Medicinal benefits, biological, and nanoencapsulation functions of riboflavin with its toxicity profile: A narrative review.

Riboflavin is a precursor of the essential coenzymes flavin mononucleotide and flavin adenine dinucleotide. Both possess antioxidant properties and are involved in oxidation-reduction reactions, which have a significant impact on energy metabolism. Also, the coenzymes participate in metabolism of pyridoxine, niacin, folate, and iron. Humans must obtain riboflavin through their daily diet because of the lack of programmed enzymatic machineries for de novo riboflavin synthesis. Because of its physiological nature and fast elimination from the human body when in excess, riboflavin consumed is unlikely to induce any negative effects or develop toxicity in humans. The use of riboflavin in pharmaceutical and clinical contexts has been previously explored, including for preventing and treating oxidative stress and reperfusion oxidative damage, creating synergistic compounds to mitigate colorectal cancer, modulating blood pressure, improving diabetes mellitus comorbidities, as well as neuroprotective agents and potent photosensitizer in killing bloodborne pathogens. Thus, the goal of this review is to provide a comprehensive understanding of riboflavin's biological applications in medicine, key considerations of riboflavin safety and toxicity, and a brief overview on the nanoencapsulation of riboflavin for various functions including the treatment of a range of diseases, photodynamic therapy, and cellular imaging.

Opportunities and challenges of 5G network technology toward precision medicine.

Moving away from traditional "one-size-fits-all" treatment to precision-based medicine has tremendously improved disease prognosis, accuracy of diagnosis, disease progression prediction, and targeted-treatment. The current cutting-edge of 5G network technology is enabling a growing trend in precision medicine to extend its utility and value to the smart healthcare system. The 5G network technology will bring together big data, artificial intelligence, and machine learning to provide essential levels of connectivity to enable a new health ecosystem toward precision medicine. In the 5G-enabled health ecosystem, its applications involve predictive and preventative measurements which enable advances in patient personalization. This review aims to discuss the opportunities, challenges, and prospects posed to 5G network technology in moving forward to deliver personalized treatments and patient-centric care via a precision medicine approach.

Genomic Surveillance of SARS-CoV-2 in Malaysia during the Era of Endemic COVID-19.

On 5 May 2023, WHO declared the end of coronavirus disease 2019 (COVID-19) as a public health emergency of international concern. However, the risk of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants causing rapid and high surges in cases and deaths remained. In Malaysia, five COVID-19 waves during the pandemic phase were well characterized, but similar studies focusing on the endemic phase were lacking. Hence, we retrieved 14,965 SARS-CoV-2 genomic sequences from the GISAID EpiCoV database for clade, lineage, and phylogenetic analysis in order to provide an insight into the population dynamics of SARS-CoV-2 that circulated in Malaysia from June 2022 to April 2023. The dominance of the Omicron variants was observed, and two new waves of infections driven by BA.5.2 and XBB.1, respectively, were detected. Data as of April 2023 also pointed to a possible eighth wave driven by XBB.1.9. Although new variants associated with higher transmissibility were behind the multiple surges, these subsequent waves had lower intensities as compared to the fourth and fifth waves. The on-going circulation and evolution of SARS-CoV-2 mean that COVID-19 still poses a serious threat, necessitating active genomic surveillance for early warning of potential new variants of concern.

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.

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.

Riboflavin as a promising antimicrobial agent? A multi-perspective review.

Riboflavin, or more commonly known as vitamin B2, forms part of the component of vitamin B complex. Riboflavin consisting of two important cofactors, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are involved in multiple oxidative-reduction processes and energy metabolism. Besides maintaining human health, different sources reported that riboflavin can inhibit or inactivate the growth of different pathogens including bacteria, viruses, fungi and parasites, highlighting the possible role of riboflavin as an antimicrobial agent. Moreover, riboflavin and flavins could produce reactive oxygen species (ROS) when exposed to light, inducing oxidative damage in cells and tissues, and thus are excellent natural photosensitizers. Several studies have illustrated the therapeutic efficacy of photoactivated riboflavin against nosocomial infections and multidrug resistant bacterial infections as well as microbial associated biofilm infections, revealing the potential role of riboflavin as a promising antimicrobial candidate, which could serve as one of the alternatives in fighting the global crisis of the emergence of antimicrobial resistance seen in different pathogenic microbes. Riboflavin could also be involved in modulating host immune responses, which might increase the pathogen clearance from host cells and increase host defense against microbial infections. Thus, the dual effects of riboflavin on both pathogens and host immunity, reflected by its potent bactericidal effect and alleviation of inflammation in host cells further imply that riboflavin could be a potential candidate for therapeutic intervention in resolving microbial infections. Hence, this review aimed to provide some insights on the promising role of riboflavin as an antimicrobial candidate and also a host immune-modulator from a multi-perspective view as well as to discuss the application and challenges on using riboflavin in photodynamic therapy against various pathogens and microbial biofilm-associated infections.

Draft Genome Sequences of Local Clinical Isolates of Drug-Resistant and Drug-Sensitive Mycobacterium tuberculosis.

In the battle against tuberculosis (TB), plasticity of the Mycobacterium tuberculosis genome is believed to contribute to the pathogen's virulence and drug resistance. Here, we report 10 draft genome sequences of clinical M. tuberculosis isolated in Malaysia as the basis for understanding the genome plasticity of the M. tuberculosis isolates.

Stress, Anxiety and Depression among a Cohort of Health Sciences Undergraduate Students: The Prevalence and Risk Factors.

Stress, anxiety, and depression (SAD) have a negative impact on the learning and academic performance of university students. Hence, this study aimed to determine the prevalence, as well as the risk factors associated with SAD among a cohort of students pursuing undergraduate degree courses in health sciences. This is part of the strategy in building a healthy nation. A questionnaire containing socio-demographic factors and the short version of Depression, Anxiety, and Stress Scale-21 (DASS-21) was used to assess the likelihood of psychological distress. Logistic regression analysis was conducted to determine the risk factors of SAD. In total, 449 students completed the questionnaire (93.9% response rate). Of these, 65% had stress, 85.1% had anxiety and 51.4% had depression. Most cases of stress (74.6%) and depression (66.2%) were of normal-to-mild level, while 74.6% of them showed moderate-to-extremely severe anxiety. There was a statistically significant association between stress score and the year of study. In the regression analysis, poor sleep quality and fatigue were risk factors of anxiety and depression, whereas low-grade fever and frequent headaches were risk factors for stress and anxiety. Stress, anxiety, and depression scores were significantly higher among students studying medical imaging. A substantial proportion of health science students are suffering from SAD. This study recommends screening and close monitoring of the above-mentioned predictors and the formulation of comprehensive intervention strategies for students with SAD.

Significant Decreased Expressions of CaN, VEGF, SLC39A6 and SFRP1 in MDA-MB-231 Xenograft Breast Tumor Mice Treated with Moringa oleifera Leaves and Seed Residue (MOLSr) Extracts.

Moringa oleifera is a miracle plant with many nutritional and medicinal properties. Chemopreventive values of the combined mixture of moringa leaves and seed residue (MOLSr) at different ratios (M1S9, M1S1 and M9S1) were investigated. MOLSr extracts were subjected to phytochemical screening, antioxidant assays, metabolite profiling and cytotoxic activity on the primary mammary epithelial cells (PMECs), non-malignant Chang's liver cells and various human cancer cell lines (including breast, cervical, colon and liver cancer cell lines). The MOLSr ratio with the most potent cytotoxic activity was used in xenograft mice injected with MDA-MB-231 cells for in vivo tumorigenicity study as well as further protein and gene expression studies. M1S9, specifically composed of saponin and amino acid, retained the lowest antioxidant activity but the highest glucosinolate content as compared to other ratios. Cell viability decreased significantly in MCF-7 breast cancer cells and PMECs after treatment with M1S9. Solid tumor from MDA-MB-231 xenograft mice was inhibited by up to 64.5% at third week after treatment with high-dose M1S9. High-dose M1S9 significantly decreased the expression of calcineurin (CaN) and vascular endothelial cell growth factor (VEGF) proteins as well as the secreted frizzled-related protein 1 (SFRP1) and solute carrier family 39 member 6 (SLC39A6) genes. This study provides new scientific evidence for the chemoprevention potential of MOLSr extracts in a breast cancer model; however, the precise mechanism warrants further investigation.

The methanolic extract of Garcinia atroviridis (MeGa) reduces body weight and food intake, and improves lipid profiles by altering the lipid metabolism: a rat model.

Garcinia species are widely used for their slimming effects via increased fat burning and suppression of satiety. However, scientific evidence for the biological effects of Garcinia atroviridis (GA) is lacking. We investigated the phytochemical composition, safety profiles, and antioxidant and antiobesity effects of methanolic extracts of Garcinia atroviridis (MeGa) in obese female rats. Repeated dose toxicity studies were conducted according to the OECD guidelines. Upon sacrifice, haematological, biochemical, lipid profile, and serum-based metabolomics analyses were performed to evaluate metabolic expression changes and their related pathways. MeGa contains several phytochemical groups and GA fruit acids. MeGa was found to be nontoxic in both male and female rats with an oral lethal dose (LD50) of 2000 mg/kg. After 9 weeks of treatment, MeGa-treated obese rats had lower weight gain and better lipid profiles (cholesterol and triglyceride), which correlated with the altered metabolic pathways involved in the metabolism of lipid (glycerophospholipid) and biosynthesis of unsaturated fatty acid. In addition, MeGa caused differential metabolism pathways of arachidonic acid and tryptophan that affect the inflammatory response and suppression of appetite. We concluded that MeGa is safe, and its slimming effects are due to the differential metabolism of lipids.

Diversified lineages and drug-resistance profiles of clinical isolates of Mycobacterium tuberculosis complex in Malaysia.

Background: Tuberculosis (TB) is still a major health problem in Malaysia with thousands of cases reported yearly. This is further burdened with the emergence of multidrug-resistant TB (MDR-TB). Whole-genome sequencing (WGS) provides high-resolution molecular epidemiological data for the accurate determination of Mycobacterium tuberculosis complex (MTBC) lineages and prediction of the drug-resistance patterns. This study aimed to investigate the diversity of MTBC in Malaysia in terms of lineage and drug-resistance patterns of the clinical MTBC isolates using WGS approach. Methods: The genomes of 24 MTBC isolated from sputum and pus samples were sequenced. The phenotypic drug susceptibility testing (DST) of the isolates was determined for ten anti-TB drugs. Bioinformatic analysis comprising genome assembly and annotation and single-nucleotide polymorphism (SNP) analysis in genes associated with resistance to the ten anti-TB drugs were done on each sequenced genome. Results: The draft assemblies covered an average of 97% of the expected genome size. Eleven isolates were aligned to the Indo-Oceanic lineage, eight were East-Asian lineage, three were East African-Indian lineage, and one was of Euro-American and Bovis lineages, respectively. Twelve of the 24 MTBC isolates were phenotypically MDR M. tuberculosis: one is polyresistance and another one is monoresistance. Twenty-six SNPs across nine genes associated with resistance toward ten anti-TB drugs were detected where some of the mutations were found in isolates that were previously reported as pan-susceptible using DST. A haplotype consisting of 65 variants was also found among the MTBC isolates with drug-resistance traits. Conclusions: This study is the first effort done in Malaysia to utilize 24 genomes of the local clinical MTBC isolates. The high-resolution molecular epidemiological data obtained provide valuable insights into the mechanistic and epidemiological qualities of TB within the vicinity of Southeast Asia.

Potential Point-of-Care Microfluidic Devices to Diagnose Iron Deficiency Anemia.

Over the past 20 years, rapid technological advancement in the field of microfluidics has produced a wide array of microfluidic point-of-care (POC) diagnostic devices for the healthcare industry. However, potential microfluidic applications in the field of nutrition, specifically to diagnose iron deficiency anemia (IDA) detection, remain scarce. Iron deficiency anemia is the most common form of anemia, which affects billions of people globally, especially the elderly, women, and children. This review comprehensively analyzes the current diagnosis technologies that address anemia-related IDA-POC microfluidic devices in the future. This review briefly highlights various microfluidics devices that have the potential to detect IDA and discusses some commercially available devices for blood plasma separation mechanisms. Reagent deposition and integration into microfluidic devices are also explored. Finally, we discuss the challenges of insights into potential portable microfluidic systems, especially for remote IDA detection.

HbF in HbE/ß-thalassemia: A clinical and laboratory correlation.

INTRODUCTION: Fetal hemoglobin (HbF) is the predominant hemoglobin in red cells during fetal life. Just after birth, the level of HbF decreases gradually to <1%, and is replaced mainly by adult hemoglobin (HbA) (∼ 97%). However, higher HbF levels could be associated with HbE/ß-thalassemia, a complex thalassemia intermedia with a diverse clinical severity ranging from mild-to-severe anemia. This study investigates the correlation of HbF level with the clinical and laboratory data of HbE/ß-thalassemia individuals. METHODS: Peripheral blood samples from 30 HbE/ß-thalassemia subjects were subjected to a full blood count, genomic as well as quantitative real-time polymerase chain reaction gene expression studies. Statistical analyses were performed using SPSS 17.0. RESULTS: HbF levels were influenced by age, mean cell volume (MCV), mean cell hemoglobin (MCH), HbA, ß-globin, and α/ß-globin expressions. DISCUSSION: HbF production is affected by the α/ß-globin chain imbalance due to the lack of ß-globin gene expression as well as inversely correlates to the amount of functional hemoglobin available in the cells.

Hematopoietic cell differentiation from embryonic and induced pluripotent stem cells.

Pluripotent stem cells, both embryonic stem cells and induced pluripotent stem cells, are undifferentiated cells that can self-renew and potentially differentiate into all hematopoietic lineages, such as hematopoietic stem cells (HSCs), hematopoietic progenitor cells and mature hematopoietic cells in the presence of a suitable culture system. Establishment of pluripotent stem cells provides a comprehensive model to study early hematopoietic development and has emerged as a powerful research tool to explore regenerative medicine. Nowadays, HSC transplantation and hematopoietic cell transfusion have successfully cured some patients, especially in malignant hematological diseases. Owing to a shortage of donors and a limited number of the cells, hematopoietic cell induction from pluripotent stem cells has been regarded as an alternative source of HSCs and mature hematopoietic cells for intended therapeutic purposes. Pluripotent stem cells are therefore extensively utilized to facilitate better understanding in hematopoietic development by recapitulating embryonic development in vivo, in which efficient strategies can be easily designed and deployed for the generation of hematopoietic lineages in vitro. We hereby review the current progress of hematopoietic cell induction from embryonic stem/induced pluripotent stem cells.

α-Haemoglobin stabilising protein expression is influenced by mean cell haemoglobin and HbF levels in HbE/ß-thalassaemia individuals.

The alpha haemoglobin stabilising protein (AHSP) acts as a molecular chaperone for α-globin by stabilising nascent α-globin before transferring it to waiting free ß-globin chains. Binding of AHSP to α-globin renders α-globin chemically inert whereby preventing it from precipitating and forming reactive oxygen species byproducts. The AHSP has been actively studied in the recent years, particularly in its relation to ß-thalassaemia. Studies have shown that AHSP is a modifier in ß-thalassaemia mice models. However, this relationship is less established in humans. Studies by some groups showed no correlation between the AHSP haplotypes and the severity of ß-thalassaemia, whereas others have shown that certain AHSP haplotype could modify the phenotype of ß-thalassaemia intermedia patients. We investigated the expression of AHSP in relation to selected demographic data, full blood count, HPLC results, HbE/ß-thalassaemia genotype, Xmn-1 Gγ polymorphism, α-globin, ß-globin and γ-globin expression. We found that AHSP expression was significantly correlated to mean cell haemoglobin level, HbF %, α-globin, ß-globin and excess α-globin expression. We concluded that AHSP could be a secondary compensatory mechanism in red blood cells to counterbalance the excess α-globin chains in HbE/ß-thalassaemia individuals.