Association between apolipoprotein E gene polymorphism and myocardial infarction.

We investigated apolipoprotein E (APOE) genotypic influence on myocardial infarction risk in South India, where the disease is emerging as a major threat to the public health care system. The study included 412 subjects: 202 myocardial infarction patients and 210 age- and sex-matched controls. DNA was isolated, the polymorphism of the APOE gene was subjected to PCR, and lipid levels were evaluated. The prevalence of E3/E4 genotypes in patients (18.3%) was 1.5-fold that of controls (11.0%, p < 0.05), and the prevalence of E2/E3 genotypes was higher in controls (6.7%) than in patients (4%). The ε4 allele was significantly associated with myocardial infarction: χ(2) = 12.4; OR 2.2 (CI 95%: 1.4-3.4), p < 0.004, for ε4 versus ε3 and χ(2) = 5.7; OR 2.7 (CI 95%: 1.1-6.5), p > 0.01, for ε4 versus ε2. A significant association of the ε4 allele, especially the E3/E4 genotype, with myocardial infarction was observed.

Low pH-Based Method to Increase the Yield of Plant-Derived Nanoparticles from Fresh Ginger Rhizomes.

Plant-derived nanoparticles (PDNPs) are naturally occurring exosome-like nanovesicles derived from dietary plants containing key plant bioactives. Ginger-derived PDNPs have a therapeutic effect on alcohol-induced liver injury, inflammatory bowel disease, and colon cancer. PDNPs are conventionally purified by differential ultracentrifugation, a technique not amenable for scale up. We have recently developed a polyethylene glycol (PEG) 6000-based method for cost-effective purification of ginger PDNPs, with comparable efficiency to differential ultracentrifugation (Sci. Rep. 2020, 10 (1), 4456.). Herein, we report a 4-5-fold higher ginger PDNP recovery when PEG precipitation was carried out in low pH conditions (pH 4 and 5). Low pH-derived ginger PDNPs were smaller in size without an overt change in zeta potential. The spontaneous intracellular entry and protection against oxidative stress in A431 cells were similar between ginger PDNPs purified under low, neutral, and alkaline pH. Low-pH purified ginger PDNPs had higher levels of total polyphenolic content compared to PDNPs purified under neutral and alkaline pH. Recently, ginger PDNP-derived microRNAs have been shown to exhibit cross-kingdom regulation by targeting human, gut microbiome, and viral transcripts. Using qRT-PCR, we also verified the presence of miRNAs that were predicted to target SARS-CoV-2 in ginger PDNPs purified under low pH. Thus, we have developed a method to purify ginger PDNPs in high yields by using low-pH conditions without affecting the major bioactive contents of PDNPs.

Lipoprotein lipase gene HindIII polymorphism and risk of myocardial infarction in South Indian population.

INTRODUCTION: Studies have reported an association between lipoprotein lipase (LPL) gene and myocardial infarction in some populations. Therefore, the present study aimed to investigate the association of the HindIII polymorphism of the (LPL) gene with myocardial infarction and to explore its potential role in susceptibility in a South Indian population. SUBJECTS AND METHODS: We included a total of 412 subjects (202 myocardial infarction patients and 210 age- and sex-matched controls). Demographic and clinical characteristics were collected. Lipid profiles were estimated. DNA was isolated and the LPL gene HindIII polymorphism was determined by polymerase chain reaction. RESULTS: Comparison of the lipid profiles between patients and controls showed that patients had statistically high significant values (p = 0.0001). The H(+) H(+) genotype of the LPL gene is associated with myocardial infarction. H(+) H(+) vs. H(-) H(-) was χ2 = 19.4, OR 3.1, CI 95% 1.8-5.2, p < 0.0001. CONCLUSION: Our study strongly suggests that the LPL gene HindIII Hþ Hþ genotype is an independent risk factor for first MI.

Mge1, a nucleotide exchange factor of Hsp70, acts as an oxidative sensor to regulate mitochondrial Hsp70 function.

Despite the growing evidence of the role of oxidative stress in disease, its molecular mechanism of action remains poorly understood. The yeast Saccharomyces cerevisiae provides a valuable model system in which to elucidate the effects of oxidative stress on mitochondria in higher eukaryotes. Dimeric yeast Mge1, the cochaperone of heat shock protein 70 (Hsp70), is essential for exchanging ATP for ADP on Hsp70 and thus for recycling of Hsp70 for mitochondrial protein import and folding. Here we show an oxidative stress-dependent decrease in Mge1 dimer formation accompanied by a concomitant decrease in Mge1-Hsp70 complex formation in vitro. The Mge1-M155L substitution mutant stabilizes both Mge1 dimer and Mge1-Hsp70 complex formation. Most important, the Mge1-M155L mutant rescues the slow-growth phenomenon associated with the wild-type Mge1 strain in the presence of H2O2 in vivo, stimulation of the ATPase activity of Hsp70, and the protein import defect during oxidative stress in vitro. Furthermore, cross-linking studies reveal that Mge1-Hsp70 complex formation in mitochondria isolated from wild-type Mge1 cells is more susceptible to reactive oxygen species compared with mitochondria from Mge1-M155L cells. This novel oxidative sensor capability of yeast Mge1 might represent an evolutionarily conserved function, given that human recombinant dimeric Mge1 is also sensitive to H2O2.