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Cardiovascular diseases (CVDs) are a set of heart and blood vessel disorders that include coronary heart disease (CHD), rheumatic heart disease, and other conditions. Traditional Chinese Medicine (TCM) has definite effects on CVDs due to its multitarget and multicomponent properties, which are gradually gaining national attention. Tanshinones, the major active chemical compounds extracted from Salvia miltiorrhiza, exhibit beneficial improvement on multiple diseases, especially CVDs. At the level of biological activities, they play significant roles, including anti-inflammation, anti-oxidation, anti-apoptosis and anti-necroptosis, anti-hypertrophy, vasodilation, angiogenesis, combat against proliferation and migration of smooth muscle cells (SMCs), as well as anti-myocardial fibrosis and ventricular remodeling, which are all effective strategies in preventing and treating CVDs. Additionally, at the cellular level, Tanshinones produce marked effects on cardiomyocytes, macrophages, endothelia, SMCs, and fibroblasts in myocardia. In this review, we have summarized a brief overview of the chemical structures and pharmacological effects of Tanshinones as a CVD treatment to expound on different pharmacological properties in various cell types in myocardia.

Yanqin Li,1,* Xiaoqian Sun,1,* Xiangning Liu,1,* Junjun Li,2 Xuan Li,1 Gang Wang,1 Yizhou Liu,1 Xiangyu Lu,2 Lingwen Cui,2 Mingyan Shao,3 Yong Wang,1,3,4 Wei Wang,1,4,5 Chun Li2,4 1College of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2Modern Research Center for Traditional Chinese Medicine, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 3School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 4Beijing Key Laboratory of TCM Syndrome and Formula, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 5Guangzhou University of Chinese Medicine, Guangdong, 510006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Wang, Guangzhou University of Chinese Medicine, Guangdong, 510006, People’s Republic of China, Tel +86 13910026960, Email wangwei26960@126.com Chun Li, Modern Research Center for Traditional Chinese Medicine, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China, Tel +86 15810068615, Email lichun19850204@163.comBackground: Acute myocardial ischemia (AMI) is a common heart disease with increasing morbidity and mortality year by year. Persistent and sterile inflammatory infiltration of myocardial tissue is an important factor triggering of acute myocardial ischemia secondary to acute myocardial infarction, and NLRP3 inflammasome activation is an important part of sterile inflammatory response after acute myocardial ischemia. Previous studies have shown that Qishen granule (QSG) can significantly inhibit the inflammatory injury of myocardial tissue caused by ischemia, but its effect and specific mechanism of inhibiting the activation of NLRP3 inflammasome have not been reported. This study was to investigate the specific mechanism of QSG inhibiting inflammation after AMI, and to validate the possible targets.Methods: The myocardial ischemia model in mice was established by ligation of the left anterior descending coronary artery. Echocardiography was used to evaluate the cardiac function of the mice. Plasma CK-MB and cTnl were detected by ELISA to evaluate the degree of myocardial injury. The extent of myocardial tissue inflammation in mice was assessed by HE staining and immunohistochemistry of IL-18, IL-1β. The expressions of NLRP3, ASC, Caspase-1, and CD86 were detected by immunofluorescence; detection of key pathway proteins P2X7R, NEK7, NLRP3, ASC, Caspase-1, and effector proteins IL-18, IL-1β by Western blot. In vitro experiments, ATP+LPS was used to construct a RAW264.7 macrophage NLRP3 inflammasome activation model. Immunofluorescence and Western blot analysis were performed to detect the expression of NLRP3 pathway activator and effector proteins. Plasmid-transfected P2X7R overexpression and immunoprecipitation assays were used to evaluate the QSG-regulated NLRP3 inflammasome activation pathway.Results: QSG rescued cardiac function and further reduced inflammatory effects in mice by inhibiting NLRP3 inflammasome activation. In vitro, QSG inhibited LPS combined with ATP-induced NLRP3 inflammasome activation in RAW264.7 macrophages by downregulating the expression of NLRP3 inflammasome key pathway proteins. In addition, inhibition or overexpression of P2X7R in RAW264.7 macrophages and immunoprecipitated protein interactions further confirmed that QSG reduces macrophages inflammasome activation via the P2X7R-NEK7-NLRP3 pathway.Conclusion: P2X7R-NEK7-NLRP3 inflammasome activation is a novel therapeutic mechanism of QSG in the treatment of acute myocardial ischemia.Keywords: acute myocardial ischemia, inflammation, macrophages, P2X7R-NEK7, NLRP3 inflammasome, Qishen granule

Purpose. This study aims to explore the application value of the 18F-FDG PET/CT imaging in diagnosing, staging, and typing Langerhans cell histiocytosis (LCH) via the morphological and metabolic analyses of the 18F-FDG PET/CT images. Methods. We retrospectively analyzed the 18F-FDG PET/CT images and clinical data of nineteen patients with LCH. The shape, size, density, distribution, and 18F-FDG uptake of all lesions were documented. In addition, the SUVmax of the lesions, liver, and blood pool was measured prior to calculating the lesion-to-liver and lesion-to-blood pool ratios. Results. Among the 19 analyzed patients, the positive rate of the PET/CT image was 94.7% (18/19), with 1 false negative (5.3%, 1/19) case occurring in the cutaneous LCH. Among the 76 lesions, 69 were FDG-avid lesions (69/76, 90.8%). Additionally, we observed no FDG uptake in 7 lesions (7/76, 9.2%). In contrast, 59 lesions (59/76, 77.6%) were abnormal on diagnostic CT scan, but 17 lesions (17/76, 22.4%) were undetected. The 18F-FDG PET/CT image revealed additional 6 lesions in the bone, 4 in the lymph node, 3 in the spleen, and 3 occult lesions, which CT scan did not detect. Additionally, there were 6 cases with single-system LCH. The remaining 13 cases were multisystem LCH. Our 18F-FDG PET/CT image analyses altered the typing of 4 LCH patients. In the case of all lesions, the mean SUVmax of the 18F-FDG-avid lesions was 5.4 ± 5.1 (range, 0.8∼26.2), and the mean lesion-to-liver SUVmax ratio was 3.1 ± 2.52 (range, 0.7∼11.9), and the mean lesion-to-blood pool SUVmax ratio was 4.6 ± 3.4 (range 0.7∼17.5). Conclusion. The 18F-FDG PET/CT image plays an essential role in LCH diagnosis, primary staging, and typing. It can accurately evaluate the distribution, range, and metabolic information of LCH, providing a vital imaging basis for the clinical evaluation of disease conditions, selection of treatment schemes, and determining patient prognosis.

Aggrephagy is a critical compensatory mechanism for the elimination of misfolded proteins resulting from stress and depends on the autolysosome degradation of protein aggregates. However, there have been few mechanism research related to aggrephagy in myocardial ischemia/reperfusion (I/R) injury. Neocryptotanshinone (NCTS) is a fat-soluble active compound extracted from Salvia miltiorrhiza, and may be cardioprotective against I/R. However, the efficacy and specific mechanism of NCTS on I/R have not been studied.The current study aimed to investigate the molecular mechanism of NCTS involved in the therapeutic effect on I/R, with a special emphasis on the up-regulation of the ERK1/2-Nrf2-LAMP2 pathway to increase autolysosomal degradation during aggrephagy.A rat model of myocardial I/R injury was constructed by left anterior descending (LAD) ligation-reperfusion. To verify cardiac protection, autolysosome clearance of protein aggregates, and their intracellular biological mechanism, an oxygen-glucose deprivation/recovery (OGD/R)-induced H9c2 cardiomyocyte model was created.NCTS was found to have a significant cardioprotective effect in I/R rats as evidenced by remarkably improved pathological anatomy, decreased myocardial damage indicators, and substantially enhanced cardiac performance. Mechanistically, NCTS might boost the levels of LAMP2 mRNA and protein, total and Ser40 phosphorylated Nrf2, andWe reported for the first time that NCTS promoted the autolysosome removal of protein aggregation both in vivo and in vitro, to exert the therapeutic advantages of myocardial I/R injury. This was reliant on the up-regulation of the ERK1/2-Nrf2-LAMP2 signaling pathway.

This study aims to explore the application value of theWe retrospectively analyzed theAmong the 19 analyzed patients, the positive rate of the PET/CT image was 94.7% (18/19), with 1 false negative (5.3%, 1/19) case occurring in the cutaneous LCH. Among the 76 lesions, 69 were FDG-avid lesions (69/76, 90.8%). Additionally, we observed no FDG uptake in 7 lesions (7/76, 9.2%). In contrast, 59 lesions (59/76, 77.6%) were abnormal on diagnostic CT scan, but 17 lesions (17/76, 22.4%) were undetected. TheThe

Aims: Cardiac lipotoxicity is the common consequence of lipid metabolism disorders in cardiomyocytes during development of heart failure (HF). Adenosine 5′monophosphate-activated protein kinase (AMPK) acts as an energy sensor and has a beneficial effect in reducing lipotoxicity. Notoginsenoside R1 (NGR1) is extracted from the traditional Chinese medicine Panax notoginseng (Burkill) F.H.Chen (P. notoginseng) and has definite cardioprotective effects. However, whether NGR1 can attenuate HF by mitigating lipotoxicity has not been elucidated yet. This study aimed to explore whether NGR1 plays a protective role against HF by ameliorating cardiac lipotoxicity via the AMPK pathway.Methods: In this study, HF mice model was established by left anterior descending (LAD) ligation. palmitic acid (PA) stimulated H9C2 cell model was applied to clarify the effects and potential mechanism of NGR1 on lipotoxicity. In vivo, NGR1 (7.14 mg/kg/days) and positive drug (simvastatin: 2.9 mg/kg/days) were orally administered for 14 days. Echocardiography was applied to assess heart functions. Lipid levels were measured by Enzyme-linked immunosorbent assay (ELISA) and key proteins in the AMPK pathway were detected by western blots. In vitro, NGR1 (40 μmol/L) or Compound C (an inhibitor of AMPK, 10 μmol/L) was co-cultured with PA stimulation for 24 h in H9C2 cells. CCK-8 assay was used to detect cell viability. Key lipotoxicity-related proteins were detected by western blots and the LipidTOX™ neutral lipid stains were used to assess lipid accumulation. In addition, Apoptosis was assessed by Hoechst/PI staining.Results: NGR1 could significantly improve the cardiac function and myocardial injury in mice with HF and up-regulate the expression of p-AMPK. Impressively, NGR1 inhibited the synthesis of diacylglycerol (DAG) and ceramide and promoted fatty acid oxidation (FAO) in vivo. Moreover, NGR1 significantly promoted expression of CPT-1A, the key enzyme in FAO pathway, and down-regulated the expression of GPAT and SPT, which were the key enzymes catalyzing production of DAG and ceramide. In vitro experiments showed that NGR1 could significantly attenuate lipid accumulation in PA-induced H9C2 cells and the Hoechst/PI staining results showed that NGR1 ameliorated lipotoxicity-induced apoptosis in PA-stimulated H9C2 cell model. Furthermore, co-treatment with inhibitor of AMPK abrogated the protective effects of NGR1. The regulative effects of NGR1 on lipid metabolism were also reversed by AMPK inhibitor.Conclusion: NGR1 could significantly improve the heart function of mice with HF and reduce cardiac lipotoxicity. The cardio-protective effects of NGR1 are mediated by the activation of AMPK pathway.

This study aims to investigate the effects of β-elemene on a mouse model of heart failure (HF) and to elucidate the underlying mechanisms in vitro approaches. In this study, left anterior descending (LAD)-induced HF mouse model and oxygen-glucose deprivation/recovery (OGD/R)-induced H9C2 model were leveraged to assess the therapeutic effects of β-elemene. Histological examination, western blot and quantitative real-time PCR analysis (RT-qPCR) and immunofluorescence staining was utilized to elucidate mechanism of β-elemene in lipid-induced inflammation. Results showed that β-elemene improved heart function in HF mice evidenced by the increase of cardiac ejection fraction (EF) and fractional shortening (FS) values. Furthermore, β-elemene administration rescued ventricular dilation, lipid accumulation, and inflammatory infiltration in arginal areas of mice myocardial infarction. At transcription level, β-elemene augmented the mRNA expression of fatty acid oxidation-associated genes, such as peroxisome proliferator-activated receptor-β (PPARβ). In vitro, treatment of β-elemene increased carnitine palmitoyltransferase 1A (CPT1A) and sirtuin 3 (SIRT3). Hallmarks of inflammation including the nuclear translocation of nuclear factor κB (NF-κB) and the degradation of inhibitory κBα (IκBα) were significantly suppressed. Consistently, we observed down-regulation of interleukin-6 (IL-6) and pro-inflammatory cytokines (such as TNFα) in β-elemene treated H9C2 cells. Finally, molecular docking model predicted an interaction between β-elemene and PPARβ protein. Furthermore, β-elemene increased the expression of PPARβ, which was validated by antagonist of PPARβ and siRNA for PPARβ.

Retinoid X receptors (RXRs) are members of ligand-dependent transcription factors whose effects on a diversity of cellular processes, including cellular proliferation, the immune response, and lipid and glucose metabolism. Knock out of RXRα causes a hypoplasia of the myocardium which is lethal during fetal life. In addition, the heart maintains a well-orchestrated balances in utilizing fatty acids (FAs) and other substrates to meet the high energy requirements. As the master transcriptional regulators of lipid metabolism, RXRs become particularly important for the energy needs of the heart. Accumulating evidence suggested that RXRs may exert direct beneficial effects in the heart both through heterodimerization with other nuclear receptors (NRs) and homodimerization, thus standing as suitable targets for treating in cardiovascular diseases. Although compounds that target RXRs are promising drugs, their use is limited by toxicity. A better understanding of the structural biology of RXRs in cardiovascular disease should enable the rational design of more selective nuclear receptor modulators to overcome these problems. Here, this review summarizes a brief overview of RXRs structure and versatility of RXR action in the control of cardiovascular diseases. And we also discussed the therapeutic potential of RXR ligand.

Ethnopharmacological relevance Panax notoginseng saponins (PNS) were extracted from Panax notoginseng (Burkill) F.H. Chen, a natural product often used as a therapeutic agent in China. PNS has showed obvious therapeutic effect in heart failure (HF) treatment. However, its targets and pharmacological mechanisms remain elusive. Aim of the study This research attempted to determine both the effects and mechanisms of PNS involved in AMI treatment, namely, acute myocardial infarction-induced HF. Materials and methods An AMI-induced HF model was generated by left anterior descending (LAD) ligation in rats. Transcriptome analyses were performed to identify differentially expressed genes (DEGs) and pathway enrichment. Real-time quantitative PCR (RT-qPCR) verified the HF-related genes differentially expressed after PNS treatment. Finally, a model of H9C2 cells subjected to OGD/R, which is equivalent to oxygen-glucose deprivation/reperfusion, was established to identify the potential mechanism of PNS in the treatment of HF. Results PNS ameliorated cardiac function and protected against structural alterations of the myocardium in HF rats. Transcriptome analysis showed that PNS upregulated 1749 genes and downregulated 1069 genes in the heart. Functional enrichment analysis demonstrated that the metabolic process was enriched among the DEGs. KEGG pathway analysis revealed that the PPAR signalling pathway was particularly involved in the protective function of PNS. The effects of PNS on the PPAR pathway were validated in vivo; PNS treatment effectively increased the expression of PPARα, RXRα, and PGC1α in rats with AMI-induced HF. In addition, PNS was shown to regulate the expression of downstream energy metabolism-related proteins. Interestingly, the addition of the PPARα inhibitor GW6471 abolished the beneficial effects of PNS. Conclusions PNS exerts a cardioprotective function in a multicomponent and multitarget manner. The PPAR signalling pathway is one of the key pathways by which PNS protects against HF, and PPARα is a possible target for HF treatment.

Polymer is an excellent electrical insulating material with well corona-resistance, such as polyimide. It has been widely applied in power system insulation, aerospace industry, marine electrical equipment and microelectronics. In this paper, DC surface flashover experiments under different temperature of polyimide are studied in vacuum to reveal the surface flashover mechanism in order to enhance the reliability of polymer in complex engineering environments. It is found that the DC surface flashover voltage firstly decreased then increased and finally decreased again with the increasing of temperature in the range of 193~353K. The flashover voltage reached the maximum at 313K and minimum at 273K, respectively. The experiment also found that flashover voltages are significantly enhanced in high temperature region (313~373 K) compared that in lower temperature region (193~273 K). The experiments indicate that the thermal electron emission near the cathode, the charge transportation of dielectric insulators and thermal activation degassing are three important factors for polymer surface flashover voltage as the temperature increased, and the thermal activation degassing which is the most critical factor affecting the surface flashover characteristics in vacuum.

Danqi pill (DQP) is a widely prescribed traditional Chinese medicine (TCM) in the treatment of cardiovascular diseases. The objective of this study is to systematically characterize altered gene expression pattern induced by myocardial ischemia (MI) in a rat model and to investigate the effects of DQP on global gene expression. Global mRNA expression was measured. Differentially expressed genes among the sham group, model group, and DQP group were analyzed. The gene ontology enrichment analysis and pathway analysis of differentially expressed genes were carried out. We quantified 10,813 genes. Compared with the sham group, expressions of 339 genes were upregulated and 177 genes were downregulated in the model group. The upregulated genes were enriched in extracellular matrix organization, response to wounding, and defense response pathways. Downregulated genes were enriched in fatty acid metabolism, pyruvate metabolism, PPAR signaling pathways, and so forth. This indicated that energy metabolic disorders occurred in rats with MI. In the DQP group, expressions of genes in the altered pathways were regulated back towards normal levels. DQP reversed expression of 313 of the 516 differentially expressed genes in the model group. This study provides insight into the multitarget mechanism of TCM in the treatment of complex diseases.

Combination therapy with multiple chemotherapeutic agents is the main approach for cancer treatment in clinic. Polyphenol-based materials are found in our diet, demonstrate good biocompatibility, and prevent numerous diseases. In this study, we encapsulate two drugs in a single polyphenol-based polymer with Fe(3+) or Mn(2+) ions as the cross-linkers for cancer therapy. The combination index of the two drugs is an essential parameter to evaluate the drug combinations. The amphiphilic polymer, poly(ethylene glycol)-block-polydopamine (PEG-PDA), was prepared by RAFT polymerization. The nanoparticles were prepared via self-assembly with Fe(3+) or Mn(2+) ions. Both doxorubicin (DOX) and simvastatin (SV) were encapsulated in the core of nanoparticles. The cell viability and combination index were evaluated in vitro. The tumor accumulation of nanoparticles was investigated by positron-emission tomography (PET) and magnetic resonance (MR) imaging. The as-prepared nanoparticles exhibited high drugs loading capacity. The drug loaded nanoparticles could kill the cancer cells effectively with a combination index < 1. Both PET and MRI revealed that the nanoparticles showed long blood circulation time and high tumor accumulation. The nanoparticles could inhibit tumor inhibition via intravenous injection of nanoparticles. The polyphenol-based nanoplatform may serve as a promising theranostic candidate for clinical application

Heart failure (HF) leads to an increase in morbidity and mortality globally. Disorders of energy metabolism and apoptosis of cardiomyocytes are critically involved in the progression of HF. Ginsenoside Rb3 (G-Rb3) is a natural product derived from ginseng that has cardio-protective effect. The pharmacological mechanism of G-Rb3 in the treatment of HF remains to be clarified. In this study, we aimed to explore the regulative effects of G-Rb3 on fatty acids oxidation and apoptosis by in vivo and in vitro studies. Myocardial infarction (MI)-induced HF mice model and a cellular H9C2 injury model was induced by oxygen-glucose deprivation/reperfusion (OGD/R) stimulation. The results showed that G-Rb3 could protect heart functions in MI-induced HF model. G-Rb3 treatment up-regulated expressions of key enzymes involved in β-oxidation of fatty acids, including carnitine palmitoyltransterase-1α (CPT-1α), acyl-CoA dehydrogenase long chain (ACADL) and the major mitochondrial deacetylase enzyme sirtuin 3 (SIRT3). The upstream transcriptional regulator, peroxisome proliferator-activated receptor α (PPARα), was also up-regulated by G-Rb3 treatment. In vitro study demonstrated that G-Rb3 could protect mitochondrial membrane integrity and exert anti-apoptotic effects, in addition to regulating fatty acids oxidation. Impressively, after cells were co-treated with PPARα inhibitor, the regulative effects of G-Rb3 on energy metabolism and apoptosis were abrogated. Our study suggests that G-Rb3 is a promising agent and PPARα is potential target in the management of HF.

Ethnopharmacological relevance Previous studies have approved that Baoyuan decoction (BYD) exerted remarkable cardioprotective effects on heart failure (HF) due to its anti-apoptotic properties. As a novel biomarker and target of HF, Cardiac ankyrin repeat protein (CARP) can exacerbate apoptosis via activation by angiotensin type 1 receptor (AT1) and subsequently deteriorate heart function. Transcriptome results in our previous study indicated BYD was beneficial to HF post-acute myocardial infarction (AMI) with a promising effect on CARP. However, the mechanism remains to be validated. Aim of the study This study aims to elucidate whether BYD ameliorates apoptosis to protect against HF via AT1-CARP signaling pathway. Materials and methods Left anterior descending ligation was applied to induce an HF rat model, Ang Ⅱ-stimulated H9C2 cells apoptotic model and overexpression of Ankrd1/CARP H9C2 cells were established to clarify the effects and potential mechanism of BYD. Ethanol extracts of BYD (0.64; 1.28; 2.57 g/kg) were orally administered for four weeks and Fosinopril (4.67 mg/kg) was selected as a positive group in vivo. In vitro, BYD (400, 600, 800 μg/ml) or RNH6270 (an inhibitor of AT1, 1 μM) was co-cultured with Ang Ⅱ stimulation for 48 h in H9C2 cells. Overexpression of Ankrd1/CARP was conducted by transient transfection with H9C2 cells to further confirm the exact mechanism. Finally, to define the active ingredients of anti-cardiomyocyte apoptosis in BYD, we furtherly used the Ang Ⅱ-induced cardiomyocyte apoptosis model to evaluate the effects. Results Echocardiography and TUNEL results showed that BYD in different doses remarkably improved heart function and inhibited apoptosis in vivo. Further study demonstrated that AT1 and CARP expressions in cardiac tissue were suppressed by BYD, accompanied with upregulation of B cell lymphoma-2 (Bcl-2) and downregulation of several pro-apoptotic molecules, including p53, Bcl-2 Associated X Protein (Bax) and Cleaved caspase 3. In parallel with the vivo experiment, in vitro research indicated BYD dramatically reduced the apoptotic cells and regulated expressions of critical apoptosis-related molecules mediated through downregulation of AT1 and CARP simultaneously which were consistent with the results in vivo experiment. Transiently transfected CARP over-expression further confirmed that BYD could suppress severe cardiomyocytes apoptosis induced by overexpression of CARP. Especially, the active ingredients of BYD including Astragaloside IV, Ginsenoside Rg3, Rb1, Rc and Re showed significantly anti-apoptosis effects. Conclusion BYD improves cardiac function and protects against cardiomyocytes injury by inhibiting apoptosis via regulating the AT1-CARP signaling pathway.

Ethnopharmacological relevance Danqi Pill (DQP), commonly known as a routinely prescribed traditional Chinese medicine (TCM), is composed of Salviae Miltiorrhizae Radix et Rhizoma and Notoginseng Radix et Rhizoma and effective in treating heart failure (HF) clinically due to their multicompound and multitarget properties. However, the exact active compounds and corresponding targets of DQP are still unknown. Aim of the study This study aimed to investigate active compounds and drug targets of DQP in heart failure based on the PPARs-RXRα pathway. Materials and methods Network pharmacology was used to predict the compound-target interactions of DQP. Left anterior descending (LAD)-induced HF mouse model and oxygen-glucose deprivation/recovery (OGD/R)-induced H9C2 model were constructed to screen the active compounds of DQP. Results According to BATMAN-TCM (a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine we previously developed), 24 compounds in DQP were significantly enriched in the peroxisome proliferator activated receptors-retinoid X receptor α (PPARs-RXRα) pathway. Among them, Ginsenoside Rb3 (G-Rb3) had the best pharmacodynamics against OGD/R-induced loss of cell viability, and it was selected to verify the compound-target interaction. In HF mice, G-Rb3 protected cardiac functions and activated the PPARs-RXRα pathway. In vitro, G-Rb3 protected against OGD/R-induced reactive oxygen species (ROS) production, promoted the expressions of RXRα and sirtuin 3 (SIRT3), thereafter improved the intracellular adenosine triphosphate (ATP) level. Immunofluorescent staining demonstrated that G-Rb3 could activate RXRα, and facilitate RXRα shifting to the nucleus. HX531, the specific inhibitor of RXRα, could abolish the protective effects of G-Rb3 on RXRα translocation. Consistently, the effect was also confirmed on RXRα siRNA cardiomyocytes model. Moreover, surface plasmon resonance (SPR) assays identified that G-Rb3 bound directly to RXRα with the affinity of KD = 10 × 10−5 M. Conclusion By integrating network pharmacology and experimental validation, we identified that as the major active compound of DQP, G-Rb3 could ameliorate ROS-induced energetic metabolism dysfunction, maintain mitochondrial function and facilitate energy metabolism via directly targeting on RXRα. This study provides a promising strategy to dissect the effective patterns for TCM and finally promote the modernization of TCM.

Heart failure (HF) leads to an increase in morbidity and mortality globally. Tanshinone IIA is an important traditional Chinese medicine monomer and has been shown to have remarkable protective effect against HF. Autophagy is critically involved in the progression of HF. The effect of Tanshinone IIA on autophagy has not been clarified yet. In this study, left anterior descending (LAD) ligation was used to induce HF model and a hydrogen peroxide-(H2O2-)-induced H9C2 cell injury model was established. in vivo, echocardiography results showed that Tanshinone IIA could significantly improve heart function. Western Blot result showed that Tanshinone IIA treatment enhanced autophagy and regulated expressions of key autophagy-related molecules, including protein 1 light chain 3 (LC3), p62 and Beclin1. Tanshinone IIA also inhibited apoptosis and regulated expressions of key apoptotic protein, including B cell lymphoma-2 (Bcl-2) and Bcl-2 Associated X Protein (Bax) and cleaved caspase-3 and -7. Further experiments demonstrated that the effects of Tanshinone IIA were mediated through upregulation of AMP-activated protein kinase (AMPK) and downregulation of mammalian target of rapamycin (mTOR) simultaneously. The mTOR agonist MHY1485 could abrogate the therapeutic effect of Tanshinone IIA in vitro. In conclusion, Tanshinone IIA protects cardiomyocytes and improves cardiac function by inhibiting apoptosis and inducing autophagy via activation of the AMPK-mTOR signaling pathway.

Coronary heart disease (CHD) is the leading cause of mortality in the world and atherosclerosis is the main cause of CHD. Traditional Chinese medicines have been applied in the treatment of CHD for centuries. In the recent years, clinical trials have been carried out to evaluate the efficacies of Chinese medicine. Meanwhile, extensive studies have also been carried out to explore the underlying pharmacological mechanisms of Chinese medicine. In this review, we will summarize the commonly prescribed Chinese medicine and patent Chinese drugs in treating patients with atherosclerotic CHD and review published clinical trials of Chinese medicine in treating CHD. The anti-atherosclerosis mechanism of Chinese medicine will also be reviewed. Finally, challenges and opportunities facing application of Chinese medicine in the treatment of CHD will be presented.

Tanshinone IIA is a monomer in traditional Chinese medicine Salvia miltiorrhiza, and has a cardioprotective effect on heart failure after myocardial infarction. The purpose of this study is that tanshinone IA could improve cardiac function through the Adenosine 5‘-monophosphate (AMP)-activated

In order to increase cotton plant resistance to Verticillium dahliae (V. dahliae), an alfalfa antifungal peptide gene (alfAFP), directed by CaMV35S promoter in recombinant binary vector pCAMBIA1301-alf, was delivered into an upland cotton cultivar 5983 (Gossypium hirsutum L.) via an Agrobacterium-mediated hypocotyl system. Molecular analysis confirmed the integration and transcripts of the alfAFP gene in the genome of 12 transformants. In vitro assays showed that crude leaf extracts from transformants was able to significantly (p

In order to study the effect of phytohormones on cotton fiber initiation, contents of four endogenous phytohormones and activities of four related enzymes in ovules (in vivo) of a fuzzless–lintless mutant (fl) and its wild-type (FL) line were measured from 4 days before anthesis (day −4) to 4 days after anthesis (day 4). The results showed that contents of indole-3-acetic acid, gibberellic acid (GA), and zeatin riboside in fl ovules were lower than those in FL ovules. Therefore, indole-3-acetic acid, GA, and zeatin riboside were thought to be the promoters of fiber initiation. Although abscisic acid (ABA) content in fl ovule was slightly higher than that in FL ovule on day 0, which might imply that ABA inhibited fiber initiation. Fiber initiation could also be influenced by enzyme through regulating synthesis and degradation of related phytohormones since fl ovules were significantly higher in activities of indole-3-acetic acid oxidase, cytokinin oxidase and peroxidase, but lower in activity of tryptophan synthetase than those in FL ovules. To test the above hypothesis, exogenous plant growth regulators were also applied for the culture of ovules from fl and FL in vitro. When no regulators were added, no fiber was induced on fl ovule, but a few fibers were induced in FL ovule. Higher total fiber units (TFU) were observed when indole-3-acetic acid and gibberellic acid (GA3) were applied either separately or in combination to media. TFU did not increased with zeatin riboside alone, but the highest TFU was achieved when zeatin riboside was applied together with indole-3 acetic acid and GA3, which implied that fiber initiation could be promoted by them as additive.

Naturally colored cotton (Gossypium hirsutum L.) fibers (CCFs) are of interest in the textile industry because they require little dyeing and result in less environmental pollution. Pigmentation is one of the most important factors that differentiate CCFs from white cotton fiber (WCF) during fiber maturation. Many factors are involved in pigmentation, some of which we compared between CCFs and WCF with isogenetic backgrounds. These included the type of pigment, the activity of phenylalanine ammonia lyase (PAL), the concentration of total carbohydrates, and the type of soluble saccharide. We aimed to determine the causes of different fiber colors and found that flavonoids were the dominant type of pigment in the CCFs. At maturity (50 d post anthesis [DPA]), the WCF had only about 1/3 the amount of flavonoids as the brown cotton fiber (BCF) and 1/10 that of the green cotton fiber (GCF). During the course of fiber maturation (in particular, the stage before 8 DPA), CCFs had much higher PAL activity than the WCF. Of the fibers, the GCF had the highest concentration of carbohydrates over the course of maturation. However, higher concentrations of total carbohydrates did not always lead to higher concentrations of cellulose. This was very likely due to the synthesis of flavonoids and their derivatives consuming a large amount of carbohydrates that otherwise might be used for the synthesis of cellulose.

Danqi pill (DQP) has been demonstrated to improve cardiac function potentially by regulating cardiac glucose metabolism in the acute myocardial infarction(AMI) rats. However, the mechanisms governing its therapeutic effects remain unclear. The objective of this study is to elucidate that the effect

The voltage and frequency (V/F) of microgrid loss support when the operation of microgrid switches from grid-connected mode to islanded mode, therefore controlling of voltage and frequency is needed. A control strategy of voltage and frequency based on battery is proposed in this paper which purposed on regulating an islanded microgrid containing kinds of distributed generators (DG). According to the problem of traditional droop control of V/F that does not take into account of load structural changes, the control of battery introduces the voltage and current feedforward based on traditional V/F control strategy. Considering the variation of structure and parameter of the load is more suitable for practical power system. At the same time, aiming at the irreasonability caused by the equivalent source of photovoltaic (PV) system, this paper constructs the detailed system of PV. The validity of proposed control strategy is demonstrated through simulating the various states of searched microgrid.

θ-Defensins are the only natural cyclic proteins found in primates. They have strong antimicrobial activity related to their trisulfide ladders and macrocyclic conformation. A non-cyclic baboon θ-defensin (BTD) was synthesized by substituting valine with phenylalanine at position 17, at the C-terminal end of the BTD; this was termed “BTD-S.” The antimicrobial activities of this synthetic peptide were investigated against Escherichia coli and two cotton phytopathogens: Verticillium dahliae and Fusarium oxysporum. The minimum inhibitory concentration (MIC) of BTD-S for E. coli was 10 μg/mL and for V. dahliae was 5 μg/mL, significantly lower than that for F. oxysporum (40.0 μg/mL). A time course analysis of fungal cultures indicated that the growth of V. dahliae was completely inhibited after 96 h of BTD-S treatment. Furthermore, hemolysis assays revealed that BTD-S was not toxic to mammalian cells as it could not induce lysis of sheep red blood cells even at ten times the MIC (50 μg/mL). Scanning electron microscopy and double-stained (calcofluor white and propidium iodide binding) fluorescence microscopy showed that exposure of spores of V. dahliae to BTD-S either disabled normal germination or disintegrated the spores. The size of cells exposed to BTD-S was significantly reduced compared with controls, and their number increased in a dose-dependent curve when measured by flow cytometry. These findings suggest that BTD-S has great potential to inhibit the growth of V. dahliae and can be utilized as an effective remedy to control economic losses caused by Verticillium wilt in the development of wilt-resistant cotton.

Graphics recognition for raster-based input discovers primitives such as lines, arrowheads, and circles. This paper focuses on graphics recognition of figures in vector-based PDF documents. The first stage consists of extracting the graphic and text primitives corresponding to figures. An interpreter was constructed to translate PDF content into a set of self-contained graphics and text objects (in Java), freed from the intricacies of the PDF file. The second stage consists of discovering simple graphics entities which we call graphemes, e.g., a pair of primitive graphic objects satisfying certain geometric constraints. The third stage uses machine learning to classify figures using grapheme statistics as attributes. A boosting-based learner (LogitBoost in the Weka toolkit) was able to achieve 100% classification accuracy in hold-out-one training/testing using 16 grapheme types extracted from 36 figures from BioMed Central journal research papers. The approach can readily be adapted to raster graphics recognition.

Diagrams are a critical part of virtually all scientificand technical documents. Analyzing diagrams will beimportant for building comprehensive document retrievalsystems. This paper focuses on the extraction andclassification of diagrams from PDF documents. Westudy diagrams available in vector (not raster) format inonline research papers.PDF files are parsed and their vector graphicscomponents installed in a spatial index. Subdiagrams arefound by analyzing white space gaps. A set of statistics isgenerated for each diagram, e.g., the number ofhorizontal lines and vertical lines. The statistics form afeature vector description of the diagram. The vectorsare used in a kernel-based machine learning system(Support Vector Machine). Separating a set of bargraphs from non-bar-graphs gathered from 20,000biology research papers gave a classification accuracy of91.7%. The approach is directly applicable to diagramsvectorized from images.