Effect of a Chinese herbal medicine on chronic periodontitis patients

published_or_final_versio

Effect of a Chinese herbal medicine on aggressive periodontitis patients

published_or_final_versio

The pharmacological regulation of cellular mitophagy

Small molecules are pharmacological tools of considerable value for dissecting complex biological processes and identifying potential therapeutic interventions. Recently, the cellular quality-control process of mitophagy has attracted considerable research interest; however, the limited availability of suitable chemical probes has restricted our understanding of the molecular mechanisms involved. Current approaches to initiate mitophagy include acute dissipation of the mitochondrial membrane potential (ΔΨm) by mitochondrial uncouplers (for example, FCCP/CCCP) and the use of antimycin A and oligomycin to impair respiration. Both approaches impair mitochondrial homeostasis and therefore limit the scope for dissection of subtle, bioenergy-related regulatory phenomena. Recently, novel mitophagy activators acting independently of the respiration collapse have been reported, offering new opportunities to understand the process and potential for therapeutic exploitation. We have summarized the current status of mitophagy modulators and analyzed the available chemical tools, commenting on their advantages, limitations and current applications

Baicalin administration attenuates hyperglycemia-induced malformation of cardiovascular system

In this study, the effects of Baicalin on the hyperglycemia-induced cardiovascular malformation during embryo development were investigated. Using early chick embryos, an optimal concentration of Baicalin (6 μM), was identified which could prevent hyperglycemia-induced cardiovascular malformation of embryos. Hyperglycemia-enhanced cell apoptosis was reduced in embryos and HUVECs in the presence of Baicalin. Hyperglycemia-induced excessive ROS production was inhibited when Baicalin was administered. Analyses of SOD, GSH-Px, MAQE and GABAA suggested Baicalin plays an antioxidant role in chick embryos possibly through suppression of outwardly rectifying Cl(-) in the high-glucose microenvironment. In addition, hyperglycemia-enhanced autophagy fell in the presence of Baicalin, through affecting the ubiquitin of p62 and accelerating autophagy flux. Both Baicalin and Vitamin C could decrease apoptosis, but CQ did not, suggesting autophagy to be a protective function on the cell survival. In mice, Baicalin reduced the elevated blood glucose level caused by streptozotocin (STZ). Taken together, these data suggest that hyperglycemia-induced embryonic cardiovascular malformation can be attenuated by Baicalin administration through suppressing the excessive production of ROS and autophagy. Baicalin could be a potential candidate drug for women suffering from gestational diabetes mellitus

Association between physical activity and metabolic syndrome: a cross sectional survey in adolescents in Ho Chi Minh City, Vietnam

<p>Abstract</p> <p>Background</p> <p>The emerging epidemic of overweight/obesity in adolescents in Ho Chi Minh City, Vietnam underlines the importance of studying the metabolic syndrome in Vietnamese adolescents who are becoming progressively more inactive. No study in Vietnam has examined the association of metabolic syndrome with moderate to vigorous physical activity (PA) levels among adolescents. We aimed to examine this association in a sample of urban adolescents from Ho Chi Minh City.</p> <p>Methods</p> <p>A cross-sectional assessment was conducted in 2007 on a representative sample of 693 high-school students from urban districts in Ho Chi Minh City. Metabolic syndrome was defined according to the International Diabetes Federation criteria and physical activity was measured with Actigraph accelerometers. The association between physical activity and metabolic syndrome was assessed by using multiple logistic regression models.</p> <p>Results</p> <p>Overall 4.6% of the adolescents and 11.8% of the overweight/obese adolescents had metabolic syndrome. Elevated BP was the most common individual component of the metabolic syndrome (21.5%), followed by hypertriglyceridemia (11.1%). After adjusting for other study factors, the odds of metabolic syndrome among youth in the lowest physical activity group (<43 minutes of physical activity/day) were five times higher than those in the highest physical activity group (>103 minutes/day) (AOR = 5.3, 95% CI: 1.5, 19.1). Metabolic syndrome was also positively associated with socioeconomic status (AOR = 9.4, 95% CI: 2.1, 42.4).</p> <p>Conclusions</p> <p>A more physically active lifestyle appears to be associated with a lower odds of metabolic syndrome in Vietnamese adolescents. Socio-economic status should be taken into account when planning interventions to prevent adolescent metabolic syndrome.</p

Machine learning versus classical electrocardiographic criteria for echocardiographic left ventricular hypertrophy in a pre-participation cohort

Background: Classical electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH) are well studied in older populations and patients with hypertension. Their utility in young pre-participation cohorts is unclear.Aims: We aimed to develop machine learning models for detection of echocardiogram-diagnosed LVH from ECG, and compare these models with classical criteria.Methods: Between November 2009 and December 2014, pre-participation screening ECG and subsequent echocardiographic data was collected from 17 310 males aged 16 to 23, who reported for medical screening prior to military conscription. A final diagnosis of LVH was made during echocardiography, defined by a left ventricular mass index &gt;115 g/m2. The continuous and threshold forms of classical ECG criteria (Sokolow–Lyon, Romhilt–Estes, Modified Cornell, Cornell Product, and Cornell) were compared against machine learning models (Logistic Regression, GLMNet, Random Forests, Gradient Boosting Machines) using receiver-operating characteristics curve analysis. We also compared the important variables identified by machine learning models with the input variables of classical criteria.Results: Prevalence of echocardiographic LVH in this population was 0.82% (143/17310). Classical ECG criteria had poor performance in predicting LVH. Machine learning methods achieved superior performance: Logistic Regression (area under the curve [AUC], 0.811; 95% confidence interval [CI], 0.738–0.884), GLMNet (AUC, 0.873; 95% CI, 0.817–0.929), Random Forest (AUC, 0.824; 95% CI, 0.749–0.898), Gradient Boosting Machines (AUC, 0.800; 95% CI, 0.738–0.862).Conclusions: Machine learning methods are superior to classical ECG criteria in diagnosing echocardiographic LVH in the context of pre-participation screening

The Arabidopsis Resistance-Like Gene SNC1 Is Activated by Mutations in SRFR1 and Contributes to Resistance to the Bacterial Effector AvrRps4

The SUPPRESSOR OF rps4-RLD1 (SRFR1) gene was identified based on enhanced AvrRps4-triggered resistance in the naturally susceptible Arabidopsis accession RLD. No other phenotypic effects were recorded, and the extent of SRFR1 involvement in regulating effector-triggered immunity was unknown. Here we show that mutations in SRFR1 in the accession Columbia-0 (Col-0) lead to severe stunting and constitutive expression of the defense gene PR1. These phenotypes were temperature-dependent. A cross between srfr1-1 (RLD background) and srfr1-4 (Col-0) showed that stunting was caused by a recessive locus in Col-0. Mapping and targeted crosses identified the Col-0-specific resistance gene SNC1 as the locus that causes stunting. SRFR1 was proposed to function as a transcriptional repressor, and SNC1 is indeed overexpressed in srfr1-4. Interestingly, co-regulated genes in the SNC1 cluster are also upregulated in the srfr1-4 snc1-11 double mutant, indicating that the overexpression of SNC1 is not a secondary effect of constitutive defense activation. In addition, a Col-0 RPS4 mutant showed full susceptibility to bacteria expressing avrRps4 at 24°C but not at 22°C, while RLD susceptibility was not temperature-dependent. The rps4-2 snc1-11 double mutant showed increased, but not full, susceptibility at 22°C, indicating that additional cross-talk between resistance pathways may exist. Intriguingly, when transiently expressed in Nicotiana benthamiana, SRFR1, RPS4 and SNC1 are in a common protein complex in a cytoplasmic microsomal compartment. Our results highlight SRFR1 as a convergence point in at least a subset of TIR-NBS-LRR protein-mediated immunity in Arabidopsis. Based on the cross-talk evident from our results, they also suggest that reports of constitutive resistance phenotypes in Col-0 need to consider the possible involvement of SNC1

Nucleotide diversity and molecular evolution of the WAG-2 gene in common wheat (Triticum aestivum L) and its relatives

In this work, we examined the genetic diversity and evolution of the WAG-2 gene based on new WAG-2 alleles isolated from wheat and its relatives. Only single nucleotide polymorphisms (SNP) and no insertions and deletions (indels) were found in exon sequences of WAG-2 from different species. More SNPs and indels occurred in introns than in exons. For exons, exons+introns and introns, the nucleotide polymorphism π decreased from diploid and tetraploid genotypes to hexaploid genotypes. This finding indicated that the diversity of WAG-2 in diploids was greater than in hexaploids because of the strong selection pressure on the latter. All dn/ds ratios were < 1.0, indicating that WAG-2 belongs to a conserved gene affected by negative selection. Thirty-nine of the 57 particular SNPs and eight of the 10 indels were detected in diploid species. The degree of divergence in intron length among WAG-2 clones and phylogenetic tree topology suggested the existence of three homoeologs in the A, B or D genome of common wheat. Wheat AG-like genes were divided into WAG-1 and WAG-2 clades. The latter clade contained WAG-2, OsMADS3 and ZMM2 genes, indicating functional homoeology among them

NOXA-Induced Alterations in the Bax/Smac Axis Enhance Sensitivity of Ovarian Cancer Cells to Cisplatin

Ovarian cancer is the most common cause of death from gynecologic malignancy. Deregulation of p53 and/or p73-associated apoptotic pathways contribute to the platinum-based resistance in ovarian cancer. NOXA, a pro-apoptotic BH3-only protein, is identified as a transcription target of p53 and/or p73. In this study, we found that genetic variants of Bcl-2 proteins exist among cisplatin-sensitive and -resistant ovarian cancer cells, and the responses of NOXA and Bax to cisplatin are regulated mainly by p53. We further evaluated the effect of NOXA on cisplatin. NOXA induced apoptosis and sensitized A2780s and SKOV3 cells to cisplatin in vitro and in vivo. The effects were mediated by elevated Bax expression, enhanced caspase activation, release of Cyt C and Smac into the cytosol. Furthermore, gene silencing of Bax or Smac significantly attenuated NOXA and/or cisplatin-induced apoptosis in chemosensitive A2780s cells, whereas overexpression of Bax or addition of Smac-N7 peptide significantly increased NOXA and/or cisplatin-induced apoptosis in chemoresistant SKOV3 cells. To our knowledge, these data suggest a new mechanism by which NOXA chemosensitized ovarian cancer cells to cisplatin by inducing alterations in the Bax/Smac axis. Taken together, our findings show that NOXA is potentially useful as a chemosensitizer in ovarian cancer therapy