Effect of physical exercise under different intensity and antioxidative supplementation for plasma superoxide dismutase in healthy adults:systematic review and network meta-analysis

BACKGROUND: The dynamic balance between oxidation and anti-oxidation in the body’s internal environment has a significant meaning for human health. Physical exercise and antioxidative supplementation could affect the balance of oxidation and anti-oxidation systems. The evidence on the effects of physical exercise and antioxidative supplementation is mixed. AIMS: To identify the effects of physical exercise, antioxidative supplementation, and their combination on the dynamic balance between oxidation and anti-oxidation in different subgroups of healthy adults. METHODS: All studies which reported randomized controlled trials with healthy participants were screened and included from the databases of PubMed, Medline, Embase, and Ovid. All participants were reclassified according to their different daily life activities. All physical exercise interventions were reclassified according to the intensity. The effect size would be calculated in percent or factor units from the mean level change with its associated random-effect variance. RESULT: There were 27 studies included in this review. The agreement between authors by using The Cochrane Collaboration Risk of Bias Assessment Tool reached a kappa-value of 0.72. Maintaining a regular physical exercise routine in an appropriate intensity would be beneficial to the body’s anti-oxidative potential. Anti-oxidative supplementation could have some positive but limited effects on the body’s anti-oxidative status and complex interaction with physical exercise. CONCLUSION: Keeping a regular physical exercise routine and gradually increasing its intensity according to the individual’s daily life activity might be a better choice to maintain and enhancing the body’s antioxidation potential, only using anti-oxidative supplementation is not recommended. More research is needed to explore the best combination protocol. REGISTRATION NUMBER: CRD42021241995

Genetic Diversity of Salmonella enteric serovar Typhi and Paratyphi in Shenzhen, China from 2002 through 2007

<p>Abstract</p> <p>Background</p> <p>Typhoid and paratyphoid fever are endemic in China. The objective of this investigation was to determine the molecular features of nalidixic acid-resistant <it>Salmonella enteric </it>serovar Typhi (<it>S. typhi</it>) and Paratyphi (<it>S. paratyphi</it>) from blood isolates in Shenzhen, China.</p> <p>Results</p> <p>Twenty-five <it>S. typhi </it>and 66 <it>S. paratyphi </it>were isolated from 91 bacteriemic patients between 2002 and 2007 at a hospital in Shenzhen, Southern China. Fifty-two percent (13/25) of <it>S. typhi </it>and 95.3% (61/64) of <it>S. paratyphi </it>A were resistant to nalidixic acid. Sixty-seven isolates of nalidixic acid-resistant <it>Salmonella </it>(NARS) showed decreased susceptibility to ciprofloxacin (MICs of 0.125-1 μg/mL). All 75 NARS isolates had a single substitution in the quinolone resistance-determining region (QRDR) of GyrA (Ser83→Phe/Pro/Tyr, or Asp87→Gly/Asn), and 90.7% of these isolates carried the substitution Ser83Phe in GyrA. No mutation was found in the QRDR of <it>gyrB</it>, <it>parC</it>, or <it>parE</it>. Plasmid mediated quinolone resistance genes including <it>qnr </it>and <it>aac(6')-Ib-cr </it>were not detected in any isolate. Twenty-two distinct pulsed field gel electrophoresis (PFGE) patterns were observed among <it>S. typhi</it>. Sixty-four isolates of <it>S. paratyphi </it>A belonged to one clone. Eighty-seven investigated inpatients were infected in the community. Six patients infected by <it>S. paratyphi </it>A had a travel history before infection.</p> <p>Conclusions</p> <p>Nalidixic acid-resistant <it>S. typhi </it>and <it>S. paratyphi </it>A blood isolates were highly prevalent in Shenzhen, China. PFGE showed the variable genetic diversity of nalidixic acid-resistant <it>S. typhi </it>and limited genetic diversity of nalidixic acid -resistant <it>S. paratyphi </it>A.</p

AZD5153 Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo

Backgrounds/Aims: Bromodomain-containing protein 4 (BRD4) overexpression participates in prostate cancer progression by enhancing the transcriptional activity and expression of several key oncogenes. AZD5153 is a novel BRD4 inhibitor. Methods: Prostate cancer cells were treated with AZD5153. Cell survival was tested by MTT assay and clonogenicity assay. Cell proliferation was tested by [H3] DNA incorporation assay. Cell apoptosis was tested by caspase-3/-9 activity assay, Histone DNA ELISA assay, Annexin V FACS assay and TUNEL staining assay. Cell cycle progression was tested by propidium iodide (PI) FACS assay. Signaling was tested by Western blotting assay. The nude mice PC-3 xenograft model was applied to test AZD5153’s activity in vivo. Results: AZD5153 inhibited proliferation and survival of established and primary prostate cancer cells. AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells. AZD5153 was non-cytotoxic to the prostate epithelial cells. AZD5153 downregulated BRD4 targets (cyclin D1, Myc, Bcl-2, FOSL1 and CDK4) in PC-3 and primary prostate cancer cells. Further studies show that AKT could be the primary resistance factor of AZD5153. Pharmacological inhibition or genetic depletion of AKT induced BRD4 downregulation, sensitizing AZD5153-induced cytotoxicity in PC-3 cells. In vivo, AZD5153 oral administration inhibited PC-3 xenograft tumor growth in nude mice. Its anti-tumor activity was further enhanced with co-treatment of the AKT specific inhibitor MK-2206. Conclusion: Together, our results indicate a promising therapeutic value of the novel BRD4 inhibitor AZD5153 against prostate cancer cells

Employing “FDAlabel” Database to Extract Pharmacogenomics Information from FDA Drug Labeling to Advance the Study of Precision Medicine

Pharmacogenomics (PGx) focuses on how genomics and genetic variants (inherited and acquired) affect drug response. A better understanding of the association between genetic markers and individual phenotypes may improve therapy by enhancing drug efficacy, safety, and advance precision medicine. The FDALabel database (https://rm2.scinet.fda.gov/druglabel/#simsearch-0) was developed from the FDA\u27s Structured Product Labeling (SPL) repository to allow users to perform full-text and customizable searches of the labeling section {e.g. Boxed Warning, Warning and Precautions, Adverse Reaction (AR) sections}. In this study, 48 known biomarkers were used to query PGx relevant contents from the FDALabel database, including Indication, Clinical Pharmacology, Clinical Studies, and Use in Specific Populations. As a result, we identified 162 drugs out of 1129 small molecule drugs with PGx biomarker information. Furthermore, statistical analysis, pattern recognition, and network visualization were applied to investigate association of drug efficacy and severe ARs with PGx biomarkers and subpopulation. The results indicated that these drugs have a higher association with certain ARs in specific patient subpopulations (e.g., a higher association between CYP2D6 poor metabolizers and ARs caused by drugs for the treatment of psychiatric disoders ), and cover a broad range of therapeutic classes (e.g., Psychiatry, Cardiology, Oncology, and Endocrinology). FDALabel database (free publicly available) provides a convenient tool to navigate and extract PGx information from FDA-approved drug. The knowledge gained from these drugs and biomarkers in this study will enhance the understanding of PGx to advance precision medicine

Exercise downregulates HIPK2 and HIPK2 inhibition protects against myocardial infarction

Background: Exercise can protect myocardial infarction (MI) and downregulate cardiac Homeodomain-Interacting Protein Kinase 2 (HIPK2). However, the role of HIPK2 in MI is unclear. Methods: HIPK2–/– mice and miR-222–/– rats, HIPK2 inhibitor (PKI1H) and adeno-associated virus serotype 9 (AAV9) carrying miR-222 were applied in the study. Animals were subjected to running, swimming, acute MI or post-MI remodeling. HIPK2 inhibition and P53 activator were used in neonatal rat cardiomyocytes (NRCMs) and human embryonic stem cell-derived cardiomyocytes (hESC-CMs) subjected to oxygen glucose deprivation/reperfusion (OGD/R). Serum miR-222 levels were analyzed in healthy people and MI patients that were survival or readmitted to the hospital and/or died. Findings: Cardiac HIPK2 protein levels were reduced by exercise while increased in MI. In vitro, HIPK2 suppression by lentiviral vectors or inhibitor prevented apoptosis induced by OGD/R in NRCMs and hESC-CMs. HIPK2 inhibitor-treated mice and HIPK2–/– mice reduced infarct size after acute MI, and preserved cardiac function in MI remodeling. Mechanistically, protective effect against apoptosis by HIPK2 suppression was reversed by P53 activators. Furthermore, increasing levels of miR-222, targeting HIPK2, protected post-MI cardiac dysfunction, whereas cardiac dysfunction post-MI was aggravated in miR-222–/– rats. Moreover, serum miR-222 levels were significantly reduced in MI patients, as well as in MI patients that were readmitted to the hospital and/or died compared to those not. Interpretation: Exercise-induced HIPK2 suppression attenuates cardiomyocytes apoptosis and protects MI by decreasing P-P53. Inhibition of HIPK2 represents a potential novel therapeutic intervention for MI. Funding: This work was supported by the grants from National Key Research and Development Project (2018YFE0113500 to JJ Xiao), National Natural Science Foundation of China (82020108002, 81722008, and 81911540486 to JJ Xiao, 81400647 to MJ Xu, 81800265 to YJ Liang), Innovation Program of Shanghai Municipal Education Commission (2017-01-07-00-09-E00042 to JJ Xiao), the grant from Science and Technology Commission of Shanghai Municipality (18410722200 and 17010500100 to JJ Xiao), the “Dawn” Program of Shanghai Education Commission (19SG34 to JJ Xiao), Shanghai Sailing Program (21YF1413200 to QL Zhou). JS is supported by Horizon2020 ERC-2016-COG EVICARE (725229)

Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition

Ishikawa, T., Kitaura, Y., Kadota, Y. et al. Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition. Sci Rep 7, 39825 (2017). https://doi.org/10.1038/srep3982

On the Lab. II building site

425 special CDSs in PCN033 (XLSX 29 kb