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2.
Int J Mol Sci ; 24(11)2023 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-37298657

RESUMO

Cancer incidence keeps increasing every year around the world and is one of the leading causes of death worldwide. Cancer has imposed a major burden on the human population, including the deterioration of physical and mental health as well as economic or financial loss among cancer patients. Conventional cancer treatments including chemotherapy, surgery, and radiotherapy have improved the mortality rate. However, conventional treatments have many challenges; for example, drug resistance, side effects, and cancer recurrence. Chemoprevention is one of the promising interventions to reduce the burden of cancer together with cancer treatments and early detection. Pterostilbene is a natural chemopreventive compound with various pharmacological properties such as anti-oxidant, anti-proliferative, and anti-inflammatory properties. Moreover, pterostilbene, due to its potential chemopreventive effect on inducing apoptosis in eliminating the mutated cells or preventing the progression of premalignant cells to cancerous cells, should be explored as a chemopreventive agent. Hence, in the review, we discuss the role of pterostilbene as a chemopreventive agent against various types of cancer via its modulation of the apoptosis pathway at the molecular levels.


Assuntos
Estilbenos , Humanos , Linhagem Celular Tumoral , Estilbenos/farmacologia , Estilbenos/uso terapêutico , Antioxidantes/farmacologia , Apoptose
3.
Microb Genom ; 9(4)2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37018040

RESUMO

Burkholderia pseudomallei, a Gram-negative pathogen, is the causative agent of melioidosis in humans. This bacterium can be isolated from the soil, stagnant and salt-water bodies, and human and animal clinical specimens. While extensive studies have contributed to our understanding of B. pseudomallei pathogenesis, little is known about how a harmless soil bacterium adapts when it shifts to a human host and exhibits its virulence. The bacterium's large genome encodes an array of factors that support the pathogen's ability to survive under stressful conditions, including the host's internal milieu. In this study, we performed comparative transcriptome analysis of B. pseudomallei cultured in human plasma versus soil extract media to provide insights into B. pseudomallei gene expression that governs bacterial adaptation and infectivity in the host. A total of 455 genes were differentially regulated; genes upregulated in B. pseudomallei grown in human plasma are involved in energy metabolism and cellular processes, whilst the downregulated genes mostly include fatty acid and phospholipid metabolism, amino acid biosynthesis and regulatory function proteins. Further analysis identified a significant upregulation of biofilm-related genes in plasma, which was validated using the biofilm-forming assay and scanning electron microscopy. In addition, genes encoding known virulence factors such as capsular polysaccharide and flagella were also overexpressed, suggesting an overall enhancement of B. pseudomallei virulence potential when present in human plasma. This ex vivo gene expression profile provides comprehensive information on B. pseudomallei's adaptation when shifted from the environment to the host. The induction of biofilm formation under host conditions may explain the difficulty in treating septic melioidosis.


Assuntos
Burkholderia pseudomallei , Melioidose , Animais , Humanos , Burkholderia pseudomallei/genética , Melioidose/microbiologia , Adaptação Fisiológica , Virulência , Fatores de Virulência
4.
Microbiol Spectr ; : e0383522, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36856434

RESUMO

Burkholderia pseudomallei, a soil and water saprophyte, is responsible for the tropical human disease melioidosis. A hundred years since its discovery, there is still much to learn about B. pseudomallei proteins that are essential for the bacterium's survival in and interaction with the infected host, as well as their roles within the bacterium's natural soil habitat. To address this gap, bacteria grown under conditions mimicking the soil environment were subjected to transcriptome sequencing (RNA-seq) analysis. A dual RNA-seq approach was used on total RNA from spleens isolated from a B. pseudomallei mouse infection model at 5 days postinfection. Under these conditions, a total of 1,434 bacterial genes were induced, with 959 induced in the soil environment and 475 induced in bacteria residing within the host. Genes encoding metabolism and transporter proteins were induced when the bacteria were present in soil, while virulence factors, metabolism, and bacterial defense mechanisms were upregulated during active infection of mice. On the other hand, capsular polysaccharide and quorum-sensing pathways were inhibited during infection. In addition to virulence factors, reactive oxygen species, heat shock proteins, siderophores, and secondary metabolites were also induced to assist bacterial adaptation and survival in the host. Overall, this study provides crucial insights into the transcriptome-level adaptations which facilitate infection by soil-dwelling B. pseudomallei. Targeting novel therapeutics toward B. pseudomallei proteins required for adaptation provides an alternative treatment strategy given its intrinsic antimicrobial resistance and the absence of a vaccine. IMPORTANCE Burkholderia pseudomallei, a soil-dwelling bacterium, is the causative agent of melioidosis, a fatal infectious disease of humans and animals. The bacterium has a large genome consisting of two chromosomes carrying genes that encode proteins with important roles for survival in diverse environments as well as in the infected host. While a general mechanism of pathogenesis has been proposed, it is not clear which proteins have major roles when the bacteria are in the soil and whether the same proteins are key to successful infection and spread. To address this question, we grew the bacteria in soil medium and then in infected mice. At 5 days postinfection, bacteria were recovered from infected mouse organs and their gene expression was compared against that of bacteria grown in soil medium. The analysis revealed a list of genes expressed under soil growth conditions and a different set of genes encoding proteins which may be important for survival, replication, and dissemination in an infected host. These proteins are a potential resource for understanding the full adaptation mechanism of this pathogen. In the absence of a vaccine for melioidosis and with treatment being reliant on combinatorial antibiotic therapy, these proteins may be ideal targets for designing antimicrobials to treat melioidosis.

5.
Life (Basel) ; 13(2)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36836914

RESUMO

High broth viscosity due to the accumulation of hyaluronic acid (HA) causes a limited yield of HA. It is a major problem of HA production using Streptococcus zooepidemicus. Extractive fermentation via in situ product recovery (ISPR) was utilized to enhance the HA production. Resins from Amberlite: IRA400 Cl; IRA900 Cl; IRA410 Cl; IRA402 Cl; and IRA67 were tested for the HA adsorption. IRA67 showed high adsorption capacity on HA. The study of the adsorption via a 2 L stirred tank bioreactor of S. zooepidemicus fermentation was investigated to elucidate the adsorption of HA onto IRA67 in dispersed and integrated internal column systems. The application of a dispersed IRA67 improved the HA production compared to the fermentation without resin addition by 1.37-fold. The HA production was further improved by 1.36-fold with an internal column (3.928 g/L) over that obtained with dispersed IRA67. The cultivation with an internal column shows the highest reduction of viscosity value after the addition of IRA67 resin: from 58.8 to 23.7 (mPa·s), suggesting the most effective ISPR of HA. The improved biosynthesis of HA indicated that an extractive fermentation by ISPR adsorption is effective and may streamline the HA purification.

6.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-997077

RESUMO

@#Introduction: Childhood anxiety is one of the common mental health problems in children. Untreated childhood anxiety will lead to a higher risk of developing mental health problems in adulthood. Thus, this study aimed to investigate the relationship between parental emotional styles and family values to anxiety level among primary school children. Methods: A cross-sectional study was conducted in a selected primary school in Kelantan, Malaysia. A set of questionnaires consisted of the Revised Child Anxiety and Depression Scale–Parents’ Report (RCADS-P 25), the Parental Emotional Style Questionnaire (PESQ), and the Asian Family Characteristics Scale (AFCS) was used for assessing anxiety, parental emotional styles, and family values, respectively. Data were collected via an online survey using Google Form, and were analysed using Multiple Linear Regression (MLR) to determine the factors associated with childhood anxiety. The significance value was set at p < 0.05. Results: A total of 150 parents of primary school children from the selected school was involved in this study. The majority of respondents were females (82.0%), married (94.7%), hold a degree (66.7%), and were working in the government sector (60.0%). Most of the respondents’ child were twelve years old (20.7%) and males (62%). Based on the MLR, emotional dismissing parental style (p = 0.025) and family values (p = 0.016) were significantly associated with anxiety in these children. Conclusion: Emotional dismissing parental style and family values were significant predictors of anxiety in primary school children. Future intervention research on childhood anxiety is needed.

7.
Imaging Sci Dent ; 53(4): 271-281, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38174035

RESUMO

Purpose: The objective of this scoping review was to investigate the applicability and performance of various convolutional neural network (CNN) models in tooth numbering on panoramic radiographs, achieved through classification, detection, and segmentation tasks. Material and Methods: An online search was performed of the PubMed, Science Direct, and Scopus databases. Based on the selection process, 12 studies were included in this review. Results: Eleven studies utilized a CNN model for detection tasks, 5 for classification tasks, and 3 for segmentation tasks in the context of tooth numbering on panoramic radiographs. Most of these studies revealed high performance of various CNN models in automating tooth numbering. However, several studies also highlighted limitations of CNNs, such as the presence of false positives and false negatives in identifying decayed teeth, teeth with crown prosthetics, teeth adjacent to edentulous areas, dental implants, root remnants, wisdom teeth, and root canal-treated teeth. These limitations can be overcome by ensuring both the quality and quantity of datasets, as well as optimizing the CNN architecture. Conclusion: CNNs have demonstrated high performance in automated tooth numbering on panoramic radiographs. Future development of CNN-based models for this purpose should also consider different stages of dentition, such as the primary and mixed dentition stages, as well as the presence of various tooth conditions. Ultimately, an optimized CNN architecture can serve as the foundation for an automated tooth numbering system and for further artificial intelligence research on panoramic radiographs for a variety of purposes.

8.
BMJ Open ; 12(9): e058420, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36581978

RESUMO

INTRODUCTION: Colorectal cancer (CRC) is the second most common cancer in Malaysia and cases are often detected late. Improving screening uptake is key in down-staging cancer and improving patient outcomes. The aim of this study is to develop, implement and evaluate an intervention to improve CRC screening uptake in Malaysia in the context of the COVID-19 pandemic. The evaluation will include ascertaining the budgetary impact of implementing and delivering the intervention. METHODS AND ANALYSIS: The implementation research logic model guided the development of the study and implementation outcome measures were informed by the 'Reach, Effectiveness, Adoption, Implementation and Maintenance' (RE-AIM) framework. This CRC screening intervention for Malaysia uses home-testing and digital, small media, communication to improve CRC screening uptake. A sample of 780 people aged 50-75 years living in Segamat district, Malaysia, will be selected randomly from the South East Asia Community Observatory (SEACO) database. Participants will receive a screening pack as well as a WhatsApp video of a local doctor to undertake a stool test safely and to send a photo of the test result to a confidential mobile number. SEACO staff will inform participants of their result. Quantitative data about follow-up clinic attendance, subsequent hospital tests and outcomes will be collected. Logistic regression will be used to investigate variables that influence screening completion and we will conduct a budget impact-analysis of the intervention and its implementation. Qualitative data about intervention implementation from the perspective of participants and stakeholders will be analysed thematically. ETHICS AND DISSEMINATION: Ethics approval has been granted by Monash University Human Research Ethics Committee (MUHREC ID: 29107) and the Medical Review and Ethics Committee (Reference: 21-02045-O7G(2)). Results will be disseminated through publications, conferences and community engagement activities. TRIAL REGISTRATION NUMBER: National Medical Research Register Malaysia: 21-02045-O7G(2).


Assuntos
COVID-19 , Neoplasias Colorretais , Humanos , Pandemias/prevenção & controle , Malásia/epidemiologia , Detecção Precoce de Câncer/métodos , COVID-19/diagnóstico , COVID-19/epidemiologia , Neoplasias Colorretais/epidemiologia
9.
Biomedicines ; 10(11)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36359262

RESUMO

Skin squamous cell carcinoma (SCC) is a type of non-melanoma skin cancer. Pterostilbene is a natural compound proven to exhibit various pharmacological properties, including chemo-preventive effects. This study aimed to explore the chemo-preventive effect of oral pterostilbene during initiation, promotion or continuous on multistage skin SCC mouse models induced by 7,12-Dimethylbenz(a)anthracene (DMBA)/12-O-Tetradecanoylphorbol-13-acetate (TPA). The experimental design consists of five groups of female Institute of Cancer Research (ICR) mice, with two control groups of vehicle and cancer. Three oral pterostilbene groups consisted of orally administered pterostilbene during initiation, promotion, or continuously. Oral pterostilbene significantly reduced the number and volume of tumours. Oral pterostilbene demonstrated less severe skin histology changes compared to the cancer control group, with less pleomorphic in the cells and nuclei, and the basement membrane remained intact. Our results showed fewer invasive tumours in oral PT-treated groups than in cancer groups that displayed mitotic bodies, highly pleomorphic cells and nuclei, and basement membrane invasion. The cell proliferation marker (Ki-67) was reduced in oral pterostilbene-treated groups. Overall, oral pterostilbene is a promising chemo-preventive intervention due to its anti-initiation and anti-promotion on skin carcinogenesis. Thus, the potential molecular mechanisms of oral pterostilbene chemo-prevention agent should be explored.

10.
Artigo em Inglês | MEDLINE | ID: mdl-35805381

RESUMO

The increase in the number of Tahfiz schools in Malaysia indicates a high demand from the community for Tahfiz education. Tahfiz schools provide a Quran memorization syllabus as the main part of the curriculum at the primary and secondary levels. There is no holistic module that combines learning and health for Tahfiz students in Malaysia. Huffaz ProHealth 1.0© Module is a health intervention module developed explicitly for Tahfiz students by a group of researchers from Universiti Kebangsaan Malaysia Kuala Lumpur (UKMKL). The module encompasses educational and motivational components for the Tahfiz students, and acts as a guide for their teachers and staff to improve the students' health and quality of life. The module consists of three components: physical health, nutritional and psychological well-being. Each component is divided into several units with specific activities. The Sidek Module Development Model (SDMM) was used as a reference model. The study involved two phases: the development (Phase I) and evaluation (Phase II). In Phase I, a needs assessment was conducted among students and teachers from Tahfiz schools to evaluate their knowledge, attitude, and practice on the related topics. Meanwhile, the module's validity and feasibility were assessed by healthcare experts and Tahfiz teachers in Phase II. The item-content validity index (I-CVI), content validity value, Tool to Evaluate Materials used in Patient Education (TEMPtEd) score, and expert feedback were evaluated. In conclusion, the Huffaz ProHealth 1.0© module was successfully developed and evaluated. Strong validity values were observed in all components, indicating high suitability to be employed at Tahfiz schools.


Assuntos
Qualidade de Vida , Estudantes , Currículo , Humanos , Malásia , Instituições Acadêmicas , Estudantes/psicologia
11.
Biomed Res Int ; 2022: 2748382, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295957

RESUMO

Despite increasing mortality rates from cardiovascular diseases (CVDs) in low- and middle-income countries, information on the estimation of 10-year CVD risk remains to be sparse. Therefore, this study was aimed at predicting the 10-year CVD risk among community dwellers in Malaysia and at identifying the association of distal (socioeconomic characteristics) and proximal (lifestyle practices) factors with 10-year CVD risk. We calculated the 10-year CVD risk score among 11,897 eligible respondents from the community health survey conducted by the South East Asia Community Observatory (SEACO) using the Framingham risk score (FRS). The findings indicate that 28% of respondents have a high chance of having CVD within the next ten years. After adjusting for the age of respondents, demographic and socioeconomic factors such as gender, ethnicity, marital status, education, income, and occupation had an association with the 10-year CVD risk. In addition, frequent eating out had an association with 10-year CVD risk, while physical activity was found to have no association with predicted CVD risk. CVD remained among the top five mortality causes in Malaysia. Health promotion strategies should emphasize the importance of having home-cooked meals as a healthy dietary behavior, to reduce the mortality rate among Malaysians due to CVDs.


Assuntos
Doenças Cardiovasculares/epidemiologia , Restaurantes , Adulto , Idoso , Doenças Cardiovasculares/mortalidade , Demografia , Feminino , Humanos , Estilo de Vida , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Socioeconômicos
12.
Nutrients ; 14(3)2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35276789

RESUMO

The DePEC-Nutrition trial is a complex dietary and behavioural intervention of salt intake reduction combined with increased high-nitrate vegetable consumption among Malaysian middle-aged and older adults with elevated blood pressure. This study aimed to assess the feasibility and acceptability of the trial. Participants were recruited from the South East Asia Community Observatory (SEACO) database and randomised into one of four groups: (1) low salt; (2) high-nitrate vegetable; (3) combined high-nitrate vegetable and low salt; and (4) control. The intervention included a combination of group counselling sessions, information booklets, reinforcement videos and text messages to modify dietary behaviour. The primary outcomes evaluated were the measures of feasibility and acceptability of (1) recruitment, follow-up attendance and retention; (2) data collection procedures and clinical outcome measures; and (3) individual and combined multi-modal dietary interventions. A total of 74 participants were recruited, and the 10-month retention rate was 73%. Data collection procedures were acceptable with minimal missing data. All intervention strategies were feasible and acceptable, with group counselling being the most acceptable strategy. This study provides important insights into improving the screening process of participants, facilitating their access to the research facilities and refining the measurement protocols and dietary recommendations, which are instrumental in formulating the design of a full-scale definitive DePEC-Nutrition trial.


Assuntos
Nitratos , Verduras , Idoso , Pressão Sanguínea , Estudos de Viabilidade , Humanos , Pessoa de Meia-Idade , Cloreto de Sódio na Dieta
13.
Rev Environ Health ; 37(2): 169-179, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34582637

RESUMO

The belief that natural products are inherently safe is a primary reason for consumers to choose traditional medicines and herbal supplements for health maintenance and disease prevention. Unfortunately, some natural products on the market have been found to contain toxic compounds, such as heavy metals and microbes, as well as banned ingredients such as aristolochic acids. It shows that the existing regulatory system is inadequate and highlights the importance of thorough safety evaluations. In Malaysia, the National Pharmaceutical Regulatory Agency is responsible for the regulatory control of medicinal products and cosmetics, including natural products. For registration purpose, the safety of natural products is primarily determined through the review of documents, including monographs, research articles and scientific reports. One of the main factors hampering safety evaluations of natural products is the lack of toxicological data from animal studies. However, international regulatory agencies such as the European Food Safety Authority and the United States Food and Drug Administration are beginning to accept data obtained using alternative strategies such as non-animal predictive toxicological tools. Our paper discusses the use of state-of-the-art techniques, including chemometrics, in silico modelling and omics technologies and their applications to the safety assessments of natural products.


Assuntos
Produtos Biológicos , Animais , Produtos Biológicos/toxicidade , Malásia , Medicina Tradicional/métodos , Preparações de Plantas , Estados Unidos
14.
Dose Response ; 19(4): 15593258211047651, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34840540

RESUMO

Pterostilbene is a potent antioxidant and anti-inflammatory agent. However, its chemopreventive effects via anti-tyrosinase activity and inhibitory effects on melanin content have not been reported previously. Hence, this study aimed to investigate the anti-melanogenic activity of pterostilbene on UVB-irradiated B164A5 mouse melanoma cells. The effects of pterostilbene and resveratrol on cell viability were determined by MTT assay, whereas melanin content and tyrosinase assay were employed to assess melanogenesis activity. Western blot analysis was performed to determine the tyrosinase expression. Based on the MTT assay, the IC50 value of pterostilbene on UVB-irradiated B164A5 cells was 34.0 ± 3.43 µM, in comparison to resveratrol (>100 µM). Next, 5 and 10 µM pterostilbene showed a significant dose-dependent inhibition (P < .01) of tyrosinase activity in UVB-irradiated B164A5 cells at 37.14 ± 2.71% and 58.36 ± 6.8%, respectively. The findings from the tyrosinase assay also confirmed the downregulation of tyrosinase expression in UVB-irradiated B164A5 cells as measured by Western blot analysis. Finally, 10 µM pterostilbene showed a significantly decreased melanin content (P < .01) in UVB-irradiated B164A5 cells, at 27.34 ± .98 µg/mL. In conclusion, pterostilbene showed anti-melanogenic activity that was 10 times more potent than resveratrol in the UVB-irradiated B164A5 cell.

15.
Int J Dent ; 2021: 1093412, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257658

RESUMO

OBJECTIVE: This study aimed to determine the radiographic characteristics of odontogenic myxomas (OMs) and their associations. MATERIALS AND METHODS: The study enrolled radiographs of patients taken between 2005 and 2019 with a confirmed histopathological diagnosis of central OM. OM radiographic features were evaluated, including location, border, locularity, involved area, the number of included teeth, root resorption, tooth displacement, bone expansion, bone perforation, and periosteal reaction. Fisher's exact test was used for statistical analysis. RESULTS: Significant associations were found between the OM border and the affected jaw (p=0.036), locularity (p=0.036), involved areas (p=0.009), and bone perforation (p=0.036). OMs with an ill-defined border were associated with maxillary lesions, multilocularity, dentate areas, and cortical bone perforation. The number of included teeth (2 or fewer or 3 or more) was significantly associated with locularity (p=0.010), involved area (p=0.045), and bone expansion (p=0.010). Larger OMs including 3 or more teeth, were associated with a multilocular appearance, dentate areas, and bone expansion. CONCLUSION: The border of OM and the number of included teeth are related to other radiographic appearances. Understanding these relationships could help in treatment decisions and help better understand the nature of OM.

16.
Sci Rep ; 11(1): 14862, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290382

RESUMO

Cell proliferation and cell death abnormalities are strongly linked to the development of cancer, including lung cancer. The purpose of this study was to investigate the effect of pterostilbene on cell proliferation and cell death via cell cycle arrest during the transition from G1 to S phase and the p53 pathway. A total of 24 female Balb/C mice were randomly categorized into four groups (n = 6): N-nitroso-tris-chloroethyl urea (NTCU) induced SCC of the lungs, vehicle control, low dose of 10 mg/kg PS + NTCU (PS10), and high dose of 50 mg/kg PS + NTCU (PS50). At week 26, all lungs were harvested for immunohistochemistry and Western blotting analysis. Ki-67 expression is significantly lower, while caspase-3 expression is significantly higher in PS10 and PS50 as compared to the NTCU (p < 0.05). There was a significant decrease in cyclin D1 and cyclin E2 protein expression in PS10 and PS50 when compared to the NTCU (p < 0.05). PS50 significantly increased p53, p21, and p27 protein expression when compared to NTCU (p < 0.05). Pterostilbene is a potential chemoprevention agent for lung SCC as it has the ability to upregulate the p53/p21 pathway, causing cell cycle arrest.


Assuntos
Anticarcinógenos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Estilbenos/farmacologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose/genética , Proliferação de Células/genética , Ciclina D1/genética , Ciclina D1/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Feminino , Camundongos Endogâmicos BALB C , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
17.
Microb Genom ; 7(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33565959

RESUMO

Burkholderia pseudomallei, a soil-dwelling Gram-negative bacterium, is the causative agent of the endemic tropical disease melioidosis. Clinical manifestations of B. pseudomallei infection range from acute or chronic localized infection in a single organ to fulminant septicaemia in multiple organs. The diverse clinical manifestations are attributed to various factors, including the genome plasticity across B. pseudomallei strains. We previously characterized B. pseudomallei strains isolated in Malaysia and noted different levels of virulence in model hosts. We hypothesized that the difference in virulence might be a result of variance at the genome level. In this study, we sequenced and assembled four Malaysian clinical B. pseudomallei isolates, UKMR15, UKMPMC2000, UKMD286 and UKMH10. Phylogenomic analysis showed that Malaysian subclades emerged from the Asian subclade, suggesting that the Malaysian strains originated from the Asian region. Interestingly, the low-virulence strain, UKMH10, was the most distantly related compared to the other Malaysian isolates. Genomic island (GI) prediction analysis identified a new island of 23 kb, GI9c, which is present in B. pseudomallei and Burkholderia mallei, but not Burkholderia thailandensis. Genes encoding known B. pseudomallei virulence factors were present across all four genomes, but comparative analysis of the total gene content across the Malaysian strains identified 104 genes that are absent in UKMH10. We propose that these genes may encode novel virulence factors, which may explain the reduced virulence of this strain. Further investigation on the identity and role of these 104 proteins may aid in understanding B. pseudomallei pathogenicity to guide the design of new therapeutics for treating melioidosis.


Assuntos
Burkholderia pseudomallei/classificação , Melioidose/microbiologia , Tipagem de Sequências Multilocus/métodos , Sequenciamento Completo do Genoma/métodos , Técnicas de Tipagem Bacteriana , Burkholderia pseudomallei/genética , Burkholderia pseudomallei/isolamento & purificação , Burkholderia pseudomallei/patogenicidade , Tamanho do Genoma , Genoma Bacteriano , Ilhas Genômicas , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Malásia , Filogenia , Fatores de Virulência/genética
18.
Asian Pac J Cancer Prev ; 21(11): 3381-3386, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33247699

RESUMO

BACKGROUND: Traditional cooling rice powder (bedak sejuk) is a fermented rice-based cosmetic that is applied topically on one's skin, as an overnight facial mask. According to user testimonies, bedak sejuk beautifies and whitens skin, whereby these benefits could be utilised as a potential melanoma chemopreventive agent. OBJECTIVE: Hence, this study aimed to determine the effects of bedak sejuk made from Oryza sativa ssp. indica (Indica) and Oryza sativa ssp. japonica (Japonica) on UVB-induced B164A5 melanoma cells, and also identify the antioxidant capacities of both types of bedak sejuk. METHODS: The optimum dose of Indica and Japonica bedak sejuk to treat the cells was determined via the MTT assay. Then, the antioxidant capacities of both types of bedak sejuk were determined using the FRAP assay. RESULTS: From the MTT assay, it was found that Indica and Japonica bedak sejuk showed no cytotoxic effects towards the cells. Hence, no IC50 can be obtained and two of the higher doses, 50 and 100 g/L were chosen for treatment. In the FRAP assay, Indica bedak sejuk at 50 and 100 g/L showed FRAP values of 0.003 ± 0.001 µg AA (ascorbic acid)/g of bedak sejuk and 0.004 ± 0.0003 µg AA/g of bedak sejuk. Whereas Japonica bedak sejuk at 50 g/L had the same FRAP value as Indica bedak sejuk at 100 g/L. As for Japonica bedak sejuk at 100 g/L, it showed the highest antioxidant capacity with the FRAP value of 0.01 ± 0.0007 µg AA/g of bedak sejuk which was statistically significant (p < 0.05) when compared to other tested concentrations. CONCLUSION: In conclusion, Japonica bedak sejuk has a higher antioxidant capacity compared to Indica bedak sejuk despite both being not cytotoxic towards the cells. Regardless, further investigations need to be done before bedak sejuk could be developed as potential melanoma chemoprevention agents.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Melanoma/tratamento farmacológico , Oryza/química , Oryza/classificação , Pós/farmacologia , Raios Ultravioleta/efeitos adversos , Animais , Sobrevivência Celular , Melanoma/etiologia , Melanoma/patologia , Pós/química
19.
Histol Histopathol ; 35(10): 1159-1170, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32893871

RESUMO

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths, and squamous cell carcinoma (SCC) is one of the most common types of lung cancer. Chemoprevention of lung cancer has gained increasing popularity as an alternative to treatment in reducing the burden of lung cancer. Pterostilbene (PS) may be developed as a chemopreventive agent due to its pharmacological activities, such as anti-proliferative, anti-inflammatory and antioxidant properties. This study aimed to investigate the effect of PS on the development of lung SCC in the mouse model. METHODS: A total of 24 seven-week-old female Balb/C mice were randomly categorised into four groups, including two control groups comprising the N-nitroso-trischloroethylurea (NTCU)-induced lung SCC and vehicle control (VC) groups and two treatment groups comprising the 10mg/kg PS (PS10) and 50mg/kg PS (PS50) groups. All lung organs were harvested at week 26 for histopathological analysis. RESULTS: All PS treatment groups showed chemopreventive activity by inhibiting the progression of lung SCC formation with PS10, resulting in mild hyperplasia, and PS50 was completely reversed in the normal bronchial epithelium layer compared with the VC group. PS treatment also reduced the expression of cytokeratin 5/6 in the bronchial epithelium layer. Both PS10 and PS50 significantly reduced the epithelium thickness compared to the NTCU group (p<0.05). PS is a potential chemopreventive agent against lung SCC growth by suppressing the progression of pre-malignant lesions and reducing the thickness of the bronchial epithelium. CONCLUSIONS: The underlying molecular mechanisms of PS in lung SCC should be further studied.


Assuntos
Anticarcinógenos/farmacologia , Carcinoma de Células Escamosas/prevenção & controle , Neoplasias Pulmonares/prevenção & controle , Pulmão/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carmustina/análogos & derivados , Modelos Animais de Doenças , Feminino , Queratina-15/metabolismo , Queratina-6/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos Endogâmicos BALB C
20.
BMJ Open ; 10(8): e035453, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32859661

RESUMO

INTRODUCTION: Global population ageing is one of the key factors linked to the projected rise of dementia incidence. Hence, there is a clear need to identify strategies to overcome this expected health burden and have a meaningful impact on populations' health worldwide. Current evidence supports the role of modifiable dietary and lifestyle risk factors in reducing the risk of dementia. In South-East Asia, changes in eating and lifestyle patterns under the influence of westernised habits have resulted in significant increases in the prevalence of metabolic, cardiovascular and neurodegenerative non-communicable diseases (NCDs). Low vegetable consumption and high sodium intake have been identified as key contributors to the increased prevalence of NCDs in these countries. Therefore, nutritional and lifestyle strategies targeting these dietary risk factors are warranted. The overall objective of this randomised feasibility trial is to demonstrate the acceptability of a dietary intervention to increase the consumption of high-nitrate green leafy vegetables and reduce salt intake over 6 months among Malaysian adults with raised blood pressure. METHODS AND ANALYSIS: Primary outcomes focus on feasibility measures of recruitment, retention, implementation and acceptability of the intervention. Secondary outcomes will include blood pressure, cognitive function, body composition and physical function (including muscle strength and gait speed). Adherence to the dietary intervention will be assessed through collection of biological samples, 24-hour recall and Food Frequency Questionnaire. A subgroup of participants will also complete postintervention focus groups to further explore the feasibility considerations of executing a larger trial, the ability of these individuals to make dietary changes and the barriers and facilitators associated with implementing these changes. ETHICS AND DISSEMINATION: Ethical approval has been obtained from Monash University Human Research Ethics Committee and Medical Research and Ethics Committee of Malaysia. Results of the study will be disseminated via peer-reviewed publications and presentations at national and international conferences.ISRCTN47562685; Pre-results.


Assuntos
Cloreto de Sódio na Dieta , Verduras , Adulto , Idoso , Pressão Sanguínea , Estudos de Viabilidade , Humanos , Malásia/epidemiologia , Pessoa de Meia-Idade , Nitratos
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