MyMedR

Displaying all 4 publications

Abstract:

Sort:

Investigating how amine structure influences drug-amine ion-pair formation and uptake via the polyamine transporter in A549 lung cells

Mohamed Sofian Z, Harun N, Mahat MM, Nor Hashim NA, Jones SA

Eur J Pharm Biopharm, 2021 Nov;168:53-61.
PMID: 34455038 DOI: 10.1016/j.ejpb.2021.08.003

Transiently associating amines with therapeutic agents through the formation of ion-pairs has been established both in vitro and in vivo as an effective means to systemically direct drug delivery to the lung via the polyamine transport system (PTS). However, there remains a need to better understand the structural traits required for effective PTS uptake of drug ion-pairs. This study aimed to use a structurally related series of amine counterions to investigate how they influenced the stability of theophylline ion-pairs and their active uptake in A549 cells. Using ethylamine (mono-amine), ethylenediamine (di-amine), spermidine (tri-amine) and spermine (tetra-amine) as counterions the ion-pair affinity was shown to increase as the number of protonated amine groups in the counterion structure increased. The mono and diamines generated a single hydrogen bond and the weakest ion-pair affinities (pKFTIR: 1.32 ± 0.04 and 1.43 ± 0.02) whereas the polyamines produced two hydrogen bonds and thus the strongest ion-pair affinities (pKFTIR: 1.93 ± 0.05 and 1.96 ± 0.04). In A549 cells depleted of endogenous polyamines using α-difluoromethylornithine (DFMO), the spermine-theophylline uptake was significantly increased (p
Identification of genetic and non-genetic risk factors for nasopharyngeal carcinoma in a Southeast Asian population

Nor Hashim NA, Ramzi NH, Velapasamy S, Alex L, Chahil JK, Lye SH, et al.

Asian Pac J Cancer Prev, 2012;13(12):6005-10.
PMID: 23464394

BACKGROUND: Nasopharyngeal carcinoma (NPC) is endemic in Southern Chinese and Southeast Asian populations. Geographical and ethnic clustering of the cancer is due to genetic, environmental, and lifestyle risk factors. This case-control study aimed to identify or confirm both genetic and non-genetic risk factors for NPC in one of the endemic countries, Malaysia.
MATERIALS AND METHOD: A panel of 768 single-nucleotide polymorphisms (SNPs) previously associated with various cancers and known non-genetic risk factors for NPC were selected and analyzed for their associations with NPC in a case-control study.
RESULTS: Statistical analysis identified 40 SNPs associated with NPC risk in our population, including 5 documented previously by genome-wide association studies (GWAS) and other case-control studies; the associations of the remaining 35 SNPs with NPC were novel. In addition, consistent with previous studies, exposure to occupational hazards, overconsumption of salt-cured foods, red meat, as well as low intake of fruits and vegetables were also associated with NPC risk.
CONCLUSIONS: In short, this study confirmed and/or identified genetic, environmental and dietary risk factors associated with NPC susceptibility in a Southeast Asian population.
Oligogenic inheritance in severe adult obesity

Almansoori S, Alsters SI, Yiorkas AM, Nor Hashim NA, Walters RG, Chahal HS, et al.

Int J Obes (Lond), 2024 Jan 31.
PMID: 38297031 DOI: 10.1038/s41366-024-01476-9

BACKGROUND/OBJECTIVE: The genetic architecture of extreme non-syndromic obesity in adults remains to be elucidated. A range of genes are known to cause monogenic obesity, but even when pathogenic mutations are present, there may be variable penetrance.
METHODS: Whole-exome sequencing (WES) was carried out on a 15-year-old male proband of Pakistani ancestry who had severe obesity. This was followed by family segregation analysis, using Sanger sequencing. We also undertook re-analysis of WES data from 91 unrelated adults with severe obesity (86% white European ancestry) from the Personalised Medicine for Morbid Obesity (PMMO) cohort, recruited from the UK National Health Service.
RESULTS: We identified an oligogenic mode of inheritance of obesity in the proband's family-this provided the impetus to reanalyze existing sequence data in a separate dataset. Analysis of PMMO participant data revealed two further patients who carried more than one rare, predicted-deleterious mutation in a known monogenic obesity gene. In all three cases, the genes involved had known autosomal dominant inheritance, with incomplete penetrance.
CONCLUSION: Oligogenic inheritance may explain some of the variable penetrance in Mendelian forms of obesity. We caution clinicians and researchers to avoid confining sequence analysis to individual genes and, in particular, not to stop looking when the first potentially-causative mutation is found.
Fulltext Synthesis and Characterization of Porous, Electro-Conductive Chitosan-Gelatin-Agar-Based PEDOT: PSS Scaffolds for Potential Use in Tissue Engineering

Ahmad Ruzaidi DA, Mahat MM, Mohamed Sofian Z, Nor Hashim NA, Osman H, Nawawi MA, et al.

Polymers (Basel), 2021 Aug 28;13(17).
PMID: 34502941 DOI: 10.3390/polym13172901

Herein we report the synthesis and characterization of electro-conductive chitosan-gelatin-agar (Cs-Gel-Agar) based PEDOT: PSS hydrogels for tissue engineering. Cs-Gel-Agar porous hydrogels with 0-2.0% (v/v) PEDOT: PSS were fabricated using a thermal reverse casting method where low melting agarose served as the pore template. Sample characterizations were performed by means of scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction analysis (XRD) and electrochemical impedance spectroscopy (EIS). Our results showed enhanced electrical conductivity of the cs-gel-agar hydrogels when mixed with DMSO-doped PEDOT: PSS wherein the optimum mixing ratio was observed at 1% (v/v) with a conductivity value of 3.35 × 10-4 S cm-1. However, increasing the PEDOT: PSS content up to 1.5 % (v/v) resulted in reduced conductivity to 3.28 × 10-4 S cm-1. We conducted in vitro stability tests on the porous hydrogels using phosphate-buffered saline (PBS) solution and investigated the hydrogels' performances through physical observations and ATR-FTIR characterization. The present study provides promising preliminary data on the potential use of Cs-Gel-Agar-based PEDOT: PSS hydrogel for tissue engineering, and these, hence, warrant further investigation to assess their capability as biocompatible scaffolds.