Epidemiology, baseline characteristics and risk of progression in the first South-Asian prospective longitudinal observational IgA nephropathy cohort

Introduction: Glomerular Research And Clinical Experiments-IgA Nephropathy in Indians (GRACE-IgANI) is the first prospective South Asian IgAN cohort with protocolized follow-up and extensive biosample collection. Here we report the baseline clinical, biochemical, and histopathologic characteristics of GRACE IgANI and calculate baseline risk of progression for the cohort. Methods: 201 incident adults with kidney biopsy-proven primary IgAN were recruited into GRACE-IgANI between March 2015 and September 2017. As of April 30, 2020, the cohort had completed a median followup of 30 months (interquartile range [IQR] 16-39). Results: The commonest clinical presentation in GRACE IgANI was hypertension, with or without proteinuria, and nephrotic-range proteinuria was present in 34%, despite Conclusions: The predicted risk of progression in this cohort was considerable. Over the next 5 years, we will dissect the pathogenic pathways that underlie this severe South Asian IgAN phenotype

Thickening of Ectatic Cornea through Regeneration Using Decellularized Corneal Matrix Injectable Hydrogel: A Strategic Advancement to Mitigate Corneal Ectasia

Ectatic corneal diseases are a group of eye disorders characterized by progressive thinning and outward bulging of the cornea, resulting in vision impairment. A few attempts have been made to use cornea-derived extracellular matrix hydrogels for corneal tissue engineering; however, no studies have investigated its application in corneal ectasia. In this study, we have first developed an animal surgical model that mimics a few specific phenotypes of ectatic cornea. Later, we investigated the potential of decellularized cornea matrix hydrogels (dCMH) from both human and bovine sources in increasing the thickness of the cornea in the developed surgical model. Our data advocate that surgical stromal depletion can be followed to establish ectatic models and can also provide information on the biocompatibility of materials, its integration with native stroma, degradation over time, and tissue remodeling. We observed that dCMH from both sources could integrate with ectatic thin corneal stroma and helps in regaining the thickness by regenerating a reasonably functional and transparent stroma; however, no significant difference was spotted between the dCMH made from human and bovine corneal tissue sources. Hence, this study is a promising step toward developing a non-invasive technique for the treatment of corneal ectasia by using dCMH. © 2021 American Chemical Society

Targeted Metabolomics Analysis of Individuals Carrying the ANGPTL8 R59W Variant

ANGPTL8 is recognized as a regulator of lipid metabolism through its role in inhibiting lipoprotein lipase activity. ANGPTL8 gene variants, particularly rs2278426 leading to the R59W variant in the protein, have been associated with lipid traits in various ethnicities. We aimed to use metabolomics to understand the impact of the ANGPTL8 R59W variant on metabolites in humans. We used the Biocrates-p400 kit to quantify 408 plasma metabolites in 60 adult male Arab individuals from Kuwait and identify differences in metabolite levels between individuals carrying reference genotypes and those with carrier genotypes at ANGPTL8 rs2278426. Individuals with carrier genotypes (CT+TT) compared to those carrying the reference genotype (CC) showed statistically significant differences in the following metabolites: acylcarnitine (perturbs metabolic pathways), phosphatidylcholine (supports liver function and cholesterol levels), cholesteryl ester (brings chronic inflammatory response to lipoprotein depositions in arteries), α-aminoadipic acid (modulates glucose homeostasis), histamine (regulates glucose/lipid metabolism), sarcosine (links amino acid and lipid metabolism), diacylglycerol 42:1 (regulates homeostasis of cellular lipid stores), and lysophosphatidylcholine (regulates oxidative stress and inflammatory response). Functional aspects attributed to these metabolites indicate that the ANGPTL8 R59W variant influences the concentrations of lipid- and inflammation-related metabolites. This observation further highlights the role of ANGPTL8 in lipid metabolism

Targeted Metabolomics Analysis on Obstructive Sleep Apnea Patients after Multilevel Sleep Surgery

Background: Obstructive sleep apnea (OSA) is caused by partial or complete obstruction of the upper airways. Corrective surgeries aim at removing obstructions in the nasopharynx, oropharynx, and hypopharynx. OSA is associated with an increased risk of various metabolic diseases. Our objective was to evaluate the effect of surgery on the plasma metabolome. Methods: This study included 39 OSA patients who underwent Multilevel Sleep Surgery (MLS). Clinical and anthropometric measures were taken at baseline and five months after surgery. Results: The mean Apnea-Hypopnea Index (AHI) significantly dropped from 22.0 ± 18.5 events/hour to 8.97 ± 9.57 events/hour (p-Value < 0.001). Epworth’s sleepiness Score (ESS) dropped from 12.8 ± 6.23 to 2.95 ± 2.40 (p-Value < 0.001), indicating the success of the surgery in treating OSA. Plasma levels of metabolites, phosphocholines (PC) PC.41.5, PC.42.3, ceremide (Cer) Cer.44.0, and triglyceride (TG) TG.53.6, TG.55.6 and TG.56.8 were decreased (p-Value < 0.05), whereas lysophosphatidylcholines (LPC) 20.0 and PC.39.3 were increased (p-Value < 0.05) after surgery. Conclusion: This study highlights the success of MLS in treating OSA. Treatment of OSA resulted in an improvement of the metabolic status that was characterized by decreased TG, PCs, and Cer metabolites after surgery, indicating that the success of the surgery positively impacted the metabolic status of these patients