Bioactive compounds derived from marine source: a potential immunotherapy treatment.

Immunotherapy using checkpoint inhibitors blocks the checkpoint proteins (programmed cell death receptor-1; PD-1) from binding with their corresponding ligands (programmed cell death receptor ligand-1; PD-L1) to regulate cell signaling pathways. The marine environment holds a huge source of small molecules that are understudied which can be developed as an inhibitor. Hence, this study investigated the inhibitory effect of 19 algae-derived small molecules against PD-L1 by using molecular docking, absorption, distribution, metabolism, and elimination (ADME) properties and molecular dynamics simulations (MDS). The molecular docking revealed that the binding energy of the six best compounds ranges from -11.1 to -9.1 kcal/mol. Fucoxanthinol, in particular, has the strongest binding energy at -11.1 kcal/mol with three hydrogen bonds (ASN:63A, GLN:66A, and ASP:122A). Meanwhile, the MDS demonstrated that the ligands were strongly bound to the protein, indicating the stability of the complexes. In summary, the identified compounds are potential PD-L1 inhibitors in immunotherapy.Communicated by Ramaswamy H. Sarma.

A review of stingless bees' bioactivity in different parts of the world.

Stingless bees, also known as meliponines, live in beehives. However, reports on the distribution of stingless bees are scattered, resulting in a lack of precision. Honey and propolis are the main components that can be harvested from their beehive, with a great commercial value of up to 610 million USD. Despite the enormous potential profits, discrepancies in their bioactivities have been observed worldwide, leading to a lack of confidence. Therefore, this review provided oversight on the potential of stingless bee products and highlighted the differences between stingless bees in Asia, Australia, Africa, and America. The bioactivity of stingless bee products is diverse and exhibits great potential as an antimicrobial agent or in various diseases such as diabetes, cardiovascular disease, cancers, and oral problems.

Identification of Natural Lead Compounds against Hemagglutinin-Esterase Surface Glycoprotein in Human Coronaviruses Investigated via MD Simulation, Principal Component Analysis, Cross-Correlation, H-Bond Plot and MMGBSA.

The pandemic outbreak of human coronavirus is a global health concern that affects people of all ages and genders, but there is currently still no effective, approved and potential drug against human coronavirus, as many other coronavirus vaccines have serious side effects while the development of small antiviral inhibitors has gained tremendous attention. For this research, HE was used as a therapeutic target, as the spike protein displays a high binding affinity for both host ACE2 and viral HE glycoprotein. Molecular docking, pharmacophore modelling and virtual screening of 38,000 natural compounds were employed to find out the best natural inhibitor against human coronaviruses with more efficiency and fewer side effects and further evaluated via MD simulation, PCA, DCCR and MMGBSA. The lead compound 'Calceolarioside B' was identified on the basis of pharmacophoric features which depict favorable binding (ΔGbind -37.6799 kcal/mol) with the HE(5N11) receptor that describes positive correlation movements in active site residues with better stability, a robust H-bond network, compactness and reliable ADMET properties. The Fraxinus sieboldiana Blume plant containing the Calceolarioside B compound could be used as a potential inhibitor that shows a higher efficacy and potency with fewer side effects. This research work will aid investigators in the testing and identification of chemicals that are effective and useful against human coronavirus.

The prevalence of hospital-acquired infections in Southeast Asia (1990-2022).

INTRODUCTION: Hospital-acquired infections (HAIs) have continually affected the quality of hospital care. Despite medical interventions by healthcare personnel and improved healthcare facilities, the rates of morbidity and mortality due to HAIs is increasing. However, a systematic review of HAIs is lacking. Therefore, this systematic review aims to determine the prevalence rate, types, as well as causes of HAIs in Southeast Asian countries. METHODOLOGY: A systematic literature search was conducted on PubMed, Cochrane library, World Health Organization database-Index Medicus for South-East Asia Region (WHO-IMSEAR), and Google Scholar databases. The search period was from 1st January 1990 until 12th May 2022. The prevalence of HAIs and subgroups were calculated using MetaXL software. RESULTS: The database search retrieved 3879 non-duplicate articles. After applying exclusion criteria, 31 articles with a total number of 47666 subjects were included and a total of 7658 cases of HAIs were recorded. The overall prevalence of HAIs in Southeast Asia was 21.6 % (95% CI: 15.5 - 29.1%) with heterogeneity statistics of I2 = 100%. Indonesia had the highest prevalence rate of 30.4% whereas Singapore had the lowest prevalence rate at 8.4%. CONCLUSIONS: This study revealed that the overall prevalence of HAIs was relatively high and the prevalence rate of each country was associated with socioeconomic status. Measures should be taken to examine and control the rates of HAIs in countries with high HAI prevalence.

The Role of Machine Learning and Deep Learning Approaches for the Detection of Skin Cancer.

Machine learning (ML) can enhance a dermatologist's work, from diagnosis to customized care. The development of ML algorithms in dermatology has been supported lately regarding links to digital data processing (e.g., electronic medical records, Image Archives, omics), quicker computing and cheaper data storage. This article describes the fundamentals of ML-based implementations, as well as future limits and concerns for the production of skin cancer detection and classification systems. We also explored five fields of dermatology using deep learning applications: (1) the classification of diseases by clinical photos, (2) der moto pathology visual classification of cancer, and (3) the measurement of skin diseases by smartphone applications and personal tracking systems. This analysis aims to provide dermatologists with a guide that helps demystify the basics of ML and its different applications to identify their possible challenges correctly. This paper surveyed studies on skin cancer detection using deep learning to assess the features and advantages of other techniques. Moreover, this paper also defined the basic requirements for creating a skin cancer detection application, which revolves around two main issues: the full segmentation image and the tracking of the lesion on the skin using deep learning. Most of the techniques found in this survey address these two problems. Some of the methods also categorize the type of cancer too.

Antimicrobial activities and phytochemical properties of Blumea balsamifera against pathogenic microorganisms.

Medicinal plants have been widely used in healthcare based on traditional knowledge. We investigated the antimicrobial activities and phytochemical contents of a plant known as Blumea balsamifera (B. balsamifera), which Sabah native people have used for health benefits. Methanolic extracts and fractions of the leaves of B. balsamifera were tested for their phytochemical contents and their antimicrobial activities against four Gram-negative and five Gram-positive strains of bacteria. The extracts of B. balsamifera showed antimicrobial activities against three Gram-positive, and one Gram-negative bacteria, with the zone of inhibition ranging from 7.8 mm±0.41 to 10.5 mm±0.71. Fraction CE.F7 exerted the broadest antimicrobial activity towards four Gram-positive or Gram-negative bacteria. The phytochemical constituents identified in the extracts were alkaloid, flavonoid, steroid, and cardiac glycosides. The plant extract demonstrated antimicrobial activities and contained multiple phytochemical constituents. Further investigations into potential antimicrobial agents containing promising fractions would validate the medicinal properties of B. balsamifera used in Sabah.

Risk Association, Linkage Disequilibrium, and Haplotype Analyses of ß-Like Globin Gene Polymorphisms with Malaria Risk in the Sabah Population of Malaysian Borneo.

Single nucleotide polymorphisms (SNPs) in the ß-like globin gene of the human hosts to the risk of malaria are unclear. Therefore, this study investigates these associations in the Sabah population, with a high incidence of malaria cases. In brief, DNA was extracted from 188 post-diagnostic blood samples infected with Plasmodium parasites and 170 healthy controls without a history of malaria. Genotyping of the ß-like globin C-158T, G79A, C16G, and C-551T SNPs was performed using a polymerase chain reaction-restriction fragment length polymorphism approach. Risk association, linkage disequilibrium (LD), and haplotype analyses of these SNPs were assessed. This study found that the variant allele in the C-158T and C16G SNPs were protective against malaria infections by 0.5-fold, while the variant allele in the G79A SNP had a 6-fold increased risk of malaria infection. No SNP combination was in perfect LD, but several haplotypes (CGCC, CGCT, and CGGC) were identified to link with different correlation levels of malaria risk in the population. In conclusion, the C-158T, G79A, and C16G SNPs in the ß-like globin gene are associated with the risk of malaria. The haplotypes (CGCC, CGCT, and CGGC) identified in this study could serve as biomarkers to estimate malaria risk in the population. This study provides essential data for the design of malaria control and management strategies.

The Prevalence of Insulin Resistance in Malaysia and Indonesia: An Updated Systematic Review and Meta-Analysis.

Background and Objectives: Noncommunicable diseases such as diabetes are strongly associated with the insulin resistance (IR) status of an individual. However, the prevalence of insulin resistance in Southeast Asia is poorly reported. Hence, this study investigated the prevalence of IR in Southeast Asia from the year 2016 to 2021. Materials and Methods: This study was carried out according to PRISMA guidelines. The literature search was conducted utilizing the PubMed and SCOPUS databases from the year 2016 to 2021 using the keywords '(insulin AND resistance) OR (insulin AND sensitivity) OR (prevalence OR incidence) AND (Malaysia OR Thailand OR Singapore OR Brunei OR Cambodia OR Indonesia OR Laos OR Myanmar OR Philippines OR Timor leste OR Vietnam)'. Funnel plot and publication bias were assessed using Egger's tests. Data were expressed as the prevalence rate. Results: A total of 12 studies with 2198 subjects were considered in the meta-analysis. Significant heterogeneity (I2 > 94% and p-value < 0.001) was observed in the meta-analysis. The overall prevalence of IR in Southeast Asia was 44.3%, with Malaysia having the highest prevalence rate at 50.4%, followed by Indonesia at 44.2%. Bias was detected in the meta-analysis. It may be that reports published before the year 2016 met the study selection criteria, but were excluded from the meta-analysis. Conclusions: The results from the meta-analysis indicate that the prevalence of IR in Southeast Asia is very high. This provided insights for healthcare policy makers and public health officials in designing IR screening programs.

The Biosynthesis and Medicinal Properties of Taraxerol.

Taraxerol is a pentacyclic triterpenoid that is actively produced by some higher plants as part of a defense mechanism. The biosynthesis of taraxerol in plants occurs through the mevalonate pathway in the cytosol, in which dimethylallyl diphosphate (DMAPP) and isopentyl pyrophosphate (IPP) are first produced, followed by squalene. Squalene is the primary precursor for the synthesis of triterpenoids, including taraxerol, ß-amyrin, and lupeol, which are catalyzed by taraxerol synthase. Taraxerol has been extensively investigated for its medicinal and pharmacological properties, and various biotechnological approaches have been established to produce this compound using in vitro techniques. This review provides an in-depth summary of the hypothesized taraxerol biosynthetic pathway, the medicinal properties of taraxerol, and recent developments on tissue culture for the in vitro production of taraxerol.

A Review: Underutilized Plant of Sabah and its Potential Value.

Underutilized plants are referred to a plant species whose potential is not fully utilized yet and they are usually found abundantly in certain local areas but are globally rare. Sabah is known for high biodiversity and contains many underutilized plants. To our knowledge, this is the first review to provide overview information of the medicinal value and pharmacological properties of underutilized plants in Sabah. Extract and metabolites in different parts of several underutilized plants contain multiple beneficial bioactive compounds and the exploitation of these compounds was supported by additional data that plays various biological activities, including anti-atherosclerotic, anti-cancer antihypercholesterolemic and anti-ulcerogenic. A handful of pharmacological studies on these underutilized plants have conclusively outlined the mode of action in treatment of several diseases and in other health aspects. This paper limits its scope to review and highlight the potential of using underutilized plants in Sabah only which could serve as reliable resource for health product development in pharmaceutical and nutraceutical through continuous discovering of more active and sustainable resources as well as ingredients for food and medicine.

Review of Nephelium lappaceum and Nephelium ramboutan-ake: A High Potential Supplement.

Nephelium lappaceum (N. lappaceum) and Nephelium ramboutan-ake (N. ramboutan-ake) are tropical fruits that gain popularity worldwide due to their tastiness. Currently, their potential to be used as pharmaceutical agents is underestimated. Chronic diseases such as cancer, diabetes and aging have high incidence rates in the modern world. Furthermore, pharmaceutical agents targeting pathogenic microorganisms have been hampered by the growing of antimicrobial resistance threats. The idea of food therapy leads to extensive nutraceuticals research on the potential of exotic fruits such as N. lappaceum and N. ramboutan-ake to act as supplements. Phytochemicals such as phenolic compounds that present in the fruit act as potent antioxidants that contribute to the protective effects against diseases induced by oxidative stress. Fruit residuals such as the peel and seeds hold greater nutraceutical potential than the edible part. This review highlights the antioxidant and biological activities (anti-neoplastic, anti-microbial, hypoglycemic actions and anti-aging), and chemical contents of different parts of N. lappaceum and N. ramboutan-ake. These fruits contain a diverse and important chemical profile that can alleviate or cure diseases.

Draft genome sequence data of Streptomyces sp. FH025.

The genome data of Streptomyces sp. FH025 comprised of 8,381,474 bp with a high GC content of 72.51%. The genome contains 7035 coding sequences spanning 1261 contigs. Streptomyces sp. FH025 contains 57 secondary metabolite gene clusters including polyketide synthase, nonribosomal polyketide synthase and other biosynthetic pathways such as amglyccycl, butyrolactone, terpenes, siderophores, lanthipeptide-class-iv, and ladderane. 16S rRNA analysis of Streptomyces sp. FH025 is similar to the Streptomyces genus. This whole genome project has been deposited at NCBI under the accession JAFLNG000000000.

Prevalence of Alpha(α)-Thalassemia in Southeast Asia (2010-2020): A Meta-Analysis Involving 83,674 Subjects.

Alpha(α)-thalassemia is a blood disorder caused by many types of inheritable α-globin gene mutations which causes no-to-severe clinical symptoms, such as Hb Bart's hydrops fetalis that leads to early foetal death. Therefore, the aim of this meta-analysis was to provide an update from year 2010 to 2020 on the prevalence of α-thalassemia in Southeast Asia. A systematic literature search was performed using PubMed and SCOPUS databases for related studies published from 2010 to 2020, based on specified inclusion and exclusion criteria. Heterogeneity of included studies was examined with the I2 index and Q-test. Funnel plots and Egger's tests were performed in order to determine publication bias in this meta-analysis. Twenty-nine studies with 83,674 subjects were included and pooled prevalence rates in this meta-analysis were calculated using random effect models based on high observed heterogeneity (I2 > 99.5, p-value < 0.1). Overall, the prevalence of α-thalassemia is 22.6%. The highest α-thalassemia prevalence was observed in Vietnam (51.5%) followed by Cambodia (39.5%), Laos (26.8%), Thailand (20.1%), and Malaysia (17.3%). No publication bias was detected. Conclusions: This meta-analysis suggested that a high prevalence of α-thalassemia occurred in selected Southeast Asia countries. This meta-analysis data are useful for designing thalassemia screening programs and improve the disease management.

Variant Alleles in XRCC1 Arg194Trp and Arg399Gln Polymorphisms Increase Risk of Gastrointestinal Cancer in Sabah, North Borneo.

BACKGROUND: The XRCC1 protein facilitates various DNA repair pathways; single-nucleotide polymorphisms (SNPs) in this gene are associated with a risk of gastrointestinal cancer (GIC) with inconsistent results, but no data have been previously reported for the Sabah, North Borneo, population. We accordingly investigated the XRCC1 Arg194Trp and Arg399Gln SNPs in terms of GIC risk in Sabah. MATERIALS AND METHODS: We performed genotyping for both SNPs for 250 GIC patients and 572 healthy volunteers using a polymerase chain reaction- restriction fragment length polymorphism approach. We validated heterozygosity and homozygosity for both SNPs using direct sequencing. RESULTS: The presence of a variant 194Trp allele in the Arg194Trp SNP was significantly associated with a higher risk of GIC, especially with gastric and colorectal cancers. We additionally found that the variant 399Gln allele in Arg399Gln SNP was associated with a greater risk of developing gastric cancer. Our combined analysis revealed that inheritance of variant alleles in both SNPs increased the GIC risk in Sabah population. Based on our etiological analysis, we found that subjects ≥50 years and males who carrying the variant 194Trp allele, and Bajau subjects carrying the 399Gln allele had a significantly increased risk of GIC. CONCLUSIONS: Our findings suggest that inheritance of variant alleles in XRCC1 Arg194Trp and Arg399Gln SNPs may act as biomarkers for the early detection of GIC, especially for gastric and colorectal cancers in the Sabah population.

Association of CYP2E1, STK15 and XRCC1 Polymorphisms with Risk of Breast Cancer in Malaysian Women.

BACKGROUND: Breast cancer is the most common type of cancer affecting Malaysian women. Recent statistics revealed that the cumulative probability of breast cancer and related deaths in Malaysia is higher than in most of the countries of Southeast Asia. Single nucleotide polymorphisms (SNPs) in CYP2E1 (rs6413432 and rs3813867), STK15 (rs2273535 and rs1047972) and XRCC1 (rs1799782 and rs25487) have been associated with breast cancer risk in a meta-analysis but any link in Southeast Asia, including Malaysia, remained to be determined. Hence, we investigated the relationship between these SNPs and breast cancer risk among Malaysian women in the present case-control study. MATERIALS AND METHODS: Genomic DNA was isolated from peripheral blood of 71 breast cancer patients and 260 healthy controls and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Our study showed that the c1/c2 genotype or subjects with at least one c2 allele in CYP2E1 rs3813867 SNP had significantly increased almost 1.8-fold higher breast cancer risk in Malaysian women overall. In addition, the variant Phe allele in STK15 rs2273535 SNP appeared to protect against breast cancer in Malaysian Chinese. No significance association was found between XRCC1 SNPs and breast cancer risk in the population. CONCLUSIONS: This study provides additional knowledge on CYP2E1, STK15 and XRCC1 SNP impact of risk of breast cancer, particularly in the Malaysian population. From our findings, we also recommend Malaysian women to perform breast cancer screening before 50 years of age.

Significant genotype difference in the CYP2E1 PstI polymorphism of indigenous groups in Sabah, Malaysia with Asian and non-Asian populations.

CYP2E1 PstI polymorphism G-1259C (rs3813867) genotype distributions vary significantly among different populations and are associated with both diseases, like cancer, and adverse drug effects. To date, there have been limited genotype distributions and allele frequencies of this polymorphism reported in the three major indigenous ethnic groups (KadazanDusun, Bajau, and Rungus) in Sabah, also known as North Borneo. The aim of this study was to investigate the genotype distributions and allele frequencies of the CYP2E1 PstI polymorphism G-1259C in these three major indigenous peoples in Sabah. A total of 640 healthy individuals from the three dominant indigenous groups were recruited for this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) at G-1259C polymorphic site of CYP2E1 gene was performed using the Pst I restriction enzyme. Fragments were analyzed using agarose gel electrophoresis and confirmed by direct sequencing. Overall, the allele frequencies were 90.3% for c1 allele and 9.7% for c2 allele. The genotype frequencies for c1/c1, c1/c2 and c2/c2 were observed as 80.9%, 18.8%, and 0.3%, respectively. A highly statistical significant difference (p<0.001) was observed in the genotype distributions between indigenous groups in Sabah with all Asian and non-Asian populations. However, among these three indigenous groups, there was no statistical significant difference (p>0.001) in their genotype distributions. The three major indigenous ethnic groups in Sabah show unique genotype distributions when compared with other populations. This finding indicates the importance of establishing the genotype distributions of CYP2E1 PstI polymorphism in the indigenous populations.