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Cytochrome P450 (CYPs) participate in the mechanisms of cardiovascular disease. The purpose of this research was to evaluate the contributions of CYP24A1 variants to coronary heart disease (CHD) among the Chinese Han population.
This study included 505 CHD cases and 508 controls. Four variants of CYP24A1 (rs2762934, rs1570669, rs6068816 and rs2296241) were chosen and genotyped by the Agena MassARRAY system among the Chinese population. The linkage between CYP24A1 variants and CHD risk were assessed by logistic regression to compute the odds ratio (OR) and 95% confidence interval (CI). Then, multifactor dimensionality reduction (MDR) was applied to analyze the interactions of CYP24A1 variants.
The results of this study showed that CYP24A1 rs6068816 significantly enhanced CHD risk in multiple genetic models (allele P = 0.014; codominant P = 0.015; dominant P = 0.043; recessive P = 0.040; additive P = 0.013), whereas rs2296241 was likely to protect individuals from CHD (codominant P = 0.019; recessive P = 0.013; additive P = 0.033). Stratification analysis revealed that CYP24A1 polymorphisms had strong relationships with CHD risk that were dependent on age, sex, Gensini grade and smoking status (P < 0.05). Moreover, a four-locus model (rs2762934, rs1570669, rs6068816 and rs2296241) had significant impact on CHD risk in MDR analysis.
It revealed that CYP24A1 variants were significantly linked with CHD susceptibility in the Chinese population.
It revealed that CYP24A1 variants were significantly linked with CHD susceptibility in the Chinese population.
China carried out a comprehensive drug price reform (CDPR) in 2017 to control the growing expense of drug effectively and reduce the financial burden of inpatients. However, early studies in pilot regions found the heterogeneity in the effectiveness of CDPR from different regions and other negative effects. This study aimed to evaluate the effects of the reform on medical expenses, medical service utilisation and government financial reimbursement for inpatients in economically weaker regions.
Shihezi was selected as the sample city, and 238,620 inpatients, who were covered by basic medical insurance (BMI) and had complete information from September 2016 to August 2018 inpublic hospitals, were extracted by cluster sampling. An interrupted series design was used to compare the changing trends in medical expenses, medical service utilisation and reimbursement of BMI for inpatients before and after the reform.
Compared with the baseline trends before the CDPR, those after the CDPR were observed with decreas in tertiary hospitals.
Activation of silent biosynthetic gene clusters (BGCs) in marine-derived actinomycete strains is a feasible strategy to discover bioactive natural products. Actinoalloteichus sp. AHMU CJ021, isolated from the seashore, was shown to contain an intact but silent caerulomycin A (CRM A) BGC-cam in its genome. Thus, a genome mining work was preformed to activate the strain's production of CRM A, an immunosuppressive drug lead with diverse bioactivities.
To well activate the expression of cam, ribosome engineering was adopted to treat the wild type Actinoalloteichus sp. AHMU CJ021. The initial mutant strain XC-11G with gentamycin resistance and CRM A production titer of 42.51 ± 4.22mg/L was selected from all generated mutant strains by gene expression comparison of the essential biosynthetic gene-camE. The titer of CRM A production was then improved by two strain breeding methods via UV mutagenesis and cofactor engineering-directed increase of intracellular riboflavin, which finally generated the optimal mutant strain XC-11GUR with a CRM A production titer of 113.91 ± 7.58mg/L. Subsequently, this titer of strain XC-11GUR was improved to 618.61 ± 16.29mg/L through medium optimization together with further adjustment derived from response surface methodology. In terms of this 14.6 folds increase in the titer of CRM A compared to the initial value, strain XC-GUR could be a well alternative strain for CRM A development.
Our results had constructed an ideal CRM A producer. More importantly, our efforts also had demonstrated the effectiveness of abovementioned combinatorial strategies, which is applicable to the genome mining of bioactive natural products from abundant actinomycetes strains.
Our results had constructed an ideal CRM A producer. this website More importantly, our efforts also had demonstrated the effectiveness of abovementioned combinatorial strategies, which is applicable to the genome mining of bioactive natural products from abundant actinomycetes strains.
The emergence of artemisinin-resistant malaria parasites highlights the need for novel drugs and their targets. Alkylation of purine bases can hinder DNA replication and if unresolved would eventually result in cell death. DNA-3-methyladenine glycosylase (MAG) is responsible for the repair of those alkylated bases. Plasmodium falciparum (Pf) MAG was characterized for its potential for development as an anti-malarial candidate.
Native PfMAG from crude extract of chloroquine- and pyrimethamine-resistant P. falciparum K1 strain was partially purified using three chromatographic procedures. From bio-informatics analysis, primers were designed for amplification, insertion into pBAD202/D-TOPO and heterologous expression in Escherichia coli of recombinant PfMAG. Functional and biochemical properties of the recombinant enzyme were characterized.
PfMAG activity was most prominent in parasite schizont stages, with a specific activity of 147U/mg (partially purified) protein. K1 PfMAG contained an insertion of AAT s. K1 PfMAG contained an indel AAT (asparagine) not present in 3D7 strain and the recombinant enzyme was twice as large as the human enzyme. Recombinant PfMAG had a wide range of optimal pH activity, and was inhibited at high (250 mM) NaCl concentration as well as by divalent cations. The properties of PfMAG provide basic data that should be of assistance in developing anti-malarials against this potential parasite target.
Immunotherapies targeting glioblastoma (GBM) have led to significant improvements in patient outcomes. TOX is closely associated with the immune environment surrounding tumors, but its role in gliomas is not fully understood.
Using data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we analyzed the transcriptomes of 1691 WHO grade I-IV human glioma samples. The R language was used to perform most of the statistical analyses. Somatic mutations and somatic copy number variation (CNV) were analyzed using GISTIC 2.0.
TOX was down-regulated in malignant gliomas compared to low grade gliomas, and upregulated in the proneural and IDH mutant subtypes of GBM. TOX
tumours are associated with the loss of PTEN and amplification of EGFR, while TOX
tumours harbor frequent mutations in IDH1 (91%). TOX was highly expressed in leading edge regions of tumours. Gene ontology and pathway analyses demonstrated that TOX was enriched in multiple immune related processes including lymphocyte migration in GBM.
