Displaying publications 1 - 20 of 23 in total

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  1. Phuna ZX, Madhavan P
    Eur J Neurosci, 2022 Jan 19.
    PMID: 35048439 DOI: 10.1111/ejn.15599
    Candida spp., Malassezia spp., Cladosporium spp. and Alternaria spp. are among the most common fungi detected in the brain of patients with Alzheimer's disease (AD). These fungi are opportunistic organisms, where they often cause infection among immunocompromised patients. Coincidentally, these fungi can reach the brain and cause fungal meningitis. In general, they enter the brain via systemic infection due to disrupted epithelial barrier from skin and gut colonization. Once it reaches the brain, Candida species has been postulated to induce fungal glial granulomas with amyloid precursor protein (APP) accumulated inside. Cleavage of APP can lead to the production of amyloid beta (Aβ). Malassezia species can lead to neuroinflammation via activating helper T-cell (Th) 1 and Th17 immune response. Besides that, the pathogenesis of Cladosporium species and Alternaria species in AD remains unknown, but it could be related to the neuroinflammation. These two fungal species may have involved in acetylcholinesterase (AChE) inhibitor production in the brain. All these four fungi can be detected at the same time in the brain, which contribute to chronic neuroinflammation and neurodegeneration in the brain. This review hopes to shed some light in understanding the presence of fungi in the brain and their possible role in AD pathogenesis.
  2. Phuna ZX, Madhavan P
    Int J Neurosci, 2023 Dec;133(10):1071-1089.
    PMID: 35282779 DOI: 10.1080/00207454.2022.2045290
    Alzheimer disease (AD) is a progressive neurological disorder that accounted for the most common cause of dementia in the elderly population. Lately, 'infection hypothesis' has been proposed where the infection of microbes can lead to the pathogenesis of AD. Among different types of microbes, human immunodeficiency virus-1 (HIV-1), herpes simplex virus-1 (HSV-1), Chlamydia pneumonia, Spirochetes and Candida albicans are frequently detected in the brain of AD patients. Amyloid-beta protein has demonstrated to exhibit antimicrobial properties upon encountering these pathogens. It can bind to microglial cells and astrocytes to activate immune response and neuroinflammation. Nevertheless, HIV-1 and HSV-1 can develop into latency whereas Chlamydia pneumonia, Spirochetes and Candida albicans can cause chronic infections. At this stage, the DNA of microbes remains undetectable yet active. This can act as the prolonged pathogenic stimulus that over-triggers the expression of Aβ-related genes, which subsequently lead to overproduction and deposition of Aβ plaque. This review will highlight the pathogenesis of each of the stated microbial infection, their association in AD pathogenesis as well as the effect of chronic infection in AD progression. Potential therapies for AD by modulating the microbiome have also been suggested. This review will aid in understanding the infectious manifestations of AD.
  3. Madhavan P, Jamal F, Chong PP, Ng KP
    Trop Biomed, 2011 Aug;28(2):269-74.
    PMID: 22041745
    The objective of our study was to study the effectiveness of CHROMagar Candida™ as the primary identification method for various clinical Candida isolates, other than the three suggested species by the manufacturer. We studied 34 clinical isolates which were isolated from patients in a local teaching hospital and 7 ATCC strains. These strains were first cultured in Sabouraud dextrose broth (SDB) for 36 hours at 35ºC, then on CHROMagar plates at 30ºC, 35ºC and 37ºC. The sensitivity of this agar to identify Candida albicans, Candida dubliniensis, Candida tropicalis, Candida glabrata, Candida rugosa, Candida krusei and Candida parapsilosis ranged between 25 and 100% at 30ºC, 14% and 100% at 35ºC, 56% and 100% at 37ºC. The specificity of this agar was 100% at 30ºC, between 97% and 100% at 35ºC, 92% and 100% at 37ºC. The efficiency of this agar ranged between 88 and 100% at 30ºC, 83% and 100% at 35ºC, 88% and 100% at 37ºC. Each species also gave rise to a variety of colony colours ranging from pink to green to blue of different colony characteristics. Therefore, the chromogenic agar was found to be useful in our study for identifying clinical Candida isolates.
  4. Madhavan P, Jamal F, Chong PP, Ng KP
    Trop Biomed, 2010 Aug;27(2):200-7.
    PMID: 20962716 MyJurnal
    The in vitro susceptibility of clinical Candida isolates towards fluconazole and voriconazole was determined using the E-test method. A total of 41 clinical isolates recovered from patients since 2004 until 2009 from two local hospitals in Kuala Lumpur, Malaysia were used. These comprised Candida tropicalis, Candida albicans, Candida krusei, Candida parapsilosis, Candida rugosa, Candida dubliniensis and Candida glabrata. Strains from American Type Culture Collection were used as quality control. Lawn cultures of the isolates on RPMI-1640 agar medium supplemented with 2% glucose were incubated with the E-test strips at 35ºC for 48 h. Our results show that 71% were susceptible to fluconazole and 90% were susceptible to voriconazole. All strains of C. krusei were resistant to fluconazole and 50% were susceptible in a dose-dependent manner to voriconazole. There were 66% and 33% of C. glabrata that were resistant to fluconazole and voriconazole. Our study revealed that majority of the clinical Candida isolates was susceptible to fluconazole and voriconazole with a small percentage being resistant to both the drugs.
  5. Abdul Manap AS, Madhavan P, Vijayabalan S, Chia A, Fukui K
    PeerJ, 2020;8:e10003.
    PMID: 33062432 DOI: 10.7717/peerj.10003
    Previously, we reported the synergistic effects of curcumin and piperine in cell cultures as potential anti-cholinesterase and anti-amyloidogenic agents. Due to limited findings on the enrolment of these compounds on epigenetic events in AD, we aimed at elucidating the expression profiles of Aβ42-induced SH-SY5Y cells using microarray profiling. In this study, an optimized concentration of 35 µM of curcumin and piperine in combination was used to treat Aβ42 fibril and high-throughput microarray profiling was performed on the extracted RNA. This was then compared to curcumin and piperine used singularly at 49.11 µM and 25 µM, respectively. Our results demonstrated that in the curcumin treated group, from the top 10 upregulated and top 10 downregulated significantly differentially expressed genes (p p p 
  6. Benchoula K, Parhar IS, Madhavan P, Hwa WE
    Biochem Pharmacol, 2021 06;188:114531.
    PMID: 33773975 DOI: 10.1016/j.bcp.2021.114531
    Diabetes mellitus is a metabolic disorder diagnosed by elevated blood glucose levels and a defect in insulin production. Blood glucose, an energy source in the body, is regenerated by two fundamental processes: glycolysis and gluconeogenesis. These two processes are the main mechanisms used by humans and many other animals to maintain blood glucose levels, thereby avoiding hypoglycaemia. The released insulin from pancreatic β-cells activates glycolysis. However, the glucagon released from the pancreatic α-cells activates gluconeogenesis in the liver, leading to pyruvate conversion to glucose-6-phosphate by different enzymes such as fructose 1,6-bisphosphatase and glucose 6-phosphatase. These enzymes' expression is controlled by the glucagon/ cyclic adenosine 3',5'-monophosphate (cAMP)/ proteinkinase A (PKA) pathway. This pathway phosphorylates cAMP-response element-binding protein (CREB) in the nucleus to bind it to these enzyme promoters and activate their expression. During fasting, this process is activated to supply the body with glucose; however, it is overactivated in diabetes. Thus, the inhibition of this process by blocking the expression of the enzymes via CREB is an alternative strategy for the treatment of diabetes. This review was designed to investigate the association between CREB activity and the treatment of diabetes and diabetes complications. The phosphorylation of CREB is a crucial step in regulating the gene expression of the enzymes of gluconeogenesis. Many studies have proven that CREB is over-activated by glucagon and many other factors contributing to the elevation of fasting glucose levels in people with diabetes. The physiological function of CREB should be regarded in developing a therapeutic strategy for the treatment of diabetes mellitus and its complications. However, the accessible laboratory findings for CREB activity of the previous research still not strong enough for continuing to the clinical trial yet.
  7. Kenny K, Omar Z, Kanavathi ES, Madhavan P
    Int J Public Health Res, 2017;7(1):765-773.
    MyJurnal
    Health care systems play a vital role in providing health services and in optimising the population’s health of each nation. The Malaysian health care system primarily consists of the public and private health services. One of the prominent private health care services offered in the General Practitioner’s (GP) Clinic. Despite the prominent role GPs play in the health care system in this country, little is known about their practices, the issues and challenges faced by GPs in this country. The objective of this study was to describe the current GP practice operations in Malaysia in terms of its general operations, financial expenditure and revenue, market competitiveness and laboratory services offered by the clinics.
  8. Phuna ZX, Panda BP, Hawala Shivashekaregowda NK, Madhavan P
    Int J Environ Health Res, 2023 Jul;33(7):670-699.
    PMID: 35253535 DOI: 10.1080/09603123.2022.2046710
    The coronavirus disease 2019 (COVID-19) has caused a worldwide outbreak. The severe acute respiratory syndrome coronavirus 2 virus can be transmitted human-to-human through droplets and close contact where personal protective equipment (PPE) is imperative to protect the individuals. The advancement of nanotechnology with significant nanosized properties can confer a higher form of protection. Incorporation of nanotechnology into facemasks can exhibit antiviral properties. Nanocoating on surfaces can achieve self-disinfecting purposes and be applied in highly populated places. Moreover, nano-based hand sanitizers can confer better sterilizing efficacies with low skin irritation as compared to alcohol-based hand sanitizers. The present review discusses the incorporation of nanotechnology into nano-based materials and coatings in facemasks, self-surface disinfectants and hand sanitizers, in the hope to contribute to the current understanding of PPE to combat COVID-19.
  9. Chong PP, Chin VK, Looi CY, Wong WF, Madhavan P, Yong VC
    Front Microbiol, 2019 08 13;10:1870.
    PMID: 31456783 DOI: 10.3389/fmicb.2019.01870
    [This corrects the article DOI: 10.3389/fmicb.2019.01136.].
  10. Peremalo T, Madhavan P, Hamzah S, Than L, Wong EH, Nasir MDM, et al.
    J Med Microbiol, 2019 Mar;68(3):346-354.
    PMID: 30724730 DOI: 10.1099/jmm.0.000940
    PURPOSE: Non-albicansCandida species have emerged as fungal pathogens that cause invasive infections, with many of these species displaying resistance to commonly used antifungal agents. This study was confined to studying the characteristics of clinical isolates of the C. rugosa complex and C. pararugosa species.

    METHODOLOGY: Seven isolates of the C. rugosa complex and one isolate of C. pararugosa were obtained from two tertiary referral hospitals in Malaysia. Their antifungal susceptibilities, biofilm, proteinase, phospholipase, esterase and haemolysin activities were characterized. Biofilms were quantified using crystal violet (CV) and tetrazolium (XTT) reduction assays at 1.5, 6, 18, 24, 48 and 72 h.Results/Key findings. The E-test antifungal tests showed that both species have elevated MICs compared to C. albicans and C. tropicalis. The highest biomass was observed in one of the C. rugosa isolates (0.237), followed by C. pararugosa (0.206) at 18 h of incubation. However, the highest bioactivity was observed in the C. rugosa ATCC 10571 strain at 24 h (0.075), followed by C. pararugosa at 48 h (0.048) and the same C. rugosa strain at 24 h (0.046), with P<0.05. All isolates exhibited high proteinase activity (+++) whereas six isolates showed very strong esterase activity (++++). All the isolates were alpha haemolytic producers. None of the isolates exhibited phospholipase activity.

    CONCLUSION: Elevated MICs were shown for the C. rugosa complex and C. pararugosa for commonly used antifungal drugs. Further studies to identify virulence genes involved in the pathogenesis and genes that confer reduced drug susceptibility in these species are proposed.

  11. Chong PP, Chin VK, Wong WF, Madhavan P, Yong VC, Looi CY
    Genes (Basel), 2018 Nov 07;9(11).
    PMID: 30405082 DOI: 10.3390/genes9110540
    Candida albicans is an opportunistic fungal pathogen, which causes a plethora of superficial, as well as invasive, infections in humans. The ability of this fungus in switching from commensalism to active infection is attributed to its many virulence traits. Biofilm formation is a key process, which allows the fungus to adhere to and proliferate on medically implanted devices as well as host tissue and cause serious life-threatening infections. Biofilms are complex communities of filamentous and yeast cells surrounded by an extracellular matrix that confers an enhanced degree of resistance to antifungal drugs. Moreover, the extensive plasticity of the C. albicans genome has given this versatile fungus the added advantage of microevolution and adaptation to thrive within the unique environmental niches within the host. To combat these challenges in dealing with C. albicans infections, it is imperative that we target specifically the molecular pathways involved in biofilm formation as well as drug resistance. With the advent of the -omics era and whole genome sequencing platforms, novel pathways and genes involved in the pathogenesis of the fungus have been unraveled. Researchers have used a myriad of strategies including transcriptome analysis for C. albicans cells grown in different environments, whole genome sequencing of different strains, functional genomics approaches to identify critical regulatory genes, as well as comparative genomics analysis between C. albicans and its closely related, much less virulent relative, C. dubliniensis, in the quest to increase our understanding of the mechanisms underlying the success of C. albicans as a major fungal pathogen. This review attempts to summarize the most recent advancements in the field of biofilm and antifungal resistance research and offers suggestions for future directions in therapeutics development.
  12. Chong PP, Chin VK, Looi CY, Wong WF, Madhavan P, Yong VC
    Front Microbiol, 2019;10:1136.
    PMID: 31244784 DOI: 10.3389/fmicb.2019.01136
    Irritable bowel syndrome (IBS) is a functional disorder which affects a large proportion of the population globally. The precise etiology of IBS is still unknown, although consensus understanding proposes IBS to be of multifactorial origin with yet undefined subtypes. Genetic and epigenetic factors, stress-related nervous and endocrine systems, immune dysregulation and the brain-gut axis seem to be contributing factors that predispose individuals to IBS. In addition to food hypersensitivity, toxins and adverse life events, chronic infections and dysbiotic gut microbiota have been suggested to trigger IBS symptoms in tandem with the predisposing factors. This review will summarize the pathophysiology of IBS and the role of gut microbiota in relation to IBS. Current methodologies for microbiome studies in IBS such as genome sequencing, metagenomics, culturomics and animal models will be discussed. The myriad of therapy options such as immunoglobulins (immune-based therapy), probiotics and prebiotics, dietary modifications including FODMAP restriction diet and gluten-free diet, as well as fecal transplantation will be reviewed. Finally this review will highlight future directions in IBS therapy research, including identification of new molecular targets, application of 3-D gut model, gut-on-a-chip and personalized therapy.
  13. Madhavan P, Jamal F, Pei CP, Othman F, Karunanidhi A, Ng KP
    Mycopathologia, 2018 Jun;183(3):499-511.
    PMID: 29380188 DOI: 10.1007/s11046-018-0243-z
    Infections by non-albicans Candida species are a life-threatening condition, and formation of biofilms can lead to treatment failure in a clinical setting. This study was aimed to demonstrate the in vitro antibiofilm activity of fluconazole (FLU) and voriconazole (VOR) against C. glabrata, C. parapsilosis and C. rugosa with diverse antifungal susceptibilities to FLU and VOR. The antibiofilm activities of FLU and VOR in the form of suspension as well as pre-coatings were assessed by XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction assay. Morphological and intracellular changes exerted by the antifungal drugs on Candida cells were examined by scanning electron microscope (SEM) and transmission electron microscope (TEM). The results of the antibiofilm activities showed that FLU drug suspension was capable of killing C. parapsilosis and C. rugosa at minimum inhibitory concentrations (MICs) of 4× MIC FLU and 256× MIC FLU, respectively. While VOR MICs ranging from 2× to 32× were capable of killing the biofilms of all Candida spp tested. The antibiofilm activities of pre-coated FLU were able to kill the biofilms at ¼× MIC FLU and ½× MIC FLU for C. parapsilosis and C. rugosa strains, respectively. While pre-coated VOR was able to kill the biofilms, all three Candida sp at ½× MIC VOR. SEM and TEM examinations showed that FLU and VOR treatments exerted significant impact on Candida cell with various degrees of morphological changes. In conclusion, a fourfold reduction in MIC50 of FLU and VOR towards ATCC strains of C. glabrata, C. rugosa and C. rugosa clinical strain was observed in this study.
  14. Abjani F, Madhavan P, Chong PP, Chinna K, Rhodes CA, Lim YAL
    Ann Hum Biol, 2023 Feb;50(1):137-147.
    PMID: 36650931 DOI: 10.1080/03014460.2023.2170464
    CONTEXT: The continuous rise in urbanisation and its associated factors has been reflected in the structure of the human gut ecosystem.

    OBJECTIVE: The main focus of this review is to discuss and summarise the major risk factors associated with urbanisation that affect human gut microbiota thus affecting human health.

    METHODS: Multiple medical literature databases, namely PubMed, Google, Google Scholar, and Web of Science were used to find relevant materials for urbanisation and its major factors affecting human gut microbiota/microbiome. Both layman and Medical Subject Headings (MeSH) terms were used in the search. Due to the scarcity of the data, no limitation was set on the publication date. Relevant materials in the English language which include case reports, chapters of books, journal articles, online news reports and medical records were included in this review.

    RESULTS: Based on the data discussed in the review, it is quite clear that urbanisation and its associated factors have long-standing effects on the human gut microbiota that result in alterations of gut microbial diversity and composition. This is a matter of serious concern as chronic inflammatory diseases are on the rise in urbanised societies.

    CONCLUSION: A better understanding of the factors associated with urbanisation will help us to identify and implement new biological and social approaches to prevent and treat diseases and improve health globally by deepening our understanding of these relationships and increasing studies across urbanisation gradients.HIGHLIGHTSHuman gut microbiota have been linked to almost every important function, including metabolism, intestinal homeostasis, immune system, biosynthesis of vitamins, brain processes, and behaviour.However, dysbiosis i.e., alteration in the composition and diversity of gut microbiota is associated with the pathogenesis of many chronic conditions.In the 21st century, urbanisation represents a major demographic shift in developed and developing countries.During this period of urbanisation, humans have been exposed to many environmental exposures, all of which have led to the dysbiosis of human gut microbiota.The main focus of the review is to discuss and summarise the major risk factors associated with urbanisation and how it affects the diversity and composition of gut microbiota which ultimately affects human health.

  15. Choo S, Chin VK, Wong EH, Madhavan P, Tay ST, Yong PVC, et al.
    Folia Microbiol (Praha), 2020 Jun;65(3):451-465.
    PMID: 32207097 DOI: 10.1007/s12223-020-00786-5
    Garlic (Allium sativum L.) is a well-known spice widely utilised for its medicinal properties. There is an extensive record of the many beneficial health effects of garlic which can be traced back to as early as the ancient Egyptian era. One of the most studied properties of garlic is its ability to cure certain ailments caused by infections. In the 1940s, the antimicrobial activities exhibited by garlic were first reported to be due to allicin, a volatile compound extracted from raw garlic. Since then, allicin has been widely investigated for its putative inhibitory activities against a wide range of microorganisms. Allicin has demonstrated a preference for targeting the thiol-containing proteins and/or enzymes in microorganisms. It has also demonstrated the ability to regulate several genes essential for the virulence of microorganisms. Recently, it was reported that allicin may function better in combination with other antimicrobials compared to when used alone. When used in combination with antibiotics or antifungals, allicin enhanced the antimicrobial activities of these substances and improved the antimicrobial efficacy. Hence, it is likely that combination therapy of allicin with additional antimicrobial drug(s) could serve as a viable alternative for combating rising antimicrobial resistance. This review focuses on the antimicrobial activities exhibited by allicin alone as well as in combination with other substances. The mechanisms of action of allicin elucidated by some of the studies are also highlighted in the present review in order to provide a comprehensive overview of this versatile bioactive compound and the mechanistic evidence supporting its potential use in antimicrobial therapy.
  16. Rad SK, Arya A, Karimian H, Madhavan P, Rizwan F, Koshy S, et al.
    Drug Des Devel Ther, 2018;12:3999-4021.
    PMID: 30538427 DOI: 10.2147/DDDT.S173970
    The pathophysiological link between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) has been suggested in several reports. Few findings suggest that T2DM has strong link in the development process of AD, and the complete mechanism is yet to be revealed. Formation of amyloid plaques (APs) and neurofibrillary tangles (NFTs) are two central hallmarks in the AD. APs are the dense composites of β-amyloid protein (Aβ) which accumulates around the nerve cells. Moreover, NFTs are the twisted fibers containing hyperphosphorylated tau proteins present in certain residues of Aβ that build up inside the brain cells. Certain factors contribute to the aetiogenesis of AD by regulating insulin signaling pathway in the brain and accelerating the formation of neurotoxic Aβ and NFTs via various mechanisms, including GSK3β, JNK, CamKII, CDK5, CK1, MARK4, PLK2, Syk, DYRK1A, PPP, and P70S6K. Progression to AD could be influenced by insulin signaling pathway that is affected due to T2DM. Interestingly, NFTs and APs lead to the impairment of several crucial cascades, such as synaptogenesis, neurotrophy, and apoptosis, which are regulated by insulin, cholesterol, and glucose metabolism. The investigation of the molecular cascades through insulin functions in brain contributes to probe and perceive progressions of diabetes to AD. This review elaborates the molecular insights that would help to further understand the potential mechanisms linking T2DM and AD.
  17. Abu Bakar NFAB, Yeo ZL, Hussin F, Madhavan P, Lim V, Jemon K, et al.
    J Taibah Univ Med Sci, 2023 Dec;18(6):1220-1236.
    PMID: 37250812 DOI: 10.1016/j.jtumed.2023.04.003
    OBJECTIVE: Triple negative breast cancer (TNBC) is the most invasive breast cancer subtype enriched with cancer stem cells. TNBCs do not express estrogen, progesterone, or human epidermal growth factor receptor 2 (HER2) receptors, making them difficult to be targeted by existing chemotherapy treatments. In this study, we attempted to identify the effects of combined cisplatin and Clinacanthus nutans treatment on MDA-MD-231 and MDA-MB-468 breast cancer cells, which represent TNBC subtypes.

    METHODS: The phytochemical fingerprint of C. nutans ethanolic leaf extract was evaluated by LC-MS/MS analysis. We investigated the effects of cisplatin (0-15.23 μg/mL), C. nutans (0-50 μg/mL), and a combination of cisplatin (3.05 μg/mL) and C. nutans (0-50 μg/mL), on cell viability, proliferation, apoptosis, invasion, mRNA expression in cancer stem cells (CD49f, KLF4), and differentiation markers (TUBA1A, KRT18) in TNBC cells. In addition, we also studied the interaction between cisplatin and C. nutans.

    RESULTS: Derivatives of fatty acids, carboxylic acid ester, and glycosides, were identified as the major bioactive compounds with potential anticancer properties in C. nutans leaf extract. Reductions in cell viability (0-78%) and proliferation (2-77%), as well as a synergistic anticancer effect, were identified in TNBC cells when treated with a combination of cisplatin and C. nutans. Furthermore, apoptotic induction via increased caspase-3/7 activity (MDA-MB-231: 2.73-fold; MDA-MB-468: 3.53-fold), and a reduction in cell invasion capacity to 36%, were detected in TNBC cells when compared to single cisplatin and C. nutans treatments. At the mRNA level, cisplatin and C. nutans differentially regulated specific genes that are responsible for proliferation and differentiation.

    CONCLUSION: Our findings demonstrate that the combination of cisplatin and C. nutans represents a potential treatment for TNBC.

  18. Rao H, Choo S, Rajeswari Mahalingam SR, Adisuri DS, Madhavan P, Md Akim A, et al.
    Molecules, 2021 Mar 26;26(7).
    PMID: 33810292 DOI: 10.3390/molecules26071870
    Biofilms play an essential role in chronic and healthcare-associated infections and are more resistant to antimicrobials compared to their planktonic counterparts due to their (1) physiological state, (2) cell density, (3) quorum sensing abilities, (4) presence of extracellular matrix, (5) upregulation of drug efflux pumps, (6) point mutation and overexpression of resistance genes, and (7) presence of persister cells. The genes involved and their implications in antimicrobial resistance are well defined for bacterial biofilms but are understudied in fungal biofilms. Potential therapeutics for biofilm mitigation that have been reported include (1) antimicrobial photodynamic therapy, (2) antimicrobial lock therapy, (3) antimicrobial peptides, (4) electrical methods, and (5) antimicrobial coatings. These approaches exhibit promising characteristics for addressing the impending crisis of antimicrobial resistance (AMR). Recently, advances in the micro- and nanotechnology field have propelled the development of novel biomaterials and approaches to combat biofilms either independently, in combination or as antimicrobial delivery systems. In this review, we will summarize the general principles of clinically important microbial biofilm formation with a focus on fungal biofilms. We will delve into the details of some novel micro- and nanotechnology approaches that have been developed to combat biofilms and the possibility of utilizing them in a clinical setting.
  19. Hasan MM, Madhavan P, Ahmad Noruddin NA, Lau WK, Ahmed QU, Arya A, et al.
    Pharm Biol, 2023 Dec;61(1):1135-1151.
    PMID: 37497554 DOI: 10.1080/13880209.2023.2230251
    CONTEXT: Arjunolic acid (AA) is a triterpenoid saponin found in Terminalia arjuna (Roxb.) Wight & Arn. (Combretaceae). It exerts cardiovascular protective effects as a phytomedicine. However, it is unclear how AA exerts the effects at the molecular level.

    OBJECTIVE: This study investigates the cardioprotective effects of arjunolic acid (AA) via MyD88-dependant TLR4 downstream signaling marker expression.

    MATERIALS AND METHODS: The MTT viability assay was used to assess the cytotoxicity of AA. LPS induced in vitro cardiovascular disease model was developed in H9C2 and C2C12 myotubes. The treatment groups were designed such as control (untreated), LPS control, positive control (LPS + pyrrolidine dithiocarbamate (PDTC)-25 µM), and treatment groups were co-treated with LPS and three concentrations of AA (50, 75, and 100 µM) for 24 h. The changes in the expression of TLR4 downstream signaling markers were evaluated through High Content Screening (HCS) and Western Blot (WB) analysis.

    RESULTS: After 24 h of co-treatment, the expression of TLR4, MyD88, MAPK, JNK, and NF-κB markers were upregulated significantly (2-6 times) in the LPS-treated groups compared to the untreated control in both HCS and WB experiments. Evidently, the HCS analysis revealed that MyD88, NF-κB, p38, and JNK were significantly downregulated in the H9C2 myotube in the AA treated groups. In HCS, the expression of NF-κB was downregulated in C2C12. Additionally, TLR4 expression was downregulated in both H9C2 and C2C12 myotubes in the WB experiment.

    DISCUSSION AND CONCLUSIONS: TLR4 marker expression in H9C2 and C2C12 myotubes was subsequently decreased by AA treatment, suggesting possible cardioprotective effects of AA.

  20. Abdul Manap AS, Vijayabalan S, Madhavan P, Chia YY, Arya A, Wong EH, et al.
    Drug Target Insights, 2019;13:1177392819866412.
    PMID: 31391778 DOI: 10.1177/1177392819866412
    Alzheimer disease is a neurodegenerative disease that is signified by cognitive decline, memory loss, and erratic behavior. Till date, no cure for Alzheimer exists and the current Alzheimer medications have limited effectiveness. However, herbal medicines may slow down the disease's progression, which may hopefully reduce the number of cases in the years to come. Numerous studies have been done on characterizing the neuroprotective properties from plants belonging to Scrophulariaceae family, particularly Bacopa monnieri and its polyphenolic compounds known as bacosides. This review presents the findings on bacosides in therapeutic plants and their impact on Alzheimer disease pathology. These reports present data on the clinical, cellular activities, phytochemistry, and biological applications that may be used in new drug treatment for Alzheimer disease.
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