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1.
J ASEAN Fed Endocr Soc ; 38(2): 20-27, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38045672

RESUMO

Objective: The primary objective was to assess beta-cell function of recently-diagnosed young-onset type 2 diabetes mellitus (T2DM) individuals using basal and stimulated C-peptide levels. The secondary objective was to examine the association between C-peptide with metabolic factors and diabetes complications. Methodology: A cross-sectional study was conducted for young-onset T2DM individuals aged 18-35 years with a disease duration of not more than 5 years. Plasma C-peptide was measured before and after intravenous glucagon injection. Demographic data, medical history and complications were obtained from medical records and clinical assessment. Continuous data were expressed as median and interquartile range (IQR). Categorical variables were described as frequency or percentage. Multivariable linear regression analysis was used to determine factors associated with C-peptide levels. Results: 113 participants with young-onset T2DM with a median (IQR) age of 29.0 (9.5) years and 24 (36) months were included in this study. The median (IQR) basal and stimulated C-peptide was 619 (655) pmol/L and 1231 (1024) pmol/L. Adequate beta-cell function was present in 78-86% of the participants based on the basal and stimulated C-peptide levels. We found hypertension, obesity and diabetic kidney disease (DKD) to be independently associated with higher C-peptide levels. In contrast, females, smokers, those on insulin therapy and with longer duration of disease had lower C-peptide levels. Conclusion: Most recently diagnosed young-onset T2DM have adequate beta-cell function. Elevated C-peptide levels associated with obesity, hypertension and diabetic kidney disease suggest insulin resistance as the key driving factor for complications.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Hipertensão , Feminino , Humanos , Diabetes Mellitus Tipo 2/complicações , Estudos Transversais , Nefropatias Diabéticas/complicações , Peptídeo C , Hipertensão/epidemiologia , Obesidade/complicações
2.
J Sci Food Agric ; 103(12): 5819-5830, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37092326

RESUMO

BACKGROUND: Snail allergy is rare but can be fatal. Pila polita, a freshwater snail, was considered as a popular exotic food, particularly in tropical countries, and consumed in processed forms. Thus, the purpose of this study was to identify the major and cross-reactive allergens of P. polita and to determine the impact of food processing on the allergen stability. RESULTS: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis fractionated raw snail extract to approximately 24 protein bands, between 9 and 245 kDa. The prominent band at 33 kDa was detected in all raw and processed snail extracts. Immunoblotting tests of the raw extract demonstrated 19 immunoglobulin E (IgE)-binding proteins, and four of them, at 30, 35, 42 and 49 kDa, were revealed as the major IgE-binding proteins of P. polita. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry identified the 49 and 42 kDa major allergens as actin, whereas the 30 and 35 kDa major allergens were identified as tropomyosin. Immunoblotting revealed that the raw snail had more allergenic proteins than the processed snail. The degree of allergenicity in decreasing order was raw > brine pickled> boiled > roasted > fried > vinegar pickled. The presence of cross-reactivity between P. polita and the shellfish tested was exhibited with either no, complete, or partial inhibitions. CONCLUSION: Actin and tropomyosin were identified as the major and cross-reactive allergens of P. polita among local patients with snail allergy. Those major allergens are highly stable to high temperatures, acidic pH, and high salt, which might played a crucial role in snail allergy in Malaysia. © 2023 Society of Chemical Industry.


Assuntos
Alérgenos , Hipersensibilidade Alimentar , Animais , Humanos , Alérgenos/química , Tropomiosina/química , Actinas , Imunoglobulina E , Caramujos , Manipulação de Alimentos , Eletroforese em Gel de Poliacrilamida , Água Doce , Immunoblotting
3.
BMC Nephrol ; 24(1): 42, 2023 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-36829106

RESUMO

Antibody-mediated rejection (AMR) still persists as the major hurdle towards successful renal allograft survival. This paper aims to report on the HLA antibody landscape of renal transplant candidates in Malaysia. A total of 2,219 adult samples from 2016 to 2019 were analysed for anti-HLA antibodies using solid-phase assay. Our findings highlight the prevalence and risk factors for antibodies against HLA antigens in renal transplant settings, which could be beneficial for selecting compatible recipients from deceased organ donors. To the best of our knowledge, this study is the first to demonstrate that ethnic Malay and Chinese showed significantly higher prevalence of anti-HLA antibodies. Based on our multivariate analysis: (i) female gender was associated with higher risk for panel reactive antibodies (PRAs) against Class I, Class II, and Class I and II (p < 0.001); (ii) older patients (≥ 38 years old) were associated with higher risk of positivity against Class I, Class II and Class I and II (p < 0.001); (iii) Malays showed significant association with Class II antibodies (p = 0.035); Chinese patients presented with higher risk of PRA positivity against Class II (p < 0.001) and Class I and II (p = 0.01); Indians were significantly associated with higher risk of HLA antibody sensitization against Class I (p = 0.022), Class II (p = 0.026) and Class I and II (p = 0.05). Thus, our findings suggested that female gender, older age (≥ 38 years old) and ethnicity may serve as independent risk factors for HLA antibody sensitization in adult renal transplant candidates.


Assuntos
Transplante de Rim , Adulto , Humanos , Feminino , Transplante de Rim/efeitos adversos , Prevalência , Anticorpos , Transplante Homólogo , Antígenos HLA , Fatores de Risco , Soro Antilinfocitário , Rejeição de Enxerto , Sobrevivência de Enxerto , Antígenos de Histocompatibilidade Classe I
4.
Mol Med Rep ; 26(6)2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36281931

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is the most common type of inherited cystic kidney disease. The feasibility of whole­exome sequencing (WES) to obtain molecular diagnosis of ADPKD is still in question as previous studies showed conflicting results. Utilizing WES on a patient with ADPKD, standard bioinformatics pipeline demonstrated no pathogenic variant in the genes of interest. By visualizing read alignments using the Integrative Genomics Viewer, a region with atypical alignment of numerous soft­clipped reads at exon 45 of polycystin 1, transient receptor potential channel interacting (PKD1) gene was demonstrated. A total of four visual inspection steps were outlined to assess the origin of these soft­clipped reads as strand bias during capture, poor mapping, sequencing error or DNA template contamination. Following assessment, the atypical alignment at PKD1 was hypothesized to be caused by an insertion/deletion mutation. Sanger sequencing confirmed the presence of a novel 20­bp insertion in PKD1 (NM_001009944.3; c.12143_12144insTCC​CCG​CAG​TCT​TCC​CCG​CA; p.Val4048LeufsTer157), which introduced a premature stop codon and was predicted to be pathogenic. The present study demonstrated that WES could be utilized as a molecular diagnostic tool for ADPKD. Furthermore, visual inspection of read alignments was key in identifying the pathogenic variant. The proposed visual inspection steps may be incorporated into a typical WES data analysis workflow to improve the diagnostic yield.


Assuntos
Rim Policístico Autossômico Dominante , Humanos , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/genética , Sequenciamento do Exoma , Códon sem Sentido , Mutação , Canais de Cátion TRPP/genética , DNA
5.
Front Pharmacol ; 13: 879495, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36249774

RESUMO

Antimicrobial resistance (AMR) occurs when microbes no longer respond to any pharmacological agents, rendering the conventional antimicrobial agents ineffective. AMR has been classified as one of the top 10 life-threatening global health problems needed multilevel attention and global cooperation to attain the Sustainable Development Goals (SDGs) according to the World Health Organization (WHO), making the discovery of a new and effective antimicrobial agent a priority. The recommended treatments for drug-resistant microbes are available but limited. Furthermore, the transformation of microbes over time increases the risk of developing drug resistance. Hence, plant metabolites such as terpenes, phenolic compounds and alkaloids are widely studied due to their antibacterial, antiviral, antifungal and antiparasitic effects. Plant-derived antimicrobials are preferred due to their desirable efficacy and safety profile. Plant metabolites work by targeting microbial cell membranes, interfering with the synthesis of microbial DNA/RNA/enzymes and disrupting quorum sensing and efflux pump expression. They also work synergistically with conventional antibiotics to enhance antimicrobial effects. Accordingly, this review aims to identify currently available pharmacological therapies against microbes and AMR, as well as to discuss the importance of plant and secondary metabolites as a possible solution for AMR together with their mechanisms of action. All the information was obtained from government databases, WHO websites, PubMed, Springer, Google Scholar and Science Direct. Based on the information obtained, AMR is regarded as a significant warning to global healthcare. Plant derivatives such as secondary metabolites may be considered as potential therapeutic targets to mitigate the non-ending AMR.

6.
Discov Oncol ; 13(1): 91, 2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36152065

RESUMO

As the fourth most diagnosed cancer, cervical cancer (CC) is one of the major causes of cancer-related mortality affecting females globally, particularly when diagnosed at advanced stage. Discoveries of CC biomarkers pave the road to precision medicine for better patient outcomes. High throughput omics technologies, characterized by big data production further accelerate the process. To date, various CC biomarkers have been discovered through the advancement in technologies. Despite, very few have successfully translated into clinical practice due to the paucity of validation through large scale clinical studies. While vast amounts of data are generated by the omics technologies, challenges arise in identifying the clinically relevant data for translational research as analyses of single-level omics approaches rarely provide causal relations. Integrative multi-omics approaches across different levels of cellular function enable better comprehension of the fundamental biology of CC by highlighting the interrelationships of the involved biomolecules and their function, aiding in identification of novel integrated biomarker profile for precision medicine. Establishment of a worldwide Early Detection Research Network (EDRN) system helps accelerating the pace of biomarker translation. To fill the research gap, we review the recent research progress on CC biomarker development from the application of high throughput omics technologies with sections covering genomics, transcriptomics, proteomics, and metabolomics.

7.
Front Pharmacol ; 13: 878407, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35800452

RESUMO

Uterine fibroids (UFs) are a common benign gynecological tumor that affect the majority of women over their lifetime. Several pharmacological agents are available to reduce the size of fibroids and ameliorate the symptoms of UF. However, these drugs are expensive and are usually associated with profound side effects. Thus, botanical drugs are gaining attention in this era due to their cost effectiveness with a comparable and more potent therapeutic efficacy while demonstrating lesser adverse effects. The objective of this review is to summarize the available information on the mechanism of various botanical drugs and polyherbal formulations with anti-uterine fibroid activity. A systematic search was performed on botanical drugs with anti-uterine fibroid activity using several search engines, which include PubMed, Google Scholar, and Science Direct. Based on the literatures identified, a total of five botanical drugs and three polyherbal formulations were included and discussed in this review, which yields useful information regarding the mechanism of different botanical drugs and polyherbal formulations in exerting anti-uterine fibroid activity for its potential use as an alternative treatment choice for uterine fibroids.

8.
Lupus Sci Med ; 9(1)2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35105721

RESUMO

OBJECTIVE: SLE is a heterogeneous autoimmune disease, in terms of clinical presentation, incidence and severity across diverse ethnic populations. We investigated the human leucocyte antigens (HLA) profile (ie, HLA-A, HLA-B and HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1 and HLA-DPB1) in Malaysian Malay female patients with SLE and determined the generalisability of the published HLA risk factors across different ethnic populations globally including Malaysia. METHODS: One hundred Malay female patients with SLE were recruited between January 2016 and October 2017 from a nephrology clinic. All patients were genotyped for HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1 and HLA-DPB1 alleles using PCR sequence-specific oligonucleotides method on Luminex platform. A total of 951 HLA genotyped population-based Malay control subjects was used for association testing by means of OR with 95% CIs. RESULTS: Our findings convincingly validated common associations between HLA-A*11 (OR=1.65, p=3.36×10-3, corrected P (Pc)=4.03×10-2) and DQB1*05:01 (OR=1.56, p=2.02×10-2, Pc=non-significant) and SLE susceptibility in the Malay population. In contrast, DQB1*03:01 (OR=0.51, p=4.06×10-4, Pc=6.50×10-3) were associated with decreased risk of SLE in Malay population. Additionally, we also detected novel associations of susceptibility HLA genes (ie, HLA-B*38:02, DPA1*02:02, DPB1*14:01) and protective HLA genes (ie, DPA1*01:03). When comparing the current data with data from previously published studies from Caucasian, African and Asian populations, DRB1*15 alleles, DQB1*03:01 and DQA1*01:02 were corroborated as universal susceptibility and protective genes. CONCLUSIONS: This study reveals multiple HLA alleles associated with susceptibility and protection against risk of developing SLE in Malay female population with renal disorders. In addition, the published data from different ethnic populations together with our study further support the notion that the genetic effects from association with DRB1*15:01/02, DQB1*03:01 and DQA1*01:02 alleles are generalised to multiple ethnic populations of Caucasian, African and Asian descents.


Assuntos
Lúpus Eritematoso Sistêmico , Alelos , Povo Asiático/genética , Feminino , Cadeias HLA-DRB1/genética , Humanos , Malásia/epidemiologia
9.
Front Biosci (Landmark Ed) ; 26(11): 1286-1304, 2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34856768

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were first detected in Wuhan, China in December 2019 and resulted in a worldwide pandemic in 2020. SARS-CoV-2 infections totalled more than 180 million with 3.9 million deaths as of June 24, 2021. Tremendous research efforts have resulted in the development of at least 64 vaccine candidates that have reached Phase I to III clinical trials within 14 months. The primary efficacy endpoint for a random placebo-controlled clinical trial of a COVID-19 vaccine to be approved by US FDA should confer at least 50% protection against COVID-19. Three COVID-19 vaccines (BNT162b2, mRNA-1273 and Sputnik V) in clinical Phase III trials have now achieved >90% efficacy in preventing COVID-19. Since SARS-CoV-2 is highly contagious, vaccines are expected to achieve at least 80% herd immunity in the world's population to effectively prevent SARS-CoV-2 infections. An overview of safety, immunogenicity and efficacy of the current frontrunner vaccines are reviewed.


Assuntos
Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , Ensaios Clínicos como Assunto , SARS-CoV-2/imunologia , COVID-19/epidemiologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Humanos , Pandemias
10.
Mol Biol Rep ; 48(10): 6709-6718, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34427887

RESUMO

BACKGROUND: Tropomyosin is a major allergen in crustaceans, including mud crab species, but its molecular and allergenic properties in Scylla olivacea are not well known. Thus, this study aimed to produce the recombinant tropomyosin protein from S. olivacea and subsequently investigate its IgE reactivity. METHODS AND RESULTS: The tropomyosin gene was cloned and expressed in the Escherichia coli system, followed by SDS-PAGE and immunoblotting test to identify the allergenic potential of the recombinant protein. The 855-base pair of tropomyosin gene produced was found to be 99.18% homologous to Scylla serrata. Its 284 amino acids matched the tropomyosin of crustaceans, arachnids, insects, and Klebsiella pneumoniae, ranging from 79.03 to 95.77%. The tropomyosin contained 89.44% alpha-helix folding with a tertiary structure of two-chain alpha-helical coiled-coil structures comprising a homodimer heptad chain. IPTG-induced histidine tagged-recombinant tropomyosin was purified at the size of 42 kDa and confirmed as tropomyosin using anti-tropomyosin monoclonal antibodies. The IgE binding of recombinant tropomyosin protein was reactive in 90.9% (20/22) of the sera from crab-allergic patients. CONCLUSIONS: This study has successfully produced an allergenic recombinant tropomyosin from S. olivacea. This recombinant tropomyosin may be used as a specific allergen for the diagnosis of allergy.


Assuntos
Braquiúros/imunologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Tropomiosina/genética , Tropomiosina/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Análise por Conglomerados , Humanos , Imunoglobulina E/metabolismo , Masculino , Modelos Moleculares , Anotação de Sequência Molecular , Filogenia , Tropomiosina/química
11.
BMC Infect Dis ; 21(1): 581, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34134646

RESUMO

BACKGROUND: Despite high childhood immunization coverage, sporadic cases of diphtheria have been reported in Malaysia in recent years. This study aims to evaluate the seroprevalence of diphtheria among the Malaysian population. METHODS: A total of 3317 respondents age 2 years old to 60 years old were recruited in this study from August to November 2017. Enzyme-linked immunosorbent assay (ELISA) was used to measure the level of IgG antibody against the toxoid of C. diphtheriae in the blood samples of respondents. We classified respondent antibody levels based on WHO definition, as protective (≥0.1 IU/mL) and susceptible (< 0.1 IU/mL) to C. diphtheriae infection. RESULTS: Among the 3317 respondents, 57% were susceptible (38.1% of children and 65.4% of adults) and 43% (61.9% of children and 34.6% of adults) had protective antibody levels against diphtheria. The mean antibody level peaked among individuals aged 1-2 years old (0.59 IU/mL) and 6-7 years old (0.64 IU/mL) but generally decreased with age, falling below 0.1 IU/mL at around 4-6 years old and after age 20 years old. There was a significant association between age [Children: χ2 = 43.22(df = 2),p < 0.001)], gender [Adults: χ2 = 5.58(df = 1),p = 0.018] and ethnicity [Adults: χ2 = 21.49(df = 5),p = 0.001] with diphtheria toxoid IgG antibody level. CONCLUSIONS: About 57% of the Malaysian population have inadequate immunity against diphtheria infection. This is apparently due to waning immunity following childhood vaccination without repeated booster vaccination in adults. Children at age 5-6 years old are particularly vulnerable to diphtheria infection. The booster vaccination dose normally given at 7 years should be given earlier, and an additional booster dose is recommended for high-risk adults.


Assuntos
Anticorpos Antibacterianos/sangue , Toxoide Diftérico/imunologia , Difteria/epidemiologia , Imunoglobulina G/sangue , Adolescente , Adulto , Criança , Pré-Escolar , Corynebacterium diphtheriae/metabolismo , Difteria/patologia , Ensaio de Imunoadsorção Enzimática , Humanos , Lactente , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Adulto Jovem
12.
Transfus Med Hemother ; 48(3): 188-195, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34177425

RESUMO

INTRODUCTION: Past studies pay little attention to the intention to donate hematopoietic stem cells (HSC) among blood donors. This study investigated the level of and the influence of socio-demographic characteristics, knowledge, attitude, subjective norm and self-efficacy on the intention to donate HSC among blood donors. METHODS: This cross-sectional study recruited blood donors at selected public hospitals in the Malaysian State of Sarawak in 2019. A structured questionnaire was developed based on the review of relevant literature. It gathered information on socio-demographic characteristics, knowledge, attitude, subjective norm and self-efficacy on the intention to donate HSC. Variables with a p value <0.200 in bivariate analysis were included in the variable selection for regression modeling to examine their associations with the intention to donate HSC. RESULTS: A total of 569 blood donors participated (94.5% response rate). Overall, 87.1% reported a positive intention to donate HSC. In the regression model, the factor with the greatest association with intention to donate HSC was subjective norms about HSC donation (ß = 0.35, 95% CI 0.27-0.42), followed by attitude about regulations of HSC donation (ß= 0.21, 95% CI 0.13-0.35), self-efficacy on HSC donation (ß = 0.15, 95% CI 0.09-0.32), attitude about the potential side effects of HSC donation (ß = 0.14, 95% CI 0.02-0.10) and highest education level (ß = 0.10, 95% CI 0.03-0.44). CONCLUSIONS: The findings can be used to formulate a better strategy in promoting HSC donation among blood donors in the region.

13.
Iran J Allergy Asthma Immunol ; 20(1): 76-87, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33639634

RESUMO

Crab allergy is reported as a serious form of food allergy in many countries. This study was aimed to identify the major allergens of the local mud crab, Scylla tranquebarica (S. tranquebarica), and subsequently, determine the effect of vinegar treatments on the crab allergens. Crab muscles were treated with synthetic and natural vinegar. Crab proteins were then extracted from the untreated and vinegar-treated crabs. All extracts were then fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and analyzed by immunoblotting; using sera from crab-allergic patients. The crab proteins were then further fractionated by two-dimensional electrophoresis (2-DE)and analyzed by mass spectrometry (MS). The untreated crab had 38 protein bands, while that was only a few bands between 18 to 73 kDa for the vinegar-treated crabs. Immunoblotting of untreated crab revealed 20 IgE-binding bands, whereas the vinegar-treated crabs could only retain a few IgE-binding bands. Five major allergens were identified with molecular weightsof38, 42, 49, 63, and 73 kDa in the untreated crab. In contrast, the vinegar-treated crabs had only a few major allergens with molecular weights of 38, 42, and 73 kDa. MS identified the 43 and 49 kDa as arginine kinase, while the 38, 63, and 73 kDa were identified as tropomyosin, actin, and hemocyanin, respectively. Inconclusion, we found three common major allergens for S. tranquebarica including tropomyosin, arginine kinase, and actin, and one novel allergen known as hemocyanin. All the major allergens could retain minimal allergenic capability in vinegar-treated crabs, suggesting that vinegar treatments might be useful to reduce crab allergenicity. These data would assist the clinicians in the management of crab-allergic patients worldwide.


Assuntos
Alérgenos/imunologia , Braquiúros/imunologia , Hipersensibilidade Alimentar/imunologia , Ácido Acético , Alérgenos/química , Animais , Culinária , Eletroforese em Gel de Poliacrilamida , Hipersensibilidade Alimentar/diagnóstico , Humanos , Immunoblotting , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Espectrometria de Massas , Peso Molecular
14.
Front Med (Lausanne) ; 7: 598665, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33644084

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease afflicting multiple organs. Lupus nephritis (LN) is a serious complication of SLE and remains a major cause of mortality and morbidity. Curative therapy remains unavailable as etiology from genetic and environmental factors is still unclear. The present study was conducted to elucidate the link between HLA-DRB1 gene polymorphisms with SLE and LN through clinical and laboratory/biological presentations in a population of Malaysian Malay females with SLE. A total of 100 Malay female SLE patients inclusive of 70 SLE patients without LN and 30 patients with LN were included in this study. HLA-DRB1 allele examination in SLE patients was performed using PCR-SSO, and the alleles' frequencies were compared with 951 publicly available datasets representing Malay healthy controls in Malaysia. Cytokines and free radical levels were detected by ELISA and bead-based multiplexed Luminex assays. The association between HLA-DRB1 alleles with clinical and serological manifestations and immune mediators was analyzed using different statistical approaches whenever applicable. Our study showed that HLA-DRB1*0405, HLA-DRB1*1502, and HLA-DRB1*1602 were associated with the increased risk of SLE while HLA-DRB1*1201 and HLADRB1*1202 alleles were associated with a lower risk of SLE development. Furthermore, HLA-DRB1*04 showed significant association to LN and arthritis while HLA-DRB1*15 was significantly associated with oral ulcer in Malay SLE patients. Association analysis of HLA-DRB1*04 with clinical and biological factors revealed that HLA-DRB1*04 was significantly associated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, anti-nuclear antibody (ANA), C-reactive protein (CRP) in the blood, and total protein in the urine. SLE carriers with the HLA-DRB1*04 allele were significantly correlated to the increased levels of cytokines (IFN-y, GM-CSF, IL-17F, IL-18, IL-21, and VEGF) and were significantly showing negative correlation to IL-5 and free radicals (LPO and catalase enzyme) levels compared to SLE carriers without HLA-DRB1*04 allele. The results suggested that disease severity in SLE may be determined by HLA-DRB1 alleles. The risk of HLA-DRB1*04 allele with LN was supported by the demonstration of an intense inflammatory response in Malay SLE patients in Malaysia. More studies inclusive of a larger and multiple SLE cohorts in the future are warranted to validate these findings.

15.
PLoS One ; 14(11): e0224707, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31697750

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disorder that is associated with lupus nephritis, initiated by the deposition of immune complexes in the kidney; subsequently, this induces the overexpression of cytokines. Lupus nephritis is known as one of the major clinical manifestations that affect the disease severity in SLE patients. An increased number of resident periglomerular and immune cells in the kidney has the potential to affect the equilibrium of different immune cell subsets, such as Th1, Th2, Th17, and Tregs, which may be central to the induction of tissue damage in kidney by exerting either proinflammatory or anti-inflammatory effects, or both. This equilibrium has yet to be confirmed, as new players such as IL-25 remain undiscovered. IL-25 is a cytokine of the IL-17 family, which stimulates Th2-mediated immune response when overly expressed. Thus, the aim of this research is to determine the plasma levels of IL-25 and Th2-associated cytokines (IL-4, IL-5, IL-6, IL-9, IL-10, IL-13) in SLE patients with (SLE-LN) and without lupus nephritis. Sixty-four (n = 64) SLE patients and fifteen (n = 15) healthy individuals were recruited. This study demonstrated that the IL-9, IL-10 and IL-25 had significantly increased expressions in SLE-LN, followed by SLE without LN, compared to healthy controls. Meanwhile, IL-5 and IL-6 had significantly reduced. No significant difference was observed with IL-13, while the level of IL-4 was undetectable. Furthermore, IL-9 and IL-10 were significantly correlated with the IL-25, and IL-25, IL-9 and IL-10 were positively correlated with the disease severity score, SLEDAI. In conclusion, IL-25 and its associated Th2 cytokines (IL-9 and IL-10) may be involved in SLE pathogenesis. These cytokines could be potential biomarkers in monitoring and predicting the disease severity during SLE pathogenesis.


Assuntos
Interleucina-17/sangue , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/imunologia , Células Th2/imunologia , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Humanos , Lúpus Eritematoso Sistêmico/sangue , Nefrite Lúpica/sangue , Índice de Gravidade de Doença
16.
Auto Immun Highlights ; 10(1): 13, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32257069

RESUMO

BACKGROUND: Multiple sclerosis is an immune mediated disease targeting the central nervous system. Association of non-human leukocyte antigen gene, CD58, with multiple sclerosis has been reported in several populations but is unclear among Southeast Asians. This pilot study was conducted to explore the association between CD58 polymorphism and multiple sclerosis among the Malay population in Malaysia. METHODS: Blood samples were collected from 27 multiple sclerosis patients, and compared with 58 age- and gender matched healthy individuals. All patients were tested negative for anti-aquaporin 4. DNA was extracted from the blood and genotyped for 3 single nucleotide polymorphisms rs12044852, rs2300747 and rs1335532 of gene CD58 by real-time PCR. RESULTS: The majority of multiple sclerosis patients were female (85.2%). The general mean age of onset was 30.5 years. Genotyping results showed that frequencies of the alleles were between 40 and 50% for MS patients and healthy individuals. Association (allelic model) between multiple sclerosis and CD58 gene polymorphism alleles rs12044852 (p = 0.410), rs2300747 (p = 0.881) and rs1335532 (p = 0.407) were indistinct. CONCLUSIONS: The impact of the CD58 gene polymorphism was not prominent in this pilot study, implying that genetic composition contributing to multiple sclerosis may be different between different populations, thus results in a heterogeneity of disease manifestation and distribution.

17.
Mult Scler Relat Disord ; 19: 20-24, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29100047

RESUMO

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) occurs worldwide in all ethnicities. Recently, population-based studies have shown that NMOSD is more common among non-White populations. There is scarce data about NMOSD prevalence in South East Asian populations. METHODS: (1) A population-based study was undertaken to estimate NMOSD prevalence in the multi-ethnic Penang Island, Malaysia, comprising Chinese, Malays, and Indians. Medical records of NMOSD patients followed up at the Penang General Hospital (the neurology referral centre in Penang Island) were reviewed. The 2015 diagnostic criteria of the International Panel for NMO Diagnosis were used for case ascertainment. (2) A review of population-based prevalence studies of NMOSD worldwide was carried out. PubMed and conference proceedings were searched for such studies. RESULTS: Of the 28 NMOSD patients, 14 were residents of Penang Island on prevalence day [13 (93%) Chinese and one (7%) Malay]. All 14 patients were females and aquaporin 4 seropositive. The prevalence of NMOSD in Penang Island was 1.99/100,000 population; according to ethnicities, the prevalence in Chinese was significantly higher than in Malays (3.31/100,000 vs 0.43/100,000, respectively, p = 0.0195). CONCLUSION: Based on our and other population-based studies, among Asians, East Asian origin populations (Chinese and Japanese) appear to have higher NMOSD prevalence than other Asian ethnic groups. Worldwide, Blacks seem to have the highest NMOSD prevalence. More studies in different geographical regions and ethnic groups will be useful to further inform about potential factors in NMOSD pathogenesis.


Assuntos
Neuromielite Óptica/etnologia , Grupos Raciais/etnologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Malásia/etnologia , Masculino , Pessoa de Meia-Idade , Prevalência
18.
Saf Health Work ; 8(3): 246-249, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28951800

RESUMO

Health-care workers are at risk of exposure to occupational infections with subsequent risk of contracting diseases, disability, and even death. A systematic collection of occupational disease data is useful for monitoring current trends in work situations and disease exposures; however, these data are usually limited due to under-reporting. The objective of this study was to review literature related to knowledge, risk perceptions, and practices regarding occupational exposures to infectious diseases in Malaysian health-care settings, in particular regarding blood-borne infections, universal precautions, use of personal protective equipment, and clinical waste management. The data are useful for determining improvements in knowledge and risk perceptions among health-care workers with developments of health policies and essential interventions for prevention and control of occupational diseases.

19.
Mult Scler Relat Disord ; 10: 22-25, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27919493

RESUMO

It is difficult to predict whether a particular attack of neuromyelitis optica spectrum disorder (NMOSD) will affect the optic nerve [optic neuritis (ON): unilateral or bilateral], spinal cord (myelitis), brain or brainstem, or a combination of the above. We report an interesting case of recurrent ON of the same eye for a total of 11 episodes in a Chinese woman. Over a period of 22 years, the attacks only involved the left eye, and never the right eye and also no myelitis. For a prolonged duration, she was diagnosed as recurrent idiopathic ON. Only until she was tested positive for aquaporin 4 antibody that her diagnosis was revised to NMOSD. Optical coherence tomography revealed thinning of the retinal nerve fibre layer (RNFL) for the affected left eye, while the RNFL thickness was within normal range for the unaffected right eye. The disability accrual in NMOSD is generally considered to be attack-related - without a clinical attack of ON, there shall be no visual impairment, and no significant subclinical thinning of RNFL. Our case is in agreement with this notion. This is in contrast to multiple sclerosis where subclinical RNFL thinning does occur. This case highlights the importance of revisiting and questioning a diagnosis of recurrent idiopathic ON particularly when new diagnostic tools are available.


Assuntos
Olho/fisiopatologia , Neuromielite Óptica/fisiopatologia , Aquaporina 4/imunologia , Autoanticorpos/sangue , Diagnóstico Diferencial , Potenciais Evocados Visuais , Olho/diagnóstico por imagem , Feminino , Lateralidade Funcional , Humanos , Pessoa de Meia-Idade , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/tratamento farmacológico , Recidiva , Tomografia de Coerência Óptica
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