Cytotoxic components from the leaves of Erythrophleum fordii induce human acute leukemia cell apoptosis through caspase 3 activation and PARP cleavage.

Cassaine diterpenoids as erythrofordins A-C (1-3), pseudo-erythrosuamin (4), and erythrofordin U (5) isolated from the leaves of Vietnamese Erythrophleum fordii Oliver were tested cytotoxic activity against human leukemia cancer cells. The results showed that these metabolites exhibited dose-dependent cytotoxicity against human leukemia HL-60 and KG cells with IC50 values ranging from 15.2 ± 1.5 to 42.2 ± 3.6 µM. Treatment with erythrofordin B led to the apoptosis of HL-60 and KG cells due to the activation of caspase 3, caspase 9, and poly (ADP-ribose) polymerase (PARP). Erythrofordin B significantly increased Bak protein expression, but downregulated the anti-apoptotic protein Bcl-2, in HL-60 cells. In silico results demonstrated that erythrofordin B can bind to both the procaspase-3 allosteric site and the PARP-1 active site, with binding energies of -7.36 and -10.76 kcal/mol, respectively. These results indicated that the leaves of Vietnamese E. fordii, which contain cassaine diterpenoids, can induce the apoptosis of human leukemia cancer cells.

The Association Between Femoral Artery Intima-Media Thickness and Serum Glucagon-Like Peptide-1 Levels Among Newly Diagnosed Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: Endothelium dysfunction and decrease of incretin effects occur early in type 2 diabetes mellitus and these changes contribute to diabetic cardiovascular complications such as atherosclerosis, thick intima-media, coronary, and peripheral arterial diseases. In patients with diabetes, the femoral artery is a site of a high incidence of injury in peripheral vascular diseases, and atherosclerotic changes may appear earlier in the femoral artery compared to the carotid artery. This study was conducted to determine the prevalence of increased femoral artery intima-media thickness (IMT) and atherosclerotic plaque and their correlation with serum glucagon-like peptide-1 (GLP-1) levels in newly-diagnosed patients with type 2 diabetes mellitus. MATERIALS AND METHODS: A cross-sectional study was conducted on 332 patients with nT2D in the National Endocrinology Hospital, Vietnam from January 2015 to May 2018. IMT was measured by Doppler ultrasound and GLP-1 by enzyme-linked immunosorbent assay (ELISA). All data were analyzed with SPSS version 26 for Windows (SPSS Inc, Chicago, IL). RESULTS: Prevalence of thick femoral artery IMT and atherosclerotic plaque was 38.2 and 22.3%, respectively. There was a relationship between IMT and age, waist to hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting GLP-1, high sensitive CRP (hsCRP) and 24-hour microalbuminuria secretion (24-h MAUS). The fasting serum GLP-1 (fGLP-1) levels were reduced significantly in patients with thickness and atherosclerosis femoral artery (p = 0.001). After adjusting with other related factors, namely, DBP and estimated glomerular filtration rate (eGFR), whilst hsCRP and 24-h MAUS showed a significantly positive correlation to IMT (Standardized B and p of 0.242, 0.004 and 0.178, 0.043, respectively), fGLP-1 showed a significantly negative correlation to IMT (Standardized B = -0.288, p = 0.001). CONCLUSION: Among n2TD, the percentage for femoral artery thick IMT and atherosclerosis was 38.2% and 22.3% respectively, and serum GLP-1 was negatively correlated with thick IMT and atherosclerosis.

Synthetic prions and other human neurodegenerative proteinopathies.

Transmissible spongiform encephalopathies (TSE) are a heterogeneous group of neurodegenerative disorders. The common feature of these diseases is the pathological conversion of the normal cellular prion protein (PrP(C)) into a ß-structure-rich conformer-termed PrP(Sc). The latter can induce a self-perpetuating process leading to amplification and spreading of pathological protein assemblies. Much evidence suggests that PrP(Sc) itself is able to recruit and misfold PrP(C) into the pathological conformation. Recent data have shown that recombinant PrP(C) can be misfolded in vitro and the resulting synthetic conformers are able to induce the conversion of PrP(C) into PrP(Sc)in vivo. In this review we describe the state-of-the-art of the body of literature in this field. In addition, we describe a cell-based assay to test synthetic prions in cells, providing further evidence that synthetic amyloids are able to template conversion of PrP into prion inclusions. Studying prions might help to understand the pathological mechanisms governing other neurodegenerative diseases. Aggregation and deposition of misfolded proteins is a common feature of several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and other disorders. Although the proteins implicated in each of these diseases differ, they share a common prion mechanism. Recombinant proteins are able to aggregate in vitro into ß-rich amyloid fibrils, sharing some features of the aggregates found in the brain. Several studies have reported that intracerebral inoculation of synthetic aggregates lead to unique pathology, which spread progressively to distal brain regions and reduced survival time in animals. Here, we review the prion-like features of different proteins involved in neurodegenerative disorders, such as α-synuclein, superoxide dismutase-1, amyloid-ß and tau.