Genome evolution driven by host adaptations results in a more virulent and antimicrobial-resistant Streptococcus pneumoniae serotype 14

<p>Abstract</p> <p>Background</p> <p><it>Streptococcus pneumoniae </it>serotype 14 is one of the most common pneumococcal serotypes that cause invasive pneumococcal diseases worldwide. Serotype 14 often expresses resistance to a variety of antimicrobial agents, resulting in difficulties in treatment. To gain insight into the evolution of virulence and antimicrobial resistance traits in <it>S. pneumoniae </it>from the genome level, we sequenced the entire genome of a serotype 14 isolate (CGSP14), and carried out comprehensive comparison with other pneumococcal genomes. Multiple serotype 14 clinical isolates were also genotyped by multilocus sequence typing (MLST).</p> <p>Results</p> <p>Comparative genomic analysis revealed that the CGSP14 acquired a number of new genes by horizontal gene transfer (HGT), most of which were associated with virulence and antimicrobial resistance and clustered in mobile genetic elements. The most remarkable feature is the acquisition of two conjugative transposons and one resistance island encoding eight resistance genes. Results of MLST suggested that the major driving force for the genome evolution is the environmental drug pressure.</p> <p>Conclusion</p> <p>The genome sequence of <it>S. pneumoniae </it>serotype 14 shows a bacterium with rapid adaptations to its lifecycle in human community. These include a versatile genome content, with a wide range of mobile elements, and chromosomal rearrangement; the latter re-balanced the genome after events of HGT.</p

THE EFFECT OF INSULIN AND CARBOHYDRATE SUPPLEMENTATION ON GLYCOGEN REPLENISHMENT AMONG DIFFERENT HINDLIMB MUSCLES IN RATS FOLLOWING PROLONGED SWIMMING

In the present study we investigated the interactive effects of insulin and carbohydrate on glycogen replenishment in different rat hindlimb muscles. Forty male Sprague Dawley rats were assigned to 5 groups, including 1) sedentary control with carbohydrate supplement (2 g glucose · kg body wt-1), 2) sedentary rats with 16 hours recovery, carbohydrate and insulin (0.5 U · kg body wt-1), 3) swimming without recovery, 4) swimming with 16 hours recovery and carbohydrate supplement, and 5) swimming with 16 hours recovery, carbohydrate and insulin. The swimming protocol consisted of two 3 h swimming sections, which were separated by a 45 min rest. The insulin and carbohydrate were administered to the rats immediately after exercise. At the end of the experiment, the soleus (S), plantaris (P), quadriceps (Q) and gastrocnemius (G) were surgically excised to evaluate glycogen utilization and replenishment. We observed that glycogen utilization was significantly lower in G and Q than S and P during swimming (p <0.05), and S showed the greatest capacity of glycogen resynthesis after post-exercise recovery (p <0.05). In the sedentary state, the glycogen synthesis did not differ among hindlimb muscles during insulin and carbohydrate treatments. Interestingly, with insulin and carbohydrate, the glycogen resynthesis in S and P were significantly greater than in Q and G following post-exercise recovery (p <0.05). We therefore concluded that the soleus and plantaris are the primary working muscles during swimming, and the greatest glycogen replenishment capacity of the soleus during post-exercise recovery is likely due to its highest insulin sensitivity

Evaluation of Antioxidant and Free Radical Scavenging Capacities of Polyphenolics from Pods of Caesalpinia pulcherrima

Thirteen polyphenolics were isolated from fresh pods of Caesalpinia pulcherrima using various methods of column chromatography. The structures of these polyphenolics were elucidated as gallic acid (1), methyl gallate (2), 6-O-galloyl-d-glucoside (3), methyl 6-O-galloyl-β-d-glucoside (4), methyl 3,6-di-O-galloyl-α-d-glucopyranoside (5), gentisic acid 5-O-α-d-(6′-O-galloyl)glucopyranoside (6), guaiacylglycerol 4-O-β-d-(6′-O-galloyl)glucopyranoside (7), 3-methoxy-4-hydroxyphenol 1-O-β-d-(6′-O-galloyl) glucopyranoside (8), (+)-gallocatechin (9), (+)-catechin (10), (+)-gallocatechin 3-O-gallate (11), myricetin 3-rhamnoside (12), and ampelopsin (13). All isolated compounds were tested for their antioxidant activities in the 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, and peroxynitrite radicals scavenging assays. Among those compounds, 11, 12, and 2 exhibited the best DPPH-, hydroxyl-, and peroxynitrite radical-scavenging activities, respectively. Compound 7 is a new compound, and possesses better scavenging activities towards DPPH but has equivalent hydroxyl radical scavenging activity when compared to BHT. The paper is the first report on free radical scavenging properties of components of the fresh pods of Caesalpinia pulcherrima. The results obtained from the current study indicate that the free radical scavenging property of fresh pods of Caesalpinia pulcherrima may be one of the mechanisms by which this herbal medicine is effective in several free radical mediated diseases

The Relationship between Qi Deficiency, Cancer-related Fatigue and Quality of Life in Cancer Patients

AbstractBackgroundQi (氣 qì) refers to the vital energy of the body in Traditional Chinese medicines (TCM). Qi deficiency (氣虛 qì xū) is the most common symptom in cancer patients according to the concept of TCM. We hypothesized that cancer patients with Qi deficiency suffer from poor quality of life (QOL) and fatigue.MethodAmong the 256 registered cancer patients screened at our outpatient clinic, a total of 198 were enrolled. The inclusion criteria were (1) age between 18 and 70years, (2) cancer diagnosis confirmed by the professional physician, (3) being Chinese, and (4) Eastern Cooperative Oncology Group (ECOG) performance status rating (PSR)≤3. The major outcome is the difference in QOL score in cancer patients with and without Qi deficiency.ResultsThe initial results showed statistically significant differences in WHO-QOL scores in physical, psychological, and social domains between the groups with and without Qi deficiency as well as the groups with and without cancerrelated fatigue (CRF). All patients with CRF present were also diagnosed as Qi deficient. In addition, among the patients with no CRF, 39.9% (69/173) were diagnosed as suffering from Qi deficiency, which led to poor QOL.ConclusionsThe present study showed statistically significant difference in WHO-QOL scores in physical, psychological, and social domains between the groups with and without Qi deficiency as well as the groups with and without CRF. Cancer patients diagnosed with Qi deficiency or CRF have poor QOL. The concept of Qi deficiency in TCM might be applied to cancer health care

The novel synthesized 2-(3-(methylamino)phenyl)-6-(pyrrolidin-1-yl)quinolin-4-one (Smh-3) compound induces G2/M phase arrest and mitochondrial-dependent apoptotic cell death through inhibition of CDK1 and AKT activity in HL-60 human leukemia cells

2-Phenyl-4-quinolone series compounds have exhibited growth inhibitory influence on several human cancer cell lines. In this study, we investigated the effects of 2-(3-(methylamino)phenyl)-6-(pyrrolidin-1-yl)quinolin-4-one (Smh-3) on viability, cell cycle and apoptotic cell death which occurred in different leukemia cell lines (HL-60, U937 and K562) in a dose- and time-dependent manner, but which did not obviously impair the viability of normal human umbilical vein endothelial cells (HUVEC) in vitro. The approximate IC50 was 103.26 ± 4.59 nM for a 48 h treatment in HL-60 cells. Cell cycle analysis showed that 100 nM Smh-3 induced signi-ficant G2/M arrest in examined cells. Within 0, 12, 24 and 48 h of treatment, Smh-3 inhibited CDK1 activity and decreased protein levels of CDK1, cyclin A and cyclin B. Smh-3-induced chromatin condensation and DNA fragmentation were determined by DAPI and TUNEL staining. Cell apoptosis was significantly reduced after pretreatment with a pan-caspase inhibitor (Z-VAD-fmk) and results indicated that Smh-3-induced apoptosis was mainly mediated by activation of the caspase cascade in HL-60 cells. Results from colorimetric assays and Western blot analysis indicated that activities of caspase-9, -7 and -3 were promoted in Smh-3-treated HL-60 cells during cell apoptosis. Smh-3-induced apoptosis in HL-60 cells was accompanied by an apparent increase in ROS production, and protein levels of cytosolic cytochrome c, apoptotic protease activating factor-1 (Apaf-1) and apoptosis-inducing factor (AIF). Strikingly, Smh-3 induced apoptosis in HL-60 cells by simultaneously suppressing protein levels of AKT, p-AKT, p-mTOR and p-BAD and inducing BAD protein levels. Taken together, we conclude that Smh-3 acts against leukemia cells in vitro via G2/M phase arrest, down-regulation of AKT activity and induction of mitochondrial-dependent apoptotic pathways

Detection of the inferred interaction network in hepatocellular carcinoma from EHCO (Encyclopedia of Hepatocellular Carcinoma genes Online)

BACKGROUND: The significant advances in microarray and proteomics analyses have resulted in an exponential increase in potential new targets and have promised to shed light on the identification of disease markers and cellular pathways. We aim to collect and decipher the HCC-related genes at the systems level. RESULTS: Here, we build an integrative platform, the Encyclopedia of Hepatocellular Carcinoma genes Online, dubbed EHCO , to systematically collect, organize and compare the pileup of unsorted HCC-related studies by using natural language processing and softbots. Among the eight gene set collections, ranging across PubMed, SAGE, microarray, and proteomics data, there are 2,906 genes in total; however, more than 77% genes are only included once, suggesting that tremendous efforts need to be exerted to characterize the relationship between HCC and these genes. Of these HCC inventories, protein binding represents the largest proportion (~25%) from Gene Ontology analysis. In fact, many differentially expressed gene sets in EHCO could form interaction networks (e.g. HBV-associated HCC network) by using available human protein-protein interaction datasets. To further highlight the potential new targets in the inferred network from EHCO, we combine comparative genomics and interactomics approaches to analyze 120 evolutionary conserved and overexpressed genes in HCC. 47 out of 120 queries can form a highly interactive network with 18 queries serving as hubs. CONCLUSION: This architectural map may represent the first step toward the attempt to decipher the hepatocarcinogenesis at the systems level. Targeting hubs and/or disruption of the network formation might reveal novel strategy for HCC treatment

Korean Red Ginseng Improves Blood Pressure Stability in Patients with Intradialytic Hypotension

Introduction. Intradialytic hypotension (IDH) is a common complication during hemodialysis which may increase mortality risks. Low dose of Korean red ginseng (KRG) has been reported to increase blood pressure. Whether KRG can improve hemodynamic stability during hemodialysis has not been examined. Methods. The 8-week study consisted of two phases: observation phase and active treatment phase. According to prehemodialysis blood pressure (BP), 38 patients with IDH were divided into group A (BP ≥ 140/90 mmHg, n = 18) and group B (BP < 140/90 mmHg, n = 20). Patients were instructed to chew 3.5 gm KRG slices at each hemodialysis session during the 4-week treatment phase. Blood pressure changes, number of sessions disturbed by symptomatic IDH, plasma levels of vasoconstrictors, blood biochemistry, and adverse effects were recorded. Results. KRG significantly reduced the degree of blood pressure drop during hemodialysis (P < 0.05) and the frequency of symptomatic IDH (P < 0.05). More activation of vasoconstrictors (endothelin-1 and angiotensin II) during hemodialysis was found. The postdialytic levels of endothelin-1 and angiotensin II increased significantly (P < 0.01). Conclusion. Chewing KRG renders IDH patients better resistance to acute BP reduction during hemodialysis via activation of vasoconstrictors. Our results suggest that KRG could be an adjuvant treatment for IDH