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Objective To study the effect of type 2 diabetes mellitus (T2DM) on the cerebral blood vessels in Alzheimer's disease (AD), and to explore its mechanism of influence on the pathogenesis of Alzheimer's disease. Methods To generate a mouse model with AD complicated with long-term T2DM, forty 6-month-old APP/PS1 transgenic mice were fed with high-sugar and high-fat diet for 6 months, that was, when mice at 12 months of age, they were intraperitoneally injected with 1% streptozotocin solution for 4 consecutive days. Then, mice were randomly divided into 4 groups: the normal control group, AD model group, T2DM model group and AD complicated with T2DM model group, 10 mice were used in each group. The learning and memory ability of the mice were tested by the mouse step-down assay, and the vascular morphology of the mice's hippocampal CAI area was observed by ink perfusion. Then oil red 0 staining and immunofluorescent staining were applied to test the pathological indices of the hippocampal area in the model. Results Compared with the control group, AD combined with T2DM mice showed decreasing significantly abilities in the learning and memory (P<0.05), and the blood vessels in the hippocampus became thinner and the vascular density decreased. Moreover, T2DM promoted lipid deposits and vascular leak in the hippocampus of the model. Additionally, the expression of β-site amyloid precursor protein cleaving enzyme-1 (BACE-1), nuclear factor (NF)-κB and matrix metalloproteinase (MMP) -9 were increased compared with the controls in the hippocampal CAI region. Conclusion T2DM plays a negative regulatory role on learning and memory functions of mice, accelerates the onset of AD and result in cerebrovascular lesions. In addition, the abnormal expression of MMP-9 may also be one of the causes of AD vascular lesions.
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<b>Objective::Evaluate the effects of Danhong injection for perioperative percutaneous coronary intervention (PCI) on cardiac function and thrombolysis in myocardial infarction (TIMI) in patients with acute myocardial infarction (AMI). <b>Method::Computer retrieving CNKI, Wanfang database, VIP database, PubMed, CBM, Web of Science, The Cochrane Library, gathering Danhong injection in percutaneous coronary intervention perioperative application in the treatment of acute myocardial infarction clinic trials. The Cochrane risk evaluation is adopted to improve the quality of literature evaluation, with Revman 5.3 software for Meta-analysis. <b>Result::Participants included in 12 clinic trials contains a total of 1 131 patients, including 569 patients in Danhong treatment and 562 patients in control group. The results showed that compared with conventional treatment, Danhong injection treated patients had LVEF increased obviously [mean difference (MD)=6.62, 95% confidence interval (CI) (4.91, 8.34), <italic>P</italic><0.000 01], the number of TIMI class 3 patients significantly increased[relative risk (RR)=0.22, 95%CI(0.12, 0.41), <italic>P</italic><0.000 01], and BNP levels significantly decreased [MD=151.86, 95%CI (-247.00, -56.72), <italic>P</italic>=0.002]. <b>Conclusion::Danhong injection can improve the function of acute myocardial infarction after percutaneous coronary intervention.
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Objective:To analyze the syndrome characteristics and distribution regularity of patients with non-ST segment elevation myocardial infarction (NSTEMI), in order to guide clinical practice and improve the efficacy of traditional Chinese medicine. Method:Inpatients with non-ST segment elevation myocardial infarction in line with the diagnostic criteria were selected, and the frequency statistics method was used to analyze the syndrome elements and their frequency degree and distribution characteristics. Result:According to the analysis of syndrome elements and their frequency degree of 263 patients with NSTEMI, the pathogenesis of NSTEMI was mostly deficiency in origin and excess in superficiality. As for deficiency in origin, Qi deficiency (171 times, 32.39%) was the most common, which was followed by Yin deficiency (42 times, 7.95%), Yang deficiency (16 times, 3.03%), and blood deficiency (1 times, 0.19%). As for excess in superficiality, blood stasis (129 frequency, 24.4%) and phlegm turbidity (125 frequency, 23.7%) were the most common, which were followed by heat accumulation (42 frequency, 7.95%), water drinking (2 frequency, 0.38%). According to the syndrome diagnosis analysis of the combination of syndrome elements, 220 cases (83.65%) had single syndrome differentiation, 42 cases (15.97%) had two syndromes at the same time, and 1 case (0.38%) had three syndromes at the same time. Among all the syndrome types, Qi deficiency and blood stasis syndrome (94 cases, 42.7%) was the most common, which were followed by phlegm and blood stasis syndrome (46 cases, 20.9%), Qi and Yin deficiency syndrome (41 cases, 18.6%) and heart and kidney deficiency syndrome (32 cases, 14.6%). And Yang deficiency and water flooding syndrome (6 cases, 2.73%) and heart fire blazing syndrome (1 case, 0.45%) were relatively rare. According to the distribution regularity of syndrome, traditional Chinese medicine therapies were mainly for tonifying vital qi and protecting kidney Qi, with equal emphasis on removing phlegm, eliminating dampness and diuresis, activating blood circulation and removing blood stasis. Conclusion:The pathogenesis of NSTEMI is deficiency in origin and excess in superficiality. Deficiency in origin is mostly Qi deficiency and Yin deficiency, while excess in superficiality is mostly blood stasis, phlegm and heat accumulation. traditional Chinese medicine therapies are mostly for invigorating Qi and nourishing Yin, promoting blood circulation and removing blood stasis, clearing heat and resolving phlegm.
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Coronary heart disease (CHD) has become a major disease that seriously endangers human health. It belongs to the category of " chest obstruction" and " genuine heart pain" in Chinese medicine, and blood stasis syndrome is its core pathogenesis of CHD, which runs through the disease all the time. On the basis of more than 30 years' clinical practice and taking " blood stasis syndrome of CHD" as the research object, the research group has carried out a comprehensive, in-depth and systematic studies on diagnostic criteria, biological basis, and evidence-based evaluation. The quantitative diagnostic criteria of blood stasis syndrome of CHD were established, and the research directions of quantification and objectivity of Chinese medicine syndromes were innovated. The biological basis of blood stasis syndrome of CHD was revealed from macroscopic characterization to organ cell molecular level. When the above research results are applied in the prevention and treatment, the accuracy of diagnosis and the clinical efficacy for CHD has been improved in Chinese medicine.
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Objetive To investigate the effect of Qingkailing injection on the expression of Toll-like receptor 4 (TLR4), gp91phox and zonula occludens-1 (ZO-1) in cerebrovascular endothelial cells induced by hypoxia activation of microglias. Methods:BV2 microglia cells were divided into six groups. They were cultured in serum-free DMEM, while the Qingkailing groups of low, middle and high dosages were cultured with 0.0625%, 0.125% and 0.25% Qingkailing injection, respectively, and minocycline group with minocycline of 200 nmol/L. The groups other than control group underwent hypoxia for 24 hours and reoxygenation for 24 hours. Then, the medium of microglia was put into the medium of Balb/c endothelial cells for 24 hours. The cell viability of endothelial cells was measured with CCK-8, the concentration of nitric oxide (NO) was detected with colorimetry, and the experission of TLR4, gp91phox and ZO-1 was detected with Western blotting. Results:Compared with the control group, the cell viability and the expression of ZO-1 decreased in the model group (P < 0.01), while the concentration of NO and the expression of TLR4 and gp91phox increased (P < 0.05). Compared with the model group, the cell viability and the expression of ZO-1 increased in the Qingkailing groups and the minocycline group (P < 0.05), while the concentration of NO and the expression of TLR4 and gp91phox decreased (P < 0.05). Conclusion:Qingkailing injection may enhance the survival and function of cerebrovascular endothelial cells by inhibiting the hypoxia activation of microglias, reducing the expression of TLR4 and gp91phox, and increasing the expression of ZO-1.
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Astragalus polysaccharide is a major component of radix astragali, a vital qi-reinforcing herb medicine with favorable immune-regulating effects. In a previous animal experiment, we demonstrated that astragalus polysaccharide effectively alleviates ischemia-reperfusion injury (IRI) of cardiac muscle through the regulation of the inflammatory reactions. However, the relationship between this herb and the cohesion molecules on the cell surface remains controversial. In this study, human cardiac microvascular endothelial cells (HCMECs) were used to validate the protective effects of astragalus under an IRI scheme simulated through hypoxia/reoxygenation in vitro. The results indicated that astragalus polysaccharide inhibited the cohesion between HCMECs and polymorphonuclear leukocyte (PMN) during IRI through the downregulation of p38 MAPK signaling and the reduction of cohesive molecule expression in HCMECs.
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BACKGROUND: Acute gastrointestinal illness (AGI) is an important public-health problem worldwide. Previous national studies of the incidence of AGI in China were performed decades ago, and detailed information was not available. This study therefore sought to determine the magnitude, distribution, and burden of self-reported AGI in China. METHODS: Twelve-month, retrospective face-to-face surveys were conducted in 20 sentinel sites from six provinces between July 2010 and July 2011. RESULTS: In total, 39686 interviews were completed. The overall adjusted monthly prevalence of AGI was 4.2% (95% confidence interval, 4.0-4.4), corresponding to 0.56 episodes of AGI per person-year. Rates of AGI were highest in children aged < 5 years. Healthcare was sought by 56.1% of those reporting illness. Of the cases who visited a doctor, 32.7% submitted a stool sample. The use of antibiotics was reported by 49.7% of the cases who sought medical care and 54.0% took antidiarrhoeals. In the multivariable model, gender, age, education, household type, residence, season, province and travel were significant risk factors of being a case of AGI. CONCLUSIONS: This first population-based study in China indicated that AGI represents a substantial burden of health. Further research into the specific pathogens is needed to better estimate the burden of AGI and foodborne disease in China.
Subject(s)
Gastrointestinal Diseases/epidemiology , Acute Disease , Adolescent , Adult , Child , Child, Preschool , China/epidemiology , Cross-Sectional Studies , Female , Gastrointestinal Diseases/etiology , Humans , Infant , Infant, Newborn , Interviews as Topic , Male , Middle Aged , Prevalence , Risk Factors , Self Report , Socioeconomic Factors , Young AdultABSTRACT
S100A8 and S100A9 are generally considered proinflammatory. Hypohalous acids generated by activated phagocytes promote novel modifications in murine S100A8 but modifications to human S100A8 are undefined and there is no evidence that these proteins scavenge oxidants in human disease. Recombinant S100A8 was exquisitely sensitive to equimolar ratios of HOCl, which generated sulfinic and sulfonic acid intermediates and novel oxathiazolidine oxide/dioxide forms (mass additions, m/z +30 and +46) on the single Cys42 residue. Met78(O) and Trp54(+16) were also present. HOBr generated sulfonic acid intermediates and oxidized Trp54(+16). Evidence for oxidation of the single Cys3 residue in recS100A9 HOCl was weak; Met63, Met81, Met83, and Met94 were converted to Met(O) in vitro. Oxidized S100A8 was prominent in lungs from patients with asthma and significantly elevated in sputum compared to controls, whereas S100A8 and S100A9 were not significantly increased. Oxidized monomeric S100A8 was the major component in asthmatic sputum, and modifications, including the oxathiazolidine adducts, were similar to those generated by HOCl in vitro. Oxidized Met63, Met81, and Met94 were variously present in S100A9 from asthmatic sputum. Results have broad implications for conditions under which hypohalous acid oxidants are generated by activated phagocytes. Identification in human disease of the novel S100A8 Cys derivatives typical of those generated in vitro strongly supports the notion that S100A8 contributes to antioxidant defense during oxidative stress.
Subject(s)
Calgranulin A/metabolism , Calgranulin B/metabolism , Free Radical Scavengers , Inflammation/metabolism , Adult , Animals , Antioxidants/chemistry , Antioxidants/metabolism , Calgranulin A/chemistry , Calgranulin B/chemistry , Humans , Mice , Oxidants/chemistry , Oxidants/metabolism , Oxidation-Reduction , Oxidative Stress , Phagocytes/chemistry , Phagocytes/metabolismABSTRACT
Acute altitude reaction is a stress response of organism to special altitude environmental factors such as hypoxia, low pressure, cold, dry and strong ultraviolet. As it is the most incident disease in high altitude areas, its prevention remains a problem to be solved. In China, the traditional Chinese (Tibetan) medicines have been recognized as an effective means of preventing and treating acute altitude sicknesses. Some single-recipe or compound traditional Chinese (Tibetan) medicines have been proved to be effective for acute altitude sicknesses. In this article, we will describe traditional Chinese (Tibetan) medicines of different types with efficacy in prevention and treatment of altitude sicknesses.
Subject(s)
Humans , Acute Disease , Altitude Sickness , Drug Therapy , Medicine, Chinese Traditional , Medicine, Tibetan TraditionalABSTRACT
OBJECTIVE: To estimate the dietary melamine exposure in Chinese infants and young children from the consumption of melamine adulterated Sanlu infant formula. METHODS: Four age groups of infants and young children (3, 6, 12, and 24 months) were chosen as the assessed subjects and the maximum amount of infant formula consumption was estimated based on the recommended usage level in the package insert of Sanlu infant formula and other brands. Melamine was analyzed in 111 Sanlu infant formula samples collected from the markets in Beijing and Gansu province using the LC-MS-MS with a limit of quantification of 0.05 mg/kg. Four levels of melamine concentration were chosen to estimate the dietary intakes, including the mean, median, 90th percentile, and maximum. RESULTS: The infants of 3 months had the highest intake of melamine, and with the increase of the age (month), the intake decreased. Based on the median melamine concentration (1,000 mg/kg) as an example, the melamine intakes for the infants of 3, 6, 12, and 24 months were 23.4, 21.4, 15.0, and 8.6 mg/kg bw/d, respectively. CONCLUSION: Dietary melamine intakes from tainted Sanlu infant formula significantly exceeded the TDI level (0.2 mg/kg bw/d) recommended by the WHO Expert Meeting in 2008. However, the present assessment has some limitations including the poor representative samples, the varied melamine concentrations in the adulterated Sanlu infant formula, and other brand infant formula possibly consumed by these infants.
Subject(s)
Diet , Food Contamination , Infant Formula/chemistry , Triazines/chemistry , Triazines/metabolism , China , Eating , Female , Flame Retardants/analysis , Flame Retardants/metabolism , Humans , Infant , MaleABSTRACT
Macrophages, cytokines, and matrix metalloproteinases (MMP) play important roles in atherogenesis. The Ca(2+)-binding protein S100A12 regulates monocyte migration and may contribute to atherosclerosis by inducing proinflammatory cytokines in macrophages. We found significantly higher S100A12 levels in sera from patients with coronary artery disease than controls and levels correlated positively with C-reactive protein. S100A12 was released into the coronary circulation from ruptured plaque in acute coronary syndrome, and after mechanical disruption by percutaneous coronary intervention in stable coronary artery disease. In contrast to earlier studies, S100A12 did not stimulate proinflammatory cytokine production by human monocytes or macrophages. Similarly, no induction of MMP genes was found in macrophages stimulated with S100A12. Because S100A12 binds Zn(2+), we studied some functional aspects that could modulate atherogenesis. S100A12 formed a hexamer in the presence of Zn(2+); a novel Ab was generated that specifically recognized this complex. By chelating Zn(2+), S100A12 significantly inhibited MMP-2, MMP-9, and MMP-3, and the Zn(2+)-induced S100A12 complex colocalized with these in foam cells in human atheroma. S100A12 may represent a new marker of this disease and may protect advanced atherosclerotic lesions from rupture by inhibiting excessive MMP-2 and MMP-9 activities by sequestering Zn(2+).
Subject(s)
Atherosclerosis/metabolism , Coronary Disease/metabolism , S100 Proteins/physiology , Adult , Aged , Atherosclerosis/pathology , Biomarkers/metabolism , Cell Line, Tumor , Cells, Cultured , Coronary Disease/pathology , Female , Humans , Inflammation Mediators/blood , Inflammation Mediators/physiology , Macrophages/enzymology , Macrophages/metabolism , Macrophages/pathology , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase Inhibitors , Middle Aged , Rupture, Spontaneous/enzymology , Rupture, Spontaneous/metabolism , Rupture, Spontaneous/prevention & control , S100 Proteins/blood , S100A12 Protein , Zinc/physiologyABSTRACT
S100A8 and S100A9, highly expressed by neutrophils, activated macrophages, and microvascular endothelial cells, are secreted during inflammatory processes. Our earlier studies showed S100A8 to be an avid scavenger of oxidants, and, together with its dependence on IL-10 for expression in macrophages, we postulated that this protein has a protective role. S-nitrosylation is an important posttranslational modification that regulates NO transport, cell signaling, and homeostasis. Relatively few proteins are targets of S-nitrosylation. To date, no inflammation-associated proteins with NO-shuttling capacity have been identified. We used HPLC and mass spectrometry to show that S100A8 and S100A9 were readily S-nitrosylated by NO donors. S-nitrosylated S100A8 (S100A8-SNO) was the preferred nitrosylated product. No S-nitrosylation occurred when the single Cys residue in S100A8 was mutated to Ala. S100A8-SNO in human neutrophils treated with NO donors was confirmed by the biotin switch assay. The stable adduct transnitrosylated hemoglobin, indicating a role in NO transport. S100A8-SNO suppressed mast cell activation by compound 48/80; intravital microscopy was used to demonstrate suppression of leukocyte adhesion and extravasation triggered by compound 48/80 in the rat mesenteric microcirculation. Although S100A8 is induced in macrophages by LPS or IFN-gamma, the combination, which activates inducible NO synthase, did not induce S100A8. Thus, the antimicrobial functions of NO generated under these circumstances would not be compromised by S100A8. Our results suggest that S100A8-SNO may regulate leukocyte-endothelial cell interactions in the microcirculation, and suppression of mast cell-mediated inflammation represents an additional anti-inflammatory property for S100A8.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/immunology , Calgranulin A/immunology , Calgranulin B/immunology , Free Radical Scavengers/immunology , Leukocytes/immunology , Protein Processing, Post-Translational/immunology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Biological Transport/drug effects , Biological Transport/immunology , Calgranulin A/chemistry , Calgranulin B/chemistry , Cysteine/chemistry , Cysteine/immunology , Endothelial Cells/immunology , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Hemoglobins/immunology , Humans , Inflammation/immunology , Interferon-gamma/pharmacology , Interleukin-10/immunology , Lipopolysaccharides/pharmacology , Mast Cells/immunology , Mice , Mice, Inbred BALB C , Microcirculation/immunology , Nitric Oxide/immunology , Nitric Oxide Synthase Type II/immunology , Oxidants/immunology , Protein Processing, Post-Translational/drug effects , Rats , p-Methoxy-N-methylphenethylamine/pharmacologyABSTRACT
S100A12 is expressed at sites of acute, chronic, and allergic inflammation. S100 proteins have regions of high sequence homology, but the "hinge" region between the conserved calcium binding domains is structurally and functionally divergent. Because the murine S100A8 hinge domain (mS100A8(42-55)) is a monocyte chemoattractant whereas the human sequence (hS100A8(43-56)) is inactive, we postulated that common hydrophobic amino acids within the S100A12 hinge sequence may be functional. The hinge domain, S100A12(38-53), was chemotactic for human monocytes and murine mast cells in vitro. S100A12(38-53) provoked an acute inflammatory response similar to that elicited by S100A12 in vivo and caused edema and leukocyte and mast cell recruitment. Circular dichroism studies showed that S100A12(38-53) had increased helical structure in hydrophobic environments. Mutations in S100A12(38-53) produced using an alanine scan confirmed that specific hydrophobic residues (I44A, I47A, and I53A) on the same face of the helix were critical for monocyte chemotaxis in vitro and generation of edema in vivo. In a hydrophobic environment such as the cell membrane, these critical residues would likely align on one face of an alpha-helix to facilitate receptor interaction. Interaction is unlikely to occur via the receptor for advanced glycation end products but, rather, via a G-protein-coupled mechanism.
Subject(s)
Mast Cells/drug effects , Monocytes/drug effects , S100 Proteins/pharmacology , Amino Acid Sequence , Amino Acids/genetics , Amino Acids/metabolism , Animals , Calcium/metabolism , Cell Line , Chemotactic Factors/metabolism , Chemotaxis/drug effects , Circular Dichroism , Cytosol/drug effects , Cytosol/metabolism , Humans , Mast Cells/cytology , Mast Cells/metabolism , Mice , Mice, Inbred BALB C , Molecular Sequence Data , Monocytes/cytology , Monocytes/metabolism , Mutation/drug effects , Peptide Fragments/chemistry , Peptide Fragments/pharmacology , S100 Proteins/chemistry , S100 Proteins/genetics , S100 Proteins/metabolism , S100A12 ProteinABSTRACT
BACKGROUND: The calcium-binding protein S100A12 might provoke inflammation and monocyte recruitment through the receptor for advanced glycation end products. OBJECTIVE: Because inflammation elicited by S100A12 in vivo had characteristics of mast cell (MC) activation, we aimed to define the mechanism. METHODS: Various MC populations were used to test S100A12 activation assessed on the basis of morphology, histamine release, leukotriene production, and cytokine induction. MC dependence of S100A12-provoked inflammation was tested in mice and on the rat microcirculation by means of intravital microscopy. Immunohistochemistry localized S100A12 in the asthmatic lung, and levels in sputum from asthmatic patients were quantitated by means of ELISA. Expression of the receptor for advanced glycation end products was evaluated by means of RT-PCR and Western blotting. RESULTS: S100A12 provoked degranulation of mucosal and tissue MCs in vitro and in vivo and amplified IgE-mediated responses. It induced a cytokine profile indicating a role in innate/T(H)1-mediated responses. S100A12-induced edema and leukocyte rolling, adhesion, and transmigration in the microcirculation were MC dependent. Eosinophils in airway tissue from asthmatic patients were S100A12 positive, and levels were increased in sputum. S100A12 responses were partially blocked by an antagonist to the receptor for advanced glycation end products, but MCs did not express mRNA or protein, suggesting an alternate receptor. CONCLUSION: This novel pathway highlights the potential importance of S100A12 in allergic responses and in infectious and chronic inflammatory diseases. CLINICAL IMPLICATIONS: MC activation by S100A12 might exacerbate allergic inflammation and asthma. S100A12 might provide a novel marker for eosinophilic asthma.
Subject(s)
Asthma/immunology , Mast Cells/drug effects , S100 Proteins/pharmacology , Adult , Animals , Bronchiectasis/immunology , Cytokines/immunology , Female , Humans , Immunity, Innate , Lung/immunology , Male , Mast Cells/immunology , Mice , Mice, Inbred BALB C , Mice, Knockout , Middle Aged , Rats , Rats, Sprague-Dawley , S100A12 Protein , Sputum/chemistryABSTRACT
<p><b>OBJECTIVE</b>To investigate the clinical implications of relationship between myeloperoxidase and acute coronary syndromes (ACS).</p><p><b>METHODS</b>176 consecutive patients who underwent coronary angiography for coronary atherosclerosis were divided into four groups according to the quartile of MPO Level. The characters and the relationship between MPO and the elements were studied in every group.</p><p><b>RESULTS</b>(1) ACS rate (36.2%) in the fourth quartile group of MPO level was 6 times higher than that (5.2%) in the first quartile group of MPO level, P < 0.01. (2) Gensini score (65.6 +/- 30.3) in the fourth quartile group of MPO level was significantly higher than that (17.3 +/- 10.2) in the first quartile group (P < 0.01). WBC [(7.7 +/- 1.6) x 10(9)/L] in the fourth quartile group was also significantly higher than that [(6.6 +/- 1.8) x 10(9)/L] in the first quartile group, P < 0.05. (3) When TnI < or = 0.05 ng/ml, MPO level had a positive correlation with Gensini score (r = 0.321, P = 0.002) and WBC (r = 0.230, P = 0.025). (4) Kaplan-meier event rate curve showed that there was a significant difference of the terminus incident (death, no causing death AMI, vessel reestablish and incidence rate of CABG add up) between the groups > or = 62.9 AUU/L and < 62.9 AUU/L of MPO serum level at 6-month follow-up visit (chi(2) = 13.5, P = 0.01).</p><p><b>CONCLUSION</b>Activity level of MPO in human serum seems a good biomarker for diagnosing and predicting ACS, which may be especially helpful in predicting the risk of myocardial infarction in patients with acute chest pain during 6-month follow up.</p>
