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Fulltext DNA methylation profiling revealed promoter hypermethylation-induced silencing of p16, DDAH2 and DUSP1 in primary oral squamous cell carcinoma

Khor GH, Froemming GR, Zain RB, Abraham MT, Omar E, Tan SK, et al.

Int J Med Sci, 2013;10(12):1727-39.
PMID: 24155659 DOI: 10.7150/ijms.6884

BACKGROUND: Hypermethylation in promoter regions of genes might lead to altered gene functions and result in malignant cellular transformation. Thus, biomarker identification for hypermethylated genes would be very useful for early diagnosis, prognosis, and therapeutic treatment of oral squamous cell carcinoma (OSCC). The objectives of this study were to screen and validate differentially hypermethylated genes in OSCC and correlate the hypermethylation-induced genes with demographic, clinocopathological characteristics and survival rate of OSCC.
METHODS: DNA methylation profiling was utilized to screen the differentially hypermethylated genes in OSCC. Three selected differentially-hypermethylated genes of p16, DDAH2 and DUSP1 were further validated for methylation status and protein expression. The correlation between demographic, clinicopathological characteristics, and survival rate of OSCC patients with hypermethylation of p16, DDAH2 and DUSP1 genes were analysed in the study.
RESULTS: Methylation profiling demonstrated 33 promoter hypermethylated genes in OSCC. The differentially-hypermethylated genes of p16, DDAH2 and DUSP1 revealed positivity of 78%, 80% and 88% in methylation-specific polymerase chain reaction and 24% and 22% of immunoreactivity in DDAH2 and DUSP1 genes, respectively. Promoter hypermethylation of p16 gene was found significantly associated with tumour site of buccal, gum, tongue and lip (P=0.001). In addition, DDAH2 methylation level was correlated significantly with patients' age (P=0.050). In this study, overall five-year survival rate was 38.1% for OSCC patients and was influenced by sex difference.
CONCLUSIONS: The study has identified 33 promoter hypermethylated genes that were significantly silenced in OSCC, which might be involved in an important mechanism in oral carcinogenesis. Our approaches revealed signature candidates of differentially hypermethylated genes of DDAH2 and DUSP1 which can be further developed as potential biomarkers for OSCC as diagnostic, prognostic and therapeutic targets in the future.
Fulltext Gut Microbiota Signature Among Asian Post-gestational Diabetes Women Linked to Macronutrient Intakes and Metabolic Phenotypes

Hasain Z, Raja Ali RA, Abdul Razak S, Azizan KA, El-Omar E, Razalli NH, et al.

Front Microbiol, 2021;12:680622.
PMID: 34248897 DOI: 10.3389/fmicb.2021.680622

Aberrant gut microbiota dysbiosis in women with a previous history of gestational diabetes mellitus (post-GDM) was comparable to that in adults with type 2 diabetes mellitus (T2DM). Nonetheless, potential relationships between diet, gut microbiota, and metabolic phenotypes in post-GDM women after delivery are yet to be discovered. In this research, we assessed the relationship of the macronutrient intakes, gut microbiota composition, and metabolic phenotypes (i.e., anthropometrics and glycemic control) in post-GDM women with and without postpartum glucose intolerance (GI). About 24 post-GDM women were included in this study, 14 women were grouped in the GI group and 10 women were grouped in the normal glucose tolerance (NGT) group according to oral glucose tolerance test. Macronutrient intake assessment using a 3-day dietary record, anthropometric measurements, biochemical analyses, and fecal sampling were done during 3-6 months postpartum. Gut microbiota profiling was determined using 16S rRNA genes sequencing targeting the V3-V4 regions. The relationships between macronutrient intakes, gut microbiota composition, and metabolic phenotypes were evaluated using Pearson's correlation coefficient and stepwise regression analyses. In this study, most post-GDM women had significantly poor dietary fiber adherence than the nutritional recommendations. Women from the GI group have significantly higher fasting blood glucose (FBG), HbA1c, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels compared to the NGT group. The group also showed significant elevation of high-sensitivity C-reactive protein (hs-CRP) level when compared to the normal value. Specific gut microbial taxa derived from Proteobacteria and Bacteroidetes such as Parasutterella, Aquicella, Haliscomenobacter, and Prevotellaceae_NK3B31_group were significantly abundant in the GI group compared to the NGT group. Prevotellaceae_NK3B31_group was significantly associated with high FBG, HOMA-IR, and HbA1c levels. Low fiber and monounsaturated fatty acids intakes were associated with Lactobacillus. Meanwhile, Lactobacillus was associated with high body mass index, waist circumference, 2-h postprandial blood glucose, and hs-CRP levels. Our study suggested that macronutrient intake is an important predictor of gut microbiota dysbiosis and is associated with obesity, low-grade inflammation, and poor glycemic control in post-GDM women. Hence, dietary intake modification to remodel gut microbiota composition is a promising T2DM preventive strategy in post-GDM women.
Correlation and assessment of coronary artery luminal stenosis: Post-mortem computed tomography angiogram versus histopathology

Chainchel Singh MK, Abdul Rashid SN, Abdul Hamid S, Mahmood MS, Feng SS, Mohd Nawawi H, et al.

Forensic Sci Int, 2020 Mar;308:110171.
PMID: 32032870 DOI: 10.1016/j.forsciint.2020.110171

BACKGROUND: Post-mortem Computed Tomography (PMCT) allows non-invasive or minimally invasive detection of findings that may or may not be visible during conventional autopsy, however, it does not allow the investigator to draw any conclusions regarding patency of the vessel's lumen. To address this deficiency, Post-mortem Computed Tomography Angiography (PMCTA) utilizing different contrast media and techniques have been introduced with various studies looking at the correlation between PMCTA, autopsy (gross) findings and coronary artery histology in diagnosing coronary artery disease.
OBJECTIVES: The aim of this study is to investigate the sensitivity and specificity of PMCTA in diagnosing coronary artery stenosis using water-based contrast media introduced though the vessels of the neck, compared to the gold standard of diagnosis i.e. gross and histological evaluation of the coronary artery.
METHOD: This was a cross sectional study of 158 arterial sections involving 37 subjects recruited from the National Institute of Forensic Medicine (IPFN), Hospital Kuala Lumpur (HKL). An unenhanced PMCT was performed followed by PMCTA using water-based contrast media introduced though the vessels of the neck. Coronary artery stenosis was determined using multiplanar reconstructionD while the degree of stenosis was determined by calculating the percentage of luminal diameter divided by the diameter of the vessel internal elastic.
RESULTS: The analysis of PMCTA and histopathology examinations revealed a sensitivity of 61.5%, specificity of 91.7%; positive predictive value (PPV) of 40.0% and negative predictive value (NPV) of 96.4%.
CONCLUSION: PMCTA utilizing water-based contrast introduced though the vessels of the neck yielded similar results as other methods and techniques of PMCTA. We would therefore conclude that PMCTA utilizing this technique could be used to assess the degree of calcification and the presence of significant stenosis.
Fulltext Ficus deltoidea suppresses endothelial activation, inflammation, monocytes adhesion and oxidative stress via NF-κB and eNOS pathways in stimulated human coronary artery endothelial cells

Mohd Ariff A, Abu Bakar NA, Abd Muid S, Omar E, Ismail NH, Ali AM, et al.

BMC Complement Med Ther, 2020 Feb 17;20(1):56.
PMID: 32066426 DOI: 10.1186/s12906-020-2844-6

BACKGROUND: Ficus deltoidea (FD) has been shown to have antidiabetic, anti-inflammatory, antinociceptive and antioxidant properties. However, its effects on key events in the pathogenesis of atherosclerosis are unknown.
AIM: To investigate the endothelial activation, inflammation, monocyte-endothelial cell binding and oxidative stress effects of four FD varieties.
METHODS: Human coronary artery endothelial cells (HCAEC) were incubated with different concentrations of aqueous ethanolic extracts of FD var. trengganuensis (FDT), var. kunstleri (FDK), var. deltoidea (FDD) and var. intermedia (FDI), together with LPS. Protein and gene expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), endothelial-leukocyte adhesion molecule-1 (E-selectin), interleukin-6 (IL-6), Nuclear factor-κB (NF-κB) p50 and p65 and endothelial nitric oxide synthase (eNOS) were measured using ELISA and QuantiGene plex, respectively. Adhesion of monocyte to HCAEC and formation of reactive oxygen species (ROS) were detected by Rose Bengal staining and 2'-7'-dichlorofluorescein diacetate (DCFH-DA) assay.
RESULTS: FDK exhibited the highest inhibition of biomarkers in relation to endothelial activation and inflammation, second in reducing monocyte binding (17.3%) compared to other varieties. FDK (25.6%) was also the most potent at decreasing ROS production.
CONCLUSION: FD has anti-atherogenic effects, possibly mediated by NF-κB and eNOS pathways; with FDK being the most potent variety. It is potentially beneficial in mitigating atherogenesis.
Ficus deltoidea reduces expression of interleukin 6 via nuclear factor kappa b pathway in human coronary artery endothelial cells

Muid S, Omar E, Ikhsan Ahmad R, Hadiani Ismail N, Alicezah Mohd Kasim N, Manaf Ali A, et al.

Atherosclerosis, 2017 Aug;263:e122.
PMID: 29365500 DOI: 10.1016/j.atherosclerosis.2017.06.392
Ficus deltoidea Trengganuensis is the most potent variant in reducing endothelial activation and monocyte-endothelial cell interaction in stimulated human coronary artery endothelial cells

Muid S, Omar E, Ahmad RI, Ismail NH, Mohd Kasim NA, Ali AM, et al.

Atherosclerosis, 2017 Aug;263:e135-e136.
PMID: 29365540 DOI: 10.1016/j.atherosclerosis.2017.06.433
A single targeted gamma-ray irradiation induced an acute modulation of immune cells and related cytokines in EMT6 mouse-bearing tumour model

Hasan N, Hasani NAH, Omar E, Sham FR, Fuad SBSA, Karim MKA, et al.

Cancer Biomark, 2023;38(1):61-75.
PMID: 37522193 DOI: 10.3233/CBM-220268

BACKGROUND: A complicated interplay between radiation doses, tumour microenvironment (TME), and host immune system is linked to the active participation of immune response.
OBJECTIVE: The effects of single targeted 2 Gy and 8 Gy gamma-ray irradiations on the immune cell population (lymphocytes, B-cells, T-cells, neutrophils, eosinophils, and macrophages) in EMT6 mouse-bearing tumour models was investigated.
METHODS: The effects of both irradiation doses in early (96 hours) and acute phase (5 to 11 days) post-irradiation on immune parameters were monitored in blood circulation and TME using flow cytometry. Simultaneously, selected cytokines related to immune cells within the TME were measured using multiplex ELISA.
RESULTS: A temporary reduction in systemic total white blood count (TWBC) resulted from an early phase (96 hours) of gamma-ray irradiation at 2 Gy and 8 Gy compared to sham control group. No difference was obtained in the acute phase. Neutrophils dominated among other immune cells in TME in sham control group. Eosinophils in TME was significantly increased after 8 Gy treatment in acute phase compared to sham control (p< 0.005). Furthermore, the increment of tumour necrosis (TNF)-α, eotaxin and interleukin (IL)-7 (p< 0.05) in both treatment groups and phases were associated with anti-tumour activities within TME by gamma-ray irradiation.
CONCLUSION: The temporary changes in immune cell populations within systemic circulation and TME induced by different doses of gamma-ray irradiation correlated with suppression of several pro-tumorigenic cytokines in mouse-bearing EMT6 tumour models.
Fulltext Development of custom lead shield and strainer for targeted irradiation for mice in the gamma cell chamber

Hasan N, Sham NFR, Karim MKA, Fuad SBSA, Hasani NAH, Omar E, et al.

Sci Rep, 2021 Jul 15;11(1):14559.
PMID: 34267293 DOI: 10.1038/s41598-021-93964-5

We presented a development of a custom lead shield and mouse strainer for targeted irradiation from the gamma-cell chamber. This study was divided into two parts i.e., to (i) fabricate the shield and strainer from a lead (Pb) and (ii) optimize the irradiation to the mice-bearing tumour model with 2 and 8 Gy absorbed doses. The lead shielding was fabricated into a cuboid shape with a canal on the top and a hole on the vertical side for the beam path. Respective deliveries doses of 28 and 75 Gy from gamma-cell were used to achieve 2 and 8 Gy absorbed doses at the tumour sites.
Fulltext Ghost admixture in eastern gorillas

Pawar H, Rymbekova A, Cuadros-Espinoza S, Huang X, de Manuel M, van der Valk T, et al.

Nat Ecol Evol, 2023 Sep;7(9):1503-1514.
PMID: 37500909 DOI: 10.1038/s41559-023-02145-2

Archaic admixture has had a substantial impact on human evolution with multiple events across different clades, including from extinct hominins such as Neanderthals and Denisovans into modern humans. In great apes, archaic admixture has been identified in chimpanzees and bonobos but the possibility of such events has not been explored in other species. Here, we address this question using high-coverage whole-genome sequences from all four extant gorilla subspecies, including six newly sequenced eastern gorillas from previously unsampled geographic regions. Using approximate Bayesian computation with neural networks to model the demographic history of gorillas, we find a signature of admixture from an archaic 'ghost' lineage into the common ancestor of eastern gorillas but not western gorillas. We infer that up to 3% of the genome of these individuals is introgressed from an archaic lineage that diverged more than 3 million years ago from the common ancestor of all extant gorillas. This introgression event took place before the split of mountain and eastern lowland gorillas, probably more than 40 thousand years ago and may have influenced perception of bitter taste in eastern gorillas. When comparing the introgression landscapes of gorillas, humans and bonobos, we find a consistent depletion of introgressed fragments on the X chromosome across these species. However, depletion in protein-coding content is not detectable in eastern gorillas, possibly as a consequence of stronger genetic drift in this species.
Fulltext Prevalence of COVID-19 vaccine reactogenicity among Bangladeshi physicians

Majumder MAA, Lutfor AB, Rabbi AMF, Alam ABMM, Rahman M, Saha N, et al.

FASEB Bioadv, 2022 Jun;4(6):379-390.
PMID: 35601057 DOI: 10.1096/fba.2021-00158

Increased COVID-19 vaccine hesitancy presents a major hurdle in global efforts to contain the COVID-19 pandemic. This study was designed to estimate the prevalence of adverse events after the first dose of the Covishield (AstraZeneca) vaccine among physicians in Bangladesh. A cross-sectional study was conducted using an online questionnaire for physicians (n = 916) in Bangladesh. Physicians who received at least one dose of the COVID-19 vaccine were included. The study was carried out from April 12 to May 31, 2021. More than 58% of respondents (n = 533) reported one or more adverse events. Soreness of the injected arm (71.9%), tiredness (56.1%), fever (54.4%), soreness of muscles (48.4%), headache (41.5%) and sleeping more than usual (26.8%) were the most commonly reported adverse events. Most vaccine-related reactogenicities were reported by the younger cohorts (<45 years). The majority of respondents reported severity of reactogenicity as "mild," experienced on the day of vaccination, and lasting for 1-3 days. The most common reactogenicity was pain at the injection site; the second most common was tiredness. Almost half (49.2%) of the physicians took acetaminophen (paracetamol) to minimize the effects of vaccine reactogenicity. Multivariate logistic regression analyses showed that physicians with diabetes and hypertension (OR = 2.729 95% CI: 1.282-5.089) and asthma with other comorbidities (OR = 1.885 95% CI: 1.001-3.551) had a significantly higher risk of vaccine-related reactogenicities than physicians without comorbidities. Further safety studies with larger cohorts are required to monitor vaccine safety and provide assurance to potential vaccine recipients.
Fulltext Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019

Global Burden of Disease 2019 Cancer Collaboration, Kocarnik JM, Compton K, Dean FE, Fu W, Gaw BL, et al.

JAMA Oncol, 2022 Mar 01;8(3):420-444.
PMID: 34967848 DOI: 10.1001/jamaoncol.2021.6987

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden.
OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019.
EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs).
FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles.
CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

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