Notoginsenoside R1 protects against myocardial ischemia/reperfusion injury in mice via suppressing TAK1-JNK/p38 signaling.

Previous studies show that notoginsenoside R1 (NG-R1), a novel saponin isolated from Panax notoginseng, protects kidney, intestine, lung, brain and heart from ischemia-reperfusion injury. In this study we investigated the cardioprotective mechanisms of NG-R1 in myocardial ischemia/reperfusion (MI/R) injury in vivo and in vitro. MI/R injury was induced in mice by occluding the left anterior descending coronary artery for 30 min followed by 4 h reperfusion. The mice were treated with NG-R1 (25 mg/kg, i.p.) every 2 h for 3 times starting 30 min prior to ischemic surgery. We showed that NG-R1 administration significantly decreased the myocardial infarction area, alleviated myocardial cell damage and improved cardiac function in MI/R mice. In murine neonatal cardiomyocytes (CMs) subjected to hypoxia/reoxygenation (H/R) in vitro, pretreatment with NG-R1 (25 µM) significantly inhibited apoptosis. We revealed that NG-R1 suppressed the phosphorylation of transforming growth factor ß-activated protein kinase 1 (TAK1), JNK and p38 in vivo and in vitro. Pretreatment with JNK agonist anisomycin or p38 agonist P79350 partially abolished the protective effects of NG-R1 in vivo and in vitro. Knockdown of TAK1 greatly ameliorated H/R-induced apoptosis of CMs, and NG-R1 pretreatment did not provide further protection in TAK1-silenced CMs under H/R injury. Overexpression of TAK1 abolished the anti-apoptotic effect of NG-R1 and diminished the inhibition of NG-R1 on JNK/p38 signaling in MI/R mice as well as in H/R-treated CMs. Collectively, NG-R1 alleviates MI/R injury by suppressing the activity of TAK1, subsequently inhibiting JNK/p38 signaling and attenuating cardiomyocyte apoptosis.

Glycoside constituents with various antioxidant effects from fresh Cynomorium songaricum.

Cynomorium songaricum Rupr. (CSR), an edible and medicinal material, is widely cultivated in desert regions of Eastern and Western Asia, Europe, and North Africa. Ten glycoside constituents 1-10 including one new songaricumone A (1) were isolated from the fresh C. songaricum. Their structures were elucidated by comprehensive NMR data analysis. Further, various antioxidant effects of isolated compounds (1-3 and 5-10) were comprehensively and comparatively investigated. In conclusion, it is obvious that different glycosides vary significantly toward different sources of free radicals, which are attributed to different aglycones and substituted positions of sugar unit in structures.

The development and evaluation of a sub-health self-rating scale for university students in China.

BACKGROUND: Sub-health status is defined as declines in vitality, physiological function and capacity for adaptation, but without the presence of clinical or sub-clinical disease. We have developed and evaluated a comprehensive questionnaire, the Sub-Health Self-Rating Scale (SSS), to assess sub-health status in university students. METHOD: The items for the draft questionnaire were discussed in focus groups. The WHOQOL-BREF was selected as the validity reference. From a professional perspective and large sample evaluation, the scale ultimately consisted of 58 items. The reliability and validity of the SSS was examined in undergraduate students and 1000 questionnaires were randomly selected from the samples for expert evaluation. RESULTS: Cronbach's α of the total scale was 0.942. The dimensions of physiological, psychological and social had high reliability: 0.915, 0.856 and 0.850, respectively. Based on scree plot and related theories, there were 10 factors to be extracted. The correlation coefficient between the total scale and sub-scale was high. The dimensions of physiological, psychological and social had high correlations with the total scale: 0.929, 0.803 and 0.774, respectively. The sub-health cut-off point of the total scale was 72; for the physiological field, it was 72; for the psychological field, it was 60; and the social field, it was 56. The fit between the expert evaluation method and the scale method was 0.758. The lower the score, the worse the health condition. CONCLUSION: We established and evaluated a valid instrument (SSS) that encompasses physiological, psychological and social factors to investigate sub-health status. It is short and easy to complete, and therefore suitable for use with undergraduate students.

[Correlation Analyses between Obesity/Overweight and Constitutions of Chinese Medicine/Cardio- vascular Risk Factors in Elderly Residents of a Community in Guangzhou].

Objective To analyze the correlation between obesity/overweight and constitutions of Chinese medicine (CM)/cardiovascular risk factors in elderly residents of Tianhe District Wushan Com- munity, Guangzhou City. Methods Recruited were 1 054 elderly residents (over 60 years), who had free health examinations in Tianhe District Wushan Community of Guangzhou City from October 2014 to September 2015. They were assigned to the obesity group (107 cases) , the overweight group (431 ca- ses) , and the normal weight group (516 cases) according to body mass index (BMI) by randomized sampling. Constitution types of CM were assessed using Classification and Judgment of Constitution Types of CM. Health files were filled in. General indices such as waist circumference, blood pressure, etc., and blood biochemical indicators such as fasting blood glucose, blood lipids, uric acid, blood creati- nine, etc. were detected. The correlation between constitution types of CM and obesity/overweight was analyzed using multivariate Logistic regression analysis. Results Among the 1 054 elderly residents, 75. 62% (797/1 054) of those were of biased constitution and 24. 38% (257/1 054) were of normal consti- tution. Phlegm dampness (247 cases, 23. 43%), yin deficiency (150 cases, 14. 23%), and qi deficiency (136 cases, 12. 90%) constitution were top 3 commonly seen biased constitution types. Multiple Logistic regression analysis showed that the risk of obese/overweight patients of phlegm dampness constitution was 61. 641 times (Cl: 24. 491 -155. 144) and 9. 393 times (Cl: 5. 910 -14. 929) that of subjects of nor- mal constitution respectively (P <0. 01) ; the risk of obese/overweight patients of dampness heat consti- tution was 21. 478 times (Cl: 6. 978 -66. 102) and 4. 505 times ( Cl: 2. 308 -8. 793) that of subjects of normal constitution respectively (P <0. 01) ; the risk of obese/overweight patients of qi deficiency consti- tution was 3.408 times ( Cl:1. 161 -10. 004) and 1. 655 times (Cl: 1. 062 -2. 580) that of subjects of nor- mal constitution respectively (P <0. 05). Compared with normal body weight senile, the incidences of ab- dominal obesity, hypertension, diabetes were obviously higher in obese/overweight senile (P <0. 01 , P < 0. 05). Their values of fasting blood glucose, triglyceride, high-density lipoprotein, and uric acid were ob- viously higher than those in normal body weight senile (P <0. 01). Conclusions Community obese/over- weighed elderly residents have the tendency of phlegm dampness, dampness heat, and qi deficiency constitutions. Compared with the normal body weight senile, they have higher risk of cardiovascular risk factors, and increased risks of suffering from hypertension, diabetes, and dyslipidemia.

Identification of metabolites from edible mushroom Morchella sextelata and their biological evaluation.

To identify bioactive metabolites from the fruiting body of Morchella sextelata, fourteen metabolites (1-14) including one undescribed morchesexten A (1) were isolated. Their structures including absolute configurations were assigned on the basis of spectroscopic data and quantum chemical computational methods. Furthermore, the anti-inflammatory and antioxidant activities of the isolated compounds were evaluated. Compounds 10-12 showed inhibitory effects on nitric oxide (NO) production with IC50 values of 15.2 ± 2.7, 10.2 ± 1.9 and 35.3 ± 10.5 µM, respectively. Compounds 7 and 9 exhibited strong antioxidant effect with IC50 values of 6.7 ± 0.4 and 7.3 ± 0.8 µM compared with Vit C (IC50 15.4 ± 0.2 µM).

Research trends and prospects on brain metastasis from breast cancer: A bibliometric analysis.

Introduction: Brain metastasis is the terminal event of breast cancer with poor prognoses. Therefore, this article aimed to provide an updated summary on the development, hotspots, and research trends of brain metastasis from breast cancer based on bibliometric analysis. Method: Publications on breast cancer with brain metastasis retrieved from the Web of Science Core Collection. CiteSpace, VOSviewer, and other online bibliometric analysis platforms were used to analyze and visualize the result. Result: In totality, 693 researchers from 3,623 institutions across 74 counties and regions published a total of 2,790 papers in 607 journals. There was a noticeable increase in publications in 2006. The United States was the dominant country with the most publications followed by China. University Texas MD Anderson Cancer Center was the most productive institution, while Dana Farber Cancer Institution was the most cited. Journal of Neuro-Oncology published the most papers, while Journal of Clinical Oncology ranked first based on cocited analysis. Nancy U. Lin was the most productive and cited author with high influence. There was a focus on basic research, clinical trials, local therapy, treatment optimization, and epidemiological studies regarding brain metastases from breast cancer. References focused on pathogenesis, prevention, treatment, and prognosis were cited most frequently, among which the clinical trial of novel treatment attracted most attention from researchers. Reference citation burst detection suggested that new therapies such as the novel tyrosine kinase inhibitor and antibody-drug conjugate may lead the research trends in the future. Conclusion: High-income countries contributed more to the field of breast cancer with brain metastasis, while developing countries like China developed quickly. Furthermore, the success of novel therapies in recent years may lead to the new era of treatment of breast cancer with brain metastasis in the future.

Overexpression of ABCB1 confers resistance to FLT3 inhibitor FN-1501 in cancer cells: in vitro and in vivo characterization.

FN-1501 is a potent FLT3 inhibitor with antitumor activity. A phase 1 trial of FN-1501 monotherapy in patients with advanced solid tumors and R/R AML is in progress. Since one of the primary causes of multidrug resistance (MDR) is the overexpression of ATP-binding cassette superfamily B member 1 (ABCB1), the objective of this study was to investigate the potential relationship between FN-1501 and the ABCB1 transporter. We found ABCB1 overexpressing-cancer cells conferred FN-1501 resistance, which could be reversed by an ABCB1 inhibitor. Molecular docking study revealed that FN-1501 docked the ligand binding site with an affinity score of -9.77 kcal/mol, denoting a strong interaction between FN-1501 and ABCB1. Additionally, the ABCB1 ATPase assay indicated that FN-1501 could significantly stimulate ABCB1 ATPase activity. Furthermore, we observed a similar trend of ABCB1-facilated FN-1501 resistance in tumor-bearing mice model. In sum, we demonstrate that FN-1501 is a substrate of ABCB1 transporter from both in vivo and in vitro studies. Therefore, our findings provide new insight on the mechanism of chemoresistance due to ABCB1 overexpression.

Development and evaluation of short-form version of the Constitution in Chinese Medicine Questionnaire: study a new and best brief instrument of Chinese medicine for health management.

BACKGROUND: More efficient instruments for body constitution identification are needed for clinical practice. We aimed to develop the short-form version of the Constitution in Chinese Medicine Questionnaire (CCMQ) and evaluate for health management. METHODS: First, the short forms were developed through expert survey, classical test theory (CTT), and modern item response (IRT) based on the CCMQ. A combination of e-mail and manual methods was used in expert survey. Then, five indexes of CTT including criteria value-critical ratio, correlation coefficient, discrete tendency, internal consistency, and factor loading were used. And, IRT method was used through analyzing the discrimination and difficulty parameters of items. Second, the three top-ranked items of each constitution scale were selected for the simplified CCMQ, based on the three combined methods of different conditions and weights. Third, The psychometric properties such as completion time, validity (Construct, criterion, and divergent validity), and reliability (test-retest and internal consistency reliability) were evaluated. Finally, the diagnostic validity of the best short-form used receiver operating characteristic (ROC) curve. RESULTS: Three short-form editions were developed, and retained items 27, 23 and 27, which are named as WangQi nine body constitution questionnaire of Traditional Chinese Medicine (short-form) (SF-WQ9CCMQ)- A, B, and C, respectively. SF-WQ9CCMQ- A is showed the best psychometric property on Construct validity, Criterion validity, test-retest reliability and internal consistency reliability. The diagnostic validity indicated that the area under the ROC curve was 0.928 (95%CI: 0.924-0.932) for the Gentleness constitution scale, and were 0.895-0.969 and 0.911-0.981 for unbalance constitution scales using the cut-off value of the original CCMQ as 40 ("yes" standard) and 30 ("tendency" standard), respectively. CONCLUSIONS: Our study successfully developed a well short-form which has good psychometric property, and excellent diagnostic validity consistent with the original. New and simplified instrument and opportunity are provided for body constitution identification, health management and primary care implementation.

Chinese herbal medicine liu jun zi tang and xiang sha liu jun zi tang for functional dyspepsia: meta-analysis of randomized controlled trials.

Objectives. To assess the efficacy and safety of Liu Jun Zi Tang (LJZT) and Xiang Sha Liu Jun Zi Tang (XSLJZT) for treating functional dyspepsia. Methods. Literature searches were carried out on Medline database, Cochrane Library, CNKI database, Chinese Biomedical Literature database, Wanfang database, and VIP database up to July 2012. Hand search for further references was conducted. Study selection, data extraction, quality assessment, and data analyses were performed according to the Cochrane standards. Results. Fifteen publications in total were suitable for inclusion. There was evidence that LJZT compared with prokinetic drugs increased symptom improvement (odds ratio 1.96, 95% CI 1.15 to 3.36). There was also evidence that XSLJZT compared with prokinetic drugs increased symptom improvement (odds ratio 2.63, 95% CI 1.72 to 4.03). No adverse events were reported in LJZT or XSLJZT group in any of these randomized controlled trials. Conclusion. LJZT and XSLJZT might be more effective compared with prokinetic drugs in the treatment of functional dyspepsia, and no side effects are identified in the included trials. However, due to poor methodological quality in the majority of included studies, the potential benefit from LJZT and XSLJZT need to be confirmed in rigorously designed, multicentre, and large-scale trials.

Baseline serum uric acid level is associated with progression-free survival, disease control rate, and safety in postoperative patients with colorectal cancer treated by FOLFOX, FOLFIRI, or XELOX.

Background: High serum uric acid (SUA) levels increase the risk of overall cancer morbidity and mortality, particularly for digestive malignancies. Nevertheless, the correlation between SUA level and clinical outcomes of the postoperative patients with colorectal cancer (CRC) treated by chemotherapy is unclear. This study aimed at exploring the relationship between baseline SUA level and progression-free survival (PFS), disease control rate (DCR), and safety in postoperative CRC patients receiving chemotherapy. Patients and Methods: We conducted a retrospective study to evaluate the relationship between baseline SUA level and PFS, DCR, and incidence of serious adverse events of 736 postoperative CRC patients treated with FOLFOX, FOLFIRI or XELOX at our center. Results: Data from our center suggested that high baseline SUA level is linked to poor PFS in non-metastatic CRC patients using FOLFOX (HR=2.59, 95%CI: 1.29-11.31, p=0.018) and in male patients using FOLFIRI (HR=3.77, 95%CI: 1.57-39.49, p=0.012). In patients treated by FOLFIRI, a high SUA is also linked to a low DCR (p=0.035). In patients using FOLFOX, high baseline SUA level is also linked to a high incidence of neutropenia (p=0.0037). For patients using XELOX, there is no significant correlation between SUA level and PFS, effectiveness, or safety. Conclusions: These findings imply that a high SUA level is a promising biomarker associated with poor PFS, DCR and safety of postoperative CRC patients when treated with FOLFOX or FOLFIRI.

Effects and mechanism of action of Huang-Lian-Jie-Du-Tang in atopic dermatitis-like skin dysfunction in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD), a disorder prevalent during childhood and adulthood, seriously affects the patient's quality of life. Although Huang-Lian-Jie-Du-Tang (HLJDT) has shown anti-inflammatory effects in previous studies, its effects and mechanism of action underlying AD disorder are still largely unknown. OBJECTIVE: This study explored the anti-inflammatory and immunomodulatory effects of HLJDT on the AD-like dermal disorder, induced in vitro by lipopolysaccharide (LPS)-triggered inflammation, and in vivo by 2,4-dinitrochlorobenzene (DNCB). MATERIALS AND METHODS: In vivo HLJDT effects were investigated by determining the severity of dermatitis, which consisted of observing signs of skin lesions, visually and through haematoxylin and eosin (HE) staining, in mouse ears and dorsal skin, measuring serum levels of interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-5, IL-6, interferon (IFN)-γ, the tumour necrosis factor (TNF)-α, and determining the splenic index, number of splenic CD4+/CD8+ T-lymphocytes, as well as the phosphorylation levels of mitogen-activated protein kinases (including MAPKs-p38, ERK, and JNK), IκB-α, and nuclear factor kappa B (NF-κB) (p65) within dermal lesions. Morphological changes in LPS-induced inflammation were observed under a microscope, and ELISA and qPCR assays were used to measure IL-1α, IL-1ß, IL-6, and TNF-α expression levels. The protein expression levels of P-ERK/ERK, P-p38/p38, P-JNK/JNK, P-IKß-α, and P-p65 were measured through western blotting. Additionally, p65 expression was assessed by immunofluorescence, and LPS binding to RAW264.7 cell membrane was studied with laser confocal microscopy. RESULTS: HLJDT could remarkably mitigate DNCB-induced AD-like lesion symptoms, alleviating inflammatory mediator infiltration in mouse ears and dorsal skin tissue, down-regulating serum expression levels of IL-1α, IL-1ß, IL-2, IL-4, IL-5, IL-6, IFN-γ, and TNF-α, normalising the splenic CD4+/CD8+ T-lymphocyte ratio, and inactivating MAPKs (including p38, ERK, and JNK), IκB-α, and NF-κB (p65) in dorsal skin. Furthermore, HLJDT inhibited LPS-induced differentiation of RAW264.7 cells, as evidenced by the decreased protein and mRNA expression of IL-1α, IL-1ß, IL-6, and TNF-α. Additionally, it decreased ERK, p38, JNK, IKß-α, and p65 phosphorylation levels in the MAPKs/NF-κB pathway, inhibited p65 nuclear translocation, and reduced LPS binding to the RAW264.7 cell membrane. CONCLUSIONS: HLJDT significantly improved AD-like symptoms via inhibition of the MAPKs/NF-κB pathway. Therefore, administration of HLJDT might be a potential treatment for AD in the clinical setting.

[Plasma metabonomics of Guifu Dihuang Wan in the treatment of yang deficiency].

OBJECTIVE: To assess the effect of Guifu Dihuang Wan (GFDHW) in the treatment of yang deficiency and explore the underlying molecular mechanism. METHODS: Sixty-two participants without diseases were randomized into control group (n=31) and experimental group (n=31) and were given lifestyle intervention additional GFDHW treatment for a month. NMR technology was used for metabonomics analysis. RESULTS: Intervention with GFDHW resulted in significantly decreased conversion scores of yang deficiency in the experimental group compared with the control group (P<0.005). The concentrations of lactate, valine, proline, arginine and 3-hydroxybutyrate were increased in the plasma of yang-deficient subjects after lifestyle intervention. GFDHW treatment with lifestyle intervention significantly increased the concentrations of lactate, valine, proline, arginine and 3-hydroxybutyrate and also the levels of alanine, glutamine, alpha glucose, isoleucine, betaine and propylene glycol. CONCLUSION: GFDHW treatment improves yang deficiency possibly by increasing the concentrations of alanine, glutamine, alpha glucose, isoleucine, betaine and propylene glycol and promoting energy metabolism of the body.

[Effect of health-promoting lifestyle on outcomes of suboptimal health status].

OBJECTIVE: To determine evaluate the effect of health-promoting lifestyle on the outcomes of suboptimal health status (SHS). METHODS: A prospective population cohort was conducted by consecutively enrolling 5676 college students who took routine health examination from March to May 2013. The participants were assessed for baseline health status and lifestyle and 2972 participants with SHS were followed up for 1.5 years. Exposure was defined as an unhealthy lifestyle. The health-promoting lifestyle was assessed via the Health-promoting Lifestyle Profile (HPLP-II). SHS was evaluated using the medical examination report and Sub-health Measurement Scale V1.0 (SHMS V1.0). RESULTS: Among the 2972 students with SHS, 422 showed recovery of the healthy status at 1.5 year follow-up, 579 showed progression into disease conditions, and 1971 remained in SHS. The participants with recovered health status presented with significant increase of SHMS V1.0 scores by 8.75∓6.95 points compared to the baseline assessment (t=-2.14, P=0.000) in physiological, psychological and social dimensions; they also showed a marked improvement of HPLP-II scores by 14.73 points in 6 dimensions (t=-15.34, P=0.000). Multivariable regression analyses with adjusted demographic variables revealed a significant association between health status and health-promoting lifestyle (P<0.05). Compared with a healthy lifestyle (minimal exposure), a 'poor' lifestyle (the highest level of exposure) was associated with a 30 times higher risk of developing SHS (OR: 30.598, 95% CI: 3.928-238.331), while a 'moderate' lifestyle (a relatively high-level exposure) had a 24 times higher risk of SHS (OR: 23.988, 95%CI: 14.695-39.158), and a suboptimal lifestyle had a nearly 4 times higher risk of SHS (OR: 4.306, 95%CI: 2.767-6.702). CONCLUSION: s SHS may evolve into either a healthy or a disease condition. A unhealthy lifestyle is the important risk factor contributing to the progression of SHS into a disease condition, suggesting the importance of intervention of unhealthy lifestyles in promoting good health.

Trichosanatine alleviates oxidized low-density lipoprotein induced endothelial cells injury via inhibiting the LOX-1/p38 MAPK pathway.

The LOX-1/p38 mitogen-activated protein kinase (MAPK) pathway has been proved to participate in the endothelial dysfunction in atherosclerosis. Trichosanatineis is an active compound isolated from the peel of Trichosanthes kirilowii. This study aims to determine whether trichosanatine prevents the oxidized low-density lipoprotein (ox-LDL)-induced insult through inhibition of the LOX-1/p38 MAPK pathway in HUVECs. HUVECs were treated with 150 mg/ml ox-LDL for 24 h to establish an ox-LDL-induced endothelial injury model. Cell viability, mitochondrial membrane potential (MMP), apoptosis, reactive oxygen species (ROS) level, LOX-1 and p38 MAPK expression level were measured. The results indicated that HUVECs were pretreated with either 100 mM trichosanatine or LOX-1 shRNA prior to exposure to ox-LDL for 24 h. Exposure of HUVECs to 150 mg/ml ox-LDL for 24 h significantly up-regulated the expression levels of LOX-1. The increased expression levels of LOX-1 were markedly attenuated by pretreatment with 100 mM trichosanatine. In addition, the ox-LDL-induced increase in phosphorylated (p) p38 MAPK expression was ameliorated by pretreatment with LOX-1 shRNA. Pretreatment of HUVECs with either trichosanatine or LOX-1 shRNA before exposure to ox-LDL significantly inhibited the ox-LDL-induced injuries, as evidenced by an increase in cell viability, a decrease in apoptotic cells, a ROS generation and a loss of MMP. In conclusion, we have demonstrated for the first time that the LOX-1/p38 MAPK pathway contributes to the ox-LDL-induced injury in HUVECs. Meanwhile, the trichosanatine protects the HUVECs against ox-LDL-induced injury at least in part by inhibiting the activated of LOX-1/p38 MAPK pathway.

[Associations between health-promoting lifestyle and suboptimal health status in Guangdong: a cross sectional study].

OBJECTIVE: To investigate associations between health-promoting lifestyle and suboptimal health status (SHS) in the population of Guangdong province. METHODS: A cross-sectional survey was conducted in a clustered sample of 24 159 individuals aged 12-80 years from 2012 to 2013. Health-promoting lifestyle was assessed via the Health-Promoting Lifestyle Profile (HPLP-II), and SHS was evaluated using the medical examination report and Sub-health Measurement Scale V1.0 (SHMS V1.0). RESULTS: Of the 24159 participants, subjects with SHS (46.0%) and disease status (35.2%) accounted for a much higher percentage than healthy subjects (18.8%). Regression analyses revealed a significant association between health status and healthy lifestyle (P<0.001). Unhealthy lifestyle was an important risk factor for SHS and disease, especially the former. Compared with the participants with a healthy lifestyle (minimal exposure), after demographic adjustment, subjects with a 'poor' lifestyle (maximal exposure) were at a 43 times higher risk of developing SHS (OR: 42.825, 95% CI: 30.567-59.997), those with a general lifestyle were at a 21 times higher risk of SHS (OR: 21.072, 95%CI: 17.258-25.729), and those with a suboptimal lifestyle had a 4 times higher risk (OR: 4.085, 95%CI: 3.352-4.979). In the general population, the major risk factors for SHS included poor stress management, poor self-actualization, inactive exercise and poor interpersonal relationship. CONCLUSION: s Unhealthy lifestyles are significantly related to an increased risk of SHS. Intervention of unhealthy lifestyles, controlling the risk factors of SHS, and rigorous management of the time window of SHS are necessary to promote the heath status.

Huangzhi Oral Liquid Prevents Arrhythmias by Upregulating Caspase-3 and Apoptosis Network Proteins in Myocardial Ischemia-Reperfusion Injury in Rats.

To study the effect of Huangzhi oral liquid (HZOL) on I/R after 2 h and 4 h and determine its regulatory function on caspase-3 and protein networks. 70 SD male rats were randomly divided into seven groups and established myocardial I/R injury model by ligating the left anterior descending coronary artery. Myocardial infarction model was defined by TTC staining and color of the heart. The levels of CK-MB, CTnI, C-RPL, SOD, and MDA were tested at 2 h and 4 h after reperfusion. HE staining and ultramicrostructural were used to observe the pathological changes. The apoptotic index (AI) of cardiomyocyte was marked by TUNEL. The expression levels of caspase-3, p53, fas, Bcl-2, and Bax were tested by immunohistochemistry and western blot. HZOL corrected arrhythmia, improved the pathologic abnormalities, decreased CK-MB, CTnI, C-RPL, MDA, AI, caspase-3, p53, fas, and Bax, and increased SOD ans Bcl-2 with different times of myocardial reperfusion; this result was similar to the ISMOC (P > 0.05). HZOL could inhibit arrhythmia at 2 and 4 h after I/R and ameliorate cardiac function, which was more significant at 4 h after reperfusion. This result may be related to decreased expression of caspase-3, p53, and fas and increased Bcl-2/Bax ratio.

[Relationship between plasminogen activator inhibitor-1 gene 4G/5G polymorphism and type 2 diabetic nephropathy in Chinese Han patients in Guangdong Province].

OBJECTIVE: To understand the association between plasminogen activator inhibitor-1 (PAI-1) gene 4G/5G polymorphism and type 2 diabetic nephropathy (DN) in Chinese Han patients in Guangdong Province. METHODS: PAI-1 gene 4G/5G polymorphism was analyzed in 26 normal individuals, 77 patients with type 2 diabetic nephropathy and 70 type 2 diabetic patients without nephropathy (DNN) by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The 4G/4G genotype frequencies of PAI-1 gene were higher in DN than in DNN patients (0.390 vs 0.171, chi(2)=13.008, P<0.01), with the odds ratio (OR) of 1.447 (95% confidence interval: 0.533-3.934, P<0.05) in comparison with 5G/5G genotypes between the 2 patient groups. The 4G allele frequencies of PAI-1 gene were similar in DN and DNN groups (0.57 vs 0.51, chi(2)=1.22, P>0.05). CONCLUSION: The PAI-1 4G/4G genotype is associated with increased risk for type 2 DN the Chinese Han population in Guangdong Province, and type 2 diabetic patients with 4G/4G PAI-1 genotype are more likely to develop DN than those with 5G/5G PAI-1 genotype.

[Effects of mitogen-activated protein kinase on phorbol 12-myristate 13-acetate-induced matrix metalloproteinase-9 gene expression in cytotrophoblastic cells].

OBJECTIVE: To explore the regulatory mechanism of matrix metalloproteinase-9 (MMP-9) gene expression induced by phorbol 12-myristate 13-acetate (PMA) in cytotrophoblastic cells. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to determine the kinase activity, and MMP-9 gene expression was detected by semi-quantitative reverse transcription (RT)-PCR in the cytotrophoblastic cells. RESULTS: Cytotrophoblastic cells treated with PMA showed markedly increased MMP-9 mRNA level. PMA treatment caused an increase in extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) activities. Both SB203580 (specific inhibitor of the p38 MAPK) and PD98059 (specific inhibitor of the ERK), when preincubated for 30 min with the cytotrophoblastic cells, substantially reduced MMP-9 mRNA accumulation in PMA-primed cells. However, neither SB203580 nor PD98059 used alone, or their combination, was able to completely inhibit MMP-9 mRNA expression. CONCLUSION: Both p38 MAPK and ERK pathways are involved in the regulation of MMP-9 gene expression in the cytotrophoblastic cells induced by PMA, and both signaling pathways are indispensable for full activation of MMP-9 gene expression.

[Role of p38 pathway in PMA-induced in vitro invasion of JAR human choriocarcinoma cell line].

OBJECTIVE: To investigate the role of p38 mitogen-activated protein kinase (MAPK) signal transduction pathways in regulating the in vitro invasion of JAR human choriocarcinoma cells induced by phorbol 12-myristate 13-acetate (PMA). METHODS: ELISA was used to detect the kinase activity of the JAR cells in response to PMA stimulation, and the in vitro invasion capabilities of the stimulated cells were observed using transwell assay. Changes in the proliferation and activity of the JAR cells cultured in vitro following PMA treatment were also observed by MTT assay. RESULTS: p38 MAPK was activated dose-dependently in JAR cells upon the stimulation by PMA, which significantly enhanced the in vitro invasion of the JAR cells, while treatment of the cells with SB203580, a specific inhibitor of p38 MAPK, inhibited the invasion of the cells. The growth of the cells, as observed from the growth curves, was not affected by the treatment of PMA and/or SB203580. CONCLUSION: Activation of p38 MAPK signal transduction pathway may enhance the invasion capability of JAR cells, and p38 MAPK inhibition may therefore yield new possibility to control the invasion of choriocarcinoma.

[Study of genes related with kidney deficiency syndrome].

Study of kidney deficiency syndrome may utilize the modern molecular biology technique, such as gene chip, representational difference analysis (RDA) and genes sequence analysis, to clone the different genes of kidney deficiency syndrome from single TCM syndrome type of the disease, to investigate the inner connection between the various phenotypes of kidney deficiency syndrome and their genes expression pattern and their function products, then to definite the related genes of kidney deficiency syndrome. The research method may also be used for the study of other TCM syndrome types.