Unraveling Compositional Study, Chemometric Analysis, and Cell-Based Antioxidant Potential of Selective High Nutraceutical Value Amaranth Cultivars Using a GC-MS and NMR-Based Metabolomics Approach.

Amaranthus (family Amaranthaceae) is a potentially nutritious pseudocereal also known as a functional food owing to its high nutritional quality grains especially rich in essential amino acids. Emerging study, however, unambiguously indicates that apart from essential nutrients like protein, other phytochemicals present in amaranth seeds provide excellent health benefits. Squalene is one such phytonutrient found in Amaranthus seeds, which is also its largest vegetal source. In this research work, GC-MS and NMR spectroscopy-based metabolomics have been utilized for the compositional analysis of Amaranthus seeds coupled with a multivariate data set. Investigation of nonpolar and polar seed extracts of six different cultivars of amaranth identified 47 primary and secondary metabolites. One-way ANOVA showed significant quantitative metabolic variations in different cultivars of amaranth. Multivariate principal component analysis of both the GC-MS and NMR analyzed data broadly classified in two groups showed significant variations in the polar (lysine, arginine, GABA, and myoinositol) and nonpolar (squalene, tryptophan, and alkylated phenols, which are potential nutraceutical agents) metabolites. The squalene content estimated using HPLC varied significantly (1.61 to 4.72 mg g-1 seed dry weight) among six different cultivars. Positive correlations were found among the cellular antioxidant activity and squalene content. Cultivar AM-3 having the maximum squalene content showed the highest antioxidant activity evaluated on the cellular level over human embryonic kidney cells, clearly revealing potent intercellular reactive oxygen species scavenging capacity and strong membrane lipid peroxidation inhibition potential. Oxidative stress markers such as MDA, SOD, GSH, and CAT levels in cells further corroborated the research work. The study also indicated high concentrations of lysine (80.49 mg g-1 dry seeds) in AM-2, squalene (0.47% by weight) in AM-3, and 2,4-di-tert-butyl phenol (18.64% peak area) and myoinositol (79.07 mg g-1 dry seeds) in AM-5. This novel comparative metabolomic study successfully profiles the nutrient composition of amaranth cultivars and provides the opportunity for the development of nutraceuticals and natural antioxidants from this functional food.

Impose of KNDy/GnRH neural circuit in PCOS, ageing, cancer and Alzheimer's disease: StAR actions in prevention of neuroendocrine dysfunction.

The Kisspeptin1 (KISS1)/neurokinin B (NKB)/Dynorphin (Dyn) [KNDy] neurons in the hypothalamus regulate the reproduction stage in human beings and rodents. KNDy neurons co-expressed all KISS1, NKB, and Dyn peptides, and hence commonly regarded as KISS1 neurons. KNDy neurons contribute to the "GnRH pulse generator" and are implicated in the regulation of pulsatile GnRH release. The estradiol (E2)-estrogen receptor (ER) interactions over GnRH neurons in the hypothalamus cause nitric oxide (NO) discharge, in addition to presynaptic GABA and glutamate discharge from respective neurons. The released GABA and glutamate facilitate the activity of GnRH neurons via GABAA-R and AMPA/kainate-R. The KISS1 stimulates MAPK/ERK1/2 signaling and cause the release of Ca2+ from intracellular store, which contribute to neuroendocrine function, increase apoptosis and decrease cell proliferation and metastasis. The ageing in women deteriorates KISS1/KISS1R interaction in the hypothalamus which causes lower levels of GnRH. Because examining the human brain is so challenging, decades of clinical research have failed to find the causes of KNDy/GnRH dysfunction. The KISS1/KISS1R interactions in the brain have a neuroprotective effect against Alzheimer's disease (AD). These findings modulate the pathophysiological role of the KNDy/GnRH neural network in polycystic ovarian syndrome (PCOS) associated with ageing and, its protective role in cancer and AD. This review concludes with protecting effect of the steroid-derived acute regulatory enzyme (StAR) against neurotoxicity in the hippocampus, and hypothalamus, and these measures are fundamental for delaying ageing with PCOS. StAR could serve as novel diagnostic marker and therapeutic target for the most prevalent hormone-sensitive breast cancers (BCs).

The Evaluation of Prognostic Scores in Spontaneous Intracerebral Hemorrhage in an Asian Population: A Retrospective Study.

OBJECTIVE: Clinical grading scales used for prognostication in spontaneous intracerebral hemorrhage facilitate informed-decision making for resource-intensive interventions. Numerous clinical prognostic scores are available for spontaneous intracerebral hemorrhage. However, these have not been validated well in Asian patients, and the most appropriate scoring system remains debatable. We evaluated the utility of clinical scores in prognosticating 30-day mortality and 90-day functional outcome in patients with spontaneous intracerebral hemorrhage. MATERIALS AND METHODS: We conducted a retrospective review of all patients with spontaneous intracerebral hemorrhage admitted to our tertiary center from December 2014 to May 2016. Data on clinical presentation, imaging, and outcomes were extracted from electronic medical records using a standardized form. The data were analyzed for predictors of outcomes. Performance of prognostic scales was compared using receiver-operator characteristic statistics. RESULTS: A total of 297 patients were included in the study. Mean age was 60.1 (SD 15.2) years and 190 (64.0%) were male. Thirty-two (10.8%) cases died within 30 days and 177 (62.8%) cases had poor functional outcome (modified Rankin scale of 3 or more) at 90 days. Dialysis dependency (OR=33.54, 95%CI=4.21-325.26, p=0.002), Glasgow coma scale (OR=0.76, 95%CI=0.64-0.88, p=0.001), hematoma volume (OR=1.02, 95%CI=1.00-1.04, p=0.027), and surgical evacuation (OR=0.15, 95%CI=0.02-0.66, p=0.024) were independent predictors for 30-day mortality. The original ICH score (0.862) and the ICH-Grading Scale (0.781) had the highest c-statistic for 30-day mortality and 90-day poor functional outcome respectively. CONCLUSIONS: Current prognostic scores performed acceptable-to-good in our patient cohort. Future studies may be useful to investigate the utility of these scores in clinical decision-making.