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A Q-marker screening strategy based on ADME studies and systems biology for Chinese herbal medicine, taking Qianghuo Shengshi decoction in treating rheumatoid arthritis as an example

Wang J, Tao C, Xu G, Ling J, Tong J, Goh BH, et al.

Mol Omics, 2023 Dec 04;19(10):769-786.
PMID: 37498608 DOI: 10.1039/d3mo00029j

Chinese herbal medicine (CHM) exhibits a broad spectrum of clinical applications and demonstrates favorable therapeutic efficacy. Nonetheless, elucidating the underlying mechanism of action (MOA) of CHM in disease treatment remains a formidable task due to its inherent characteristics of multi-level, multi-linked, and multi-dimensional non-linear synergistic actions. In recent years, the concept of a Quality marker (Q-marker) proposed by Liu et al. has significantly contributed to the monitoring and evaluation of CHM products, thereby fostering the advancement of CHM research. Within this study, a Q-marker screening strategy for CHM formulas has been introduced, particularly emphasising efficacy and biological activities, integrating absorption, distribution, metabolism, and excretion (ADME) studies, systems biology, and experimental verification. As an illustrative case, the Q-marker screening of Qianghuo Shengshi decoction (QHSSD) for treating rheumatoid arthritis (RA) has been conducted. Consequently, from a pool of 159 compounds within QHSSD, five Q-markers exhibiting significant in vitro anti-inflammatory effects have been identified. These Q-markers encompass notopterol, isoliquiritin, imperatorin, cimifugin, and glycyrrhizic acid. Furthermore, by employing an integrated analysis of network pharmacology and metabolomics, several instructive insights into pharmacological mechanisms have been gleaned. This includes the identification of key targets and pathways through which QHSSD exerts its crucial roles in the treatment of RA. Notably, the inhibitory effect of QHSSD on AKT1 and MAPK3 activation has been validated through western blot analysis, underscoring its potential to mitigate RA-related inflammatory responses. In summary, this research demonstrates the proposed strategy's feasibility and provides a practical reference model for the systematic investigation of CHM formulas.
A Systematic Review of the Burden of Multidrug-Resistant Healthcare-Associated Infections Among Intensive Care Unit Patients in Southeast Asia: The Rise of Multidrug-Resistant Acinetobacter baumannii

Teerawattanapong N, Panich P, Kulpokin D, Na Ranong S, Kongpakwattana K, Saksinanon A, et al.

Infect Control Hosp Epidemiol, 2018 05;39(5):525-533.
PMID: 29580299 DOI: 10.1017/ice.2018.58

OBJECTIVETo summarize the clinical burden (cumulative incidence, prevalence, case fatality rate and length of stay) and economic burden (healthcare cost) of healthcare-associated infections (HAIs) due to multidrug-resistant organisms (MDROs) among patients in intensive care units (ICUs) in Southeast Asia.DESIGNSystematic review.METHODSWe conducted a comprehensive literature search in PubMed, EMBASE, CINAHL, EconLit, and the Cochrane Library databases from their inception through September 30, 2016. Clinical and economic burdens and study quality were assessed for each included study.RESULTSIn total, 41 studies met our inclusion criteria; together, 22,876 ICU patients from 7 Southeast Asian countries were included. The cumulative incidence of HAI caused by A. baumannii (AB) in Southeast Asia is substantially higher than has been reported in other regions, especially carbapenem-resistant AB (CRAB; 64.91%) and multidrug-resistant AB (MDR-AB) (58.51%). Evidence of a dose-response relationship between different degrees of drug resistance and excess mortality due to AB infections was observed. Adjusted odds ratios were 1.23 (95% confidence interval [CI], 0.51-3.00) for MDR-AB, 1.72 (95% CI, 0.77-3.80) for extensively drug-resistant AB (XDR-AB), and 1.82 (95% CI, 0.55-6.00) for pandrug-resistant AB (PDR-AB). There is, however, a paucity of published data on additional length of stay and costs attributable to MDROs.CONCLUSIONSThis review highlights the challenges in addressing MDROs in Southeast Asia, where HAIs caused by MDR gram-negative bacteria are abundant and have a strong impact on society. With our findings, we hope to draw the attention of clinicians and policy makers to the problem of antibiotic resistance and to issue a call for action in the management of MDROs.Infect Control Hosp Epidemiol 2018;39:525-533.
A critical review on the current state of antimicrobial glove technologies: advances, challenges and future prospects

How SW, Low DYS, Leo BF, Manickam S, Goh BH, Tang SY

J Hosp Infect, 2023 Jul;137:24-34.
PMID: 37044283 DOI: 10.1016/j.jhin.2023.03.022

Following recent viral outbreaks, there has been a significant increase in global demand for gloves. Biomedical research focuses increasingly on antimicrobial gloves to combat microbial transmission and hospital-acquired infections. Most antimicrobial gloves are manufactured using antimicrobial chemicals such as disinfectants, biocides and sanitizers. The design of antimicrobial gloves incorporates advanced technologies, including colloidal particles and nanomaterials, to enhance antimicrobial effectiveness. A category of antimicrobial gloves also explores and integrates natural antimicrobial benefits from animals, plants and micro-organisms. Many types of antimicrobial agents are available; however, it is crucial that the selected agent exhibits a broad spectrum of activity and is not susceptible to promoting resistance. Additionally, future research should focus on the potential effect of antimicrobial gloves on the skin microbiota and irritation during extended wear. Careful integration of the antimicrobial agent is essential to ensure optimal effectiveness without compromising the mechanical properties of the gloves.
Fulltext A review of ethnobotany, phytochemistry, antimicrobial pharmacology and toxicology of Nigella sativa L

Hossain MS, Sharfaraz A, Dutta A, Ahsan A, Masud MA, Ahmed IA, et al.

Biomed Pharmacother, 2021 Nov;143:112182.
PMID: 34649338 DOI: 10.1016/j.biopha.2021.112182

Nigella sativa L. is one of the most extensively used traditional medicinal plants. This widely studied plant is known to display diverse pharmacological actions, including antimicrobial activities. Current literature has documented its multi-target mode of antimicrobial actions. N. sativa or its bioactive compounds, such as thymoquinone, can induce oxidative stress, cell apoptosis (by producing reactive oxygen species), increase membrane permeability, inhibit efflux pumps, and impose strong biocidal actions. Despite its well-documented antimicrobial efficacy in the experimental model, to the best of our knowledge its antimicrobial mechanisms highlighting the multi-targeting properties have yet to be well discussed. Is N. sativa or thymoquinone a valuable lead compound for therapeutic development for infectious diseases? Are N. sativa's bioactive compounds potential antimicrobial agents or able to overcome antimicrobial resistance? This review aims to discuss the antimicrobial pharmacology of N. sativa-based treatments. Additionally, it provides a holistic overview of the ethnobotany, ethnopharmacology, and phytochemistry of N. sativa.
Fulltext A risk scoring system for predicting Streptococcus suis hearing loss: A 13-year retrospective cohort study

Rayanakorn A, Katip W, Goh BH, Oberdorfer P, Lee LH

PLoS One, 2020;15(2):e0228488.
PMID: 32017787 DOI: 10.1371/journal.pone.0228488

BACKGROUND: Streptococcus suis (S.suis) is an emerging zoonosis disease with a high prevalence in Southeast Asia. There are over 1,500 cases reported globally in which majority of cases are from Thailand followed by Vietnam. The disease leads to meningitis in human with sensorineural hearing loss (SNHL) as the most common complication suffered by the patients. Early diagnosis and treatment is important to prevent severe neurological complication. In this study, we aim to develop an easy-to-use risk score to promote early diagnosis and detection of S.suis in patients who potentially develop hearing loss.
METHODS: Data from a retrospective review of 13-year S.suis patient records in a tertiary hospital in Chiang Mai, Northern, Thailand was obtained. Univariate and multivariate logistic regressions were employed to develop a predictive model. The clinical risk score was constructed from the coefficients of significant predictors. Area under the receiver operator characteristic curve (AuROC) was identified to verify the model discriminative performance. Bootstrap technique with 1000-fold bootstrapping was used for internal validation.
KEY RESULTS: Among 133 patients, the incidence of hearing loss was 31.6% (n = 42). Significant predictors for S. suis hearing loss were meningitis, raw pork consumption, and vertigo. The predictive score ranged from 0-4 and correctly classified 81.95% patients as being at risk of S.suis hearing loss. The model showed good power of prediction (AuROC: 0.859; 95%CI 0.785-0.933) and calibration (AuROC: 0.860; 95%CI 0.716-0.953).
CONCLUSIONS: To our best knowledge, this is the first risk scoring system development for S.suis hearing loss. We identified meningitis, raw pork consumption and vertigo as the main risk factors of S.suis hearing loss. Future studies are needed to optimize the developed scoring system and investigate its external validity before recommendation for use in clinical practice.
Fulltext Acute toxicity profiling of the ethyl acetate fraction of Swietenia macrophylla seeds and in-vitro neuroprotection studies

Sayyad M, Tiang N, Kumari Y, Goh BH, Jaiswal Y, Rosli R, et al.

Saudi Pharm J, 2017 Feb;25(2):196-205.
PMID: 28344469 DOI: 10.1016/j.jsps.2016.05.002

Swietenia macrophylla (SM) is a medicinally important plant found in tropical and subtropical regions of the world. The ethyl acetate fraction of the seeds of S. macrophylla (SMEAF) is reported to exhibit potent anticancer, antitumor, anti-inflammatory and antifeedant activities. Till date, there have been no studies reported on the acute oral toxicity profile of the ethyl acetate fraction of the seeds of SM. The objective of the present study was to determine the acute toxicity of SMEAF and evaluate the in-vitro neuroprotective activity of SMEAF using primary neuronal cell cultures. In acute oral toxicity study, the SMEAF did not produce any lethal signs of morbidity and mortality. Histo-pathological findings, support the safety of SMEAF, as there were no significant changes observed in any of the parameters studied. Based on the results obtained in MTT assay, we infer that SMEAF has a significant neuroprotective effect, as it increased the cell viability and exhibited protection to the neuronal cells against TBHP induced oxidative stress. Thus, SMEAF can be suggested for use in the development of herbal drug formulations with neuroprotective potential.
Fulltext Algae Metabolites in Cosmeceutical: An Overview of Current Applications and Challenges

Thiyagarasaiyar K, Goh BH, Jeon YJ, Yow YY

Mar Drugs, 2020 Jun 19;18(6).
PMID: 32575468 DOI: 10.3390/md18060323

Cosmetics are widely used by people around the world to protect the skin from external stimuli. Consumer preference towards natural cosmetic products has increased as the synthetic cosmetic products caused adverse side effects and resulted in low absorption rate due to the chemicals' larger molecular size. The cosmetic industry uses the term "cosmeceutical", referring to a cosmetic product that is claimed to have medicinal or drug-like benefits. Marine algae have gained tremendous attention in cosmeceuticals. They are one of the richest marine resources considered safe and possessed negligible cytotoxicity effects on humans. Marine algae are rich in bioactive substances that have shown to exhibit strong benefits to the skin, particularly in overcoming rashes, pigmentation, aging, and cancer. The current review provides a detailed survey of the literature on cosmeceutical potentials and applications of algae as skin whitening, anti-aging, anticancer, antioxidant, anti-inflammation, and antimicrobial agents. The biological functions of algae and the underlying mechanisms of all these activities are included in this review. In addition, the challenges of using algae in cosmeceutical applications, such as the effectiveness of different extraction methods and processing, quality assurance, and regulations concerning extracts of algae in this sector were also discussed.
Fulltext Algae-Derived Anti-Inflammatory Compounds against Particulate Matters-Induced Respiratory Diseases: A Systematic Review

Tan PX, Thiyagarasaiyar K, Tan CY, Jeon YJ, Nadzir MSM, Wu YJ, et al.

Mar Drugs, 2021 May 30;19(6).
PMID: 34070821 DOI: 10.3390/md19060317

Air pollution has recently become a subject of increasing concern in many parts of the world. The World Health Organization (WHO) estimated that nearly 4.2 million early deaths are due to exposure to fine particles in polluted air, which causes multiple respiratory diseases. Algae, as a natural product, can be an alternative treatment due to potential biofunctional properties and advantages. This systematic review aims to summarize and evaluate the evidence of metabolites derived from algae as potential anti-inflammatory agents against respiratory disorders induced by atmospheric particulate matter (PM). Databases such as Scopus, Web of Science, and PubMed were systematically searched for relevant published full articles from 2016 to 2020. The main key search terms were limited to "algae", "anti-inflammation", and "air pollutant". The search activity resulted in the retrieval of a total of 36 publications. Nine publications are eligible for inclusion in this systematic review. A total of four brown algae (Ecklonia cava, Ishige okamurae, Sargassum binderi and Sargassum horneri) with phytosterol, polysaccharides and polyphenols were reported in the nine studies. The review sheds light on the pathways of particulate matter travelling into respiratory systems and causing inflammation, and on the mechanisms of actions of algae in inhibiting inflammation. Limitations and future directions are also discussed. More research is needed to investigate the potential of algae as anti-inflammatory agents against PM in in vivo and in vitro experimental models, as well as clinically.
Fulltext An Observational Longitudinal Study Investigating the Effectiveness of 75 mg Pregabalin Post-Hemodialysis among Uremic Pruritus Patients

Khan TM, Wu DB, Goh BH, Lee LH, Alhafez AA, Syed Sulaiman SA

Sci Rep, 2016 11 08;6:36555.
PMID: 27824127 DOI: 10.1038/srep36555

A prospective, observational, longitudinal study was conducted to assess the effectiveness of 75 mg pregabalin (PG) post-hemodialysis (pHD) for treatment-resistant uremic pruritus (UP). A total of forty-five patients completed the entire six week follow-up. At the baseline assessment, the majority of the patients were distressed by the UP frequency and intensity. Sleep (mean = 3.30 ± 1.1), leisure/social activities (mean = 2.90 ± 0.80) and distribution (mean = 2.92 ± 0.34) were the three domains that were primarily effected by the UP. Overall, further reduction in the 5D-itching scale (IS) was noted at day 42, which confirmed a sustained (B = -12.729, CI -13.257 to -12.201, p
Fulltext Angelicin-A Furocoumarin Compound With Vast Biological Potential

Mahendra CK, Tan LTH, Lee WL, Yap WH, Pusparajah P, Low LE, et al.

Front Pharmacol, 2020;11:366.
PMID: 32372949 DOI: 10.3389/fphar.2020.00366

Angelicin, a member of the furocoumarin group, is related to psoralen which is well known for its effectiveness in phototherapy. The furocoumarins as a group have been studied since the 1950s but only recently has angelicin begun to come into its own as the subject of several biological studies. Angelicin has demonstrated anti-cancer properties against multiple cell lines, exerting effects via both the intrinsic and extrinsic apoptotic pathways, and also demonstrated an ability to inhibit tubulin polymerization to a higher degree than psoralen. Besides that, angelicin too demonstrated anti-inflammatory activity in inflammatory-related respiratory and neurodegenerative ailments via the activation of NF-κB pathway. Angelicin also showed pro-osteogenesis and pro-chondrogenic effects on osteoblasts and pre-chondrocytes respectively. The elevated expression of pro-osteogenic and chondrogenic markers and activation of TGF-β/BMP, Wnt/β-catenin pathway confirms the positive effect of angelicin bone remodeling. Angelicin also increased the expression of estrogen receptor alpha (ERα) in osteogenesis. Other bioactivities, such as anti-viral and erythroid differentiating properties of angelicin, were also reported by several researchers with the latter even displaying an even greater aptitude as compared to the commonly prescribed drug, hydroxyurea, which is currently on the market. Apart from that, recently, a new application for angelicin against periodontitis had been studied, where reduction of bone loss was indirectly caused by its anti-microbial properties. All in all, angelicin appears to be a promising compound for further studies especially on its mechanism and application in therapies for a multitude of common and debilitating ailments such as sickle cell anaemia, osteoporosis, cancer, and neurodegeneration. Future research on the drug delivery of angelicin in cancer, inflammation and erythroid differentiation models would aid in improving the bioproperties of angelicin and efficacy of delivery to the targeted site. More in-depth studies of angelicin on bone remodeling, the pro-osteogenic effect of angelicin in various bone disease models and the anti-viral implications of angelicin in periodontitis should be researched. Finally, studies on the binding of angelicin toward regulatory genes, transcription factors, and receptors can be done through experimental research supplemented with molecular docking and molecular dynamics simulation.
Fulltext Anti-Cancer Properties of the Naturally Occurring Aphrodisiacs: Icariin and Its Derivatives

Tan HL, Chan KG, Pusparajah P, Saokaew S, Duangjai A, Lee LH, et al.

Front Pharmacol, 2016;7:191.
PMID: 27445824 DOI: 10.3389/fphar.2016.00191

Epimedium (family Berberidaceae), commonly known as Horny Goat Weed or Yin Yang Huo, is commonly used as a tonic, aphrodisiac, anti-rheumatic and anti-cancer agent in traditional herbal formulations in Asian countries such as China, Japan, and Korea. The major bioactive compounds present within this plant include icariin, icaritin and icariside II. Although it is best known for its aphrodisiac properties, scientific and pharmacological studies suggest it possesses broad therapeutic capabilities, especially for enhancing reproductive function and osteoprotective, neuroprotective, cardioprotective, anti-inflammatory and immunoprotective effects. In recent years, there has been great interest in scientific investigation of the purported anti-cancer properties of icariin and its derivatives. Data from in vitro and in vivo studies suggests these compounds demonstrate anti-cancer activity against a wide range of cancer cells which occurs through various mechanisms such as apoptosis, cell cycle modulation, anti-angiogenesis, anti-metastasis and immunomodulation. Of note, they are efficient at targeting cancer stem cells and drug-resistant cancer cells. These are highly desirable properties to be emulated in the development of novel anti-cancer drugs in combatting the emergence of drug resistance and overcoming the limited efficacy of current standard treatment. This review aims to summarize the anti-cancer mechanisms of icariin and its derivatives with reference to the published literature. The currently utilized applications of icariin and its derivatives in cancer treatment are explored with reference to existing patents. Based on the data compiled, icariin and its derivatives are shown to be compounds with tremendous potential for the development of new anti-cancer drugs.
Fulltext Anti-neuroinflammatory Activity of Elephantopus scaber L. via Activation of Nrf2/HO-1 Signaling and Inhibition of p38 MAPK Pathway in LPS-Induced Microglia BV-2 Cells

Chan CK, Tan LT, Andy SN, Kamarudin MNA, Goh BH, Kadir HA

Front Pharmacol, 2017;8:397.
PMID: 28680404 DOI: 10.3389/fphar.2017.00397

Elephantopus scaber L. (family: Asteraceae) has been traditionally utilized as a folkloric medicine and scientifically shown to exhibit anti-inflammatory activities in various in vivo inflammatory models. Given the lack of study on the effect of E. scaber in neuroinflammation, this study aimed to investigate the anti-neuroinflammatory effect and the underlying mechanisms of ethyl acetate fraction from the leaves of E. scaber (ESEAF) on the release of pro-inflammatory mediators in lipopolysaccharide (LPS)-induced microglia cells (BV-2). Present findings showed that ESEAF markedly attenuated the translocation of NF-κB to nucleus concomitantly with the significant mitigation on the LPS-induced production of NO, iNOS, COX-2, PGE2, IL-1β, and TNF-α. These inflammatory responses were reduced via the inhibition of p38. Besides, ESEAF was shown to possess antioxidant activities evident by the DPPH and SOD scavenging activities. The intracellular catalase enzyme activity was enhanced by ESEAF in the LPS-stimulated BV-2 cells. Furthermore, the formation of ROS induced by LPS in BV-2 cells was reduced upon the exposure to ESEAF. Intriguingly, the reduction of ROS was found in concerted with the activation of Nrf2 and HO-1. It is conceivable that the activation promotes the scavenging power of antioxidant enzymes as well as to ameliorate the inflammatory response in LPS-stimulated BV-2 cells. Finally, the safety profile analysis through oral administration of ESEAF at 2000 mg/kg did not result in any mortalities, adverse effects nor histopathologic abnormalities of organs in mice. Taken altogether, the cumulative findings suggested that ESEAF holds the potential to develop as nutraceutical for the intervention of neuroinflammatory disorders.
Fulltext Antibacterial, Anticancer and Neuroprotective Activities of Rare Actinobacteria from Mangrove Forest Soils

Azman AS, Othman I, Fang CM, Chan KG, Goh BH, Lee LH

Indian J Microbiol, 2017 Jun;57(2):177-187.
PMID: 28611495 DOI: 10.1007/s12088-016-0627-z

Mangrove is a complex ecosystem that contains diverse microbial communities, including rare actinobacteria with great potential to produce bioactive compounds. To date, bioactive compounds extracted from mangrove rare actinobacteria have demonstrated diverse biological activities. The discovery of three novel rare actinobacteria by polyphasic approach, namely Microbacterium mangrovi MUSC 115T, Sinomonas humi MUSC 117T and Monashia flava MUSC 78T from mangrove soils at Tanjung Lumpur, Peninsular Malaysia have led to the screening on antibacterial, anticancer and neuroprotective activities. A total of ten different panels of bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, ATCC 70069, Pseudomonas aeruginosa NRBC 112582 and others were selected for antibacterial screening. Three different neuroprotective models (hypoxia, oxidative stress, dementia) were done using SHSY5Y neuronal cells while two human cancer cells lines, namely human colon cancer cell lines (HT-29) and human cervical carcinoma cell lines (Ca Ski) were utilized for anticancer activity. The result revealed that all extracts exhibited bacteriostatic effects on the bacteria tested. On the other hand, the neuroprotective studies demonstrated M. mangrovi MUSC 115T extract exhibited significant neuroprotective properties in oxidative stress and dementia model while the extract of strain M. flava MUSC 78T was able to protect the SHSY5Y neuronal cells in hypoxia model. Furthermore, the extracts of M. mangrovi MUSC 115T and M. flava MUSC 78T exhibited anticancer effect against Ca Ski cell line. The chemical analysis of the extracts through GC-MS revealed that the majority of the compounds present in all extracts are heterocyclic organic compound that could explain for the observed bioactivities. Therefore, the results obtained in this study suggested that rare actinobacteria discovered from mangrove environment could be potential sources of antibacterial, anticancer and neuroprotective agents.
Fulltext Anticancer Activities of Surfactin and Potential Application of Nanotechnology Assisted Surfactin Delivery

Wu YS, Ngai SC, Goh BH, Chan KG, Lee LH, Chuah LH

Front Pharmacol, 2017;8:761.
PMID: 29123482 DOI: 10.3389/fphar.2017.00761

Surfactin, a cyclic lipopeptide biosurfactant produced by various strains of Bacillus genus, has been shown to induce cytotoxicity against many cancer types, such as Ehrlich ascites, breast and colon cancers, leukemia and hepatoma. Surfactin treatment can inhibit cancer progression by growth inhibition, cell cycle arrest, apoptosis, and metastasis arrest. Owing to the potent effect of surfactin on cancer cells, numerous studies have recently investigated the mechanisms that underlie its anticancer activity. The amphiphilic nature of surfactin allows its easy incorporation nano-formulations, such as polymeric nanoparticles, micelles, microemulsions, liposomes, to name a few. The use of nano-formulations offers the advantage of optimizing surfactin delivery for an improved anticancer therapy. This review focuses on the current knowledge of surfactin properties and biosynthesis; anticancer activity against different cancer models and the underlying mechanisms involved; as well as the potential application of nano-formulations for optimal surfactin delivery.
Fulltext Antioxidant Activities of Streptomyces sp. strain MUSC 14 from Mangrove Forest Soil in Malaysia

Kemung HM, Tan LT, Chan KG, Ser HL, Law JW, Lee LH, et al.

Biomed Res Int, 2020;2020:6402607.
PMID: 32258133 DOI: 10.1155/2020/6402607

The mangrove ecosystem of Malaysia remains yet to be fully explored for potential microbes that produce biologically active metabolites. In the present study, a mangrove-derived Streptomyces sp. strain MUSC 14 previously isolated from the state of Pahang, Malaysia Peninsula, was studied for its potential in producing antioxidant metabolites. The identity of Streptomyces sp. strain MUSC14 was consistent with the genotypic and phenotypic characteristics of the Streptomyces genus. The antioxidant potential of Streptomyces sp. strain MUSC 14 was determined through screening of its methanolic extract against sets of antioxidant assays. The results were indicative of Streptomyces sp. strain MUSC 14 displaying strong antioxidant activity against ABTS, DPPH free radicals and metal chelating activity of 62.71 ± 3.30%, 24.71 ± 2.22%, and 55.82 ± 2.35%, respectively. The result of ferric reducing activity measured in terms of dose was equivalent to 2.35-2.45 μg of positive control ascorbic acid. Furthermore, there was a high correlation between the total phenolic content and the antioxidant activities with r = 0.979, r = 0.858, and r = 0.983 representing ABTS, DPPH, and metal chelation, respectively. Overall, the present study suggests that Streptomyces sp. strain MUSC 14 from mangrove forest soil has potential to produce antioxidant metabolites that can be further exploited for therapeutic application.
Fulltext Antioxidative Potential of a Streptomyces sp. MUM292 Isolated from Mangrove Soil

Tan LT, Chan KG, Chan CK, Khan TM, Lee LH, Goh BH

Biomed Res Int, 2018;2018:4823126.
PMID: 29805975 DOI: 10.1155/2018/4823126

Mangrove derived microorganisms constitute a rich bioresource for bioprospecting of bioactive natural products. This study explored the antioxidant potentials of Streptomyces bacteria derived from mangrove soil. Based on 16S rRNA phylogenetic analysis, strain MUM292 was identified as the genus Streptomyces. Strain MUM292 showed the highest 16S rRNA gene sequence similarity of 99.54% with S. griseoruber NBRC12873T. Furthermore, strain MUM292 was also characterized and showed phenotypic characteristics consistent with Streptomyces bacteria. Fermentation and extraction were performed to obtain the MUM292 extract containing the secondary metabolites of strain MUM292. The extract displayed promising antioxidant activities, including DPPH, ABTS, and superoxide radical scavenging and also metal-chelating activities. The process of lipid peroxidation in lipid-rich product was also retarded by MUM292 extract and resulted in reduced MDA production. The potential bioactive constituents of MUM292 extract were investigated using GC-MS and preliminary detection showed the presence of pyrazine, pyrrole, cyclic dipeptides, and phenolic compound in MUM292 extract. This work demonstrates that Streptomyces MUM292 can be a potential antioxidant resource for food and pharmaceutical industries.
Fulltext Aqueous fraction of Nephelium ramboutan-ake rind induces mitochondrial-mediated apoptosis in HT-29 human colorectal adenocarcinoma cells

Chan CK, Goh BH, Kamarudin MN, Kadir HA

Molecules, 2012 May 31;17(6):6633-57.
PMID: 22728359 DOI: 10.3390/molecules17066633

The aim of this study was to investigate the cytotoxic and apoptotic effects of Nephelium ramboutan-ake (pulasan) rind in selected human cancer cell lines. The crude ethanol extract and fractions (ethyl acetate and aqueous) of N. ramboutan-ake inhibited the growth of HT-29, HCT-116, MDA-MB-231, Ca Ski cells according to MTT assays. The N. ramboutan-ake aqueous fraction (NRAF) was found to exert the greatest cytotoxic effect against HT-29 in a dose-dependent manner. Evidence of apoptotic cell death was revealed by features such as chromatin condensation, nuclear fragmentation and apoptotic body formation. The result from a TUNEL assay strongly suggested that NRAF brings about DNA fragmentation in HT-29 cells. Phosphatidylserine (PS) externalization on the outer leaflet of plasma membranes was detected with annexin V-FITC/PI binding, confirming the early stage of apoptosis. The mitochondrial permeability transition is an important step in the induction of cellular apoptosis, and the results clearly suggested that NRAF led to collapse of mitochondrial transmembrane potential in HT-29 cells. This attenuation of mitochondrial membrane potential (Δψm) was accompanied by increased production of ROS and depletion of GSH, an increase of Bax protein expression, and induced-activation of caspase-3/7 and caspase-9. These combined results suggest that NRAF induces mitochondrial-mediated apoptosis.
Fulltext Association of diabetes knowledge with glycemic control and self-care practices among Pakistani people with type 2 diabetes mellitus

Bukhsh A, Khan TM, Sarfraz Nawaz M, Sajjad Ahmed H, Chan KG, Goh BH

Diabetes Metab Syndr Obes, 2019;12:1409-1417.
PMID: 31616171 DOI: 10.2147/DMSO.S209711

Objective: This study explored the relationship of disease knowledge with glycemic control and self-care practices in adult Pakistani people diabetes (PWD).
Methods: People diagnosed with type 2 diabetes (n=218) were selected from three health care centers, located in different cities of Pakistan. Disease knowledge and self-care practices were assessed by Urdu versions of Diabetes Knowledge Questionnaire (DKQ) and Diabetes Self-Management Questionnaire (DSMQ), using a cross-sectional design. Chi-square and correlation analysis were applied to explore the relationship of disease knowledge with glycemic control and self-care practices. Linear regression was used to explore the predictors for disease knowledge.
Results: Majority of the sample was >45-60 years old (48.8%), suffering from type 2 diabetes mellitus for <5 years (49.5%) and had poor glycemic control (HbA1C≥7%; n=181 participants). Disease knowledge was significantly associated (p<0.05) with patient's gender, level of education, family history of diabetes, nature of euglycemic therapy, and glycemic control. Correlation matrix showed strongly inverse correlations of DKQ with glycated hemoglobin levels (r=-0.62; p<0.001) and strongly positive with DSMQ sum scale (r=0.63; p<0.001). PWD having university-level education (β=0.22; 95% Confidence Interval (CI) 0.189, 0.872; p<0.01), doing job (β=0.22; 95% CI 0.009, 0.908]; p=0.046), and use of oral hypoglycemic agents in combination with insulin (β=-0.16; 95% CI [-1.224, -0.071]; p=0.028) were the significant predictors for disease knowledge.
Conclusion: Disease knowledge significantly correlated with glycated hemoglobin levels and self-care activities of PWD. These findings will help in designing patient-tailored diabetes educational interventions for yielding a higher probability of achieving target glycemic control.
Fulltext Association of diabetes-related self-care activities with glycemic control of patients with type 2 diabetes in Pakistan

Bukhsh A, Khan TM, Nawaz MS, Ahmed HS, Chan KG, Lee LH, et al.

Patient Prefer Adherence, 2018;12:2377-2385.
PMID: 30519003 DOI: 10.2147/PPA.S177314

Objective: Association of various self-care activities on glycemic control of people with diabetes (PWD) in Pakistan is yet to be explored. The current study aimed to evaluate the association of various diabetes-related self-care activities with glycated hemoglobin (HbA1c) levels and to examine the predictive relationship of patients' demographic variables with their self-care activities.

Patients and methods: A cross-sectional study was conducted on adult PWD (N=218) who were diagnosed with type 2 diabetes mellitus of at least 1 year duration. Self-care activities were examined by using the Urdu version of Diabetes Self-management Questionnaire. Linear regression analysis was conducted to examine the significant predictors for diabetes-related self-care activities and glycemic control.

Results: Mean age of the patients was 50.77±13.3 years. Poor glycemic control (HbA1c $7%) was observed in majority of the patients (83%). Linear regression analysis revealed that glucose management (β=-0.44; 95% CI -0.438, -0.209; P<0.001) was the strongest predictor for low levels of patients' HbA1c, followed by dietary control (β=-0.19; 95% CI -0.248, -0.018; P=0.024) and physical activity (β=-0.17; 95% CI -0.165, -0.023; P=0.010), respectively. Linear regression analysis showed that use of oral hypoglycemic agents only (β=-0.218; 95% CI -0.956, -0.200; P=0.003) and higher education level (β=0.204; 95% CI 0.138, 0.777; P=0.005) were significant predictors for higher scores of patients' self-care activities.

Conclusion: The findings support that PWD having better self-reported self-care activities achieve better glycemic control. Patients' self-care activities should be monitored on a regular basis, especially for those who are at risk of poor glycemic control.
Attenuating influenza a virus infection by heparin binding EGF-like growth factor

Lai KM, Goh BH, Lee WL

Growth Factors, 2021 03 15;38(3-4):167-176.
PMID: 33719806 DOI: 10.1080/08977194.2021.1895144

Cell entry of influenza A virus (IAV) was reported to be promoted by epidermal growth factor receptor (EGFR). On the other hand, binding of heparin-binding EGF-like growth factor (HB-EGF) to EGFR leads to internalisation and degradation of the receptors. This study aimed to testify whether or not HB-EGF-induced downregulation of EGFR could attenuate IAV cell entry and subsequently diminish the infection. Immunoblotting and plaque assay revealed that HB-EGF-induced degradation of EGFR led to reduction of viral matrix 1 protein level and suppressed virion production. In addition, immunoblotting and imaging flow cytometric analysis demonstrated that IAV-induced phosphorylation of STAT1 and its localisation to nucleus in the early stage of infection were inhibited by HB-EGF treatment. This suggested the potential of HB-EGF in modulating uncontrolled and exaggerated inflammatory response caused by IAV infection. Together these findings attest the potential of HB-EGF mediated endocytosis and degradation of EGFR as a novel anti-IAV strategy.

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