[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.

[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.

[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.

[Role of macrophages in heart failure and traditional Chinese medicine intervention].

As the disease with high morbidity and mortality in the world, heart failure affects the development of human society. Due to its complicated pathology and limited treatment options, it is urgent to discover new disease targets and develop new treatment strategies. As innate immune cells accompanied by the evolution of heart failure, macrophages play an important role in cardiac homeostasis and stress. In recent years, the role of macrophages in the heart has attracted more and more attention as a potential target for heart failure intervention, and the research on cardiac macrophages has made important progress. Traditional Chinese medicine(TCM) has significant effects on regulating inflammatory response, treating heart failure, and maintaining homeostasis. In this article, researches on the functions of cardiac macrophages and application of TCM were reviewed from the source and classification of cardiac macrophages and the relationship of macrophages and cardiac inflammation, myocardial fibrosis, cardiac angiogenesis, and cardiac electrical conduction, which provided a basis for further basic research and clinical applications.

[Common anti-inflammatory effects of heat-clearing and toxin-removing Chinese medicines on diverse cardiovascular diseases].

Cardiovascular diseases seriously affect human health and their prevalence continues to increase with the aging of the population. The integrated therapy of traditional Chinese medicine(TCM) and western medicine for cardiovascular diseases has achieved certain results, but it is still faced with new challenges. Studies have shown that inflammation plays an important role in the development of cardiovascular diseases and some of these mechanisms have common features. For example, in cardiovascular diseases, C-C motif chemokine receptor 2(CCR2)-expressing macrophages increase and promote inflammation, and excessive activation of NOD-like receptor protein 3(NLRP3) inflammasome leads to the elevation of inflammatory factors. There is also new understanding of the pathogenesis and treatment of cardiovascular diseases in TCM. The heat-toxicity theory in cardiovascular diseases and the therapeutic principle of clearing heat and removing toxin have attracted attention. The clinical and pharmacological studies on the treatment of cardiovascular diseases such as Huanglian Jiedu Decoction and Simiao Yong'an Decoction are also gradually increasing. The present study analyzed the common features of the inflammatory response mechanisms in diverse cardiovascular diseases and discussed the significance of the prevention and treatment of diverse cardiovascular diseases by the treatment method of clearing heat and removing toxin to regulate inflammation, which is expected to provide new ideas and references for clinical treatment and drug research on cardiovascular diseases with the same treatment method for different diseases.

[Detoxification of cardiotoxic traditional Chinese medicine and traditional Chinese medicine for prevention of cardiotoxicity: a review].

Cardiotoxicity is smong the main safety problems of drugs in clinical application. In recent years, traditional Chinese medicine has been gradually emphasized and studies on the evaluation of cardiac safety and prevention of cardiotoxicity of Chinese medicine have been on the rise, particularly the cardiotoxic Chinese medicine or the Chinese medicine components targeting cardiotoxicity. As for the research methods for cardiac safety evaluation of Chinese medicine, this review introduces the related clinical indexes and cell and animal models. As to the improvement of heart safety, this study reviews the material basis and mechanism of cardiotoxic Chinese medicines as well as the alleviation of cardiotoxicity by controlling the content of toxic compounds and changing dosage form, processing method, and compatibility of Chinese medicine. In addition, the effective components and mechanisms of prescriptions and active compounds in Chinese medicine for preventing and treating cardiotoxicity induced by chemotherapeutic drugs in recent years were summarized. This review is expected to serve as a reference for cardiac safety evaluation and clinical rational application of Chinese medicine.

[Construction of "2R network pharmacology" research method for effective components of traditional Chinese medicine based on "prediction of dominant components-screening of potential targets"].

Chinese traditional medicine compound is the main form of Chinese medicine clinical application. The elucidation of the effective components of traditional Chinese medicine is one of the key scientific issues to promote the modernization of traditional Chinese medicine. At present, there are many research ideas on the effective components of traditional Chinese medicine compounds. By analyzing the current status and existing problems of existing research ideas, the author proposes a "double reduction network pharmacology"(2 R network pharmacology) research method based on "prediction of dominant components-potential target selection". Chemical components with good properties were selected by ADMET property prediction technology, and compared with the blood components and target organ components to determine the dominant components with potential therapeutic effect, that is "reducing constituents"; the potential core regulatory pathway of traditional Chinese medicine compound was enriched by RNA-Seq technology combined with network database, and then the target of traditional Chinese medicine compound was mined based on the signal pathway, that is "reducing targets". To improve the efficiency and accuracy of effective component screening, the network relationship of "component target" was established by the related technology of network pharmacology. The purpose of this study is to provide practical research ideas and methods for clarifying the effective components of traditional Chinese medicine, revealing the law of compatibility of traditional Chinese medicine and clarifying the target of drug action.

Deciphering the effective combinatorial components from Si-Miao-Yong-An decoction regarding the intervention on myocardial hypertrophy.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Miao-Yong-An decoction (SMYAD), a classical traditional Chinese medicine (TCM) formula, has been used to treat various cardiovascular diseases in clinics. AIM OF THE STUDY: The aim of this study is to investigate the effective combinatorial components from SMYAD and its mechanism regarding the intervention on myocardial hypertrophy. MATERIALS AND METHODS: SMYAD constituents absorbed in rat plasma and heart were identified using UHPLC Q-Exactive-Orbitrap MS/MS. The identified constituents in SMYAD were further analyzed using ADMET (absorption, distribution, metabolism, excretion and toxicity) prediction and molecular docking. The effective constituents were identified using isoproterenol (ISO)-induced H9c2 cardiomyocyte hypertrophy, and neochlorogenic acid (NCA), chlorogenic acid (CA), cryptochlorogenic acid (CCA), isochlorogenic acid C (ICAC), angoroside C (AGDC), isochlorogenic acid A (ICAA), sweroside (SRD), and harpagide (HPD) in SMYAD extract were quantified by HPLC for compatibility. Finally, anti-hypertrophic activities of candidate effective combinatorial components, which were prepared according to the determined molar concentration ratio of effective constituents using reference substance solution, were analyzed using immunofluorescence staining and Quantitative real-time PCR. The expression levels of PI3Kα, p-ERK, p-Akt, Akt, p-mTOR, mTOR and HIF-1α were measured using Western blot. RESULTS: 32 prototypes of SMYAD were identified from plasma and heart tissue of rat. Combining with ADMET prediction, 31 dominant constituents were focused. Based on HIF-1 pathway identified in preliminary result, 17 targets were focused, which were used to dock with 31 constituents. 27 constituents were therefore hit as the potential effective constituents of SMYAD in inhibiting myocardial hypertrophy. Bioactivity evaluation showed that NCA, CA, CCA, ICAC, AGDC, ICAA, SRD, and HPD significantly inhibited the increase of H9c2 cell surface area induced by ISO. Except for ICAA and AGDC, the remaining 6 effective constituents, showing a certain inhibitory effect on ISO-induced ANP mRNA overexpression at high and low concentrations, participated in compatibility based on the molar concentration ratio determined by HPLC. Effective combinatorial components composed of the 6 effective constituents (effective combinatorial components ABC) showed significant inhibitory effect on the increase of cell surface area, and the overexpression of ANP and ß-MHC mRNA in H9c2 cells induced by ISO. Moreover, effective combinatorial components ABC significantly inhibited the protein overexpressions of p-Akt, p-mTOR and HIF-1α. Based on the results, we put forward the strategy of "Focusing constituents" and "Focusing targets" for the effective constituents research of TCM formula. CONCLUSION: Effective combinatorial components ABC composed of NCA, CA, CCA, ICAC, SRD and HPD from SMYAD inhibited ISO-induced cardiomyocyte hypertrophy and down-regulated expression of ANP and ß-MHC mRNA through the inactivation of Akt/mTOR/HIF-1α pathway.

iTRAQ-based quantitative proteomic analysis provides insight for molecular mechanism of neuroticism.

BACKGROUND: Neuroticism is a core personality trait and a major risk factor for several mental and physical diseases, particularly in females, who score higher on neuroticism than men, on average. However, a better understanding of the expression profiles of proteins in the circulating blood of different neurotic female populations may help elucidate the intrinsic mechanism of neurotic personality and aid prevention strategies on mental and physical diseases associated with neuroticism. METHODS: In our study, female subjects were screened for inclusion by the Eysenck Personality Questionnaire (EPQ), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) scales and routine physical examination. Subjects who passed the examination and volunteered to participate were grouped by neuroticism using EPQ scores (0 and 1 = low neuroticism group; > 5 = high neuroticism group). Proteins in serum samples of the two neuroticism groups were identified using isobaric tags for relative and absolute quantification (iTRAQ) technology. RESULTS: A total of 410 proteins exhibited significant differences between high and low neuroticism, 236 proteins were significantly upregulated and 174 proteins were significantly downregulated. Combine the results of GO and KEGG enrichment analysis of differences proteins between high and low neuroticism with the PPI network, it could be observed that the Alpha-synuclein (SNCA), ATP7A protein (ATP7A), Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (GNG2), cyclin-dependent kinase 6 (CDK6), myeloperoxidase (MPO), azurocidin (AZU1), Histone H2B type 1-H (HIST1H2BH), Integrin alpha-M (ITGAM) and Matrix metalloproteinase-9 (MMP9) might participate in the intrinsic mechanism of neuroticism by regulating response to catecholamine stimulus, catecholamine metabolic process, limbic system development and transcriptional misregulation in cancer pathway. CONCLUSIONS: Our study revealed the characteristics of the neurotic personality proteome, which might be intrinsic mechanism of the neurotic population.

Chlorogenic acid: A potent molecule that protects cardiomyocytes from TNF-α-induced injury via inhibiting NF-κB and JNK signals.

The traditional Chinese herb Lonicerae Japonicae Flos has shown significant clinical benefits in the treatment of heart failure, but the mechanism remains unclear. As the main active ingredient found in the plasma after oral administration of Lonicerae Japonicae Flos, chlorogenic acid (CGA) has been reported to possess anti-inflammatory, anti-oxidant and anti-apoptosis function. We firstly confirmed the cardioprotective effects of CGA in transverse aortic constriction (TAC)-induced heart failure mouse model, through mitigating the TNF-α-induced toxicity. We further used TNF-α-induced cardiac injury in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to elucidate the underlying mechanisms. CGA pre-treatment could reverse TNF-α-induced cellular injuries, including improved cell viability, increased mitochondrial membrane potential and inhibited cardiomyocytes apoptosis. We then examined the NF-κB/p65 and major mitogen-activated protein kinases (MAPKs) signalling pathways involved in TNF-α-induced apoptosis of hiPSC-CMs. Importantly, CGA can directly inhibit NF-κB signal by suppressing the phosphorylation of NF-κB/p65. As for the MAPKs, CGA suppressed the activity of only c-Jun N-terminal kinase (JNK), but enhanced extracellular signal-regulated kinase1/2 (ERK1/2) and had no effect on p38. In summary, our study revealed that CGA has profound cardioprotective effects through inhibiting the activation of NF-κB and JNK pathway, providing a novel therapeutic alternative for prevention and treatment of heart failure.

[Anti-inflammatory mechanism of heat-clearing and detoxifying Chinese herbs].

Heat-clearing and detoxifying Chinese herbs (HDCHs) are mainly used to treat carbuncle, sore throat, erysipelas, gills, dysentery and other diseases induced by heat-toxicity. Inflammation is a defensive response to damaging factors in living organism with vascular system. In recent years, a large amount of experimental and clinical studies showed that HDCHs had good therapeutic effect on inflammation. This review analyzed the anti-inflammatory mechanism of 11 HDCHs by retrieving literature in past 5 years, including Lonicerae Japonicae Flos (Jinyinhua), Lonicerae Flos (Jinyinhua), Lonicerae Japonicae Caulis (Rendongteng), Forsythiae Fructus (Lianqiao), Rhizoma Coptidis（Huanglian）, Gardeniae Fructus (Zhizi), Andrographis Herba (Chuanxinlian), Taraxaci Herba (Pugongying), Scrophulariae Radix (Xuanshen), Pulsatillae Radix (Baitouweng), and Agrimoniae Herba (Xianhecao). The data showed that the regulatory effect of HDCHs on inflammation may be involved mainly in the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK) or janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, with similarity of action links among these three. Based upon the analysis of literature, we proposed some promising directions in this research field, providing a reliable theoretical basis for both experimental researches and clinical practices of HDCHs.

[Overview of research projects funding in traditional Chinese medicine oncology field supported by National Natural Science Foundation of China].

In this paper, the funding situation of traditional Chinese medicine oncology research projects supported by National Natural Science Fund from 1986-2016 was reviewed. The characteristics of funded projects were summarized from funding amount, funding expenses, funding category, and the main research contents of projects, etc. At the same time, the main problems in the projects were analyzed in this paper, in order to provide reference for the relevant fund applicants.

The protective effect of the active components of ERPC on diabetic peripheral neuropathy in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Euonymus alatus, Radix trichosanthis, Panax notoginseng and Coptis chinensis are popular plants used in traditional Chinese medicine to treat diabetes. AIM OF THE STUDY: The aim of the study is to investigate the therapeutic effect of the active components of Euonymus alatus, Radix trichosanthis, Panax notoginseng and Coptis chinensis (cERPC) on diabetic peripheral neuropathy in the rats and explore the underlying mechanism involved. METHODS: After diabetes was induced in rats for 20 weeks, cERPC or water was administered for 12 weeks. After a hot plate test, motor nerve conduction velocity and sciatic nerve blood flow were determined; the sciatic nerves were isolated for toluidine blue staining; and the fibre area, fibre diameter, axon area, axon diameter and myelin thickness were evaluated. The levels of the myelin basic protein, myelin protein zero, Oct6 and Krox20 were measured by western blot or immunofluorescence. RESULTS: cERPC was efficient in reducing the response latency, increasing motor nerve conduction velocity, enhancing sciatic nerve blood flow and ameliorating the pathological changes in diabetic rats. cERPC also had a role in increasing the levels of myelin basic protein and myelin protein zero and improving the expression of Oct6 and Krox20 in sciatic nerves of diabetic rats. CONCLUSIONS: cERPC ameliorates diabetic peripheral neuropathy by attenuating electrophysiological, circulatory and morphological alterations, which is mediated by the Oct6-Krox20 pathway.

Metabolomic profiling reveals distinct patterns of tricarboxylic acid disorders in blood stasis syndrome associated with coronary heart disease.

OBJECTIVE: To investigate the underlying metabolomic profifiling of coronary heart disease (CHD) with blood stasis syndrome (BSS). METHODS: CHD model was induced by a nameroid constrictor in Chinese miniature swine. Fifteen miniature swine were randomly divided into a model group (n=9) and a control group (n=6), respectively according to arandom number table. After 4 weeks, plasma hemorheology was detected by automatic hemorheological analyzer, indices including hematocrit, plasma viscosity, blood viscosity, rigidity index and erythrocyte sedimentation rate; cardiac function was assessed by echocardiograph to detect left ventricular end-systolic diameter (LVED), left ventricular end-diastolic diameter (LVEDd), ejection fraction (EF), fractional shortening (FS) and other indicators. Gas chromatography coupled with mass spectrometry (GC-MS) and bioinformatics were applied to analyze spectra of CHD plasma with BSS. RESULTS: The results of hemorheology analysis showed signifificant changes in viscosity, with low shear whole blood viscosity being lower and plasma viscosity higher in the model group compared with the control group. Moreover, whole blood reduction viscosity at high shear rate and whole blood reduction viscosity at low shear rate increased signifificantly (P <0.05). The echocardiograph results demonstrated that cardiac EF and FS showed signifificant difference (P <0.05), with EF values being decreased to 50% or less. The GC-MS data showed that principal component analysis can clearly separate the animals with BSS from those in the control group. The enriched Kyoto Encyclopedia of Genes and Genomes biological pathways results suggested that the patterns involved were associated with dysfunction of energy metabolism including glucose and lipid disorders, especially in glycolysis/gluconeogenesis, galactose metabolism and adenosine-triphosphate-binding cassette transporters. CONCLUSIONS: Glucose metabolism and lipid metabolism disorders were the major contributors to the syndrome classifification of CHD with BSS.

[Analysis of projects funded by NSFC in field of Chinese material medica resource in recent three years].

The paper reviewed the sponsorship and final reports of projects focus on Science of Chinese materia medica resource in Medical Science Department, National Natural Science Foundation of China. The applicant and supportive organizations were analyzed. The progress and results of some projects were summarized by research fields including formation mechanism of Dao-di herbs, research of plant taxonomy, breeding and cultivation of medical plants, ecological and environmental adaptability of Chinese materia medica resource, quality assessment of Chinese materia medica resource, and biosynthesis and regulation of active compounds. In addition, the potential problems and the most and least focused areas in the application were summarized for reference.

Targeting the neurovascular unit in brain trauma.

Although the neurovascular unit was originally developed as a conceptual framework for stroke, it is now recognized that these cell-cell interactions play critical roles in many other CNS disorders as well. In brain trauma, perturbations within the neurovascular unit may be especially important. Changes in neurovascular coupling may disrupt blood flow and metabolic regulation. Disruption of transmitter release-reuptake kinetics in neurons and astrocytes may augment excitotoxicity. Alterations in gliovascular signaling may underlie blood-brain barrier disruptions and traumatic edema. Perturbations in cell-cell signaling between all neuronal, glial, and vascular compartments may increase susceptibility to cell death. Finally, repairing the brain after trauma requires the integrated restoration of all neural, glial, and vascular connectivity for effective functional recovery. Just as in stroke, saving neurons alone may also be insufficient for treating brain trauma. In this minireview, we attempt to briefly highlight some of these pathways to underscore the importance of rescuing the entire neurovascular unit in brain trauma.

Role of SIRT1 in Streptococcus pneumoniae-induced human ß-defensin-2 and interleukin-8 expression in A549 cell.

Streptococcus pneumoniae is an important pathogen of pneumonia in human. Human alveolar epithelium acts as an effective barrier and is an active participant in host defense against invasion of bacterial by production of various mediators. Sirtuin 1 (SIRT1), the prototypic class III histone deacetylase, is involved in the molecular control of lifespans and immune responses. This study aimed at examining the role of SIRT1 in mediating S. pneumoniae-induced human ß-defensin-2 (hBD2) and interleukin-8(IL-8) expression in the alveolar epithelial cell line A549 and the underlying mechanisms involved. A549 cells were infected with S. pneumoniae for indicated times. Exposure of A549 cells to S. pneumoniae increased the expressions of SIRT1 protein, hBD2 and IL-8 mRNA, and protein. The SIRT1 activator resveratrol enhanced S. pneumoniae-induced gene expression of hBD2 but decreased IL-8 mRNA levels. Blockade of SIRT1 activity by the SIRT1 inhibitors nicotinamide reduced S. pneumoniae-induced hBD2 mRNA expression but increased its stimulatory effects on IL-8 mRNA. S. pneumoniae-induced activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). SIRT1 expression was attenuated by selective inhibitors of ERK and p38 MAPK. The hBD2 mRNA production was decreased by pretreatment with p38 MAPK inhibitor but not with ERK inhibitor, whereas the IL-8 mRNA expression was controlled by phosphorylation of ERK. These results suggest that SIRT1 mediates the induction of hBD2 and IL-8 gene expression levels in A549 cell by S. pneumoniae. SIRT1 may play a key role in host immune and defense response in A549.

An update on antitumor activity of naturally occurring chalcones.

Chalcones, which have characteristic 1,3-diaryl-2-propen-1-one skeleton, are mainly produced in roots, rhizomes, heartwood, leaves, and seeds of genera Angelica, Sophora, Glycyrrhiza, Humulus, Scutellaria, Parartocarpus, Ficus, Dorstenia, Morus, Artocarpus, and so forth. They have become of interest in the research and development of natural antitumor agents over the past decades due to their broad range of mechanisms including anti-initiation, induction of apoptosis, antiproliferation, antimetastasis, antiangiogenesis, and so forth. This review summarizes the studies on the antitumor activity of naturally occurring chalcones and their underlying mechanisms in detail during the past decades.

Energy metabolism disorder and myocardial injury in chronic myocardial ischemia with Qi deficiency and blood stasis syndrome based on 2-DE proteomics.

OBJECTIVE: To inquire the characteristic proteins in chronic myocardial ischemia by testing twodimensional electrophoresis (2-DE) map to explore the possible inherent pathological mechanism and the therapeutic intervention of qi deficiency and blood stasis syndrome. METHODS: Ameroid constrictor ring was placed on the first interval of left anterior descending coronary artery to prepare chronic myocardial ischemia model on Chinese miniature swine. Animals were randomly divided into sham group and model group with 10 animals in each group, respectively. The dynamic symptoms observation of the four diagnostic information was collected from 0 to 12 weeks. Echocardiography was employed to evaluate cardiac function and the degree of myocardial ischemia, 2-DE and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) were used to carry out proteomics research on animals. Enzyme-linked immunosorbent assay was applied to identify the relevant differential proteins on chronic myocardial ischemia with qi deficiency and blood stasis syndrome. RESULTS: The preliminary study found that at the 12th week, chronic myocardial ischemia with qi deficiency and blood stasis syndrome model was established stably. Compared with the sham group, there were 8 different proteins down-regulated, 22 proteins up-regulated significantly. After validated by MALDITOF-MS/MS, 11 protein spots were identified. Distinct proteins were mainly associated with energy metabolism and myocardial structural injury, including isocitrate dehydrogenase 3 (NAD+) alpha, NADH dehydrogenase (NAD) Fe-S protein 1, chain A (crystal structure of aldose reductase by binding domain reveals a new Nadph), heat shock protein 27 (HSP27), oxidoreductase (NAD-binding protein), antioxidant protein isoform, cardiac troponin T (cTnT), myosin (myosin light polypeptide), cardiac alpha tropomyosin, apolipoprotein A-I and albumin. CONCLUSION: Down-regulated energy metabolism disorder mediated by NADH respiratory chain and myocardial injury may be the pathogenesis of myocardial ischemia with qi deficiency and blood stasis syndrome. These proteins may be the potential diagnostic marker(s) for qi deficiency and blood stasis syndrome, finally provided new clues for new therapeutic drug target of Chinese medicine.

Clinical characteristics of hand, foot and mouth disease in Harbin and the prediction of severe cases.

BACKGROUND: Hand, foot and mouth disease (HFMD) is an emerging public health problem in China, not only threatening the health of children, but also causing tremendous loss and burden to both families and society. The aim of this study was to characterize the epidemiology and clinical features of HFMD, and to understand the key factors affecting HFMD in the Harbin region to provide scientific evidence for effective prevention and control strategies. METHODS: Epidemiological and clinical information from 2379 randomly chosen cases of HFMD treated at the Harbin Center for Disease Control and Prevention from May 2008 to November 2011 were analyzed. All cases were separated into common and severe HFMD, with key factors for severe HFMD analyzed using multivariable Logistic regression. RESULTS: Among the 2379 patients, 1798 were common cases and 581 severe cases, 14 of which resulted in death. Most cases were in children younger than 5 years. Morbidity peaked in July and was higher in the surrounding country and cities than in Harbin proper. Medical expenses were significantly higher for severe than for common cases (P < 0.001). The primary clinical symptoms were fever and erythema; laboratory examination showed leucocytosis together with pneumonia, carditis, and abnormal electrocardiogram and electroencephalogram in severe cases. Multivariable Logistic regression analysis showed that the key factors for severe HFMD were age, morbidity location, morbidity area, fever duration, mouth mucosal symptoms, and abnormal serum levels of neutrophils (NEUT), hemoglobin and glucose (P < 0.05). CONCLUSIONS: To improve prognosis, reduce medical expense and prevent the development of severe cases, we should improve the epidemiological detection of HFMD to treat patients quickly. We should also closely monitor children with the EV71 virus, who present with continuous fever as well as abnormal laboratory results, from areas highly susceptible to HFMD attacks.