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Fulltext Early mortality after late initiation of antiretroviral therapy in the TREAT Asia HIV Observational Database (TAHOD) of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Asia-Pacific

Rupasinghe D, Kiertiburanakul S, Kamarulzaman A, Zhang F, Kumarasamy N, Chaiwarith R, et al.

HIV Med, 2020 07;21(6):397-402.
PMID: 31852025 DOI: 10.1111/hiv.12836

OBJECTIVES: Early mortality among those still initiating antiretroviral therapy (ART) with advanced stages of HIV infection in resource-limited settings remains high despite recommendations for universal HIV treatment. We investigated risk factors associated with early mortality in people living with HIV (PLHIV) starting ART at low CD4 levels in the Asia-Pacific.
METHODS: PLHIV enrolled in the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD) who initiated ART with a CD4 count death within 1 year of ART initiation. PLHIV in follow-up for > 1 year were censored at 12 months. Competing risk regression was used to analyse risk factors with loss to follow-up as a competing risk.
RESULTS: A total of 1813 PLHIV were included in the study, of whom 74% were male. With 73 (4%) deaths, the overall first-year mortality rate was 4.27 per 100 person-years (PY). Thirty-eight deaths (52%) were AIDS-related, 10 (14%) were immune reconstituted inflammatory syndrome (IRIS)-related, 13 (18%) were non-AIDS-related and 12 (16%) had an unknown cause. Risk factors included having a body mass index (BMI) 100 cells/μL: SHR 0.12; 95% CI 0.05-0.26) was associated with reduced hazard for mortality compared to CD4 count ≤ 25 cells/μL.
CONCLUSIONS: Fifty-two per cent of early deaths were AIDS-related. Efforts to initiate ART at CD4 counts > 50 cell/μL are associated with improved short-term survival rates, even in those with late stages of HIV disease.

Matched MeSH terms: Cause of Death
Fulltext Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection

Yong YK, Saeidi A, Tan HY, Rosmawati M, Enström PF, Batran RA, et al.

Front Immunol, 2018;9:472.
PMID: 29616020 DOI: 10.3389/fimmu.2018.00472

Mucosal-associated invariant T (MAIT) cells, defined as CD161++TCR iVα7.2+ T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV) infection. The peripheral CD3+CD161++TCR iVα7.2+ MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression. The frequency of MAIT cells was significantly decreased among chronic HBV-infected individuals as compared to controls. Expression of CD57, PD-1, CTLA-4, as well as HLA-DR and CD38 on MAIT cells was significantly elevated in chronic HBV-infected individuals relative to controls. The percentage of T cell receptor (TCR) iVα7.2+ CD161+ MAIT cells did not correlate with HBV viral load but inversely with HLA-DR on CD4+ T cells and MAIT cells and with CD57 on CD8+ T cells suggesting that decrease of MAIT cells may not be attributed to direct infection by HBV but driven by HBV-induced chronic immune activation. The percentage and expression levels of PD-1 as well as CTLA-4 on MAIT cells inversely correlated with plasma HBV-DNA levels, which may suggest either a role for MAIT cells in the control of HBV infection or the effect of HBV replication in the liver on MAIT cell phenotype. We report that decrease of TCR iVα7.2+ MAIT cells in the peripheral blood and their functions were seemingly impaired in chronic HBV-infected patients likely because of the increased expression of PD-1.

Matched MeSH terms: Programmed Cell Death 1 Receptor
Fulltext Changes in rats' breast tumor ultrastructure and immune and messenger RNA responses caused by dietary Seaweed (Kappaphycus alvarezii) extract

Bakar NA, Tengku Ibrahim TA, Mohamad Shalan NA, Mohamed S

J Microsc Ultrastruct, 2016 08 21;5(2):70-81.
PMID: 30023239 DOI: 10.1016/j.jmau.2016.08.001

The edible red seaweed Kappaphycus alvarezii or Eucheuma cottonii is commercially cultivated in the pristine tropical seas for carrageenan production. The systemic, cellular, and molecular effects of E. cottonii 50% alcohol extract [seaweed E. cottonii ethanol extract (SECE)] on breast cancer were investigated in a rat model. Mammary tumor was induced by subcutaneously injecting LA7 cells in female rat mammary pads. After 2 weeks of cancer growth, the rats received oral administration of either SECE [150 mg/kg body weight (BW) and 300 mg/kg BW] or tamoxifen. Electron microscopy imaging results confirmed macrophage activity and hematoxylin and eosin staining indicated that tumor histopathological alterations were restored toward normal structures by the seaweed extract. The extract suppressed tumor development and modulated the immune responses. This was evidenced by the microscopic observations, the increased spleen weight, size, spleen CD19 B cells, and blood immunoglobulin G (IgG) levels. The extract also increased the circulating total white blood cells, lymphocytes, segmented neutrophils count, T cells (CD3), T-helper cells (CD4), cytotoxic T cell (CD8), and nuclear factor-kappa beta expressions. The extract enhanced cancer cell death, by upregulating the Birc5, Chk1, and p53 levels and downregulating the tumor growth cellular Mdm2 (transformed mouse 3T3 cell double minute 2) messenger RNA (mRNA) expression. The extract showed no toxicity at 150 mg/kg BW in rats. The lectin-rich SECE showed tumor suppression by enhancing immune responses and upregulating the cancer cell apoptosis mRNA expressions.

Matched MeSH terms: Cell Death
Studies on the interaction of mononuclear metal(II) complexes of amino‑naphthoquinone with bio-macromolecules

Kosiha A, Lo KM, Parthiban C, Elango KP

Mater Sci Eng C Mater Biol Appl, 2019 Jan 01;94:778-787.
PMID: 30423764 DOI: 10.1016/j.msec.2018.10.021

Three metal(II) complexes [CoLCl2], [CuLCl2] and [ZnL2Cl2] {L = 2‑chloro‑3‑((3‑dimethylamino)propylamino)naphthalene‑1,4‑dione} have been synthesized and characterized using analytical, thermal and spectral techniques (FT-IR, UV-Vis, ESR and ESI-MS). The structure of the L has been confirmed by single crystal XRD study. The complexes show good binding propensity to bovine serum albumin (BSA) having relatively higher binding constant values (104 M-1) than the ligand. Fluorescence spectral studies indicate that [CoLCl2] binds relatively stronger with CT DNA through intercalative mode, exhibiting higher binding constant (2.22 × 105 M-1). Agarose gel electrophoresis run on plasmid DNA (pUC18) prove that all the complexes showed efficient DNA cleavage via hydroxyl radical mechanism. The complexes were identified as potent anticancer agents against two human cancer cell lines (MCF7 and A549) by comparing with cisplatin. Co(II) complex demonstrated greater cytotoxicity against MCF7 and A549 cells with IC50 values at 19 and 22 μM, respectively.

Matched MeSH terms: Cell Death
Factors Influencing Attitude Toward Organ and Tissue Donation Among Patients in Primary Clinic, Sabah, Malaysia

Lim KJ, Cheng TTJ, Jeffree MS, Hayati F, Cheah PK, Nee KO, et al.

Transplant Proc, 2020 Apr;52(3):680-686.
PMID: 32146022 DOI: 10.1016/j.transproceed.2020.01.007

INTRODUCTION: Worldwide, the gap between organ supply and demand has widened over the years. Malaysia has one of the lowest deceased organ donation rates. Success rate of organ or tissue procurement depends on not only the approach rate by health care providers but also the awareness among the public, whereby it can be a platform for family initiation of organ donation. The purpose of this study is to assess the knowledge of and determine the factors influencing attitude toward organ and tissue donation among patients in a primary clinic.
METHODS: A cross-sectional analytical study was carried out. Self-administered questionnaires were given to 400 patients who registered at an outpatient clinic in April 2018. Convenience sampling was applied.
RESULTS: Monthly income, education level, occupation, and knowledge level are significantly associated with attitude of the respondents toward organ and tissue donation. Occupation influenced attitude toward organ donation. Knowledge of organ donation and brain death both significantly affected attitude toward organ donation.
CONCLUSION: The greater the knowledge of organ donation and brain death, the more positive impression or attitude toward organ donation. Education level and income are the main predictors that influence attitude toward organ donation. Hence, it is important for public health units to promote and deliver public education on organ donation, change public misconceptions, and work parallel with hospitals to increase organ donation rates in Sabah.

Matched MeSH terms: Brain Death
Fulltext Association of Symptoms of Depression With Cardiovascular Disease and Mortality in Low-, Middle-, and High-Income Countries

Rajan S, McKee M, Rangarajan S, Bangdiwala S, Rosengren A, Gupta R, et al.

JAMA Psychiatry, 2020 10 01;77(10):1052-1063.
PMID: 32520341 DOI: 10.1001/jamapsychiatry.2020.1351

Importance: Depression is associated with incidence of and premature death from cardiovascular disease (CVD) and cancer in high-income countries, but it is not known whether this is true in low- and middle-income countries and in urban areas, where most people with depression now live.
Objective: To identify any associations between depressive symptoms and incident CVD and all-cause mortality in countries at different levels of economic development and in urban and rural areas.
Design, Setting, and Participants: This multicenter, population-based cohort study was conducted between January 2005 and June 2019 (median follow-up, 9.3 years) and included 370 urban and 314 rural communities from 21 economically diverse countries on 5 continents. Eligible participants aged 35 to 70 years were enrolled. Analysis began February 2018 and ended September 2019.
Exposures: Four or more self-reported depressive symptoms from the Short-Form Composite International Diagnostic Interview.
Main Outcomes and Measures: Incident CVD, all-cause mortality, and a combined measure of either incident CVD or all-cause mortality.
Results: Of 145 862 participants, 61 235 (58%) were male and the mean (SD) age was 50.05 (9.7) years. Of those, 15 983 (11%) reported 4 or more depressive symptoms at baseline. Depression was associated with incident CVD (hazard ratio [HR], 1.14; 95% CI, 1.05-1.24), all-cause mortality (HR, 1.17; 95% CI, 1.11-1.25), the combined CVD/mortality outcome (HR, 1.18; 95% CI, 1.11-1.24), myocardial infarction (HR, 1.23; 95% CI, 1.10-1.37), and noncardiovascular death (HR, 1.21; 95% CI, 1.13-1.31) in multivariable models. The risk of the combined outcome increased progressively with number of symptoms, being highest in those with 7 symptoms (HR, 1.24; 95% CI, 1.12-1.37) and lowest with 1 symptom (HR, 1.05; 95% CI, 0.92 -1.19; P for trend

Matched MeSH terms: Cause of Death
Changing sex ratio of mortality in the Semai Senoi, 1969-1987

Fix AG

Hum Biol, 1991 Apr;63(2):211-20.
PMID: 2019414

An excess of male over female deaths is characteristic of modern national populations, whereas in some high-mortality societies female mortality exceeds that of males. Among the Semai Senoi, a Malaysian Orang Asli ("aboriginal") population, women experienced higher mortality than males in the decades before 1969. This differential occurred in all age classes older than 15 years so that the sex ratio progressively increased with age. A recent (1987) restudy of the Semai population found that sex-specific differential mortality is much reduced. A comparison of the 1969 and 1987 life tables shows a sharp shift in the sex ratios of mortality for the post-15-year-old age classes (the geometric means of age classes 15-44 were 0.768 in 1969 and 0.997 in 1987) so that male and female expectations of further life at age 15 are now nearly identical. In contrast to the best-known cases of high female mortality (mostly in South Asia), Semai sex differential mortality does not include the childhood ages. The Semai have traditionally been relatively sexually egalitarian, and sex bias in care has not occurred. Analysis of sex-specific causes of death for the pre-1969 population suggests that maternal mortality is the major cause of the excess female deaths. The reduced number of maternal deaths seems largely due to better health care, particularly the availability of hospital services. Interestingly, the reduction in female mortality has occurred simultaneously with increased fertility, and overall mortality has continued at relatively high levels (eO less than 36). Thus, rather than forming a component of a unitary demographic transition, declining sex differences in mortality can be accounted for by a specific factor, better maternal care.

Matched MeSH terms: Cause of Death
The Role of Public Health Nutrition in Achieving the Sustainable Development Goals in the Asia Pacific Region

Binns C, Lee MK, Low WY, Zerfas A

Asia Pac J Public Health, 2017 Oct;29(7):617-624.
PMID: 29094630 DOI: 10.1177/1010539517736441

The Sustainable Development Goals (SDGs) replaced the Millennium Development Goals (MDCs) in 2015, which included several goals and targets primarily related to nutrition: to eradicate extreme poverty and hunger and to reduce child mortality and improve maternal health. In the Asia-Pacific Academic Consortium for Public Health (APACPH) member countries as a group, infant and child mortality were reduced by more than 65% between 1990 and 2015, achieving the MDG target of two-thirds reduction, although these goals were not achieved by several smaller countries. The SDGs are broader in focus than the MDGs, but include several goals that relate directly to nutrition: 2 (zero hunger-food), 3 (good health and well-being-healthy life), and 12 (responsible consumption and production-sustainability). Other SDGs that are closely related to nutrition are 4 and 5 (quality education and equality in gender-education and health for girls and mothers, which is very important for infant health) and 13 (climate action). Goal 3 is "good health and well-being," which includes targets for child mortality, maternal mortality, and reducing chronic disease. The Global Burden of Disease Project has confirmed that the majority of risk for these targets can be attributed to nutrition-related targets. Dietary Guidelines were developed to address public health nutrition risk in the Asia Pacific region at the 48th APACPH 2016 conference and they are relevant to the achievement of the SDGs. Iron deficiency increases the risk of maternal death from haemorrhage, a cause of 300000 deaths world-wide each year. Improving diets and iron supplementation are important public health interventions in the APACPH region. Chronic disease and obesity rates in the APACPH region are now a major challenge and healthy life course nutrition is a major public health priority in answering this challenge. This article discusses the role of public health nutrition in achieving the SDGs. It also examines the role of APACPH in education and advocacy and in fulfilling the educational needs of public health students in public health nutrition.

Matched MeSH terms: Maternal Death
Fulltext Hepatitis in Malaysia: Past, Present, and Future

Raihan R

Euroasian J Hepatogastroenterol, 2016 Jan-Jun;6(1):52-55.
PMID: 29201726 DOI: 10.5005/jp-journals-10018-1167

Malaysia is multiethnic, with a population of 31,127,247 comprising a mixture of Malays (50.1%), Chinese (22.6%), Indians (6.7%), Aborigines (11.8%), others (0.7%), and noncitizens (8.2%). Like other countries in the region, viral hepatitis is an important public health problem in Malaysia. The 3 most common causes for hepatitis in Malaysia are hepatitis A, B, and C. Hepatitis A has been a reportable disease in Malaysia since 1988. Due to the introduction of government control programs, the national incidence rate has dropped steadily. It is now estimated that 50% of Malaysians less than 30 years of age do not have antibodies to hepatitis A and are therefore susceptible to the disease, which can be prevented by reinforcing the hygiene status of the general population. Malaysia is a country of medium seroprevalence for the hepatitis B virus (HBV) surface antigen (HBsAg) in the general population (1.5-9.8%). The major route of transmission is from infected mother to fetus. There are an estimated 1 million people chronically infected with hepatitis B in Malaysia. Approximately 75% of all viral hepatitis cases are due to hepatitis B infection, with a male-to-female ratio of 2:1. Chronic hepatitis B (CHB) accounts for more than 80% of the hepatocellular carcinoma (HCC) cases seen in Malaysia and HCC is the 3rd most common malignant neoplasm and among the 10 leading causes of death. Most common genotypes are B and C. Incidence rates among Chinese, Malays, and Indians are 36, 26, and 15% respectively. The hepatitis B vaccination program for children was introduced in 1989, which successfully managed to reduce the seroprevalence of infection among Malaysians to 0.01% (graph 4, 2014). But the disease burden will still remain high for some time as the infected people are getting older and living longer. Hepatitis C virus (HCV) infection is a growing problem in Malaysia. An estimated 453,700 people were living with HCV infection in Malaysia in 2009 (2.5% of the population aged 15-64 years), of whom 59% acquired their infection through injection and the most common genotypes found are genotype 3 and 1. The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia.

How to cite this article: Raihan R. Hepatitis in Malaysia: Past, Present, and Future. Euroasian J Hepato-Gastroenterol 2016;6(1):52-55.

Matched MeSH terms: Cause of Death
Fulltext Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis

WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Shankar-Hari M, Vale CL, Godolphin PJ, Fisher D, Higgins JPT, et al.

JAMA, 2021 Aug 10;326(6):499-518.
PMID: 34228774 DOI: 10.1001/jama.2021.11330

IMPORTANCE: Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.
OBJECTIVE: To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.
DATA SOURCES: Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts.
STUDY SELECTION: Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria.
DATA EXTRACTION AND SYNTHESIS: In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality.
MAIN OUTCOMES AND MEASURES: The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days.
RESULTS: A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P death, compared with usual care or placebo, were 0.77 (95% CI, 0.70-0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66-0.82) for tocilizumab, and 1.00 (95% CI, 0.74-1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85-1.16).
CONCLUSIONS AND RELEVANCE: In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.
TRIAL REGISTRATION: PROSPERO Identifier: CRD42021230155.

Matched MeSH terms: Cause of Death
Fulltext Mortality and morbidity of the small for gestational age (SGA) very low birth weight (VLBW) Malaysian infant

Ho J, Malaysian Very Low Birth Weight Study Group

Singapore Med J, 2001 Aug;42(8):355-9.
PMID: 11764052

To compare the neonatal course of small for gestational age (SGA) and appropriate for gestational age (AGA) preterm infants 1500 g or less birthweight.

Matched MeSH terms: Cause of Death
Fulltext Spontaneous pneumothorax: a review of 29 admissions into Hospital Universiti Sains Malaysia 1984-90

Harun MH, Yaacob I, Mohd Kassim Z

Singapore Med J, 1993 Apr;34(2):150-2.
PMID: 8266158

Twenty-nine patients (16 males, 13 females) with spontaneous pneumothorax admitted into Hospital Universiti Sains Malaysia, Kubang Kerian, from September 1984 to September 1990 were reviewed. Their ages ranged from newborn to 75 years. The commonest chief presenting symptom was dyspnoea (69%), followed by chest pain (35%). Four patients had chronic obstructive airway disease, 7 had pneumonia, 2 had pulmonary tuberculosis, one patient had emphysema while 4 patients had multiple underlying lung disorders. The left and right lungs were involved with equal frequency. Bilateral pneumothorax occurred in one patient. Most patients had a single episode of pneumothorax but recurrent pneumothoraces occurred in 3 patients (10%). Six patients were observed conservatively, 20 patients required chest tube insertion alone and 3 patients also required pleurodesis. Death occurred in 8 patients (28%) mainly due to coexisting infection and respiratory failure.

Matched MeSH terms: Cause of Death
Para-phenylenediamine-induces apoptosis via a pathway dependent on PTK-Ras-Raf-JNK activation but independent of the PI3K/Akt pathway in NRK-52E cells

Kasi RA, Moi CS, Kien YW, Yian KR, Chin NW, Yen NK, et al.

Mol Med Rep, 2015 Mar;11(3):2262-8.
PMID: 25411820 DOI: 10.3892/mmr.2014.2979

para‑Phenylenediamine (p‑PD) is a potential carcinogen, and widely used in marketed hair dye formulations. In the present study, the role of the protein tyrosine kinase (PTK)/Ras/Raf/c‑Jun N‑terminal kinase (JNK) and phosphoinositide 3‑kinase (PI3k)/protein kinase B (Akt) pathways on the growth of NRK‑52E cells was investigated. The results demonstrated that p‑PD reduced cell viability in a dose‑dependent manner. The cell death due to apoptosis was confirmed by cell cycle analysis and an Annexin‑V‑fluorescein isothiocyanate binding assay. Subsequent to staining with 2',7'‑dichlorofluorescin diacetate, the treated cells demonstrated a significant increase in reactive oxygen species (ROS) generation compared with the controls. The effects of p‑PD on the signalling pathways were analysed by western blotting. p‑PD‑treated cells exhibited an upregulated phospho‑stress‑activated protein kinase/JNK protein expression level and downregulated Ras and Raf protein expression levels; however, Akt, Bcl‑2, Bcl‑XL and Bad protein expression levels were not significantly altered compared with the control. In conclusion, p‑PD induced apoptosis by a PTK/Ras/Raf/JNK‑dependent pathway and was independent of the PI3K/Akt pathway in NRK‑52E cells.

Matched MeSH terms: bcl-Associated Death Protein/metabolism
Fulltext (R)-(+)-α-lipoic acid protected NG108-15 cells against H₂O₂-induced cell death through PI3K-Akt/GSK-3β pathway and suppression of NF-κβ-cytokines

Kamarudin MN, Mohd Raflee NA, Hussein SS, Lo JY, Supriady H, Abdul Kadir H

Drug Des Devel Ther, 2014;8:1765-80.
PMID: 25336920 DOI: 10.2147/DDDT.S67980

Alpha-lipoic acid, a potent antioxidant with multifarious pharmacological benefits has been reported to be neuroprotective in several neuronal models and used to treat neurological disorders such as Alzheimer's disease. Nonetheless, conclusive mechanisms of alpha-lipoic acid for its protective effects particularly in NG108-15 cells have never been investigated. In this study, the intricate neuroprotective molecular mechanisms by (R)-(+)-alpha-lipoic acid (R-LA) against H2O2-induced cell death in an in vitro model of neurodegeneration were elucidated. Pretreatment with R-LA (2 hours) significantly increased NG108-15 cell viability as compared to H2O2-treated cells and mitigated the induction of apoptosis as evidenced by Hoechst 33342/propidium iodide staining. R-LA (12.5-50 μM) aggrandized the reduced glutathione over glutathione disulfide ratio followed by a reduction in the intracellular reactive oxygen species level and an increase in mitochondrial membrane potential following H2O2 exposure. Moreover, pretreatment with R-LA stimulated the activation of PI3K-Akt through mTORC1 and mTORC2 components (mTOR, rictor and raptor) and production of antiinflammatory cytokine, IL-10 which led to the inactivation of glycogen synthase kinase-3β (GSK-3β) and reduction of both Bax/Bcl2 and Bax/Bcl-xL ratios, accompanied by inhibition of the cleaved caspase-3. Additionally, this observation was preceded by the suppression of NF-κβ p65 translocation and production of proinflammatory cytokines (IL-6 and TNF-α). The current findings accentuate new mechanistic insight of R-LA against apoptogenic and brain inflammatory factors in a neuronal model. These results further advocate the therapeutic potential of R-LA for the treatment of neurodegenerative diseases.

Matched MeSH terms: Cell Death/drug effects
Fulltext Edible bird's nest ameliorates oxidative stress-induced apoptosis in SH-SY5Y human neuroblastoma cells

Yew MY, Koh RY, Chye SM, Othman I, Ng KY

BMC Complement Altern Med, 2014;14:391.
PMID: 25308934 DOI: 10.1186/1472-6882-14-391

Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting the senile population with manifestation of motor disability and cognitive impairment. Reactive oxygen species (ROS) is implicated in the progression of oxidative stress-related apoptosis and cell death of the midbrain dopaminergic neurons. Its interplay with mitochondrial functionality constitutes an important aspect of neuronal survival in the perspective of PD. Edible bird's nest (EBN) is an animal-derived natural food product made of saliva secreted by swiftlets from the Aerodamus genus. It contains bioactive compounds which might confer neuroprotective effects to the neurons. Hence this study aims to investigate the neuroprotective effect of EBN extracts in the neurotoxin-induced in vitro PD model.

Matched MeSH terms: Cell Death/drug effects
Cytotoxic benzophenone and triterpene from Garcinia hombroniana

Jamila N, Khairuddean M, Yaacob NS, Kamal NN, Osman H, Khan SN, et al.

Bioorg Chem, 2014 Jun;54:60-7.
PMID: 24813683 DOI: 10.1016/j.bioorg.2014.04.003

Garcinia hombroniana (seashore mangosteen) in Malaysia is used to treat itching and as a protective medicine after child birth. This study was aimed to investigate the bioactive chemical constituents of the bark of G. hombroniana. Ethyl acetate and dichloromethane extracts of G. hombroniana yielded two new (1, 9) and thirteen known compounds which were characterized by the spectral techniques of NMR, UV, IR and EI/ESI-MS, and identified as; 2,3',4,5'-tetrahydroxy-6-methoxybenzophenone(1), 2,3',4,4'-tetrahydroxy-6-methoxybenzophenone (2), 2,3',4,6-tetrahydroxybenzophenone (3), 1,3,6,7-tetrahydroxyxanthone (4), 3,3',4',5,7-pentahydroxyflavone (5),3,3',5,5',7-pentahydroxyflavanone (6), 3,3',4',5,5',7-hexahydroxyflavone (7), 4',5,7-trihydroxyflavanone-7-rutinoside (8), 18(13→17)-abeo-3β-acetoxy-9α,13β-lanost-24E-en-26-oic acid (9), garcihombronane B (10), garcihombronane D (11), friedelan-3-one (12), lupeol (13), stigmasterol (14) and stigmasterol glucoside (15). In the in vitro cytotoxicity against MCF-7, DBTRG, U2OS and PC-3 cell lines, compounds 1 and 9 displayed good cytotoxic effects against DBTRG cancer cell lines. Compounds 1-8 were also found to possess significant antioxidant activities. Owing to these properties, this study can be further extended to explore more significant bioactive components of this plant.

Matched MeSH terms: Cell Death/drug effects
Fulltext Inhibition of oxidative stress and lipid peroxidation by anthocyanins from defatted Canarium odontophyllum pericarp and peel using in vitro bioassays

Khoo HE, Azlan A, Ismail A, Abas F, Hamid M

PLoS One, 2014;9(1):e81447.
PMID: 24416130 DOI: 10.1371/journal.pone.0081447

Canarium odontophyllum, also known as CO, is a highly nutritious fruit. Defatted parts of CO fruit are potent sources of nutraceutical. This study aimed to determine oxidative stress and lipid peroxidation effects of defatted CO pericarp and peel extracts using in vitro bioassays. Cell cytotoxic effect of the CO pericarp and peel extracts were also evaluated using HUVEC and Chang liver cell lines. The crude extracts of defatted CO peel and pericarp showed cytoprotective effects in t-BHP and 40% methanol-induced cell death. The crude extracts also showed no toxic effect to Chang liver cell line. Using CD36 ELISA, NAD(+) and LDL inhibition assays, inhibition of oxidative stress were found higher in the crude extract of defatted CO peel compared to the pericarp extract. Hemoglobin and LDL oxidation assays revealed both crude extracts had significantly reduced lipid peroxidation as compared to control. TBARS values among defatted CO pericarp, peel, and cyanidin-3-glucoside showed no significant differences for hemoglobin and LDL oxidation assays. The protective effects of defatted CO parts, especially its peel is related to the presence of high anthocyanin that potentially offers as a pharmaceutical ingredient for cardioprotection.

Matched MeSH terms: Cell Death/drug effects
Oral cancer secretome: identification of cancer-associated proteins

Chang HY, Hor SY, Lim KP, Zain RB, Cheong SC, Rahman MA, et al.

Electrophoresis, 2013 Aug;34(15):2199-208.
PMID: 23712713 DOI: 10.1002/elps.201300126

This study aims to identify cancer-associated proteins in the secretome of oral cancer cell lines. We have successfully established four primary cell cultures of normal cells with a limited lifespan without human telomerase reverse transcriptase (hTERT) immortalization. The secretome of these primary cell cultures were compared with that of oral cancer cell lines using 2DE. Thirty five protein spots were found to have changed in abundance. Unambiguous identification of these proteins was achieved by MALDI TOF/TOF. In silico analysis predicted that 24 of these proteins were secreted via classical or nonclassical mechanisms. The mRNA expression of six genes was found to correlate with the corresponding protein abundance. Ingenuity Pathway Analysis (IPA) core analysis revealed that the identified proteins were relevant in, and related to, cancer development with likely involvements in tumor growth, metastasis, hyperproliferation, tumorigenesis, neoplasia, hyperplasia, and cell transformation. In conclusion, we have demonstrated that a comparative study of the secretome of cancer versus normal cell lines can be used to identify cancer-associated proteins.

Matched MeSH terms: Cell Death/physiology
Fulltext Controlled-release formulation of antihistamine based on cetirizine zinc-layered hydroxide nanocomposites and its effect on histamine release from basophilic leukemia (RBL-2H3) cells

Hasan S, Al Ali H, Al-Qubaisi M, Zobir Hussein M, Ismail M, Zainal Z, et al.

Int J Nanomedicine, 2012;7:3351-63.
PMID: 22848164 DOI: 10.2147/IJN.S30809

A controlled-release formulation of an antihistamine, cetirizine, was synthesized using zinc-layered hydroxide as the host and cetirizine as the guest. The resulting well-ordered nanolayered structure, a cetirizine nanocomposite "CETN," had a basal spacing of 33.9 Å, averaged from six harmonics observed from X-ray diffraction. The guest, cetirizine, was arranged in a horizontal bilayer between the zinc-layered hydroxide (ZLH) inorganic interlayers. Fourier transform infrared spectroscopy studies indicated that the intercalation takes place without major change in the structure of the guest and that the thermal stability of the guest in the nanocomposites is markedly enhanced. The loading of the guest in the nanocomposites was estimated to be about 49.4% (w/w). The release study showed that about 96% of the guest could be released in 80 hours by phosphate buffer solution at pH 7.4 compared with about 97% in 73 hours at pH 4.8. It was found that release was governed by pseudo-second order kinetics. Release of histamine from rat basophilic leukemia cells was found to be more sensitive to the intercalated cetirizine in the CETN compared with its free counterpart, with inhibition of 56% and 29%, respectively, at 62.5 ng/mL. The cytotoxicity assay toward Chang liver cells line show the IC₅₀ for CETN and ZLH are 617 and 670 μg/mL, respectively.

Matched MeSH terms: Cell Death/drug effects
Fulltext The effect of environmental conditions on biofilm formation of Burkholderia pseudomallei clinical isolates

Ramli NS, Eng Guan C, Nathan S, Vadivelu J

PLoS One, 2012;7(9):e44104.
PMID: 22970167 DOI: 10.1371/journal.pone.0044104

Burkholderia pseudomallei, a Gram-negative saprophytic bacterium, is the causative agent of the potentially fatal melioidosis disease in humans. In this study, environmental parameters including temperature, nutrient content, pH and the presence of glucose were shown to play a role in in vitro biofilm formation by 28 B. pseudomallei clinical isolates, including four isolates with large colony variants (LCVs) and small colony variants (SCVs) morphotypes. Enhanced biofilm formation was observed when the isolates were tested in LB medium, at 30 °C, at pH 7.2, and in the presence of as little as 2 mM glucose respectively. It was also shown that all SVCs displayed significantly greater capacity to form biofilms than the corresponding LCVs when cultured in LB at 37 °C. In addition, octanoyl-homoserine lactone (C(8)-HSL), a quorum sensing molecule, was identified by mass spectrometry analysis in bacterial isolates referred to as LCV CTH, LCV VIT, SCV TOM, SCV CTH, 1 and 3, and the presence of other AHL's with higher masses; decanoyl-homoserine lactone (C(10)-HSL) and dodecanoyl-homoserine lactone (C(12)-HSL) were also found in all tested strain in this study. Last but not least, we had successfully acquired two Bacillus sp. soil isolates, termed KW and SA respectively, which possessed strong AHLs degradation activity. Biofilm formation of B. pseudomallei isolates was significantly decreased after treated with culture supernatants of KW and SA strains, demonstrating that AHLs may play a role in B. pseudomallei biofilm formation.

Matched MeSH terms: Cell Death/drug effects

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