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Fulltext Association of hOGG1 Ser326Cys, ITGA2 C807T, TNF-A -308G>A and XPD Lys751Gln polymorphisms with the survival of Malaysian NPC patients

Ban EZ, Lye MS, Chong PP, Yap YY, Lim SYC, Abdul Rahman H

PLoS One, 2018;13(6):e0198332.
PMID: 29912899 DOI: 10.1371/journal.pone.0198332

BACKGROUND: Nasopharyngeal carcinoma is a rare form of cancer across the world except in certain areas such as Southern China, Hong Kong and Malaysia. NPC is considered a relatively radiosensitive tumor and patients diagnosed at early stages tend to survive longer compared to those with advanced disease. Given that early symptoms of NPC are non-specific and that the nasopharynx is relatively inaccessible, less invasive screening methods such as biomarker screening might be the key to improve NPC survival and management. A number of genes with their respective polymorphisms have been shown in past studies to be associated with survival of various cancers. hOGG1 and XPD genes encode for a DNA glycosylase and a DNA helicase respectively; both are proteins that are involved in DNA repair. ITGA2 is the alpha subunit of the transmembrane receptor integrin and is mainly responsible for cell-cell and cell-extracellular matrix interaction. TNF-α is a cytokine that is released by immune cells during inflammation.
METHODS: Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to genotype all the aforementioned gene polymorphisms. Kaplan-Meier survival function, log-rank test and Cox regression were used to investigate the effect of gene polymorphisms on the all-cause survival of NPC.
RESULTS: NPC cases carrying T/T genotype of ITGA2 C807T have poorer all-cause survival compared to those with C/C genotypes, with an adjusted HR of 2.06 (95% CI = 1.14-3.72) in individual model. The 5-year survival rate of C/C carriers was 55% compared to those with C/T and T/T where the survival rates were 50% and 43%, respectively.
CONCLUSION: The finding from the present study showed that ITGA2 C807T polymorphism could be potentially useful as a prognostic biomarker for NPC. However, the prognostic value of ITGA2 C807T polymorphism has to be validated by well-designed further studies with larger patient numbers.

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics*
Fulltext Analysis of serum and gene expression profile of cytokines (IL-6, TNF-α and TGF-β1) in chronic hepatitis C virus infection

Che Noh I, Avoi R, Abdullah Nurul A, Ahmad I, Abu Bakar R

PeerJ, 2022;10:e13330.
PMID: 35469194 DOI: 10.7717/peerj.13330

BACKGROUND: Chronic hepatitis C virus (HCV) infection is one of the major causes of liver cirrhosis and liver carcinoma. Studies have indicated that an imbalance of cytokine activities could contribute to the pathogenesis of chronic HCV infection. This study aimed to investigate serum levels and gene expression of cytokines (IL-6, TNF-α and TGF-β1) in chronic HCV infection among Malay male subjects.
METHODS: Thirty-nine subjects were enrolled from various health clinics in Kelantan, Malaysia, and divided into two groups: patients with chronic HCV infection (HP) and healthy control (HS). The serum cytokines IL-6, TNF-a-were measured using Luminex assay, and serum TGF-β1 was measured by ELISA. The mRNA gene expression for IL-6, TNF-α and TGF-β1 was measured by real-time reverse transcriptase polymerase chain reaction (RT-PCR).
RESULTS: There were statistically significant differences in the mean serum levels of IL-6, and TGF-β1 in HP compared to HS group (p = 0.0180 and p = 0.0005, respectively). There was no significant difference in the mean serum level of TNF-α in HP compared to HS group. The gene expression for the studied cytokines showed no significant differences in HP compared to HS group.
CONCLUSION: Serum IL-6 was significantly associated with chronic HCV infection.

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics
Fulltext High producing tumor necrosis factor alpha gene alleles in protection against severe manifestations of dengue

Sam SS, Teoh BT, Chinna K, AbuBakar S

Int J Med Sci, 2015;12(2):177-86.
PMID: 25589894 DOI: 10.7150/ijms.8988

Dengue virus (DENV) infection usually presents with mild self-limiting dengue fever (DF). Few however, would present with the more severe form of the disease, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). In the present study, the association between IL-12B, IL-10 and TNF-α gene polymorphisms and dengue severity was investigated.
METHODS: A case-control study was performed on a total of 120 unrelated controls, 86 DF patients and 196 DHF/DSS patients. The polymorphisms in IL-12B, IL-10 and TNF-α genes were genotyped using PCR-RFLP and PCR-sequencing methods.
RESULTS: A protective association of TNF-α -308A allele and -308GA genotype against DHF/DSS was observed, while TNF-α -238A allele and -238GA genotype were associated with DHF/DSS. A combination of TNF-α -308GA+AA genotype and IL-10 non-GCC haplotypes, IL-12B pro homozygotes (pro1/pro1, pro2/pro2) and IL-12B 3'UTR AC were significantly correlated with protective effects against DHF/DSS. An association between the cytokine gene polymorphisms and protection against the clinical features of severe dengue including thrombocytopenia and increased liver enzymes was observed in this study.
CONCLUSION: The overall findings of the study support the correlation of high-producer TNF-α genotypes combined with low-producer IL-10 haplotypes and IL-12B genotypes in reduced risk of DHF/DSS.
KEYWORDS: Infectious disease; cytokine; dengue; genetics; polymorphism.; tropical

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics*
Fulltext Anti-inflammatory, gastroprotective and anti-ulcerogenic effects of red algae Gracilaria changii (Gracilariales, Rhodophyta) extract

Shu MH, Appleton D, Zandi K, AbuBakar S

BMC Complement Altern Med, 2013;13:61.
PMID: 23497105 DOI: 10.1186/1472-6882-13-61

Gracilaria changii (Xia et Abbott) Abbott, Zhang et Xia, a red algae commonly found in the coastal areas of Malaysia is traditionally used for foods and for the treatment of various ailments including inflammation and gastric ailments. The aim of the study was to investigate anti-inflammatory, gastroprotective and anti-ulcerogenic activities of a mass spectrometry standardized methanolic extract of Gracilaria changii.

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics
Fulltext Vitamin C suppresses cell death in MCF-7 human breast cancer cells induced by tamoxifen

Subramani T, Yeap SK, Ho WY, Ho CL, Omar AR, Aziz SA, et al.

J Cell Mol Med, 2014 Feb;18(2):305-13.
PMID: 24266867 DOI: 10.1111/jcmm.12188

Vitamin C is generally thought to enhance immunity and is widely taken as a supplement especially during cancer treatment. Tamoxifen (TAM) has both cytostatic and cytotoxic properties for breast cancer. TAM engaged mitochondrial oestrogen receptor beta in MCF-7 cells and induces apoptosis by activation of pro-caspase-8 followed by downstream events, including an increase in reactive oxygen species and the release of pro-apoptotic factors from the mitochondria. In addition to that, TAM binds with high affinity to the microsomal anti-oestrogen-binding site and inhibits cholesterol esterification at therapeutic doses. This study aimed to investigate the role of vitamin C in TAM-mediated apoptosis. Cells were loaded with vitamin C by exposure to dehydroascorbic acid, thereby circumventing in vitro artefacts associated with the poor transport and pro-oxidant effects of ascorbic acid. Pre-treatment with vitamin C caused a dose-dependent attenuation of cytotoxicity, as measured by acridine-orange/propidium iodide (AO/PI) and Annexin V assay after treatment with TAM. Vitamin C dose-dependently protected cancer cells against lipid peroxidation caused by TAM treatment. By real-time PCR analysis, an impressive increase in FasL and tumour necrosis factor-α (TNF-α) mRNA was detected after TAM treatment. In addition, a decrease in mitochondrial transmembrane potential was observed. These results support the hypothesis that vitamin C supplementation during cancer treatment may detrimentally affect therapeutic response.

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics
Hot water extract of Pleurotus pulmonarius stalk waste enhances innate immune response and immune-related gene expression in red hybrid tilapia Oreochromis sp. following challenge with pathogen-associated molecular patterns

Ching JJ, Shuib AS, Abdullah N, Majid NA, Taufek NM, Sutra J, et al.

Fish Shellfish Immunol, 2021 Sep;116:61-73.
PMID: 34157396 DOI: 10.1016/j.fsi.2021.06.005

In aquaculture, commercial fish such as red hybrid tilapia are usually raised at high density to boost the production within a short period of time. This overcrowded environment, however, may cause stress to the cultured fish and increase susceptibility to infectious diseases. Antibiotics and chemotherapeutics are used by fish farmers to overcome these challenges, but this may increase the production cost. Studies have reported on the potential of mushroom polysaccharides that can act as immunostimulants to enhance the immune response and disease resistance in fish. In the current study, hot water extract (HWE) from mushroom stalk waste (MSW) was used to formulate fish feed and hence administered to red hybrid tilapia to observe the activation of immune system. Upon 30 days of feeding, the fish were challenged with pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharides (LPS) and polyinosinic:polycytidylic acid (poly (I:C)) to mimic bacterial and viral infection, respectively. HWE supplementation promoted better feed utilisation in red hybrid tilapia although it did not increase the body weight gain and specific growth rate compared to the control diet. The innate immunological parameters such as phagocytic activity and respiratory burst activity were significantly higher in HWE-supplemented group than that of the control group following PAMPs challenges. HWE-supplemented diet also resulted in higher mRNA transcription of il1b and tnfa in midgut, spleen and head kidney at 1-day post PAMPs injection. Tlr3 exhibited the highest upregulation in the HWE fed fish injected with poly (I:C). At 3-days post PAMPs injection, both ighm and tcrb expression were upregulated significantly in the spleen and head kidney. Results showed that HWE supplementation enhances the immune responses of red hybrid tilapia and induced a higher serum bactericidal activity against S. agalactiae.

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics
Association of cytokine gene polymorphisms with oral lichen planus in Malayalam-speaking ethnicity from South India (Kerala)

Chauhan I, Beena VT, Srinivas L, Sathyan S, Banerjee M

J Interferon Cytokine Res, 2013 Aug;33(8):420-7.
PMID: 23651237 DOI: 10.1089/jir.2012.0115

Oral lichen planus (OLP) is a chronic mucocutaneous condition that affects the oral mucous membrane as well as skin. It is a chronic cell-mediated autoimmune condition where the T-cell-mediated immune response plays an important part in the pathogenesis by causing damage to basal keratinocytes in oral mucosa. Cytokine gene polymorphisms have an unquestionable role in the orchestration of the immune response, leading to different functional scenarios, which in turn influence the outcome of the disease establishment and evolution. The purpose of this study was to understand the role of these cytokine gene polymorphisms in the tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 genes with OLP in 101 individuals of Malayalam-speaking ethnicity from South India (Kerala). We further investigated the role of these polymorphisms in patients suffering from OLP with other comorbid factors. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism. The results demonstrate that the A allele in the TNF-α -308 polymorphism could play an important role in the susceptibility to OLP. IL-1β +3954 in OLP was associated with other comorbid factors in both allelic and genotypic combinations. However, when patients suffering from OLP were stratified to understand the involvement of other comorbid factors, we observed that the T and C alleles were independent risk factors for chronic periodontitits and diabetes mellitus. On the other hand, IL-6 -597 did not show any disease association with OLP in the study population. This study indicates that proinflammatory cytokines are an important factor in understanding the disease burden of OLP and their comorbid factors.

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics*
Inhibitory effects of dynorphin 3-14 on the lipopolysaccharide-induced toll-like receptor 4 signalling pathway

Rahiman SSF, Morgan M, Gray P, Shaw PN, Cabot PJ

Peptides, 2017 04;90:48-54.
PMID: 28219695 DOI: 10.1016/j.peptides.2017.02.004

Dynorphin 1-17 (DYN 1-17) is biotransformed rapidly to a range of fragments in rodent inflamed tissue with dynorphin 3-14 (DYN 3-14) being the most stable and prevalent. DYN 1-17 has been shown previously to be involved in the regulation of inflammatory response following tissue injury, in which the biotransformation fragments of DYN 1-17 may possess similar features. This study investigated the effects of DYN 3-14 on lipopolysaccharide (LPS)-induced nuclear factor-kappaB/p65 (NF-κB/p65) nuclear translocation and the release of pro-inflammatory cytokines interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in differentiated THP-1 cells. Treatment with DYN 3-14 (10nM) resulted in 35% inhibition of the LPS-induced nuclear translocation of NF-κB/p65. Furthermore, DYN 3-14 modulated both IL-1β and TNF-α release; inhibiting IL-1β and paradoxically augmenting TNF-α release in a concentration-independent manner. A number of opioids have been implicated in the modulation of the toll-like receptor 4 (TLR4), highlighting the complexity of their immunomodulatory effects. To determine whether DYN 3-14 modulates TLR4, HEK-Blue™-hTLR4 cells were stimulated with LPS in the presence of DYN 3-14. DYN 3-14 (10μM) inhibited TLR4 activation in a concentration-dependent fashion by suppressing the LPS signals around 300-fold lower than LPS-RS, a potent TLR4 antagonist. These findings indicate that DYN 3-14 is a potential TLR4 antagonist that alters cellular signaling in response to LPS and cytokine release, implicating a role for biotransformed endogenous opioid peptides in immunomodulation.

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics
Fulltext Genetic risk factors of systemic lupus erythematosus in the Malaysian population: a minireview

Chai HC, Phipps ME, Chua KH

Clin. Dev. Immunol., 2012;2012:963730.
PMID: 21941582 DOI: 10.1155/2012/963730

SLE is an autoimmune disease that is not uncommon in Malaysia. In contrast to Malays and Indians, the Chinese seem to be most affected. SLE is characterized by deficiency of body's immune response that leads to production of autoantibodies and failure of immune complex clearance. This minireview attempts to summarize the association of several candidate genes with risk for SLE in the Malaysian population and discuss the genetic heterogeneity that exists locally in Asians and in comparison with SLE in Caucasians. Several groups of researchers have been actively investigating genes that are associated with SLE susceptibility in the Malaysian population by screening possible reported candidate genes across the SLE patients and healthy controls. These candidate genes include MHC genes and genes encoding complement components, TNF, FcγR, T-cell receptors, and interleukins. However, most of the polymorphisms investigated in these genes did not show significant associations with susceptibility to SLE in the Malaysian scenario, except for those occurring in MHC genes and genes coding for TNF-α, IL-1β, IL-1RN, and IL-6.

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics
Fingolimod affects gene expression profile associated with LPS-induced memory impairment

Omidbakhsh R, Rajabli B, Nasoohi S, Khallaghi B, Mohamed Z, Naidu M, et al.

Exp Brain Res, 2014 Nov;232(11):3687-96.
PMID: 25098558 DOI: 10.1007/s00221-014-4052-4

Lipopolysaccharide is an endotoxin to induce sickness behavior in several animal models to explore the link between immune activation and cognition. Neuroinflammation playing a pivotal role in disease progress is evidently influenced by sphingosine-1-phosphate. As one of the sphingosine analogs in clinical use for multiple sclerosis, fingolimod (FTY720) was shown to substantially affect gene expression profile in the context of AD in our previous experiments. The present study was designed to evaluate the drug efficacy in the context of the mere inflammatory context leading to memory impairment. FTY720 was repeatedly administered for a few days before or after intracerebral lipopolysaccharide (LPS) injection in rats. Animal's brains were then assigned to histological as well as multiplex mRNA assay following memory performance test. Both FTY720 pre-treatment and post-treatment were similarly capable of ameliorating LPS-induced memory impairment as assessed by passive avoidance test. Such amending effects may be partly accountable by the concomitant alterations in transcriptional levels of mitogen-activated protein kinases as well as inflammatory genes determined by QuantiGene Plex analysis. These findings confirming FTY720 application benefits suggest its efficacy may not differ significantly while considered either as a preventive or as a therapeutic approach against neuroinflammation.

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics
Styryl-lactone goniothalamin inhibits TNF-α-induced NF-κB activation

Orlikova B, Schumacher M, Juncker T, Yan CC, Inayat-Hussain SH, Hajjouli S, et al.

Food Chem Toxicol, 2013 Sep;59:572-8.
PMID: 23845509 DOI: 10.1016/j.fct.2013.06.051

(R)-(+)-Goniothalamin (GTN), a styryl-lactone isolated from the medicinal plant Goniothalamus macrophyllus, exhibits pharmacological activities including cytotoxic and anti-inflammatory effects. In this study, GTN modulated TNF-α induced NF-κB activation. GTN concentrations up to 20 μM showed low cytotoxic effects in K562 chronic myelogenous leukemia and in Jurkat T cells. Importantly, at these concentrations, no cytotoxicity was observed in healthy peripheral blood mononuclear cells. Our results confirmed that GTN inhibited tumor necrosis factor-α (TNF-α)-induced NF-κB activation in Jurkat and K562 leukemia cells at concentrations as low as 5 μM as shown by reporter gene assays and western blots. Moreover, GTN down-regulated translocation of the p50/p65 heterodimer to the nucleus, prevented binding of NF-κB to its DNA response element and reduced TNF-α-activated interleukin-8 (IL-8) expression. In conclusion, GTN inhibits TNF-α-induced NF-κB activation at non-apoptogenic concentrations in different leukemia cell models without presenting toxicity towards healthy blood cells underlining the anti-leukemic potential of this natural compound.

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics
Differential positive selection of malaria resistance genes in three indigenous populations of Peninsular Malaysia

Liu X, Yunus Y, Lu D, Aghakhanian F, Saw WY, Deng L, et al.

Hum Genet, 2015 Apr;134(4):375-92.
PMID: 25634076 DOI: 10.1007/s00439-014-1525-2

The indigenous populations from Peninsular Malaysia, locally known as Orang Asli, continue to adopt an agro-subsistence nomadic lifestyle, residing primarily within natural jungle habitats. Leading a hunter-gatherer lifestyle in a tropical jungle environment, the Orang Asli are routinely exposed to malaria. Here we surveyed the genetic architecture of individuals from four Orang Asli tribes with high-density genotyping across more than 2.5 million polymorphisms. These tribes reside in different geographical locations in Peninsular Malaysia and belong to three main ethno-linguistic groups, where there is minimal interaction between the tribes. We first dissect the genetic diversity and admixture between the tribes and with neighboring urban populations. Later, by implementing five metrics, we investigated the genome-wide signatures for positive natural selection of these Orang Asli, respectively. Finally, we searched for evidence of genomic adaptation to the pressure of malaria infection. We observed that different evolutionary responses might have emerged in the different Orang Asli communities to mitigate malaria infection.

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics
Fulltext Simvastatin modulates cellular components in influenza A virus-infected cells

Mehrbod P, Hair-Bejo M, Tengku Ibrahim TA, Omar AR, El Zowalaty M, Ajdari Z, et al.

Int J Mol Med, 2014 Jul;34(1):61-73.
PMID: 24788303 DOI: 10.3892/ijmm.2014.1761

Influenza A virus is one of the most important health risks that lead to significant respiratory infections. Continuous antigenic changes and lack of promising vaccines are the reasons for the unsuccessful treatment of influenza. Statins are pleiotropic drugs that have recently served as anti-influenza agents due to their anti-inflammatory activity. In this study, the effect of simvastatin on influenza A-infected cells was investigated. Based on the MTT cytotoxicity test, hemagglutination (HA) assay and qPCR it was found that simvastatin maintained cell viability and decreased the viral load significantly as compared to virus-inoculated cells. The expression of important pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6 and interferon-γ), which was quantified using ELISA showed that simvastatin decreased the expression of pro-inflammatory cytokines to an average of 2-fold. Furthermore, the modulation of actin filament polymerization was determined using rhodamine staining. Endocytosis and autophagy processes were examined by detecting Rab and RhoA GTPase protein prenylation and LC3 lipidation using western blotting. The results showed that inhibiting GTPase and LC3 membrane localization using simvastatin inhibits influenza replication. Findings of this study provide evidence that modulation of RhoA, Rabs and LC3 may be the underlying mechanisms for the inhibitory effects of simvastatin as an anti-influenza compound.

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics
Fulltext Association of TNF-α G308A gene polymorphism in essential hypertensive patients without type 2 diabetes mellitus

Ghodsian N, Akhlaghi M, Ramachandran V, Heidari F, Haghvirdizadeh P, Eshkoor SA, et al.

Genet. Mol. Res., 2015 Dec 29;14(4):18974-9.
PMID: 26782547 DOI: 10.4238/2015.December.29.4

This study aims to investigate the effects of tumor necrosis factor alpha (TNF-α) G308A gene polymorphism on essential hypertension (EHT) with or without type 2 diabetes mellitus (T2DM). The project was conducted on buccal epithelial and blood cells for case and control patients, respectively. Epithelial cells were obtained from the inner part of the cheeks. Techniques including DNA extraction, polymerase chain reaction (PCR), and restriction fragment length polymorphism (RFLP) were utilized to assess biomarkers of DNA damage. Our results demonstrated significant differences between wild and mutated genotypes among EHT patients without T2DM. We also found a significant association between wild and mutated allele frequencies in EHT patients (P < 0.05). Clinical characteristics between the groups (EHT with or without T2DM and controls) showed statistically significant association (P < 0.05). Overall, we show that G308A polymorphism of the TNF-αgene may be a significant genetic risk factor for EHT without T2DM patients in Malaysia.

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics*
Fulltext Asymptomatic SARS-CoV-2 infection: is it all about being refractile to innate immune sensing of viral spare-parts?-Clues from exotic animal reservoirs

Shankar EM, Che KF, Yong YK, Girija ASS, Velu V, Ansari AW, et al.

Pathog Dis, 2021 Jan 09;79(1).
PMID: 33289808 DOI: 10.1093/femspd/ftaa076

A vast proportion of coronavirus disease 2019 (COVID-19) individuals remain asymptomatic and can shed severe acute respiratory syndrome (SARS-CoV) type 2 virus to transmit the infection, which also explains the exponential increase in the number of COVID-19 cases globally. Furthermore, the rate of recovery from clinical COVID-19 in certain pockets of the globe is surprisingly high. Based on published reports and available literature, here, we speculated a few immunovirological mechanisms as to why a vast majority of individuals remain asymptomatic similar to exotic animal (bats and pangolins) reservoirs that remain refractile to disease development despite carrying a huge load of diverse insidious viral species, and whether such evolutionary advantage would unveil therapeutic strategies against COVID-19 infection in humans. Understanding the unique mechanisms that exotic animal species employ to achieve viral control, as well as inflammatory regulation, appears to hold key clues to the development of therapeutic versatility against COVID-19.

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics
Association of leptin/receptor and TNF-α gene variants with adolescent obesity in Malaysia

Ng ZY, Veerapen MK, Hon WM, Lim RL

Pediatr Int, 2014 Oct;56(5):689-97.
PMID: 24628746 DOI: 10.1111/ped.12336

BACKGROUND: Leptin (LEP) G-2548A (rs7799039), leptin receptor (LEPR) Q223R (rs1137101) and tumor necrosis factor (TNF)-α G-308A (rs1800629) gene variants have been reported to be associated with obesity, although results for subjects from different countries have been controversial. The aim of this study was to determine the prevalence of overweight and obesity in Malaysian adolescents and the association of these polymorphisms with overweight and obese or over-fat adolescents.
METHODS: A total of 613 adolescents (241 Malay, 219 Chinese, 153 Indian) were enrolled. Anthropometric measurements of body mass index (BMI) and body fat percentage were used to classify subjects as controls (non-overweight/obese or normal fat) or as cases (overweight/obese or over-fat). Genomic DNA was extracted from oral buccal mucosa cells for genotyping using polymerase chain reaction-restriction fragment length polymorphism and data obtained were statistically analyzed.
RESULTS: A total of 23.3% of subjects were overweight/obese whereas 11.4% were over-fat; there were significantly more overweight/obese and over-fat Indian and Malay adolescents compared to Chinese (P < 0.001). A allele was the minor one for LEPR Q223R and TNF-α G-308A in all ethnic groups, whereas G allele was minor for LEP G-2548A in Chinese and Malay adolescents, except for Indian adolescents. Indian male adolescents with AA genotype for LEP G-2548A were associated with overweight/obesity (P = 0.025; odds ratio, 3.64; 95% confidence interval: 1.15-11.54). Despite the lack of association observed for LEPR Q223R and TNF-α G-308A, Indian and Chinese subjects with AA risk genotype for LEPR Q223R/LEP G-2548A and TNF-α G-308A/LEP G-2548A, respectively, had increased mean BMI (P = 0.049, P = 0.016).
CONCLUSIONS: Genotype distribution and association of these polymorphisms with overweight/obesity vary between ethnic groups and genders. Nevertheless, the LEP G-2548A risk allele may be associated with overweight/obese Indian male adolescents in Malaysia.
KEYWORDS: adolescents; body fat percentage; body mass index; leptin; leptin receptor; single nucleotide polymorphism; tumor necrosis factor-α

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics*
Maslinic acid modulates secreted phospholipase A2-IIA (sPLA2-IIA)-mediated inflammatory effects in macrophage foam cells formation

Yap WH, Ooi BK, Ahmed N, Lim YM

J Biosci, 2018 Jun;43(2):277-285.
PMID: 29872016

Secretory phospholipase A2-IIA (sPLA2-IIA) is one of the key enzymes causing lipoprotein modification and vascular inflammation. Maslinic acid is a pentacyclic triterpene which has potential cardioprotective and anti-inflammatory properties. Recent research showed that maslinic acid interacts with sPLA2-IIA and inhibits sPLA2-IIA-mediated monocyte differentiation and migration. This study elucidates the potential of maslinic acid in modulating sPLA2-IIA-mediated inflammatory effects in THP-1 macrophages. We showed that maslinic acid inhibits sPLA2-IIA-mediated LDL modification and suppressed foam cell formation. Further analysis revealed that sPLA2-IIA only induced modest LDL oxidation and that inhibitory effect of maslinic acid on sPLA2-IIA-mediated foam cells formation occurred independently of its anti-oxidative properties. Interestingly, maslinic acid was also found to significantly reduce lipid accumulation observed in macrophages treated with sPLA2-IIA only. Flow cytometry analysis demonstrated that the effect observed in maslinic acid might be contributed in part by suppressing sPLA2-IIA-induced endocytic activity, thereby inhibiting LDL uptake. The study further showed that maslinic acid suppresses sPLA2-IIA-induced up-regulation of PGE2 levels while having no effects on COX-2 activity. Other pro-inflammatory mediators TNF-a and IL-6 were not induced in sPLA2-IIA-treated THP-1 macrophages. The findings of this study showed that maslinic acid inhibit inflammatory effects induced by sPLA2-IIA, including foam cells formation and PGE2 production.

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics
The molecular mechanisms of probiotic strains in improving ageing bone and muscle of d-galactose-induced ageing rats

Hor YY, Ooi CH, Lew LC, Jaafar MH, Lau AS, Lee BK, et al.

J Appl Microbiol, 2021 Apr;130(4):1307-1322.
PMID: 32638482 DOI: 10.1111/jam.14776

AIM: The aim of this study was to evaluate the molecular mechanisms of Lactobacillus strains in improving ageing of the musculoskeletal system.
METHODS AND RESULTS: The anti-ageing mechanism of three probiotics strains Lactobacillus fermentum DR9, Lactobacillus paracasei OFS 0291 and L. helveticus OFS 1515 were evaluated on gastrocnemius muscle and tibia of d-galactose-induced ageing rats. Upon senescence induction, aged rats demonstrated reduced antioxidative genes CAT and SOD expression in both bone and muscle compared to the young rats (P

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics
Macrophage and colon tumor cells as targets for a binuclear silver(I) N-heterocyclic carbene complex, an anti-inflammatory and apoptosis mediator

Iqbal MA, Umar MI, Haque RA, Khadeer Ahamed MB, Asmawi MZ, Majid AM

J Inorg Biochem, 2015 May;146:1-13.
PMID: 25699476 DOI: 10.1016/j.jinorgbio.2015.02.001

Chronic inflammation intensifies the risk for malignant neoplasm, indicating that curbing inflammation could be a valid strategy to prevent or cure cancer. Cancer and inflammation are inter-related diseases and many anti-inflammatory agents are also used in chemotherapy. Earlier, we have reported a series of novel ligands and respective binuclear Ag(I)-NHC complexes (NHC=N-heterocyclic carbene) with potential anticancer activity. In the present study, a newly synthesized salt (II) and respective Ag(I)-NHC complex (III) of comparable molecular framework were prepared for a further detailed study. Preliminarily, II and III were screened against HCT-116 and PC-3 cells, wherein III showed better results than II. Both the compounds showed negligible toxicity against normal CCD-18Co cells. In FAM-FLICA caspase assay, III remarkably induced caspase-3/7 in HCT-116 cells most probably by tumor necrosis factor-alpha (TNF-α) independent intrinsic pathway and significantly inhibited in vitro synthesis of cytokines, interleukin-1 (IL-1) and TNF-α in human macrophages (U937 cells). In a cell-free system, both the compounds inhibited cyclooxygenase (COX) activities, with III being more selective towards COX-2. The results revealed that III has strong antiproliferative property selectively against colorectal tumor cells which could be attributed to its pro-apoptotic and anti-inflammatory abilities.

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics
Fulltext Association of tumour necrosis factor-α (TNF-α) gene polymorphisms (-308 G>A and -238 G>A) and the risk of severe dengue: A meta-analysis and trial sequential analysis

Naing C, Htet NH, Siew Tung W, Basavaraj AK, Mak JW

PLoS One, 2018;13(10):e0205413.
PMID: 30300401 DOI: 10.1371/journal.pone.0205413

Individual studies have assessed the association between TNF-α-308G>A and TNF-α-238 G>A polymorphisms and severity of dengue infection. However, the results are inconclusive and most studies had small sample sizes. The objective of this study was to summarize the evidence of association between TNF-α-308 G>A and TNF-α-238 G>A and severity of dengue infection. This study follows the preferred reporting items for systematic reviews and meta- analyses of genetic association studies, recommended by PLOS One. We calculated pooled odds ratio and its 95% confidence interval (CI) to estimate the association between TNF-α-308 G>A or TNF-α-238 G>A and the risk of severe dengue infections. To determine the information size required for this meta-analysis study, a trial sequential analysis (TSA) was done. Eight studies (640 cases and 1275 controls), which assessed the association of TNF-α-308 G>A or TNF-α-238 G>A and the risk of DHF were included. Overall, we found no significant association between TNF-α-308 G>A and the DHF risk in the allelic model (OR, 0.91; 95% CI, 0.51-1.63), the recessive model (OR,1.32;95%CI,0.73-2.37), the dominant model (OR,0.93;95%CI:0.59-1.47) or the additive model (OR,1.43,95;95%CI:0.79-2.59). There was also no significant association between TNF-α-238 G>A and DHF risk under the allele contrast model (OR:1.51;95%CI:0.88-2.58), the recessive model (OR,1.48,95% CI:0.33-6.58), the dominant model (OR,1.48;95%CI:0.56-3.92), or the additive model (OR:1.5;95%CI:0.34-6.69). On subgroup analysis, neither the Asian population nor the non-Asian population showed significant association between TNF-α-308 G>A/TNF-α-238 G>A and the DHF risk under any genetic models. Leave-one-out meta-analysis showed stability of the results. TSA plots suggested that the sample size in this meta-analysis study was below the required information size. The findings suggest an inclusive evidence of the association between TNF-α-308/ TNF-α-238 G>A and the risk of developing severe dengue infection. Large studies with evidence of Hardy-Weinberg equilibrium, assessing gene-gene interactions are recommended.

Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics*

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