially in relation to the highest LDL-C/HDL-C.

Evaluation of Biological Mechanisms of Eucommiae Folium in Hypertensive Kidney Injury by Integration of Untargeted Metabolomics and Network Pharmacology.

Hypertensive kidney injury (Hki) is one of the most common complications of hypertension. Early prevention and treatment of renal injury in patients with hypertension is great significance. The study, which used an integrated ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS) analysis, network pharmacology approach, and plasma metabolomics, aimed to discover the active ingredients and therapeutic mechanisms of Eucommiae folium (Ef) in treating Hki. The chemical components of Ef were analyzed by UPLC-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS), and the "compound-target-disease" network was constructed by screening the closely related drug targets from the drug-target database, then the signaling pathways related to Hki were analyzed. Finally, the enzyme-linked immunosorbent assay (ELISA) and real-time quantitative reverse-transcription polymerase chain reaction were used to test and verify the key targets in the common pathways of metabolomics and network pharmacology. The results indicated that Eucommiae folium might play an excellent role in treating Hki, likely through regulating the vascular endothelial growth factor signaling pathway, hypoxia inducible factor 1 (HIF-1) signaling pathway, and glycerophospholipid metabolism pathway, which were validated by increasing levels of nitric oxide, endothelial nitric oxide synthase and reducing levels of endothelin 1, angiotensin II, renin, cyclic guanosine monophosphate, blood urea nitrogen, and serum creatinine, as well as the reduced gene expression of Ache, Ddah2, Egfr, Lcat, Pla2g2a, Stat3 and Vegfa. The study systematically explored the protective mechanisms of Ef against Hki and also provided the practical treatment strategies of Hki from the Chinese herb.

A network pharmacology-integrated metabolomics strategy for clarifying the action mechanisms of Schisandrae Chinensis Fructus for treating drug-induced liver injury by acetaminophen.

Schisandrae Chinensis Fructus (SCF) was a Traditional Chinese Medicine (TCM) for protecting liver. However, underlying therapeutic mechanisms of SCF for drug-induced liver injury (DILI) by acetaminophen (APAP) are still unclear. This study aims to discover the potential regulation mechanisms of SCF in the treatment of DILI by APAP using the integrated network pharmacology, plasma metabolomics profiling with UPLC-Q-TOF-MS approach. The key targets in the shared pathways of network pharmacology and metabolomics were screened and experimentally validated by Quantitative Real-time PCR analysis. The results showed that SCF could exert excellent effects on DILI by APAP probably through regulating ErbB signaling pathway and Arachidonic acid metabolism pathway, which was reflected by the reduced gene expression of TNF-α, IL-6, IL-1ß, COX-2 and EGFR, as well as the increased gene expression of Nrf2, HO-1, MDM2, MAPK8, SRC, PLD1, CYP2E1, CYP1A2, CYP3A1. This study systematically explored the pharmacological mechanisms of SCF in the treatment of DILI, meanwhile, metabolomics combine with network pharmacology approach might be a useful strategy for early diagnosis of DILI by APAP.

Network pharmacology based investigation into the bioactive compounds and molecular mechanisms of Schisandrae Chinensis Fructus against drug-induced liver injury.

OBJECTIVE: To investigate the against Drug-induced liver injury ingredients and their functional mechanisms in S. Chinensis Fructus. METHODS: Liquid chromatograph-mass spectrometry analysis was performed on S. Chinensis Fructus extrac. The "Components-Target-Disease" network model was constructed by network pharmacology-based approaches. String analysis was performed to reveal enrichment of these target proteins, protein-protein interactions, pathways and related diseases. And experiment of APAP-induced drug-induced liver injury was to be verified. RESULTS: Cytoscape was used to determine the potential protein targets for these components in S. Chinensis Fructus, indicating that 17 against Drug-induced liver injury compounds in S. Chinensis Fructus regulate 52 diabetes-related proteins in 15 signal pathways and involve 14 core key targets. Verification experiment results that S. Chinensis Fructus prevented the elevation of serum biochemical parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), purine nucleoside phosphorylase (PNP) and alkaline phosphatase (ALP) against acute liver failure. Additionally, S. Chinensis Fructus reduced the content of malondialdehyde (MDA), increased the levels of the Superoxide dismutase (SOD) and Glutathione (GSH), and inhibited the production of proinflammatory cytokines in APAP-induced hepatotoxicity. CONCLUSION: The mechanisms of S. Chinensis Fructus against Drug-induced liver injury were involved in the regulation of multiple targets, especially affecting the ErbB signaling pathways. The active ingredients of S. Chinensis Fructus may play a role against Drug-induced liver injury by participating in the regulation of inflammatory factors, oxidative stress.