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Molecular characterization of Antarctic actinobacteria and screening for antimicrobial metabolite production

Lee LH, Cheah YK, Mohd Sidik S, Ab Mutalib NS, Tang YL, Lin HP, et al.

World J Microbiol Biotechnol, 2012 May;28(5):2125-37.
PMID: 22806035 DOI: 10.1007/s11274-012-1018-1

The present study aimed to isolate actinobacteria from soil samples and characterized them using molecular tools and screened their secondary metabolites for antimicrobial activities. Thirty-nine strains from four different location of Barrientos Island, Antarctica using 12 types of isolation media was isolated. The isolates were preceded to screening of secondary metabolites for antimicrobial and antifungal activities. Using high-throughput screening methods, 38% (15/39) of isolates produced bioactive metabolites. Approximately 18% (7/39), 18% (7/39), 10% (4/39) and 2.5% (1/39) of isolates inhibited growth of Candida albicans ATCC 10231(T), Staphylococcus aurues ATCC 51650(T), methicillin-resistant Staphylococcus aurues (MRSA) ATCC BAA-44(T) and Pseudomonas aeruginosa ATCC 10145(T), respectively. Molecular characterization techniques like 16S rRNA analysis, Enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR), Random amplified polymorphic DNA (RAPD) and composite analyses were used to characterize the actinobacteria strains. Analysis of 16S rRNA sequences is still one of the most powerful methods to determine higher taxonomic relationships of Actinobacteria. Both RAPD and ERIC-PCR fingerprinting have shown good discriminatory capability but RAPD proved to be better in discriminatory power than ERIC-PCR. Our results demonstrated that composite analysis of both fingerprinting generally increased the discrimination ability and generated best clustering for actinobacteria strains in this study.
Fulltext Molecular Markers of Diabetic Retinopathy: Potential Screening Tool of the Future?

Pusparajah P, Lee LH, Abdul Kadir K

Front Physiol, 2016;7:200.
PMID: 27313539 DOI: 10.3389/fphys.2016.00200

Diabetic retinopathy (DR) is among the leading causes of new onset blindness in adults. Effective treatment may delay the onset and progression of this disease provided it is diagnosed early. At present retinopathy can only be diagnosed via formal examination of the eye by a trained specialist, which limits the population that can be effectively screened. An easily accessible, reliable screening biomarker of diabetic retinopathy would be of tremendous benefit in detecting the population in need of further assessment and treatment. This review highlights specific biomarkers that show promise as screening markers to detect early diabetic retinopathy or even to detect patients at increased risk of DR at the time of diagnosis of diabetes. The pathobiology of DR is complex and multifactorial giving rise to a wide array of potential biomarkers. This review provides an overview of these pathways and looks at older markers such as advanced glycation end products (AGEs), inflammatory markers, vascular endothelial growth factor (VEGF) as well as other newer proteins with a role in the pathogenesis of DR including neuroprotective factors such as brain derived neurotrophic factor (BDNF) and Pigment Epithelium Derived Factor (PEDF); SA100A12, pentraxin 3, brain natriuretic peptide, apelin 3, and chemerin as well as various metabolites such as lipoprotein A, folate, and homocysteine. We also consider the possible role of proteins identified through proteomics work whose levels are altered in the sera of patients with DR as screening markers though their role in pathophysiology remains to be characterized. The role of microRNA as a promising new screening marker is also discussed.
Fulltext Microsatellite Instability in Colorectal Cancer Liquid Biopsy-Current Updates on Its Potential in Non-Invasive Detection, Prognosis and as a Predictive Marker

Tieng FYF, Abu N, Lee LH, Ab Mutalib NS

Diagnostics (Basel), 2021 Mar 18;11(3).
PMID: 33803882 DOI: 10.3390/diagnostics11030544

Colorectal cancer (CRC) is the third most commonly-diagnosed cancer in the world and ranked second for cancer-related mortality in humans. Microsatellite instability (MSI) is an indicator for Lynch syndrome (LS), an inherited cancer predisposition, and a prognostic marker which predicts the response to immunotherapy. A recent trend in immunotherapy has transformed cancer treatment to provide medical alternatives that have not existed before. It is believed that MSI-high (MSI-H) CRC patients would benefit from immunotherapy due to their increased immune infiltration and higher neo-antigenic loads. MSI testing such as immunohistochemistry (IHC) and PCR MSI assay has historically been a tissue-based procedure that involves the testing of adequate tissue with a high concentration of cancer cells, in addition to the requirement for paired normal tissues. The invasive nature and specific prerequisite of such tests might hinder its application when surgery is not an option or when the tissues are insufficient. The application of next-generation sequencing, which is highly sensitive, in combination with liquid biopsy, therefore, presents an interesting possibility worth exploring. This review aimed to discuss the current body of evidence supporting the potential of liquid biopsy as a tool for MSI testing in CRC.
Microbacterium mangrovi sp. nov., an amylolytic actinobacterium isolated from mangrove forest soil

Lee LH, Azman AS, Zainal N, Eng SK, Mutalib NA, Yin WF, et al.

Int J Syst Evol Microbiol, 2014 Oct;64(Pt 10):3513-3519.
PMID: 25056298 DOI: 10.1099/ijs.0.062414-0

Strain MUSC 115(T) was isolated from mangrove soil of the Tanjung Lumpur river in the state of Pahang, Peninsular Malaysia. Cells of this strain stained Gram-positive and were non-spore-forming, short rods that formed yellowish-white colonies on different agar media. The taxonomy of strain MUSC 115(T) was studied by a polyphasic approach, and the organism showed a range of phylogenetic and chemotaxonomic properties consistent with those of the genus Microbacterium. The cell-wall peptidoglycan was of type B2β, containing the amino acids ornithine, alanine, glycine, glutamic acid and homoserine. The muramic acid was of the N-glycolyl form. The predominant menaquinones detected were MK-12, MK-13 and MK-11. The polar lipids consisted of phosphatidylglycerol, phosphoglycolipid, diphosphatidylglycerol, two unidentified lipids, three unidentified phospholipids and four unidentified glycolipids. The major fatty acids of the cell membrane were anteiso-C15:0 and anteiso-C17:0. The whole-cell sugars detected were ribose, glucose, mannose and galactose. Based on the 16S rRNA gene sequence, strain MUSC 115(T) showed the highest sequence similarity to Microbacterium immunditiarum SK 18(T) (98.1%), M. ulmi XIL02(T) (97.8%) and M. arborescens DSM 20754(T) (97.5%) and lower sequence similarity to strains of other species of the genus Microbacterium. DNA-DNA hybridization experiments revealed a low level of DNA-DNA relatedness (less than 24%) between strain MUSC 115(T) and the type strains of closely related species. Furthermore, BOX-PCR fingerprint comparison also indicated that strain MUSC 115(T) represented a unique DNA profile. The DNA G+C content determined was 70.9 ± 0.7 mol%, which is lower than that of M. immunditiarum SK 18(T). Based on the combination of genotypic and phenotypic data, it is proposed that strain MUSC 115(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium mangrovi sp. nov. is proposed. The type strain is MUSC 115(T) ( = MCCC 1K00251(T) = DSM 28240(T) = NBRC 110089(T)).
Fulltext Mangrove rare actinobacteria: taxonomy, natural compound, and discovery of bioactivity

Azman AS, Othman I, Velu SS, Chan KG, Lee LH

Front Microbiol, 2015;6:856.
PMID: 26347734 DOI: 10.3389/fmicb.2015.00856

Actinobacteria are one of the most important and efficient groups of natural metabolite producers. The genus Streptomyces have been recognized as prolific producers of useful natural compounds as they produced more than half of the naturally-occurring antibiotics isolated to-date and continue as the primary source of new bioactive compounds. Lately, Streptomyces groups isolated from different environments produced the same types of compound, possibly due to frequent genetic exchanges between species. As a result, there is a dramatic increase in demand to look for new compounds which have pharmacological properties from another group of Actinobacteria, known as rare actinobacteria; which is isolated from special environments such as mangrove. Recently, mangrove ecosystem is becoming a hot spot for studies of bioactivities and the discovery of natural products. Many novel compounds discovered from the novel rare actinobacteria have been proven as potential new drugs in medical and pharmaceutical industries such as antibiotics, antimicrobials, antibacterials, anticancer, and antifungals. This review article highlights the latest studies on the discovery of natural compounds from the novel mangrove rare actinobacteria and provides insight on the impact of these findings.
Fulltext Mangrove derived Streptomyces sp. MUM265 as a potential source of antioxidant and anticolon-cancer agents

Tan LT, Chan KG, Pusparajah P, Yin WF, Khan TM, Lee LH, et al.

BMC Microbiol, 2019 02 13;19(1):38.
PMID: 30760201 DOI: 10.1186/s12866-019-1409-7

BACKGROUND: Colon cancer is the third most commonly diagnosed cancer worldwide, with a commensurately high mortality rate. The search for novel antioxidants and specific anticancer agents which may inhibit, delay or reverse the development of colon cancer is thus an area of great interest; Streptomyces bacteria have been demonstrated to be a source of such agents.
RESULTS: The extract from Streptomyces sp. MUM265- a strain which was isolated and identified from Kuala Selangor mangrove forest, Selangor, Malaysia- was analyzed and found to exhibit antioxidant properties as demonstrated via metal-chelating ability as well as superoxide anion, DPPH and ABTS radical scavenging activities. This study also showed that MUM265 extract demonstrated cytotoxicity against colon cancer cells as evidenced by the reduced cell viability of Caco-2 cell line. Treatment with MUM265 extract induced depolarization of mitochondrial membrane potential and accumulation of subG1 cells in cell cycle analysis, suggesting that MUM265 exerted apoptosis-inducing effects on Caco-2 cells.
CONCLUSION: These findings indicate that mangrove derived Streptomyces sp. MUM265 represents a valuable bioresource of bioactive compounds for the future development of chemopreventive agents, with particular promise suggested for treatment of colon cancer.
Fulltext Investigation of Antioxidative and Anticancer Potentials of Streptomyces sp. MUM256 Isolated from Malaysia Mangrove Soil

Tan LT, Ser HL, Yin WF, Chan KG, Lee LH, Goh BH

Front Microbiol, 2015;6:1316.
PMID: 26635777 DOI: 10.3389/fmicb.2015.01316

A Streptomyces strain, MUM256 was isolated from Tanjung Lumpur mangrove soil in Malaysia. Characterization of the strain showed that it has properties consistent with those of the members of the genus Streptomyces. In order to explore the potential bioactivities, extract of the fermented broth culture of MUM256 was prepared with organic solvent extraction method. DPPH and SOD activity were utilized to examine the antioxidant capacity and the results have revealed the potency of MUM256 in superoxide anion scavenging activity in dose-dependent manner. The cytotoxicity of MUM256 extract was determined using cell viability assay against 8 different panels of human cancer cell lines. Among all the tested cancer cells, HCT116 was the most sensitive toward the extract treatment. At the highest concentration of tested extract, the result showed 2.3-, 2.0-, and 1.8-folds higher inhibitory effect against HCT116, HT29, and Caco-2 respectively when compared to normal cell line. This result has demonstrated that MUM256 extract was selectively cytotoxic toward colon cancer cell lines. In order to determine the constituents responsible for its bioactivities, the extract was then subjected to chemical analysis using GC-MS. The analysis resulted in the identification of chemical constituents including phenolic and pyrrolopyrazine compounds which may responsible for antioxidant and anticancer activities observed. Based on the findings of this study, the presence of bioactive constituents in MUM256 extract could be a potential source for the development of antioxidative and chemopreventive agents.
Fulltext Insights into Bacteriophage Application in Controlling Vibrio Species

Letchumanan V, Chan KG, Pusparajah P, Saokaew S, Duangjai A, Goh BH, et al.

Front Microbiol, 2016;7:1114.
PMID: 27486446 DOI: 10.3389/fmicb.2016.01114

Bacterial infections from various organisms including Vibrio sp. pose a serious hazard to humans in many forms from clinical infection to affecting the yield of agriculture and aquaculture via infection of livestock. Vibrio sp. is one of the main foodborne pathogens causing human infection and is also a common cause of losses in the aquaculture industry. Prophylactic and therapeutic usage of antibiotics has become the mainstay of managing this problem, however, this in turn led to the emergence of multidrug resistant strains of bacteria in the environment; which has raised awareness of the critical need for alternative non-antibiotic based methods of preventing and treating bacterial infections. Bacteriophages - viruses that infect and result in the death of bacteria - are currently of great interest as a highly viable alternative to antibiotics. This article provides an insight into bacteriophage application in controlling Vibrio species as well underlining the advantages and drawbacks of phage therapy.
Fulltext Incidence of methicillin resistant Staphylococcus aureus (MRSA) in burn intensive care unit: a systematic review

Khan TM, Kok YL, Bukhsh A, Lee LH, Chan KG, Goh BH

Germs, 2018 Sep;8(3):113-125.
PMID: 30250830 DOI: 10.18683/germs.2018.1138

Background: Burn victims admitted in burn intensive care units (ICU) are at a high risk of nosocomial infections generated by methicillin resistant Staphylococcus aureus (MRSA). This systematic review aims to estimate the incidence of MRSA among burn patients admitted to the ICU setting, with an emphasis on the incidence rate and antibiotic resistance profile of the MRSA strains.
Methods: A systematic literature search was performed in five electronic databases limited to publication dates from 1st January 2000 until 31st August 2017. After screening n=481 articles, n=21 were found to meet the inclusion criteria of this systematic review.
Results: Results from the meta-analysis revealed that the risk for MRSA isolates in the burn ICU was 55.0% higher (OR 0.55, 95%CI 0.32-0.94). Therefore, timely testing, appropriate hygiene practice and suggested wound care must be practiced while handling such patients.
Conclusion: Further studies are needed to identify the risk factors of MRSA infections among burn patients and to develop new antimicrobial agents for MRSA infections.
IRF5-mediated immune responses and its implications in immunological disorders

Kaur A, Lee LH, Chow SC, Fang CM

Int Rev Immunol, 2018;37(5):229-248.
PMID: 29985675 DOI: 10.1080/08830185.2018.1469629

Transcription factors are gene regulators that activate or repress target genes. One family of the transcription factors that have been extensively studied for their crucial role in regulating gene network in the immune system is the interferon regulatory factors (IRFs). IRFs possess a novel turn-helix turn motif that recognizes a specific DNA consensus found in the promoters of many genes that are involved in immune responses. IRF5, a member of IRFs has recently gained much attention for its role in regulating inflammatory responses and autoimmune diseases. Here, we discuss the role of IRF5 in regulating immune cells functions and how the dysregulation of IRF5 contributes to the pathogenesis of immune disorders. We also review the latest findings of potential IRF5 inhibitors that modulate IRF5 activity in the effort of developing therapeutic approaches for treating inflammatory disorders.
Fulltext Gynura procumbens: An Overview of the Biological Activities

Tan HL, Chan KG, Pusparajah P, Lee LH, Goh BH

Front Pharmacol, 2016;7:52.
PMID: 27014066 DOI: 10.3389/fphar.2016.00052

Gynura procumbens (Lour.) Merr. (Family Asteraceae) is a medicinal plant commonly found in tropical Asia countries such as China, Thailand, Indonesia, Malaysia, and Vietnam. Traditionally, it is widely used in many different countries for the treatment of a wide variety of health ailments such as kidney discomfort, rheumatism, diabetes mellitus, constipation, and hypertension. Based on the traditional uses of G. procumbens, it seems to possess high therapeutic potential for treatment of various diseases making it a target for pharmacological studies aiming to validate and provide scientific evidence for the traditional claims of its efficacy. Although there has been considerable progress in the research on G. procumbens, to date there is no review paper gathering the reported biological activities of G. procumbens. Hence, this review aims to provide an overview of the biological activities of G. procumbens based on reported in vitro and in vivo studies. In brief, G. procumbens has been reported to exhibit antihypertensive, cardioprotective, antihyperglycemic, fertility enhancement, anticancer, antimicrobial, antioxidant, organ protective, and antiinflammatory activity. The commercial applications of G. procumbens have also been summarized in this paper based on existing patents. The data compiled illustrate that G. procumbens is a potential natural source of compounds with various pharmacological actions which can be utilized for the development of novel therapeutic agents.
Fulltext Golden Needle Mushroom: A Culinary Medicine with Evidenced-Based Biological Activities and Health Promoting Properties

Tang C, Hoo PC, Tan LT, Pusparajah P, Khan TM, Lee LH, et al.

Front Pharmacol, 2016;7:474.
PMID: 28003804 DOI: 10.3389/fphar.2016.00474

Flammulina velutipes (enoki, velvet shank, golden needle mushroom or winter mushroom), one of the main edible mushrooms on the market, has long been recognized for its nutritional value and delicious taste. In recent decades, research has expanded beyond detailing its nutritional composition and delved into the biological activities and potential health benefits of its constituents. Many bioactive constituents from a range of families have been isolated from different parts of the mushroom, including carbohydrates, protein, lipids, glycoproteins, phenols, and sesquiterpenes. These compounds have been demonstrated to exhibit various biological activities, such as antitumour and anticancer activities, anti-atherosclerotic and thrombosis inhibition activity, antihypertensive and cholesterol lowering effects, anti-aging and antioxidant properties, ability to aid with restoring memory and overcoming learning deficits, anti-inflammatory, immunomodulatory, anti-bacterial, ribosome inactivation and melanosis inhibition. This review aims to consolidate the information concerning the phytochemistry and biological activities of various compounds isolated from F. velutipes to demonstrate that this mushroom is not only a great source of nutrients but also possesses tremendous potential in pharmaceutical drug development.
Genome sequence of Streptomyces pluripotens MUSC 135(T) exhibiting antibacterial and antioxidant activity

Ser HL, Tan WS, Ab Mutalib NS, Cheng HJ, Yin WF, Chan KG, et al.

Mar Genomics, 2015 Dec;24 Pt 3:281-3.
PMID: 26452302 DOI: 10.1016/j.margen.2015.09.010

Isolated from intertidal soil, Streptomyces pluripotens MUSC 135(T) produces a broad-spectrum bacteriocin against the pathogens methicillin-resistant Staphylococcus aureus (MRSA) ATCC BAA-44(T), Salmonella typhi ATCC 19430(T) and Aeromonas hydrophila ATCC 7966(T). Along with antibacterial activity, fermentation studies on strain MUSC 135(T) revealed production of antioxidant(s). The high quality draft genome of MUSC 135(T) comprises 7,480,269 bp with G+C content of 70.00%. Through bioinformatics analysis, 72 gene clusters identified in the genome were associated with the production of secondary metabolites, which may shed light on the identity of these bioactive compounds.
Fulltext Genome sequence of Streptomyces mangrovisoli MUSC 149T isolated from intertidal sediments

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

Braz J Microbiol, 2017 09 06;49(1):13-15.
PMID: 28927873 DOI: 10.1016/j.bjm.2017.01.013

As the largest genus in Actinobacteria family, Streptomyces species have the ability to synthesize numerous compounds of diverse structures with bioactivities. Streptomyces mangrovisoli MUSC 149T was previously isolated as a novel streptomycete from mangrove forest in east coast of Peninsular Malaysia. The high quality draft genome of MUSC 149T comprises 9,165,825bp with G+C content of 72.5%. Through bioinformatics analysis, 21 gene clusters identified in the genome were associated with the production of bioactive secondary metabolites. The presence of these biosynthetic gene clusters in MUSC 149T suggests the potential exploitation of the strain for production of medically important compounds.
Fulltext Genome sequence of Streptomyces gilvigriseus MUSC 26T isolated from mangrove forest

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

Braz J Microbiol, 2018 02 02;49(2):207-209.
PMID: 29428207 DOI: 10.1016/j.bjm.2017.04.012

Streptomycetes remain as one of the important sources for bioactive products. Isolated from the mangrove forest, Streptomyces gilvigriseus MUSC 26T was previously characterised as a novel streptomycete. The high quality draft genome of MUSC 26T contained 5,213,277bp with G+C content of 73.0%. Through genome mining, several gene clusters associated with secondary metabolites production were revealed in the genome of MUSC 26T. These findings call for further investigations into the potential exploitation of the strain for production of pharmaceutically important compounds.
Fulltext Genome Sequence of Vibrio parahaemolyticus VP152 Strain Isolated from Penaeus indicus in Malaysia

Letchumanan V, Ser HL, Tan WS, Ab Mutalib NS, Goh BH, Chan KG, et al.

Front Microbiol, 2016;7:1410.
PMID: 27656174 DOI: 10.3389/fmicb.2016.01410
Genome Sequence of Vibrio parahaemolyticus VP103 Strain Isolated from Shrimp in Malaysia

Letchumanan V, Ser HL, Chan KG, Goh BH, Lee LH

Front Microbiol, 2016;7:1496.
PMID: 27708636
Fructose promotes pyoluteorin biosynthesis via the CbrAB-CrcZ-Hfq/Crc pathway in the biocontrol strain Pseudomonas PA1201

Cui Y, Song K, Jin ZJ, Lee LH, Thawai C, He YW

Synth Syst Biotechnol, 2023 Dec;8(4):618-628.
PMID: 37823038 DOI: 10.1016/j.synbio.2023.09.004

Biocontrol strain Pseudomonas PA1201 produces pyoluteorin (Plt), which is an antimicrobial secondary metabolite. Plt represents a promising candidate pesticide due to its broad-spectrum antifungal and antibacterial activity. Although PA1201 contains a complete genetic cluster for Plt biosynthesis, it fails to produce detectable level of Plt when grown in media typically used for Pseudomonas strains. In this study, minimum medium (MM) was found to favor Plt biosynthesis. Using the medium M, which contains all the salts of MM medium except for mannitol, as a basal medium, we compared 10 carbon sources for their ability to promote Plt biosynthesis. Fructose, mannitol, and glycerol promoted Plt biosynthesis, with fructose being the most effective carbon source. Glucose or succinic acid had no significant effect on Plt biosynthesis, but effectively antagonized fructose-dependent synthesis of Plt. Promoter-lacZ fusion reporter strains demonstrated that fructose acted through activation of the pltLABCDEFG (pltL) operon but had no effect on other genes of plt gene cluster; glucose or succinic acid antagonized fructose-dependent pltL induction. Mechanistically, fructose-mediated Plt synthesis involved carbon catabolism repression. The two-component system CbrA/CbrB and small RNA catabolite repression control Z (crcZ) were essential for fructose-induced Plt synthesis. The small RNA binding protein Hfq and Crc negatively regulated fructose-induced Plt. Taken together, this study provides a new model of fructose-dependent Plt production in PA1201 that can help improve Plt yield by biosynthetic approaches.
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 Focused Review: Potential Rare and Atypical Symptoms as Indicator for Targeted COVID-19 Screening

Ng SL, Ong YS, Khaw KY, Teh SP, Tan CS, Ming LC, et al.

Medicina (Kaunas), 2021 Feb 23;57(2).
PMID: 33672384 DOI: 10.3390/medicina57020189

The global pandemic of the coronavirus disease 2019 is a known consequence of infection of severe respiratory syndrome coronavirus-2 (SARS-CoV-2). It has affected nations worldwide with soaring number of cases daily. Symptoms such as fever, cough, and shortness of breath, diarrhea, nausea and vomiting are commonly presented in COVID-19 patients. This focused review aims to discuss these uncommon and atypical COVID-19 symptoms that may be presented which might affect neurological, cardiovascular, cutaneous and ocular systems and their possible mode of actions. Nonetheless, there are some cases of reported uncommon or atypical symptoms which may warrant healthcare professionals to be aware of, especially when in contact with patients. The knowledge and information concerning these symptoms might be able to provide additional cues for healthcare professional by subjecting patients to COVID-19 screening. Meanwhile, it might be able to further enhance the alertness and additional precautions being taken by healthcare personnel, which eventually lead to reduced risk of infections.

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