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Fulltext Streptomyces sp. MUM273b: A mangrove-derived potential source for antioxidant and UVB radiation protectants

Tan LT, Mahendra CK, Yow YY, Chan KG, Khan TM, Lee LH, et al.

Microbiologyopen, 2019 10;8(10):e859.
PMID: 31199601 DOI: 10.1002/mbo3.859

Microbial natural products serve as a good source for antioxidants. The mangrove-derived Streptomyces bacteria have been evidenced to produce antioxidative compounds. This study reports the isolation of Streptomyces sp. MUM273b from mangrove soil that may serve as a promising source of antioxidants and UV-protective agents. Identification and characterization methods determine that strain MUM273b belongs to the genus Streptomyces. The MUM273b extract exhibits antioxidant activities, including DPPH, ABTS, and superoxide radical scavenging activities and also metal-chelating activity. The MUM273b extract was also shown to inhibit the production of malondialdehyde in metal-induced lipid peroxidation. Strong correlation between the antioxidant activities and the total phenolic content of MUM273b extract was shown. In addition, MUM273b extract exhibited cytoprotective effect on the UVB-induced cell death in HaCaT keratinocytes. Gas chromatography-mass spectrometry analysis detected phenolics, pyrrole, pyrazine, ester, and cyclic dipeptides in MUM273b extract. In summary, Streptomyces MUM273b extract portrays an exciting avenue for future antioxidative drugs and cosmeceuticals development.
Fulltext Comparative efficacy of antibiotic(s) alone or in combination of corticosteroids in adults with acute bacterial meningitis: A systematic review and network meta-analysis

Rayanakorn A, Ser HL, Pusparajah P, Chan KG, Goh BH, Khan TM, et al.

PLoS One, 2020;15(5):e0232947.
PMID: 32469959 DOI: 10.1371/journal.pone.0232947

OBJECTIVE: To compare relative efficacy of different antibiotic therapies either with or without the addition of corticosteroids among adult patients with acute bacterial meningitis on all-cause mortality, neurological complications and any hearing loss.
METHODS: We searched nine databases from inception to 8 February 2018 for randomized controlled trials evaluating pharmacological interventions and clinical outcomes in adult bacterial meningitis. An updated search from 9 February to 9 March 2020 was performed, and no new studies met the inclusion criteria. Study quality was assessed using the revised Cochrane Risk of Bias Tool. The Grading of Recommendations Assessment, Development and Evaluation system was used for quality of evidences evaluation. Meta-analyses were conducted to estimate the risk ratio with 95% confidence interval for both direct and indirect comparisons on the primary outcomes of all-cause mortality, neurologic sequelae and any hearing loss. The study was registered in PROSPERO (CRD42018108062).
RESULTS: Nine RCTs were included in systematic review, involving 1,002 participants with a mean age ranging between 25.3 to 50.56 years. Six RCTs were finally included in the network-meta analysis. No significant difference between treatment was noted in meta-analysis. Network meta-analysis suggests that corticosteroids in combination with antibiotic therapy was more effective in reducing the risk of any hearing loss compared to mono antibiotic therapy (RR 0.64; 95%CI, 0.45 to 0.91, 4 RCTs, moderate certainty of evidence). Numerical lower risk of mortality and neurological complications was also shown for adjunctive corticosteroids in combination with antibiotic therapy versus mono antibiotic therapy (RR 0.65; 95%CI, 0.42 to 1.02, 6 RCTs, moderate certainty of evidence; RR 0.75; 95%CI, 0.47 to 1.18, 6 RCTs, moderate certainty of evidence). No differences were noted in the adverse events between different therapies. The overall certainty of evidence was moderate to very low for all primary outcomes examined.
CONCLUSIONS: Results of this study suggest that corticosteroids therapy in combination with antibiotic is more effective than mono antibiotic therapy in reducing the risk of any hearing loss in adult patients with acute bacterial meningitis. More well-design RCTs to investigate relative effective treatments in acute bacterial meningitis particularly in adult population should be mandated to aid clinicians in treatment recommendations.
Fulltext Streptomyces sp.-A Treasure Trove of Weapons to Combat Methicillin-Resistant Staphylococcus aureus Biofilm Associated with Biomedical Devices

Pusparajah P, Letchumanan V, Law JW, Ab Mutalib NS, Ong YS, Goh BH, et al.

Int J Mol Sci, 2021 Aug 28;22(17).
PMID: 34502269 DOI: 10.3390/ijms22179360

Biofilms formed by methicillin-resistant S. aureus (MRSA) are among the most frequent causes of biomedical device-related infection, which are difficult to treat and are often persistent and recurrent. Thus, new and effective antibiofilm agents are urgently needed. In this article, we review the most relevant literature of the recent years reporting on promising anti-MRSA biofilm agents derived from the genus Streptomyces bacteria, and discuss the potential contribution of these newly reported antibiofilm compounds to the current strategies in preventing biofilm formation and eradicating pre-existing biofilms of the clinically important pathogen MRSA. Many efforts are evidenced to address biofilm-related infections, and some novel strategies have been developed and demonstrated encouraging results in preclinical studies. Nevertheless, more in vivo studies with appropriate biofilm models and well-designed multicenter clinical trials are needed to assess the prospects of these strategies.
Unraveling the Immunopathogenesis and Genetic Variants in Vasculitis Toward Development of Personalized Medicine

Yap BJM, Lai-Foenander AS, Goh BH, Ong YS, Duangjai A, Saokaew S, et al.

Front Cardiovasc Med, 2021;8:732369.
PMID: 34621800 DOI: 10.3389/fcvm.2021.732369

Leukocytoclastic vasculitis (LCV) is a systemic autoimmune disease characterized by the inflammation of the vascular endothelium. Cutaneous small vessel vasculitis (CSVV) and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) are two examples of LCV. Advancements in genomic technologies have identified risk haplotypes, genetic variants, susceptibility loci and pathways that are associated with vasculitis immunopathogenesis. The discovery of these genetic factors and their corresponding cellular signaling aberrations have enabled the development and use of novel therapeutic strategies for vasculitis. Personalized medicine aims to provide targeted therapies to individuals who show poor response to conventional interventions. For example, monoclonal antibody therapies have shown remarkable efficacy in achieving disease remission. Here, we discuss pathways involved in disease pathogenesis and the underlying genetic associations in different populations worldwide. Understanding the immunopathogenic pathways in vasculitis and identifying associated genetic variations will facilitate the development of novel and targeted personalized therapies for patients.
Fulltext Mitigation of Environmental Stress-Impacts in Plants: Role of Sole and Combinatory Exogenous Application of Glutathione

Koh YS, Wong SK, Ismail NH, Zengin G, Duangjai A, Saokaew S, et al.

Front Plant Sci, 2021;12:791205.
PMID: 35003181 DOI: 10.3389/fpls.2021.791205

Glutathione (GSH; γ-glutamyl-cysteinyl-glycine), a low-molecular-weight thiol, is the most pivotal metabolite involved in the antioxidative defense system of plants. The modulation of GSH on the plant in response to environmental stresses could be illustrated through key pathways such as reactive oxygen species (ROS) scavenging and signaling, methylglyoxal (MG) detoxification and signaling, upregulation of gene expression for antioxidant enzymes, and metal chelation and xenobiotic detoxification. However, under extreme stresses, the biosynthesis of GSH may get inhibited, causing an excess accumulation of ROS that induces oxidative damage on plants. Hence, this gives rise to the idea of exploring the use of exogenous GSH in mitigating various abiotic stresses. Extensive studies conducted borne positive results in plant growth with the integration of exogenous GSH. The same is being observed in terms of crop yield index and correlated intrinsic properties. Though, the improvement in plant growth and yield contributed by exogenous GSH is limited and subjected to the glutathione pool [GSH/GSSG; the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG)] homeostasis. Therefore, recent studies focused on the sequenced application of GSH was performed in order to complement the existing limitation. Along with various innovative approaches in combinatory use with different bioactive compounds (proline, citric acid, ascorbic acid, melatonin), biostimulants (putrescine, Moringa leaf extract, selenium, humic acid), and microorganisms (cyanobacteria) have resulted in significant improvements when compared to the individual application of GSH. In this review, we reinforced our understanding of biosynthesis, metabolism and consolidated different roles of exogenous GSH in response to environmental stresses. Strategy was also taken by focusing on the recent progress of research in this niche area by covering on its individualized and combinatory applications of GSH prominently in response to the abiotic stresses. In short, the review provides a holistic overview of GSH and may shed light on future studies and its uses.
Fibroblast-derived matrices-based human skin equivalent as an in vitro psoriatic model for drug testing

Yap WH, Cheah TY, Yong LC, Chowdhury SR, Ng MH, Kwan Z, et al.

J Biosci, 2021;46.
PMID: 34475316

Psoriasis is a chronic skin disease characterized by thickening and disorganization of the skin's protective barrier. Although current models replicate some aspects of the disease, development of therapeutic strategies have been hindered by absence of more relevant models. This study aimed to develop and characterize an in vitro psoriatic human skin equivalent (HSE) using human keratinocytes HaCat cell line grown on fibroblasts-derived matrices (FDM). The constructed HSEs were treated with cytokines (IL-1α, TNF-α, IL-6, and IL22) to allow controlled induction of psoriasis-associated features. Histological stainings showed that FDMHSE composed of a fully differentiated epidermis and fibroblast-populated dermis comparable to native skin and rat tail collagen-HSE. Hyperproliferation (CK16 and Ki67) and inflammatory markers (TNF-α and IL-6) expression were significantly enhanced in the cytokine-induced FDM- and rat tail collagen HSEs compared to non-treated HSE counterparts. The characteristics were in line with those observed in psoriasis punch biopsies. Treatment with all-trans retinoic acid (ATRA) has shown to suppress these effects, where HSE models treated with both ATRA and cytokines exhibit histological characteristics, hyperproliferation and differentiation markers expression like non-treated control HSEs. Cytokine-induced FDM-HSE, constructed entirely from human cell lines, provides an excellent opportunity for psoriasis research and testing new therapeutics.
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 Cancer protective effects of plums: A systematic review

Bahrin AA, Moshawih S, Dhaliwal JS, Kanakal MM, Khan A, Lee KS, et al.

Biomed Pharmacother, 2022 Feb;146:112568.
PMID: 34963086 DOI: 10.1016/j.biopha.2021.112568

Plums is one of the most cultivated stone fruits due to its fast growing popularity. It has various traditionally recognized health benefits. There are two main commercial types of plums: the European plum (Prunus domestica) and the Japanese plum (Prunus salicina), each having many varieties. Researchers are gathering further evidence of pharmacological effects for plums by scientifically studying its anti-inflammatory, antioxidant properties. A systematic review analysing the literature related to the effects of plums on prevention and treatment of cancer is warranted. This is the first review examining the cancer-related effects of plums. Antioxidation properties of the active constituents of plum were also compared. Scopus, Google Scholar, PubMed, Medxriv and Cochrane Library databases, from their date of inception until July 2021 were utilized. The risk of bias was assessed using CONSORT checklist. A total of 6639 studies were screened and eventually only 54 studies were included. Full-text review of included studies revealed that plum extracts were rich in antioxidants. Overall, most of the studies that fulfilled the eligibility criteria were in vitro and a few clinical studies involving in vivo work. Therefore, it would be beneficial to perform more studies on animals or humans, to confirm that the result obtained from these in vitro studies are able to be extrapolated in a wider range of applications. Further clinical and in vivo studies are warranted to validate plums as a functional food for treatment and prevention of cancer.
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 Targeting Membrane Lipid a Potential Cancer Cure?

Tan LT, Chan KG, Pusparajah P, Lee WL, Chuah LH, Khan TM, et al.

Front Pharmacol, 2017;8:12.
PMID: 28167913 DOI: 10.3389/fphar.2017.00012

Cancer mortality and morbidity is projected to increase significantly over the next few decades. Current chemotherapeutic strategies have significant limitations, and there is great interest in seeking novel therapies which are capable of specifically targeting cancer cells. Given that fundamental differences exist between the cellular membranes of healthy cells and tumor cells, novel therapies based on targeting membrane lipids in cancer cells is a promising approach that deserves attention in the field of anticancer drug development. Phosphatidylethanolamine (PE), a lipid membrane component which exists only in the inner leaflet of cell membrane under normal circumstances, has increased surface representation on the outer membrane of tumor cells with disrupted membrane asymmetry. PE thus represents a potential chemotherapeutic target as the higher exposure of PE on the membrane surface of cancer cells. This feature as well as a high degree of expression of PE on endothelial cells in tumor vasculature, makes PE an attractive molecular target for future cancer interventions. There have already been several small molecules and membrane-active peptides identified which bind specifically to the PE molecules on the cancer cell membrane, subsequently inducing membrane disruption leading to cell lysis. This approach opens up a new front in the battle against cancer, and is of particular interest as it may be a strategy that may be prove effective against tumors that respond poorly to current chemotherapeutic agents. We aim to highlight the evidence suggesting that PE is a strong candidate to be explored as a potential molecular target for membrane targeted novel anticancer therapy.
Health-related quality of life of dialysis patients during early COVID-19 lockdowns: a snapshot from a public hospital in Malaysia

Paneerselvam GS, Goh KW, Kassab YW, Farrukh MJ, Goh BH, Lua PL, et al.

Front Med (Lausanne), 2023;10:992870.
PMID: 37305144 DOI: 10.3389/fmed.2023.992870

BACKGROUND: End-stage renal disease is the last stage of chronic kidney disease and can affect the quality of life (QOL) of dialysis patients. The aim of this study was to assess the quality of life and examine its determinants.
METHODS: A cross-sectional survey involving patients on dialysis in a tertiary hospital was conducted from July 2020 to September 2020. Demographic data were collected using a predesigned questionnaire. QOL was measured using the 36-item KDQOL questionnaire, and statistical analysis was carried out using SPSS version 25.
RESULTS: Of the 108 patients, 59 were men and 49 were women, and the mean age was 48.15 ± 15.4 years. The results showed that there was no significant difference in the mean score of all components of health-related quality of life in different types of dialysis. The demographic data, which included age, gender, ethnicity, marital status, education level, occupation, and monthly income, did not significantly affect the QOL of dialysis patients. Patients with a dialysis duration of more than 5 years had a better QOL compared to other groups. Laboratory parameters such as low albumin and low hemoglobin showed a significant correlation with the health-related quality of life of dialysis patients.
CONCLUSION: The quality of life among patients on dialysis was impaired, especially in terms of burden of the kidney disease. Hypoalbuminemia and anemia were the two factors that influenced QOL.
Fulltext Mentha longifolia Essential Oil and Pulegone in Edible Coatings of Alginate and Chitosan: Effects on Pathogenic Bacteria in Lactic Cheese

Shahdadi F, Faryabi M, Khan H, Sardoei AS, Fazeli-Nasab B, Goh BH, et al.

Molecules, 2023 Jun 05;28(11).
PMID: 37299028 DOI: 10.3390/molecules28114554

Mentha longifolia is a valuable medicinal and aromatic plant that belongs to Lamiaceae family. This study looked at the antibacterial effects of M. longifolia essential oil and pulegone in edible coatings made of chitosan and alginate on the growth of Staphylococcus aureus, Listeria monocytogenes, and Escherichia coli in cheese. For this purpose, first fresh mint plant was collected from the cold region of Jiroft in Kerman province. Plant samples were dried in the shade at ambient temperature, and essential oil was prepared using Clevenger. The essential oil was analyzed by gas chromatography using mass spectrometric (GC/MS) detection. The major composition of M. longifolia oil was pulegone (26.07%), piperitone oxide (19.72%), and piperitone (11.88%). The results showed that adding M. longifolia essential oils and pulegone to edible coatings significantly reduced the growth of bacteria during storage. The bacterial population decreased by increasing the concentration of chitosan, M. longifolia, and pulegone in edible coatings. When the effects of pulegone and M. longifolia essential oils on bacteria were compared, it was found that pulegone had a stronger effect on bacterial population reduction. Coating treatments showed more antibacterial activity on E. coli than other bacteria. In general, the results of this research showed that alginate and chitosan coatings along with M. longifolia essential oil and its active ingredient pulegone had antibacterial effects against S. aureus, L. monocytogenes, and E. coli in cheese.
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 Streptomyces sp. MUM256: A Source for Apoptosis Inducing and Cell Cycle-Arresting Bioactive Compounds against Colon Cancer Cells

Tan LT, Chan CK, Chan KG, Pusparajah P, Khan TM, Ser HL, et al.

Cancers (Basel), 2019 Nov 06;11(11).
PMID: 31698795 DOI: 10.3390/cancers11111742

New and effective anticancer compounds are much needed as the incidence of cancer continues to rise. Microorganisms from a variety of environments are promising sources of new drugs; Streptomyces sp. MUM256, which was isolated from mangrove soil in Malaysia as part of our ongoing efforts to study mangrove resources, was shown to produce bioactive metabolites with chemopreventive potential. This present study is a continuation of our previous efforts and aimed to investigate the underlying mechanisms of the ethyl acetate fraction of MUM256 crude extract (MUM256 EA) in inhibiting the proliferation of HCT116 cells. Our data showed that MUM256 EA reduced proliferation of HCT116 cells via induction of cell-cycle arrest. Molecular studies revealed that MUM256 EA regulated the expression level of several important cell-cycle regulatory proteins. The results also demonstrated that MUM256 EA induced apoptosis in HCT116 cells mediated through the intrinsic pathway. Gas chromatography-mass spectrometry (GC-MS) analysis detected several chemical compounds present in MUM256 EA, including cyclic dipeptides which previous literature has reported to demonstrate various pharmacological properties. The cyclic dipeptides were further shown to inhibit HCT116 cells while exerting little to no toxicity on normal colon cells in this study. Taken together, the findings of this project highlight the important role of exploring the mangrove microorganisms as a bioresource which hold tremendous promise for the development of chemopreventive drugs against colorectal cancer.
Bacterial extracellular vesicles in biofluids as potential diagnostic biomarkers

Su KY, Koh Kok JY, Chua YW, Ong SD, Ser HL, Pusparajah P, et al.

Expert Rev Mol Diagn, 2022 Dec;22(12):1057-1062.
PMID: 36629056 DOI: 10.1080/14737159.2022.2166403

INTRODUCTION: Extracellular vesicles (EVs) are spherical membrane-derived lipid bilayers released by cells. The human microbiota consists of trillions of microorganisms, with bacteria being the largest group secreting microbial EVs. The discovery of bacterial EVs (BEVs) has garnered interest among researchers as potential diagnostic markers, given that the microbiota is known to be associated with various diseases and EVs carry important macromolecular cargo for intercellular interaction.
AREAS COVERED: The differential bacterial composition identified from BEVs isolated from biofluids between patients and healthy controls may be valuable for detecting diseases. Therefore, BEVs may serve as novel diagnostic markers. Literature search on PubMed and Google Scholar databases was conducted. In this special report, we outline the commonly used approach for investigating BEVs in biofluids, the 16S ribosomal RNA gene sequencing of V3-V4 hypervariable regions, and the recent studies exploring the potential of BEVs as biomarkers for various diseases.
EXPERT OPINION: The emerging field of BEVs offers new possibilities for the diagnosis of various types of diseases, although there remain issues that need to be resolved in this research area to implement BEVs in clinical applications. Hence, it is important for future studies to take these challenges into consideration when investigating the diagnostic value of BEVs.
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.
Fulltext Polymorphism of HLA and Susceptibility of Breast Cancer

Aboulaghras S, Khalid A, Makeen HA, Alhazmi HA, Albratty M, Mohan S, et al.

Front Biosci (Landmark Ed), 2024 Feb 05;29(2):55.
PMID: 38420797 DOI: 10.31083/j.fbl2902055

Breast cancer (BC) is the second most common malignancy in the world. Numerous studies have demonstrated the association between human leukocyte antigen (HLA) and cancer. The occurrence and development of BC are closely linked to genetic factors. Human leukocyte antigens G and E (HLA-G and HLA-E) are non-classical major histocompatibility complex (MHC) class I molecules. These molecules play an important role in immune surveillance by inhibiting the cytotoxic and natural killer T cells responsible for immune escape. The expression of HLA-G and HLA-E has been associated with several diseases, including tumors. The HLA system plays a key role in the escape of tumor cells from immune surveillance. This review aims to determine the correlation between BC susceptibility and HLA markers specific HLA alleles such as HLA-B07, HLA-DRB111, HLA-DRB113, and HLA-DRB115 are associated with an increased risk of developing BC. Furthermore, HLA-G mutations have been attributed to an elevated likelihood of metastasis in BC patients. Understanding the complex associations between the HLA system and BC development is critical for developing novel cancer prevention, detection, and treatment strategies. This review emphasizes the importance of analyzing HLA polymorphisms in the management of BC patients, as well as the urgent need for further research in this area.
Fulltext Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review

Ser HL, Law JW, Chaiyakunapruk N, Jacob SA, Palanisamy UD, Chan KG, et al.

Front Microbiol, 2016;7:522.
PMID: 27148211 DOI: 10.3389/fmicb.2016.00522

The β-lactamase inhibitor, clavulanic acid is frequently used in combination with β-lactam antibiotics to treat a wide spectrum of infectious diseases. Clavulanic acid prevents drug resistance by pathogens against these β-lactam antibiotics by preventing the degradation of the β-lactam ring, thus ensuring eradication of these harmful microorganisms from the host. This systematic review provides an overview on the fermentation conditions that affect the production of clavulanic acid in the firstly described producer, Streptomyces clavuligerus. A thorough search was conducted using predefined terms in several electronic databases (PubMed, Medline, ScienceDirect, EBSCO), from database inception to June 30th 2015. Studies must involve wild-type Streptomyces clavuligerus, and full texts needed to be available. A total of 29 eligible articles were identified. Based on the literature, several factors were identified that could affect the production of clavulanic acid in S. clavuligerus. The addition of glycerol or other vegetable oils (e.g., olive oil, corn oil) could potentially affect clavulanic acid production. Furthermore, some amino acids such as arginine and ornithine, could serve as potential precursors to increase clavulanic acid yield. The comparison of different fermentation systems revealed that fed-batch fermentation yields higher amounts of clavulanic acid as compared to batch fermentation, probably due to the maintenance of substrates and constant monitoring of certain entities (such as pH, oxygen availability, etc.). Overall, these findings provide vital knowledge and insight that could assist media optimization and fermentation design for clavulanic acid production in S. clavuligerus.
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.

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