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The Rho guanosine triphosphatases (GTPases) Rac1 and Rac2 are critical signaling regulators in mammalian cells. The deletion of both Rac1 and Rac2 murine alleles leads to a massive egress of hematopoietic stem/progenitor cells (HSC/Ps) into the blood from the marrow, whereas Rac1-/- but not Rac2-/- HSC/Ps fail to engraft in the bone marrow of irradiated(More)
This study evaluated the preclinical pharmacokinetics (PK) and disposition of Fruquintinib (HMPL-013), a small molecule vascular endothelial growth factor receptors inhibitor. In vitro and in vivo PK/ADME assays were conducted. Allometry and PK modeling/simulation were conducted to predict human PK parameters and the time course profiles. HMPL-013 has high(More)
Two intracellular cysteine proteases (calpains and caspases) and inducible nitric oxide synthase (iNOS) participate in the ischemic brain injury. In vitro nitric oxide (NO) regulates calpain and caspase-3 activation. The present study investigated whether aminoguanidine (AG), an iNOS inhibitor, protected brain against experimental stroke through inhibiting(More)
The pharmacokinetic characteristics of ginsenoside Rh2, an anticancer nutrient, were analyzed in dogs and rats, including plasma kinetics, bioavailability, tissue distribution, plasma protein binding and excretion. The bioavailability of Rh2 is about 5% in rats and 16% in dogs. Multiple-dosing (7 days, 1 mg/kg bid) did not affect the pharmacokinetics in(More)
BACKGROUND The prevalence of BRCA1/2 variants in Chinese breast cancer patients varies among studies. Germline or somatic BRCA1/2 mutations are associated with sensitivity to poly(ADP-ribose) polymerase-1 inhibitors and DNA-damaging agents. We aimed to investigate the distribution of both somatic and germline BRCA1/2 variants in unselected Chinese breast(More)
P-glycoprotein (P-gp) is an ATP-dependent efflux transporter highly expressed in gastrointestinal tract and multidrug resistance tumor cells. Inhibition or induction of P-gp can cause drug-drug interactions and thus influence the effects of P-gp substrate drugs. Previous studies indicated that 20(S)-ginsenoside Rh2 [20(S)-Rh2] could synergistically enhance(More)
RhoH is a hematopoietic-specific, GTPase-deficient member of the Rho GTPase family with unknown physiological function. Here we demonstrate that Rhoh-/- mice have impaired T cell receptor (TCR)-mediated thymocyte selection and maturation, resulting in T cell deficiency. RhoH deficiency resulted in defective CD3zeta phosphorylation, impaired translocation of(More)
BACKGROUND To describe a study design that focuses on risk factors and patterns of chronic obstructive pulmonary disease (COPD) exacerbations. METHODS A 2-year, single centre, observational study was conducted in Guangzhou in China. The study enrolled 318 subjects with COPD aged 40-79 years, stratified into different but equally sized groups according to(More)
In vitro nitric oxide (NO) regulates calpain and caspase-3 activation, and in vivo neuronal nitric oxide synthase (nNOS), calpain and caspase-3 participate in the ischemic brain injury. Our objective was to investigate whether nNOS was involved in the ischemic brain injury through activating calpain and caspase-3 during experimental stroke. Rats received(More)
BACKGROUND Venous thromboembolism (VTE) is a complex disease and several inherited and acquired factors are relevant to its occurrence. Among these, an elevated level of plasma coagulation factor VIII (FVIII) is an established risk factor for VTE; copy number variations (CNVs) have also been discovered to be associated with many diseases. OBJECTIVE To(More)