ObjectiveThis study aimed to evaluate the effects of cycloastragenol （CAG） on mitochondrial dysfunction during cardiac remodeling and to elucidate its regulatory role in myocardial energy metabolic homeostasis and the associated transcriptional regulatory axis. MethodsA rat model of heart failure （HF） was established by ligation of the left anterior descending coronary artery. Rats were randomly divided into a control group， a model group， a captopril group （3.25 mg·kg^-1）， a low-dose CAG group （10 mg·kg^-1， CAG-L）， and a high-dose CAG group （20 mg·kg^-1， CAG-H）. After 28 days of treatment， left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular end-diastolic diameter （LVIDd）， and left ventricular end-systolic diameter （LVIDs） were assessed by echocardiography. Serum levels of N-terminal pro-brain natriuretic peptide （NT-proBNP）， creatine kinase-MB （CK-MB）， cardiac troponinⅠ （cTnI）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and cyclic adenosine monophosphate （cAMP） were measured by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） and Masson's trichrome staining were used to evaluate myocardial histopathology and fibrosis. Wheat germ agglutinin （WGA）， reactive oxygen species （ROS）， and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） staining were performed to assess cardiomyocyte hypertrophy， oxidative stress， and apoptosis. Adenosine triphosphate （ATP） content and the activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ were determined by colorimetric assays. The mRNA expression of α-smooth muscle actin （α-SMA）， Col Ⅰ， and Col Ⅲ was detected by Real-time quantitative polymerase chain reaction （Real-time PCR）， while the protein levels of β₂-adrenergic receptor （ADRB2）， protein kinase A （PKA）， phosphorylated cAMP response element-binding protein/total cAMP response element-binding protein （p-CREB/CREB）， peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）， nuclear respiratory factor 1 （NRF1）， and mitochondrial transcription factor A （TFAM） were analyzed by Western blot. ResultsCompared with the control group， the model group exhibited significantly decreased LVEF， LVFS， and ATP levels （P<0.05）， and markedly increased LVIDd， LVIDs， NT-proBNP， CK-MB， cTnI， IL-1β， IL-6， TNF-α， ROS levels， TUNEL-positive rate， Col deposition area， and the mRNA expression of α-SMA， Col Ⅰ， and Col Ⅲ （P<0.05）. In addition， the activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ， the protein expression of ADRB2， PKA， p-CREB， PGC-1α， NRF1， and TFAM， as well as the cAMP content， were significantly reduced （P<0.05）. Compared with the model group， both low- and high-dose CAG significantly increased LVEF and LVFS， and decreased LVIDd， LVIDs， and the levels of NT-proBNP， CK-MB， and cTnI （P<0.05）. CAG treatment alleviated myocardial disarray and Collagen deposition， and downregulated the mRNA expression of α-SMA， Col Ⅰ， and Col Ⅲ. The treatment markedly reduced ROS generation and the TUNEL-positive rate （P<0.05）， thereby attenuating cardiomyocyte hypertrophy and inflammatory responses. Furthermore， CAG treatment increased ATP content and the activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ， accompanied by upregulation of PGC-1α， NRF1， TFAM， ADRB2， PKA， and p-CREB protein expression as well as cAMP levels （P<0.05）. The CAG-H group showed the most pronounced improvements， which were superior to those of the captopril group and the CAG-L group. ConclusionCycloastragenol delays adverse cardiac remodeling and improves cardiac function by activating the ADRB2-mediated GPCR/cAMP/PKA/CREB signaling pathway， enhancing the PGC-1α/NRF1/TFAM activity， promoting mitochondrial energy metabolism remodeling， and suppressing oxidative stress， inflammation， and myocardial fibrosis.

ObjectiveThis study aimed to evaluate the effects of cycloastragenol （CAG） on mitochondrial dysfunction during cardiac remodeling and to elucidate its regulatory role in myocardial energy metabolic homeostasis and the associated transcriptional regulatory axis. MethodsA rat model of heart failure （HF） was established by ligation of the left anterior descending coronary artery. Rats were randomly divided into a control group， a model group， a captopril group （3.25 mg·kg^-1）， a low-dose CAG group （10 mg·kg^-1， CAG-L）， and a high-dose CAG group （20 mg·kg^-1， CAG-H）. After 28 days of treatment， left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular end-diastolic diameter （LVIDd）， and left ventricular end-systolic diameter （LVIDs） were assessed by echocardiography. Serum levels of N-terminal pro-brain natriuretic peptide （NT-proBNP）， creatine kinase-MB （CK-MB）， cardiac troponinⅠ （cTnI）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and cyclic adenosine monophosphate （cAMP） were measured by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） and Masson's trichrome staining were used to evaluate myocardial histopathology and fibrosis. Wheat germ agglutinin （WGA）， reactive oxygen species （ROS）， and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） staining were performed to assess cardiomyocyte hypertrophy， oxidative stress， and apoptosis. Adenosine triphosphate （ATP） content and the activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ were determined by colorimetric assays. The mRNA expression of α-smooth muscle actin （α-SMA）， Col Ⅰ， and Col Ⅲ was detected by Real-time quantitative polymerase chain reaction （Real-time PCR）， while the protein levels of β₂-adrenergic receptor （ADRB2）， protein kinase A （PKA）， phosphorylated cAMP response element-binding protein/total cAMP response element-binding protein （p-CREB/CREB）， peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）， nuclear respiratory factor 1 （NRF1）， and mitochondrial transcription factor A （TFAM） were analyzed by Western blot. ResultsCompared with the control group， the model group exhibited significantly decreased LVEF， LVFS， and ATP levels （P<0.05）， and markedly increased LVIDd， LVIDs， NT-proBNP， CK-MB， cTnI， IL-1β， IL-6， TNF-α， ROS levels， TUNEL-positive rate， Col deposition area， and the mRNA expression of α-SMA， Col Ⅰ， and Col Ⅲ （P<0.05）. In addition， the activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ， the protein expression of ADRB2， PKA， p-CREB， PGC-1α， NRF1， and TFAM， as well as the cAMP content， were significantly reduced （P<0.05）. Compared with the model group， both low- and high-dose CAG significantly increased LVEF and LVFS， and decreased LVIDd， LVIDs， and the levels of NT-proBNP， CK-MB， and cTnI （P<0.05）. CAG treatment alleviated myocardial disarray and Collagen deposition， and downregulated the mRNA expression of α-SMA， Col Ⅰ， and Col Ⅲ. The treatment markedly reduced ROS generation and the TUNEL-positive rate （P<0.05）， thereby attenuating cardiomyocyte hypertrophy and inflammatory responses. Furthermore， CAG treatment increased ATP content and the activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ， accompanied by upregulation of PGC-1α， NRF1， TFAM， ADRB2， PKA， and p-CREB protein expression as well as cAMP levels （P<0.05）. The CAG-H group showed the most pronounced improvements， which were superior to those of the captopril group and the CAG-L group. ConclusionCycloastragenol delays adverse cardiac remodeling and improves cardiac function by activating the ADRB2-mediated GPCR/cAMP/PKA/CREB signaling pathway， enhancing the PGC-1α/NRF1/TFAM activity， promoting mitochondrial energy metabolism remodeling， and suppressing oxidative stress， inflammation， and myocardial fibrosis.

OBJECTIVEThis study aimed to investigate the effect of a lactoperoxidase-peroxidase-thiocyanate (LPO-H2O-SCN-) system with different concentrations of iodine (I-) on Streptococcus mutans (S. mutans), particularly on various parameters, including growth, adhesion, glucosyltransferase (GTF) enzyme activity, and insoluble exopolysaccharide synthesis.

METHODSS. mutans ATCC 25175 was used as experimental species. Clonal formation unit (CFU) were counted to investigate the inhibitory effect on bacterial growth. The inhibition rate of bacterial adherence was calculated to analyze the effect on adhesion. Anthrone method was used to determine the content of insoluble exopolysaccharides and the amount of reducing saccharides. GTF activity and enzyme activity were then determined.

RESULTSThe inhibitory ability of the LPO-H2O2-SCN- system with I- on the cariogenicinity of S. mutans was strengthened as I- concentration was increased. At I- concentration > or = 100 micromol x L(-1) the antibacterial effects were significantly increased compared with those of the control group (P < 0.05). At I- concentration > or = 1,000 micromol x L(-1), the antibacterial effects were significantly improved compared with those of the group with SCN-only (P < 0.05). At I- concentration > or = 100 micromol x L(-1), the inhibition rate of bacterial adherence was > 50%; insoluble exopolysaccharide synthesis and GTF enzyme activity were reduced (P < 0.05).

CONCLUSIONThe antibacterial effects of the LPO-H2O2-I- system were enhanced by adding I- to overcome the antagonistic effect of physiological SCN- concentration. LPO-H2O2-SCN- system with different concentrations of I- showed statistically significant inhibitory effects on growth, adhesion, insoluble exopolysaccharide synthesis, and GTF enzyme activity.

Anti-Bacterial Agents ; Bacterial Adhesion ; Hydrogen Peroxide ; In Vitro Techniques ; Iodine ; Lactoperoxidase ; Oxidation-Reduction ; Streptococcus mutans ; Thiocyanates

OBJECTIVETo introduce the recent developments in cancer immunoinformatics with an emphasis on the latest trends and future direction.

DATA SOURCESAll related articles in this review were searched from PubMed published in English from 1992 to 2013. The search terms were cancer, immunoinformatics, immunological databases, and computational vaccinology.

STUDY SELECTIONOriginal articles and reviews those were related to application of cancer immunoinformatics about tumor basic and clinical research were selected.

RESULTSCancer immunoinformatics has been widely researched and applied in a series of fields of cancer research, including computational tools for cancer, cancer immunological databases, computational vaccinology, and cancer diagnostic workflows. Furthermore, the improvement of its theory and technology brings an enlightening insight into understanding and researching cancer and helps expound more deep and complete mechanisms of tumorigenesis and progression.

CONCLUSIONCancer immunoinformatics provides promising methods and novel strategies for the discovery and development of tumor basic and clinical research.

Cancer Vaccines ; therapeutic use ; Computational Biology ; methods ; Humans ; Neoplasms ; diagnosis ; immunology ; prevention & control

Objective This study aimed to investigate the effect of a lactoperoxidase-peroxidase-thiocyanate (LPO-H2O2- SCN-) system with different concentrations of iodine (I-) on Streptococcus mutans (S. mutans), particularly on various parameters, including growth, adhesion, glucosyltransferase (GTF) enzyme activity, and insoluble exopolysaccharide synthesis. Methods S. mutans ATCC 25175 was used as experimental species. Clonal formation unit (CFU) were counted to investigate the inhibitory effect on bacterial growth. The inhibition rate of bacterial adherence was calculated to analyze the effect on adhesion. Anthrone method was used to determine the content of insoluble exopolysaccharides and the amount of reducing saccharides. GTF activity and enzyme activity were then determined. Results The inhibitory ability of the LPO-H2O2-SCN- system with I- on the cariogenicinity of S. mutans was strengthened as I- concentration was increased. At I- concentration≥100 μmol·L-1, the antibacterial effects were significantly increased compared with those of the control group (P<0.05). At I- concentration≥ 1 000 μmol·L-1, the antibacterial effects were significantly improved compared with those of the group with SCN- only (P< 0.05). At I- concentration≥100 μmol·L-1, the inhibition rate of bacterial adherence was>50%; insoluble exopolysaccharide synthesis and GTF enzyme activity were reduced (P<0.05). Conclusion The antibacterial effects of the LPO-H2O2-I- system were enhanced by adding I- to overcome the antagonistic effect of physiological SCN- concentration. LPO-H2O2-SCN- system with different concentrations of I- showed statistically significant inhibitory effects on growth, adhesion, insoluble exopolysaccharide synthesis, and GTF enzyme activity.

Objective To observe the effect of Wenxiao Granule on the expression of MCP-1 and TNF-? in experimental atherosclerosis rabbit, and explore its mechanism in treating atherosclerosis. Methods Thirty-six New Zealand rabbits were randomized to four groups: control group, Wenxiao granule group, Simvastatin group. They were fed a high-fat diet except normal group until the mature atherosclerotic plaques formed. The rabbits in two drug-treated groups were treated with respective drug for 8 weeks. All rabbits were sacrificed. The morphology and composition of atherosclerotic plaques in aortic roots were examined. The expression of MCP-1 and TNF-? were determined by immunohistochemical staining. Results The expression of MCP-1 and TNF-? in plaque of Wenxiao Granule group and simvastatin group were significantly dereased compared with the model group (P 0.05). Conclusion Wenxiao Granule can inhibit the expression of MCP-1 and TNF-?, which may stabilize plaque of atherosclerosis.

Objective:To observe clinical therapeutic effects of method for supplementing Qi,activating blood circulation and resolving phlegm and effects on vascular endothelial function and blood coagulation system in senile patient of hyperlipemia.Methods:96 senile patients of hyperlipemia were randomly divided into a treatment group(n=56)and a control group(n=40).The patients of the treatment group were treated by oral administration of Danshen Jueming Granules and the control group by oral administration of Xuezhikang Capsules.Blood lipids,vascular endothelial function,blood coagulation system and safety were observed.Results:After treatment,the treatment group in decrease of plasma total cholesterol(TC)and low density lipoprotein-cholesterol(LDL-C)was superior to the control group(P