MyMedR

Displaying all 7 publications

Abstract:

Sort:

Fulltext Hyperphagia in Prader-Willi syndrome with obesity: From development to pharmacological treatment

Rahman QFA, Jufri NF, Hamid A

Intractable Rare Dis Res, 2023 Feb;12(1):5-12.
PMID: 36873672 DOI: 10.5582/irdr.2022.01127

Prader-Willi syndrome (PWS) is a rare genetic disorder due to lack of genes expression inherited from the paternal chromosome 15q11-q13 region usually from paternal deletions, maternal uniparental disomy 15 or imprinting defect. There are two different nutritional stages reported in an individual with PWS; first stage during infancy marked by feeding and growth difficulties and second stage where hyperphagia starts and leads to development of obesity. However, the exact mechanism of hyperphagia development, from having difficulties in feeding during early years to insatiable appetite after they grow is still unknown and is the focused in this review. The keywords used for literature search such as "Prader-Willi syndrome", "hyperphagia", "obesity", and "treatment" were used to create the search strings by using synonyms in order to retrieve the relevant records from PubMed, Scopus and Science Direct. The possible mechanism of hyperphagia can be classed into hormonal abnormalities such as increase in ghrelin and leptin from infancy to adulthood. Low level of hormones was observed in the thyroid, insulin and peptide YY at certain ages. Neuronal abnormalities contributed by Orexin A and brain structure alteration was documented at 4-30 years old. Treatment in the form of drugs such as livoletide, topiramate, and diazoxide could potentially alleviate these abnormalities and make hyperphagia less prominent in PWS. The approaches are important to regulate the hormonal changes and neuronal involvement as potentially controlling hyperphagia and obesity.
Fulltext Classical and alternative receptors for SARS-CoV-2 therapeutic strategy

Masre SF, Jufri NF, Ibrahim FW, Abdul Raub SH

Rev Med Virol, 2021 09;31(5):1-9.
PMID: 33368788 DOI: 10.1002/rmv.2207

Understanding the molecules that are essential for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) entry can provide insights into viral infection and dissemination. Recently, it has been identified from several studies that angiotensin-converting enzyme 2 receptor and transmembrane serine protease 2 are the main entry molecules for the SARS-CoV-2, which produced the pandemic of Covid-19. However, additional evidence showed several other viral receptors and cellular proteases that are also important in facilitating viral entry and transmission in the target cells. In this review, we summarized the types of SARS-CoV-2 entry molecules and discussed their crucial roles for virus binding, protein priming and fusion to the cellular membrane important for SARS-CoV-2 infection.
Fulltext Hepatoprotective Effects of Zerumbone against Paracetamol-Induced Acute Hepatotoxicity in Rats

Hamid A, Lee LS, Karim SR, Jufri NF

Malays J Med Sci, 2018 Mar;25(2):64-71.
PMID: 30918456 MyJurnal DOI: 10.21315/mjms2018.25.2.7

Background: Zerumbone (ZER) is a major bioactive compound of Zingiber zerumbet, a wild ginger plant that has been documented to have anti-proliferative, anti-inflammatory and anti-oxidant properties. To investigate its hepatoprotective potential, this study was designed to determine the treatment effects of ZER on acute hepatotoxicity induced by paracetamol (PCM) in rats.
Methods: The control group was administered with phosphate buffer solution (PBS) while the other two groups received PCM alone (1000 mg/kg) and PCM + 25 mg/kg ZER, respectively, at 0 h and 4 h after PCM injection. After 24 h, the blood and liver were collected for differential white blood cell count, liver histological observation and biochemical analysis including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total protein concentration in serum and liver.
Results: Treatment with ZER was found to significantly reduce ALT (P = 0.041), AST (P = 0.044) and total hepatic protein (P = 0.045) in comparison to PCM-induced rats. Rats treated with ZER exhibited the normal structure of hepatocytes with no vacuolisation or necrosis and showed significantly reduced neutrophil count (P = 0.037). This finding suggests its ability to suppress the inflammatory processes caused by PCM overdosage and decrease the hepatocytes tendency to go through necrotic processes.
Conclusion: ZER possessed protective activity against PCM-induced acute hepatotoxicity in a rat model.
Fulltext Lysosomal dysfunction induced cytosolic vacuolation and increased intracellular amyloid-beta 42 (Aβ42) in human brain endothelial cells (HBEC-5i)

Laili IN, Nasir MHM, Jufri NF, Ibrahim FW, Hamid A

Biomed Pharmacother, 2023 May;161:114501.
PMID: 36931027 DOI: 10.1016/j.biopha.2023.114501

Lysosome is a primary degradative organelle and is crucial in cellular homeostasis. A reduction in its function due to ageing has been associated with the development of Alzheimer's disease (AD), a common neurodegenerative disorder characterised by the deposition of neurotoxic amyloid plaque in the brain and cerebral vessel walls. The breakdown of the blood-brain barrier (BBB) plays a vital role in the pathogenesis of AD. However, the impact of lysosomal dysfunction on brain endothelial cells, the key component of the BBB, in the disease progression is yet to be fully understood. In this study, human brain endothelial cells (HBEC-5i) were exposed to a lysosomotropic compound, chloroquine (CQ) for 24 h. Cell viability was assessed with the 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay to determine the inhibitory concentration (IC) at IC10 (17.5 µM), IC25 (70.5 µM), and IC50 (125 µM). The morphological changes observed include vacuoles arrested in the cytosols and cell shrinkage that were more prominent at IC25 and IC50. Lysosomal dysfunction was evaluated by measuring the lysosomal-associated membrane protein-1 (LAMP-1) and microtubule-associated protein light chain 3-II (LC3-II) using the capillary-based immunoassay. LC3-II was significantly increased at IC25 and IC50 (p
Cellular and DNA Toxicity Study of Triphenyltin Ethyl Phenyl Dithiocarbamate and Triphenyltin Butyl Phenyl Dithiocarbamate on K562, Leukemia Cell Line

Hamid A, Rajab NF, Charmagne Y, Awang N, Jufri NF, Rasli NR

Anticancer Agents Med Chem, 2024;24(1):58-65.
PMID: 37921147 DOI: 10.2174/0118715206266851231025054446

INTRODUCTION: Continuous research for new effective drugs to treat cancer has improved our understanding on the mechanism of action of these drugs and paved new potential for their application in cancer treatments. In this study, organotin compounds known as triphenyltin ethyl phenyl dithiocarbamate and triphenyltin butyl phenyl dithiocarbamate were investigated for their toxicity on leukemia cell line (K562) and non-cancerous cell line (Chang liver cell and lung fibroblast, V79 cell).
METHODS: MTT assay was performed to evaluate the cytotoxic effects of both compounds toward the cells after 24, 48 and 72 hours of exposure or treatment. The alkaline comet assay was conducted to determine the DNA damage on K562 cells after been exposed to both compounds for 30, 60 and 90 minutes.
RESULTS: The IC50 values obtained from K562 cells ranged from 0.01 to 0.30 μM, whereas for both Chang liver cell and lung fibroblast V79 cell, the values ranged from 0.10 to 0.40 μM. For genotoxicity evaluation, the percentage of damaged DNA is measured as an average of tail moment, and was found to be within 1.20 to 2.20 A.U while the percentage of DNA intensity ranging from 1.50 to 3.50% indicating no genotoxic effects.
CONCLUSION: Both compounds are cytotoxic toward leukemia cells and non-cancerous cells but do not exert their genotoxic effects towards leukemia cell.
Fulltext Pulsatile stretch as a novel modulator of amyloid precursor protein processing and associated inflammatory markers in human cerebral endothelial cells

Gangoda SVS, Avadhanam B, Jufri NF, Sohn EH, Butlin M, Gupta V, et al.

Sci Rep, 2018 01 26;8(1):1689.
PMID: 29374229 DOI: 10.1038/s41598-018-20117-6

Amyloid β (Aβ) deposition is a hallmark of Alzheimer's disease (AD). Vascular modifications, including altered brain endothelial cell function and structural viability of the blood-brain barrier due to vascular pulsatility, are implicated in AD pathology. Pulsatility of phenomena in the cerebral vasculature are often not considered in in vitro models of the blood-brain barrier. We demonstrate, for the first time, that pulsatile stretch of brain vascular endothelial cells modulates amyloid precursor protein (APP) expression and the APP processing enzyme, β-secretase 1, eventuating increased-Aβ generation and secretion. Concurrent modulation of intercellular adhesion molecule 1 and endothelial nitric oxide synthase (eNOS) signaling (expression and phosphorylation of eNOS) in response to pulsatile stretch indicates parallel activation of endothelial inflammatory pathways. These findings mechanistically support vascular pulsatility contributing towards cerebral Aβ levels.
Retrospective data analysis on the prevalence and demographic risk factors for latent tuberculosis infection (LTBI) cases from a private laboratory in Malaysia

Sayuti NASA, Ibrahim FW, Jufri NF, Masre SF, Abdullah AHA, Raub SHA, et al.

Trop Biomed, 2024 Sep 01;41(3):257-263.
PMID: 39548778 DOI: 10.47665/tb.41.3.004

Tuberculosis (TB) is a critical disease that predominantly affects the lungs. This disease remains a global health threat. Currently, the incidence of TB is estimated to be 92 cases in every 100 000 population. However, latent TB infection (LTBI) cases among Malaysians are another great health concern that requires immediate steps to be taken to detect, diagnose, and treat LTBI as one of the key strategies to end TB. Although individuals with LTBI are unlikely to infect others, the threat of infection is still imminent as these individuals can potentially develop into active TB cases. As such, this study aims to identify the prevalence of LTBI among asymptomatic individuals that underwent QuantiFERON®-TB Gold Plus test from a private laboratory in Malaysia to determine the association between the risk factors and the detected LTBI cases. A retrospective study was conducted by analyzing the archive records of 3 877 samples from January 2021 to March 2022. The cases underwent QuantiFERON®-TB Gold Plus tests for LTBI at Premier Integrated Labs. This study underlines that those who were LTBI positive had a prevalence of 638/3 877 (16.46%) with males contributing to 343/638 cases (53.76%). Furthermore, the majority of the positive cases were between the age of 30-43 years old with 197/638 (30.88%), and Chinese ethnicity with 225/638 (35.27%). The risk factors significantly associated with LTBI cases were age (p = 0.001) and ethnicity (p = 0.001). The prevalence of LTBI determined through this study is considered remarkably low for an intermediate TB burden country. Although LTBI is not contagious, specific clinical and preventative considerations are needed for the diagnosis, treatment, and implementation of appropriate safety measures to curb the spread of TB in Malaysia.