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Fulltext COVID-19: Insights into Potential Vaccines

Loo KY, Letchumanan V, Ser HL, Teoh SL, Law JW, Tan LT, et al.

Microorganisms, 2021 Mar 15;9(3).
PMID: 33804162 DOI: 10.3390/microorganisms9030605

People around the world ushered in the new year 2021 with a fear of COVID-19, as family members have lost their loved ones to the disease. Millions of people have been infected, and the livelihood of many has been jeopardized due to the pandemic. Pharmaceutical companies are racing against time to develop an effective vaccine to protect against COVID-19. Researchers have developed various types of candidate vaccines with the release of the genetic sequence of the SARS-CoV-2 virus in January. These include inactivated viral vaccines, protein subunit vaccines, mRNA vaccines, and recombinant viral vector vaccines. To date, several vaccines have been authorized for emergency use and they have been administered in countries across the globe. Meanwhile, there are also vaccine candidates in Phase III clinical trials awaiting results and approval from authorities. These candidates have shown positive results in the previous stages of the trials, whereby they could induce an immune response with minimal side effects in the participants. This review aims to discuss the different vaccine platforms and the clinical trials of the candidate vaccines.
Fulltext A Keystone Gut Bacterium Christensenella minuta-A Potential Biotherapeutic Agent for Obesity and Associated Metabolic Diseases

Ang WS, Law JW, Letchumanan V, Hong KW, Wong SH, Ab Mutalib NS, et al.

Foods, 2023 Jun 26;12(13).
PMID: 37444223 DOI: 10.3390/foods12132485

A new next-generation probiotic, Christensenella minuta was first discovered in 2012 from healthy human stool and described under the phylum Firmicutes. C. minuta is a subdominant commensal bacterium with highly heritable properties that exhibits mutual interactions with other heritable microbiomes, and its relative abundance is positively correlated with the lean host phenotype associated with a low BMI index. It has been the subject of numerous studies, owing to its potential health benefits. This article reviews the evidence from various studies of C. minuta interventions using animal models for managing metabolic diseases, such as obesity, inflammatory bowel disease, and type 2 diabetes, characterized by gut microbiota dysbiosis and disruption of host metabolism. Notably, more studies have presented the complex interaction between C. minuta and host metabolism when it comes to metabolic health. Therefore, C. minuta could be a potential candidate for innovative microbiome-based biotherapy via fecal microbiota transplantation or oral administration. However, the detailed underlying mechanism of action requires further investigation.
Fulltext Focused Review: Cytotoxic and Antioxidant Potentials of Mangrove-Derived Streptomyces

Ser HL, Tan LT, Law JW, Chan KG, Duangjai A, Saokaew S, et al.

Front Microbiol, 2017;8:2065.
PMID: 29163380 DOI: 10.3389/fmicb.2017.02065

Human life expectancy is rapidly increasing with an associated increasing burden of chronic diseases, such as neurodegenerative diseases and cancer. However, there is limited progress in finding effective treatment for these conditions. For this reason, members of the genus Streptomyces have been explored extensively over the past decades as these filamentous bacteria are highly efficient in producing bioactive compounds with human health benefits. Being ubiquitous in nature, streptomycetes can be found in both terrestrial and marine environments. Previously, two Streptomyces strains (MUSC 137T and MUM 256) isolated from mangrove sediments in Peninsular Malaysia demonstrated potent antioxidant and cytotoxic activities against several human cancer cell lines on bioactivity screening. These results illustrate the importance of streptomycetes from underexplored regions aside from the terrestrial ecosystem. Here we provide the insights and significance of Streptomyces species in the search of anticancer and/or chemopreventive agents and highlight the impact of next generation sequencing on drug discovery from the Streptomyces arsenal.
Whole genome sequencing of Malaysian colorectal cancer patients reveals specific druggable somatic mutations

Mohd Yunos RI, Ab Mutalib NS, Khoo JS, Saidin S, Ishak M, Syafruddin SE, et al.

Front Mol Biosci, 2022;9:997747.
PMID: 36866106 DOI: 10.3389/fmolb.2022.997747

The incidences of colorectal cancer (CRC) are continuously increasing in some areas of the world, including Malaysia. In this study, we aimed to characterize the landscape of somatic mutations using the whole-genome sequencing approach and identify druggable somatic mutations specific to Malaysian patients. Whole-genome sequencing was performed on the genomic DNA obtained from 50 Malaysian CRC patients' tissues. We discovered the top significantly mutated genes were APC, TP53, KRAS, TCF7L2 and ACVR2A. Four novel, non-synonymous variants were identified in three genes, which were KDM4E, MUC16 and POTED. At least one druggable somatic alteration was identified in 88% of our patients. Among them were two frameshift mutations in RNF43 (G156fs and P192fs) predicted to have responsive effects against the Wnt pathway inhibitor. We found that the exogenous expression of this RNF43 mutation in CRC cells resulted in increased cell proliferation and sensitivity against LGK974 drug treatment and G1 cell cycle arrest. In conclusion, this study uncovered our local CRC patients' genomic landscape and druggable alterations. It also highlighted the role of specific RNF43 frameshift mutations, which unveil the potential of an alternative treatment targeting the Wnt/β-Catenin signalling pathway and could be beneficial, especially to Malaysian CRC patients.
Fulltext COVID-19 in Malaysia: exposure assessment and prevention practices among healthcare workers at a teaching hospital

Muhammad Azami NA, Abdul Murad NA, Mohammed Nawi A, Salleh SA, Periyasamy P, Kori N, et al.

J Infect Dev Ctries, 2021 12 31;15(12):1816-1824.
PMID: 35044938 DOI: 10.3855/jidc.15277

INTRODUCTION: During the second wave of the coronavirus disease 19 (COVID-19) pandemic, Malaysia reported several COVID-19 clusters related to healthcare workers. Thus, addressing and understanding the risk of exposure in healthcare workers is important to prevent future infection and reduce secondary COVID-19 transmission within the healthcare settings. In this study, we aim to assess exposure and prevention practices against COVID-19 among healthcare workers at the Hospital Canselor Tuanku Muhriz, a university teaching hospital based in Kuala Lumpur, Malaysia.
METHODOLOGY: A total of 571 healthcare workers at COVID-19 and non-COVID-19 wards as well as the emergency department and laboratory staff at COVID-19 testing labs were recruited. The presence of novel human coronavirus (SARS-CoV-2) and IgM/IgG antibodies were confirmed in all healthcare workers. The healthcare workers responded to an online Google Forms questionnaire that evaluates demographic information and comorbidities, exposure and adherence to infection prevention and control measures against COVID-19. Descriptive analysis was performed using Statistical Package for the Social Sciences 24.0.
RESULTS: Three healthcare workers (0.5%) tested positive for SARS-CoV-2, while the remaining 568 (99.5%) were negative. All were negative for IgM and IgG antibodies during recruitment (day 1) and follow-up (day 15). More than 90% of the healthcare workers followed infection prevention and control practices recommendations regardless of whether they have been exposed to occupational risk for COVID-19.
CONCLUSIONS: The healthcare workers' high level of adherence to infection prevention practices at this hospital helped reduce and minimize their occupational exposure to COVID-19.
Fulltext SARS-CoV-2 genomic surveillance in Malaysia: displacement of B.1.617.2 with AY lineages as the dominant Delta variants and the introduction of Omicron during the fourth epidemic wave

Azami NAM, Perera D, Thayan R, AbuBakar S, Sam IC, Salleh MZ, et al.

Int J Infect Dis, 2022 Dec;125:216-226.
PMID: 36336246 DOI: 10.1016/j.ijid.2022.10.044

OBJECTIVES: This study reported SARS-CoV-2 whole genome sequencing results from June 2021 to January 2022 from seven genome sequencing centers in Malaysia as part of the national surveillance program.
METHODS: COVID-19 samples that tested positive by reverse transcription polymerase chain reaction and with cycle threshold values <30 were obtained throughout Malaysia. Sequencing of SARS-CoV-2 complete genomes was performed using Illumina, Oxford Nanopore, or Ion Torrent platforms. A total of 6163 SARS-CoV-2 complete genome sequences were generated over the surveillance period. All sequences were submitted to the Global Initiative on Sharing All Influenza Data database.
RESULTS: From June 2021 to January 2022, Malaysia experienced the fourth wave of COVID-19 dominated by the Delta variant of concern, including the original B.1.617.2 lineage and descendant AY lineages. The B.1.617.2 lineage was identified as the early dominant circulating strain throughout the country but over time, was displaced by AY.59 and AY.79 lineages in Peninsular (west) Malaysia, and the AY.23 lineage in east Malaysia. In December 2021, pilgrims returning from Saudi Arabia facilitated the introduction and spread of the BA.1 lineage (Omicron variant of concern) in the country.
CONCLUSION: The changing trends of circulating SARS-CoV-2 lineages were identified, with differences observed between west and east Malaysia. This initiative highlighted the importance of leveraging research expertise in the country to facilitate pandemic response and preparedness.