Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.21.6 (
thromboplastin
)
13,278
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Ghilantens are a family of cysteine-rich inhibitors of the clotting enzyme,
factor Xa
, that are produced in the salivary glands of the South American leech Haementeria ghilianii. In this study, a gene, designed from the amino acid sequence of a specific ghilanten isoform, was assembled from eight double-stranded oligonucleotide fragments. A yeast expression plasmid, pPIC9HG-2, was constructed by making an inframe fusion of the ghilanten-coding sequences with the region encoding the pre-pro alpha-mating factor signal sequence for secretion. The expression of ghilanten in pPIC9HG-2 was under the control of the methanol-inducible, alcohol oxidase (AOX1) promoter. Pichia pastoris yeast strains KM 71 and
SMD
1168 were transformed with linearized pPIC9HG-2 to target integration of the plasmid to the chromosomal 5'-AOX1 locus via homologous recombination. Both strains yielded His+ transformants that secreted a potent anticoagulant activity into the medium. Product yield was improved by using buffered media (pH 6.0) supplemented with either casamino acids or a mixture of yeast extract and peptone. The protease-deficient strain,
SMD
1168, secreted about a twofold higher level of r-ghilanten than KM 71. Significant clonal variation in the expression of r-ghilanten was found among the His+ transformants. A high producing clone was selected for production at the 2-liter shake flask and 10-liter bioreactor scales. r-Ghilanten was recovered from the fermentation broths in a single step by heparin Sepharose affinity chromatography. Protein sequence analysis of the amino terminus showed that the correct processing to yield mature ghilanten varied with the fermentation conditions.
...
PMID:Expression of a synthetic gene encoding the anticoagulant-antimetastatic protein ghilanten by the methylotropic yeast Pichia pastoris. 874 34
COVID-19 patients frequently exhibit coagulation abnormalities and thrombotic events. In this meta-analysis, we investigated the association between coagulopathy and the severity of COVID-19 illness. Using PubMed, Embase, Cochrane, WanFang Database, CNKI, and medRxiv, a systematic literature search was conducted for studies published between December 1, 2019 and May 1, 2020. We then analyzed coagulation parameters in COVID-19 patients exhibiting less severe and more severe symptoms. All statistical analyses were performed using Stata14.0 software. A total of 3,952 confirmed COVID-19 patients from 25 studies were included in the meta-analysis. Patients with severe symptoms exhibited higher levels of D-dimer, prothrombin time (PT), and fibrinogen (FIB) than patients with less severe symptoms (
SMD
0.83, 95% CI: 0.70-0.97, I
2
56.9%;
SMD
0.39, 95% CI: 0.14-0.64, I
2
79.4%; and
SMD
0.35, 95% CI: 0.17-0.53, I
2
42.4%, respectively). However, platelet and activated partial
thromboplastin
times did not differ (
SMD
-0.26, 95% CI: -0.56-0.05, I
2
82.2%; and
SMD
-0.14, 95% CI: -0.45-0.18, I
2
75.7%, respectively). These findings demonstrate that hypercoagulable coagulopathy is associated with the severity of COVID-19 symptoms and that D-dimer, PT, and FIB values are the main parameters that should be considered when evaluating coagulopathy in COVID-19 patients.
...
PMID:Coagulopathy in patients with COVID-19: a systematic review and meta-analysis. 3322 25
