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Fulltext Safety and Efficacy of Pneumococcal Vaccination in Pediatric Nephrotic Syndrome

Goonewardene ST, Tang C, Tan LT, Chan KG, Lingham P, Lee LH, et al.

Front Pediatr, 2019;7:339.
PMID: 31456997 DOI: 10.3389/fped.2019.00339

Nephrotic syndrome affects both children and adults. Idiopathic nephrotic syndrome is reported to be one of the most frequent renal pathologies in childhood. Nephrotic children are at high risk for severe pneumococcal infections as one of the life-threatening complications of nephrotic syndrome due to involvement of the immunosuppressive regimen and the acquired immune deficiency induced by nephrotic syndrome including decreased plasma IgG and low complement system components. Aiming to prevent pneumococcal infection is of paramount importance especially in this era of ever-increasing pneumococcal resistance to penicillins and cephalosporins. The pneumococcal vaccines currently available are inactivated vaccines-the two main forms in use are polysaccharide vaccines and conjugated vaccines. However, the data supporting the use of these vaccines and to guide the timing and dosage recommendations is still limited for nephrotic children. Thus, this review discusses the evidences of immunogenicity and safety profile of both vaccinations on nephrotic patients as well as the effect of nephrotic syndrome treatment on vaccine seroresponses.
Fulltext Formononetin: A Review of Its Anticancer Potentials and Mechanisms

Tay KC, Tan LT, Chan CK, Hong SL, Chan KG, Yap WH, et al.

Front Pharmacol, 2019;10:820.
PMID: 31402861 DOI: 10.3389/fphar.2019.00820

Cancer, a complex yet common disease, is caused by uncontrolled cell division and abnormal cell growth due to a variety of gene mutations. Seeking effective treatments for cancer is a major research focus, as the incidence of cancer is on the rise and drug resistance to existing anti-cancer drugs is major concern. Natural products have the potential to yield unique molecules and combinations of substances that may be effective against cancer with relatively low toxicity/better side effect profile compared to standard anticancer therapy. Drug discovery work with natural products has demonstrated that natural compounds display a wide range of biological activities correlating to anticancer effects. In this review, we discuss formononetin (C16H12O4), which originates mainly from red clovers and the Chinese herb Astragalus membranaceus. The compound comes from a class of 7-hydroisoflavones with a substitution of methoxy group at position 4. Formononetin elicits antitumorigenic properties in vitro and in vivo by modulating numerous signaling pathways to induce cell apoptosis (by intrinsic pathway involving Bax, Bcl-2, and caspase-3 proteins) and cell cycle arrest (by regulating mediators like cyclin A, cyclin B1, and cyclin D1), suppress cell proliferation [by signal transducer and activator of transcription (STAT) activation, phosphatidylinositol 3-kinase/protein kinase-B (PI3K/AKT), and mitogen-activated protein kinase (MAPK) signaling pathway], and inhibit cell invasion [by regulating growth factors vascular endothelial growth factor (VEGF) and Fibroblast growth factor 2 (FGF2), and matrix metalloproteinase (MMP)-2 and MMP-9 proteins]. Co-treatment with other chemotherapy drugs such as bortezomib, LY2940002, U0126, sunitinib, epirubicin, doxorubicin, temozolomide, and metformin enhances the anticancer potential of both formononetin and the respective drugs through synergistic effect. Compiling the evidence thus far highlights the potential of formononetin to be a promising candidate for chemoprevention and chemotherapy.
Fulltext Biological Activities of Snowdrop (Galanthus spp., Family Amaryllidaceae)

Kong CK, Low LE, Siew WS, Yap WH, Khaw KY, Ming LC, et al.

Front Pharmacol, 2020;11:552453.
PMID: 33679383 DOI: 10.3389/fphar.2020.552453

Snowdrop is an iconic early spring flowering plant of the genus Galanthus (Amaryllidaceae). Galanthus species (Galanthus spp.) are economically important plants as ornaments. Galanthus spp has gained significance scientific and commercial interest due to the discovery of Galanthamine as symptomatic treatment drug for Alzhiermer disease. This review aims to discuss the bioactivities of Galanthus spp including anticholinesterase, antimicrobial, antioxidant and anticancer potential of the extracts and chemical constituents of Galanthus spp. This review highlights that Galanthus spp. as the exciting sources for drug discovery and nutraceutical development.
Fulltext Controlled Release Fertilizers: A Review on Coating Materials and Mechanism of Release

Lawrencia D, Wong SK, Low DYS, Goh BH, Goh JK, Ruktanonchai UR, et al.

Plants (Basel), 2021 Jan 26;10(2).
PMID: 33530608 DOI: 10.3390/plants10020238

Rising world population is expected to increase the demand for nitrogen fertilizers to improve crop yield and ensure food security. With existing challenges on low nutrient use efficiency (NUE) of urea and its environmental concerns, controlled release fertilizers (CRFs) have become a potential solution by formulating them to synchronize nutrient release according to the requirement of plants. However, the most significant challenge that persists is the "tailing" effect, which reduces the economic benefits in terms of maximum fertilizer utilization. High materials cost is also a significant obstacle restraining the widespread application of CRF in agriculture. The first part of this review covers issues related to the application of conventional fertilizer and CRFs in general. In the subsequent sections, different raw materials utilized to form CRFs, focusing on inorganic and organic materials and synthetic and natural polymers alongside their physical and chemical preparation methods, are compared. Important factors affecting rate of release, mechanism of release and mathematical modelling approaches to predict nutrient release are also discussed. This review aims to provide a better overview of the developments regarding CRFs in the past ten years, and trends are identified and analyzed to provide an insight for future works in the field of agriculture.
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 Targeting Gut Microbial Biofilms-A Key to Hinder Colon Carcinogenesis?

Chew SS, Tan LT, Law JW, Pusparajah P, Goh BH, Ab Mutalib NS, et al.

Cancers (Basel), 2020 Aug 13;12(8).
PMID: 32823729 DOI: 10.3390/cancers12082272

Colorectal cancer (CRC) is a global public health issue which poses a substantial humanistic and economic burden on patients, healthcare systems and society. In recent years, intestinal dysbiosis has been suggested to be involved in the pathogenesis of CRC, with specific pathogens exhibiting oncogenic potentials such as Fusobacterium nucleatum, Escherichia coli and enterotoxigenic Bacteroides fragilis having been found to contribute to CRC development. More recently, it has been shown that initiation of CRC development by these microorganisms requires the formation of biofilms. Gut microbial biofilm forms in the inner colonic mucus layer and is composed of polymicrobial communities. Biofilm results in the redistribution of colonic epithelial cell E-cadherin, increases permeability of the gut and causes a loss of function of the intestinal barrier, all of which enhance intestinal dysbiosis. This literature review aims to compile the various strategies that target these pathogenic biofilms and could potentially play a role in the prevention of CRC. We explore the potential use of natural products, silver nanoparticles, upconverting nanoparticles, thiosalicylate complexes, anti-rheumatic agent (Auranofin), probiotics and quorum-sensing inhibitors as strategies to hinder colon carcinogenesis via targeting colon-associated biofilms.
Fulltext Counteracting the Ramifications of UVB Irradiation and Photoaging with Swietenia macrophylla King Seed

Mahendra CK, Abidin SAZ, Htar TT, Chuah LH, Khan SU, Ming LC, et al.

Molecules, 2021 Apr 01;26(7).
PMID: 33916053 DOI: 10.3390/molecules26072000

In this day and age, the expectation of cosmetic products to effectively slow down skin photoaging is constantly increasing. However, the detrimental effects of UVB on the skin are not easy to tackle as UVB dysregulates a wide range of molecular changes on the cellular level. In our research, irradiated keratinocyte cells not only experienced a compromise in their redox system, but processes from RNA translation to protein synthesis and folding were also affected. Aside from this, proteins involved in various other processes like DNA repair and maintenance, glycolysis, cell growth, proliferation, and migration were affected while the cells approached imminent cell death. Additionally, the collagen degradation pathway was also activated by UVB irradiation through the upregulation of inflammatory and collagen degrading markers. Nevertheless, with the treatment of Swietenia macrophylla (S. macrophylla) seed extract and fractions, the dysregulation of many genes and proteins by UVB was reversed. The reversal effects were particularly promising with the S. macrophylla hexane fraction (SMHF) and S. macrophylla ethyl acetate fraction (SMEAF). SMHF was able to oppose the detrimental effects of UVB in several different processes such as the redox system, DNA repair and maintenance, RNA transcription to translation, protein maintenance and synthesis, cell growth, migration and proliferation, and cell glycolysis, while SMEAF successfully suppressed markers related to skin inflammation, collagen degradation, and cell apoptosis. Thus, in summary, our research not only provided a deeper insight into the molecular changes within irradiated keratinocytes, but also serves as a model platform for future cosmetic research to build upon. Subsequently, both SMHF and SMEAF also displayed potential photoprotective properties that warrant further fractionation and in vivo clinical trials to investigate and obtain potential novel bioactive compounds against photoaging.
Pleiotropic ameliorative effects of ellagitannin geraniin against metabolic syndrome induced by high-fat diet in rats

Cheng HS, Goh BH, Phang SCW, Amanullah MM, Ton SH, Palanisamy UD, et al.

Nutrition, 2020 08 12;79-80:110973.
PMID: 32916379 DOI: 10.1016/j.nut.2020.110973

OBJECTIVES: Metabolic syndrome (MetS), a multiplex risk factor for cardiovascular disease and type 2 diabetes, is increasingly prevalent worldwide. Ellagitannin geraniin, a polyphenol found in the rind of rambutan (Nephelium lappaceum), has demonstrated therapeutic effects against metabolism dysfunction. The aim of this study was to characterize the metabolic effects and possible mechanism of geraniin in rats with MetS induced by a high-fat diet (HFD).
METHODS: MetS was induced in Sprague Dawley rats on an HFD, followed by a daily oral gavage of geraniin (25 mg/kg) for 4 wk. The outcomes of geraniin-treated rats were compared with those of untreated rats on either a control diet or an HFD and with rats with MetS treated with metformin on a daily basis (200 mg/kg).
RESULTS: The supplementation of geraniin ameliorated multiple metabolic abnormalities caused by HFD, including hypertension, impaired glucose and lipid metabolism, ectopic fat deposition in the visceral fat and liver, and disturbed antioxidant mechanism and inflammatory response. The benefits conferred by geraniin were comparable to metformin. Transcriptomic analysis revealed a profound influence of geraniin on the hepatic expression profiles. The lipid and steroid metabolic processes that were aberrantly activated by HFD were suppressed by geraniin. Based on the differential transcriptomes, geraniin also exerted a significant modulatory effect on the expression of mitochondrial genes, potentially influencing the mitochondrial activity and leading to the observed beneficial effects.
CONCLUSION: Geraniin supplementation mitigated metabolic anomalies of MetS in rats, making it an attractive drug candidate for further investigation.
Microenvironment-tailored nanoassemblies for the diagnosis and therapy of neurodegenerative diseases

Low LE, Wang Q, Chen Y, Lin P, Yang S, Gong L, et al.

Nanoscale, 2021 Jun 17;13(23):10197-10238.
PMID: 34027535 DOI: 10.1039/d1nr02127c

Neurodegenerative disorder is an illness involving neural dysfunction/death attributed to complex pathological processes, which eventually lead to the mortality of the host. It is generally recognized through features such as mitochondrial dysfunction, protein aggregation, oxidative stress, metal ions dyshomeostasis, membrane potential change, neuroinflammation and neurotransmitter impairment. The aforementioned neuronal dysregulations result in the formation of a complex neurodegenerative microenvironment (NME), and may interact with each other, hindering the performance of therapeutics for neurodegenerative disease (ND). Recently, smart nanoassemblies prepared from functional nanoparticles, which possess the ability to interfere with different NME factors, have shown great promise to enhance the diagnostic and therapeutic efficacy of NDs. Herein, this review highlights the recent advances of stimuli-responsive nanoassemblies that can effectively combat the NME for the management of ND. The first section outlined the NME properties and their interrelations that are exploitable for nanoscale targeting. The discussion is then extended to the controlled assembly of functional nanoparticles for the construction of stimuli-responsive nanoassemblies. Further, the applications of stimuli-responsive nanoassemblies for the enhanced diagnosis and therapy of ND are introduced. Finally, perspectives on the future development of NME-tailored nanomedicines are given.
In vitro evaluation of the involvement of Nrf2 in maslinic acid-mediated anti-inflammatory effects in atheroma pathogenesis

Ooi BK, Phang SW, Yong PVC, Chellappan DK, Dua K, Khaw KY, et al.

Life Sci, 2021 Aug 01;278:119658.
PMID: 34048809 DOI: 10.1016/j.lfs.2021.119658

AIMS: Maslinic acid (MA) is a naturally occurring pentacyclic triterpene known to exert cardioprotective effects. This study aims to investigate the involvement of nuclear factor erythroid 2-related factor 2 (Nrf2) for MA-mediated anti-inflammatory effects in atheroma pathogenesis in vitro, including evaluation of tumor necrosis factor-alpha (TNF-α)-induced monocyte recruitment, oxidized low-density lipoprotein (oxLDL)-induced scavenger receptors expression, and nuclear factor-kappa B (NF-ĸB) activity in human umbilical vein endothelial cells (HUVECS) and human acute monocytic leukemia cell line (THP-1) macrophages.
MATERIALS AND METHODS: An in vitro monocyte recruitment model utilizing THP-1 and HUVECs was developed to evaluate TNF-α-induced monocyte adhesion and trans-endothelial migration. To study the role of Nrf2 for MA-mediated anti-inflammatory effects, Nrf2 inhibitor ML385 was used as the pharmacological inhibitor. The expression of Nrf2, monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 36 (CD36), and scavenger receptor type A (SR-A) in HUVECs and THP-1 macrophages were investigated using RT-qPCR and Western blotting. The NF-κB activity was determined using NF-κB (p65) Transcription Factor Assay Kit.
KEY FINDINGS: The results showed opposing effects of MA on Nrf2 expression in HUVECs and THP-1 macrophages. MA suppressed TNF-α-induced Nrf2 expression in HUVECs, but enhanced its expression in THP-1 macrophages. Combined effects of MA and ML385 suppressed MCP-1, VCAM-1, and SR-A expressions. Intriguingly, at the protein level, ML385 selectively inhibited SR-A but enhanced CD36 expression. Meanwhile, ML385 further enhanced MA-mediated inhibition of NF-κB activity in HUVECs. This effect, however, was not observed in THP-1 macrophages.
SIGNIFICANCE: MA attenuated foam cell formation by suppressing VCAM-1, MCP-1, and SR-A expression, as well as NF-κB activity, possibly through Nrf2 inhibition. The involvement of Nrf2 for MA-mediated anti-inflammatory effects however differs between HUVECs and macrophages. Future investigations are warranted for a detailed evaluation of the contributing roles of Nrf2 in foam cells formation.
Fulltext Streptomyces antioxidans sp. nov., a Novel Mangrove Soil Actinobacterium with Antioxidative and Neuroprotective Potentials

Ser HL, Tan LT, Palanisamy UD, Abd Malek SN, Yin WF, Chan KG, et al.

Front Microbiol, 2016;7:899.
PMID: 27379040 DOI: 10.3389/fmicb.2016.00899

A novel strain, Streptomyces antioxidans MUSC 164(T) was recovered from mangrove forest soil located at Tanjung Lumpur, Malaysia. The Gram-positive bacterium forms yellowish-white aerial and brilliant greenish yellow substrate mycelium on ISP 2 agar. A polyphasic approach was used to determine the taxonomy status of strain MUSC 164(T). The strain showed a spectrum of phylogenetic and chemotaxonomic properties consistent with those of the members of the genus Streptomyces. The cell wall peptidoglycan was determined to contain LL-diaminopimelic acid. The predominant menaquinones were identified as MK-9(H6) and MK-9(H8), while the identified polar lipids consisted of aminolipid, diphosphatidylglycerol, glycolipid, hydroxyphosphatidylethanolamine, phospholipid, phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol and lipid. The cell wall sugars consist of galactose, glucose and ribose. The predominant cellular fatty acids (>10.0%) were identified as iso-C15: 0 (34.8%) and anteiso-C15: 0(14.0%). Phylogenetic analysis identified that closely related strains for MUSC 164(T) as Streptomyces javensis NBRC 100777(T) (99.6% sequence similarity), Streptomyces yogyakartensis NBRC 100779(T) (99.6%) and Streptomyces violaceusniger NBRC 13459(T) (99.6%). The DNA-DNA relatedness values between MUSC 164(T) and closely related type strains ranged from 23.8 ± 0.3% to 53.1 ± 4.3%. BOX-PCR fingerprints comparison showed that MUSC 164(T) exhibits a unique DNA profile, with DNA G + C content determined to be 71.6 mol%. Based on the polyphasic study of MUSC 164(T), it is concluded that this strain represents a novel species, for which the name Streptomyces antioxidans sp. nov. is proposed. The type strain is MUSC 164(T) (=DSM 101523(T) = MCCC 1K01590(T)). The extract of MUSC 164(T) showed potent antioxidative and neuroprotective activities against hydrogen peroxide. The chemical analysis of the extract revealed that the strain produces pyrazines and phenolic-related compounds that could explain for the observed bioactivities.
Fulltext The Effectiveness and Safety of Topical Capsaicin in Postherpetic Neuralgia: A Systematic Review and Meta-analysis

Yong YL, Tan LT, Ming LC, Chan KG, Lee LH, Goh BH, et al.

Front Pharmacol, 2016;7:538.
PMID: 28119613 DOI: 10.3389/fphar.2016.00538

In particular, neuropathic pain is a major form of chronic pain. This type of pain results from dysfunction or lesions in the central and peripheral nervous system. Capsaicin has been traditionally utilized as a medicine to remedy pain. However, the effectiveness and safety of this practice is still elusive. Therefore, this systematic review aimed to investigate the effect of topical capsaicin as a pain-relieving agent that is frequently used in pain management. In brief, all the double-blinded, randomized placebo- or vehicle-controlled trials that were published in English addressing postherpetic neuralgia were included. Meta-analysis was performed using Revman(®) version 5.3. Upon application of the inclusion and exclusion criteria, only six trials fulfilled all the criteria and were included in the review for qualitative analysis. The difference in mean percentage change in numeric pain rating scale score ranges from -31 to -4.3. This demonstrated high efficacy of topical capsaicin application and implies that capsaicin could result in pain reduction. Furthermore, meta-analysis was performed on five of the included studies. All the results of studies are in favor of the treatment using capsaicin. The incidence of side effects from using topical capsaicin is consistently higher in all included studies, but the significance of safety data cannot be quantified due to a lack of p-values in the original studies. Nevertheless, topical capsaicin is a promising treatment option for specific patient groups or certain neuropathic pain conditions such as postherpetic neuralgia.
Draft Genome Sequence of Mangrove-Derived Streptomyces sp. MUSC 125 with Antioxidant Potential

Ser HL, Tan WS, Ab Mutalib NS, Yin WF, Chan KG, Goh BH, et al.

Front Microbiol, 2016;7:1470.
PMID: 27695452
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.
Fulltext Streptomyces sp. MUM212 as a Source of Antioxidants with Radical Scavenging and Metal Chelating Properties

Tan LT, Chan KG, Khan TM, Bukhari SI, Saokaew S, Duangjai A, et al.

Front Pharmacol, 2017;8:276.
PMID: 28567016 DOI: 10.3389/fphar.2017.00276

Reactive oxygen species and other radicals potentially cause oxidative damage to proteins, lipids, and DNA which may ultimately lead to various complications including mutations, carcinogenesis, neurodegeneration, cardiovascular disease, aging, and inflammatory disease. Recent reports demonstrate that Streptomyces bacteria produce metabolites with potent antioxidant activity that may be developed into therapeutic drugs to combat oxidative stress. This study shows that Streptomyces sp. MUM212 which was isolated from mangrove soil in Kuala Selangor, Malaysia, could be a potential source of antioxidants. Strain MUM212 was characterized and determined as belonging to the genus Streptomyces using 16S rRNA gene phylogenetic analysis. The MUM212 extract demonstrated significant antioxidant activity through DPPH, ABTS and superoxide radical scavenging assays and also metal-chelating activity of 22.03 ± 3.01%, 61.52 ± 3.13%, 37.47 ± 1.79%, and 41.98 ± 0.73% at 4 mg/mL, respectively. Moreover, MUM212 extract was demonstrated to inhibit lipid peroxidation up to 16.72 ± 2.64% at 4 mg/mL and restore survival of Vero cells from H2O2-induced oxidative damages. The antioxidant activities from the MUM212 extract correlated well with its total phenolic contents; and this in turn was in keeping with the gas chromatography-mass spectrometry analysis which revealed the presence of phenolic compounds that could be responsible for the antioxidant properties of the extract. Other chemical constituents detected included hydrocarbons, alcohols and cyclic dipeptides which may have contributed to the overall antioxidant capacity of MUM212 extract. As a whole, strain MUM212 seems to have potential as a promising source of novel molecules for future development of antioxidative therapeutic agents against oxidative stress-related diseases.
Rhizoma Coptidis: A Potential Cardiovascular Protective Agent

Tan HL, Chan KG, Pusparajah P, Duangjai A, Saokaew S, Mehmood Khan T, et al.

Front Pharmacol, 2016;7:362.
PMID: 27774066

Cardiovascular diseases (CVDs) are among the leading causes of morbidity and mortality in both the developed and developing world. Rhizoma coptidis (RC), known as Huang Lian in China, is the dried rhizome of medicinal plants from the family Ranunculaceae, such as Coptis chinensis Franch, C. deltoidea C.Y. Cheng et Hsiao, and C. teeta Wall which has been used by Chinese medicinal physicians for more than 2000 years. In China, RC is a common component in traditional medicines used to treat CVD associated problems including obesity, diabetes mellitus, hyperlipidemia, hyperglycemia and disorders of lipid metabolism. In recent years, numerous scientific studies have sought to investigate the biological properties of RC to provide scientific evidence for its traditional medical uses. RC has been found to exert significant beneficial effects on major risk factors for CVDs including anti-atherosclerotic effect, lipid-lowering effect, anti-obesity effect and anti-hepatic steatosis effect. It also has myocardioprotective effect as it provides protection from myocardial ischemia-reperfusion injury. These properties have been attributed to the presence of bioactive compounds contained in RC such as berberine, coptisine, palmatine, epiberberine, jatrorrhizine, and magnoflorine; all of which have been demonstrated to have cardioprotective effects on the various parameters contributing to the occurrence of CVD through a variety of pathways. The evidence available in the published literature indicates that RC is a herb with tremendous potential to reduce the risks of CVDs, and this review aims to summarize the cardioprotective properties of RC with reference to the published literature which overall indicates that RC is a herb with remarkable potential to reduce the risks and damage caused by CVDs.
The Potential of Streptomyces as Biocontrol Agents against the Rice Blast Fungus, Magnaporthe oryzae (Pyricularia oryzae)

Law JW, Ser HL, Khan TM, Chuah LH, Pusparajah P, Chan KG, et al.

Front Microbiol, 2017;8:3.
PMID: 28144236 DOI: 10.3389/fmicb.2017.00003

Rice is a staple food source for more than three billion people worldwide. However, rice is vulnerable to diseases, the most destructive among them being rice blast, which is caused by the fungus Magnaporthe oryzae (anamorph Pyricularia oryzae). This fungus attacks rice plants at all stages of development, causing annual losses of approximately 10-30% in various rice producing regions. Synthetic fungicides are often able to effectively control plant diseases, but some fungicides result in serious environmental and health problems. Therefore, there is growing interest in discovering and developing new, improved fungicides based on natural products as well as introducing alternative measures such as biocontrol agents to manage plant diseases. Streptomyces bacteria appear to be promising biocontrol agents against a wide range of phytopathogenic fungi, which is not surprising given their ability to produce various bioactive compounds. This review provides insight into the biocontrol potential of Streptomyces against the rice blast fungus, M. oryzae. The ability of various Streptomyces spp. to act as biocontrol agents of rice blast disease has been studied by researchers under both laboratory and greenhouse/growth chamber conditions. Laboratory studies have shown that Streptomyces exhibit inhibitory activity against M. oryzae. In greenhouse studies, infected rice seedlings treated with Streptomyces resulted in up to 88.3% disease reduction of rice blast. Studies clearly show that Streptomyces spp. have the potential to be used as highly effective biocontrol agents against rice blast disease; however, the efficacy of any biocontrol agent may be affected by several factors including environmental conditions and methods of application. In order to fully exploit their potential, further studies on the isolation, formulation and application methods of Streptomyces along with field experiments are required to establish them as effective biocontrol agents.
Overexpression of oxyR Increases Phenazine-1-Carboxylic Acid Biosynthesis via Small RNA phrS in the Rhizobacterium Strain Pseudomonas PA1201

Sun S, Tan LT, Fang YL, Jin ZJ, Zhou L, Goh BH, et al.

Mol Plant Microbe Interact, 2020 Mar;33(3):488-498.
PMID: 31710580 DOI: 10.1094/MPMI-09-19-0264-R

Phenazine-1-carboxylic acid (PCA) is the primary active component in the newly registered, commercial biopesticide Shenqinmycin and is produced during fermentation by the engineered rhizobacterium strain Pseudomonas PA1201. Both phz1 and phz2 gene clusters contribute to PCA biosynthesis. In this study, we evaluated the role of OxyR in the regulation of PCA biosynthesis in PA1201. We first showed a functional link between oxyR expression and PCA biosynthesis. Deletion of oxyR and overexpression of oxyR both increase PCA biosynthesis. The molecular mechanisms underlying OxyR regulation of PCA production were investigated using several approaches. OxyR acts divergently in phz1 and phz2. Overexpression of oxyR activated the expression of phz1 and phz1-dependent PCA production. However, overexpression of oxyR had little effect on phz2-dependent PCA biosynthesis, while deletion of oxyR promoted phz2-dependent PCA production and exerted a negative effect on phz2 expression. Further, OxyR directly bound to the phz2 promoter region. In addition, the regulation of PCA biosynthesis by OxyR was associated with quorum sensing (QS) systems. Overexpression of OxyR positively regulated pqs QS system. Finally, transcriptomic analysis and subsequent genetic analysis revealed the small RNA phrS plays a key role in OxyR-dependent PCA accumulation. Specifically, OxyR directly binds to the phrS promoter region to positively regulate phrS expression wherein PhrS regulates the PCA positive regulator MvfR in order to control PCA biosynthesis.
Fulltext Author Correction: Streptomyces monashensis sp. nov., a novel mangrove soil actinobacterium from East Malaysia with antioxidative potential

Law JW, Ser HL, Ab Mutalib NS, Saokaew S, Duangjai A, Khan TM, et al.

Sci Rep, 2020 Jan 10;10(1):319.
PMID: 31924829 DOI: 10.1038/s41598-019-55964-4

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Fulltext Streptomyces monashensis sp. nov., a novel mangrove soil actinobacterium from East Malaysia with antioxidative potential

Law JW, Ser HL, Ab Mutalib NS, Saokaew S, Duangjai A, Khan TM, et al.

Sci Rep, 2019 02 28;9(1):3056.
PMID: 30816228 DOI: 10.1038/s41598-019-39592-6

A new Streptomyces species discovered from Sarawak mangrove soil is described, with the proposed name - Streptomyces monashensis sp. nov. (strain MUSC 1JT). Taxonomy status of MUSC 1JT was determined via polyphasic approach. Phylogenetic and chemotaxonomic properties of strain MUSC 1JT were in accordance with those known for genus Streptomyces. Based on phylogenetic analyses, the strains closely related to MUSC 1JT were Streptomyces corchorusii DSM 40340T (98.7%), Streptomyces olivaceoviridis NBRC 13066T (98.7%), Streptomyces canarius NBRC 13431T (98.6%) and Streptomyces coacervatus AS-0823T (98.4%). Outcomes of DNA-DNA relatedness between strain MUSC 1JT and its closely related type strains covered from 19.7 ± 2.8% to 49.1 ± 4.3%. Strain MUSC 1JT has genome size of 10,254,857 bp with DNA G + C content of 71 mol%. MUSC 1JT extract exhibited strong antioxidative activity up to 83.80 ± 4.80% in the SOD assay, with significant cytotoxic effect against colon cancer cell lines HCT-116 and SW480. Streptomyces monashensis MUSC 1JT (=DSM 103626T = MCCC 1K03221T) could potentially be a producer of novel bioactive metabolites; hence discovery of this new species may be highly significant to the biopharmaceutical industry as it could lead to development of new and useful chemo-preventive drugs.

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