ORCID Profile
0000-0003-0759-4035
Current Organisations
Peter MacCallum Cancer Centre
,
University of Melbourne
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2019
Publisher: American Society for Clinical Investigation
Date: 08-02-2021
Publisher: Oxford University Press (OUP)
Date: 10-2019
Abstract: Small non-coding microRNAs (miRNAs) are increasingly recognized as key regulators of the host response to sepsis. However, the molecular mechanisms implicated in the role of miRNAs during sepsis progression is still unclear. It is hypothesized that differentially expressed genes in septic patients with worse outcomes are associated with dysregulation of miRNA expression. This study aimed to identify specific miRNA-gene pairs that may be implicated in the development of shock and renal failure in sepsis. miRNA from serum and RNA from PBMCs were acquired from n = 40 participants in a prospective cohort of Filipino septic patients: n = 15 developed septic shock and n = 17 developed renal failure. RT-qPCR was done to measure the expression of 21 sepsis-associated miRNAs. Differentially expressed miRNAs (DEMs) for each outcome was identified, followed by gene target prediction for each DEM. Gene expression microarrays covering 18,616 genes were also performed to identify differentially expressed genes (DEGs P 0.05, log FC |0.3|) for each outcome. Significant miRNA-gene pairs were selected by evaluating the overlap of the predicted gene targets of the DEMs with the DEGs for each corresponding outcome. Given the gene-silencing mechanism of miRNAs, overlap analysis was performed on only the downregulated DEGs when the specific DEM was upregulated (and vice versa). Septic participants who developed shock, compared with those who did not, had higher expression of 1 DEM, miR-223-5p, and downregulation of 20 DEGs. NUS1 was the only predicted gene target of miR-223-5p that was also downregulated in septic shock. Participants who developed renal failure, vs. those who did not, had lower expression 6 DEMs and upregulation of 6 DEGs. KPNA4 is a gene target of the DEMs, miR-126-5p, and miR-181a-5p, that was also upregulated in renal failure. Significant miRNA–gene pairs related to worse clinical outcomes in sepsis were identified: miR-223-5p with NUS1 for shock and either miR-126-5p or miR-181-5p with KPNA4 for renal failure. While the biological significance of these miRNA-gene pairs still needs to be evaluated, these findings can potentially help future efforts in developing prognostic markers or therapeutic targets for shock and renal failure in sepsis. All authors: No reported disclosures.
Publisher: Mary Ann Liebert Inc
Date: 07-2017
Publisher: The Endocrine Society
Date: 29-06-2022
Abstract: A study among Filipinos revealed that only 15% of patients with diabetes achieved glycemic control, and poor response to metformin could be one of the possible reasons. Recent studies demonstrate how genetic variations influence response to metformin. Hence, the present study aimed to determine genetic variants associated with poor response to metformin. Using a candidate variant approach, 195 adult Filipino participants with newly diagnosed type 2 diabetes mellitus (T2DM) were enrolled in a case-control study. Genomic DNA from blood s les were collected. Allelic and genotypic associations of variants with poor response to metformin were determined using exact statistical methods. Several polymorphisms were nominally associated with poor response to metformin (Puncorr & 0.05). The most notable is the association of multiple variants in the SLC2A10 gene—rs2425911, rs3092412, and rs2425904—with common additive genetic mode of inheritance. Other variants that have possible associations with poor drug response include rs340874 (PROX-AS1), rs815815 (CALM2), rs1333049 (CDKN2B-AS1), rs2010963 (VEGFA), rs1535435 and rs9494266 (AHI1), rs11128347 (PDZRN3), rs1805081 (NPC1), and rs13266634 (SLC30A8). In Filipinos, a trend for the association for several variants was noted, with further observation that several mechanisms may be involved. The results may serve as pilot data for further validation of candidate variants for T2DM pharmacotherapy.
Publisher: Journal of the ASEAN Federation of Endocrine Societies (JAFES)
Date: 10-05-2023
Publisher: MDPI AG
Date: 22-02-2022
Abstract: Preecl sia is one of the major hypertensive diseases of pregnancy. Genetic factors contribute to abnormal placentation. The inadequate transformation of cytotrophoblasts causes failure of maternal spiral arteries’ remodeling and results in narrow, atherotic-prone vessels, leading to relative placental ischemia. This study aims to explore the possibility of identifying dysregulated gene networks that may offer a potential target in the possible prevention of preecl sia. We performed a weighted gene correlated network analysis (WGCNA) on a subset of gene expression profiles of placental tissues from severe preecl tic pregnancies. We identified a gene module (number of genes = 402, GS = 0.35, p = 0.02) enriched for several G-protein-coupled receptor (GPCR)-related genes with significant protein–protein molecular interaction (number of genes = 38, FDR = 0.0007) that may play key roles in preecl sia. Some genes are noted to play key roles in preecl sia, including LPAR4/5, CRLR, NPY, TACR1/2, and SFRP4/5, whose functions generally relate to angiogenesis and vasodilation or vasoconstriction. Other upregulated genes, including olfactory and orexigenic genes, serve limited functions in the disease pathogenesis. Altogether, this study shows the utility of WGCNA in exploring possible new gene targets, and additionally reinforces the feasibility of targeting GPCRs that may offer intervention against development and disease progression among severe preecl sia patients.
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1016/J.JNUTBIO.2022.109152
Abstract: Preventive strategies for hypertension and its sequelae require an understanding of their predisposing conditions and recognition of at-risk in iduals. Several factors, both genetic and nongenetic, are influential, and likely vary in their effects across ethnicities. This study aimed to identify dietary, lifestyle-related differences and genetic variants associated with hypertension in Filipinos. The study included 147 adult Filipino respondents of the 2013 Philippine National Nutrition Survey living in the National Capital Region. Data on the socio-demographic profile and selected lifestyle factors were obtained via face-to-face interviews. Blood pressure, anthropometric and biochemical indicators of health were determined using standard procedures. Hypertension incidence was determined following American College of Cardiology/American Heart Association guideline. Genotyping utilized the customized Illumina Golden Gate genotyping array, with subsequent allele and genotypic association analytics. Genetic variant effects were adjusted to clinical parameters via logistic regression. Between those with and without hypertension, there was relatively higher intake of dietary protein, fat but not carbohydrates in the latter (P<.05). Of note, other established risk factors for hypertension, such as high lipid levels and fasting blood sugar, were consistently frequently seen among hypertensive respondents. Of the gene markers, 3 SNPs (rs10492602 of APOC [3' UTR], rs12721054 of CYP2C19 [exon] and rs4244285 [intergenic between PCDH17-DIAPH3 locus]) remained significant after multivariable logistic regression. The study highlights that both nutrition and genetic information may contribute to hypertension among Filipinos. This could guide public health initiatives to identify Filipinos susceptible to hypertension and recommend control strategies in lowering its morbidity rate.
Location: United States of America
Location: Philippines
No related grants have been discovered for Christian Deo Deguit.