Displaying publications 21 - 40 of 52 in total

Abstract:
Sort:
  1. Fulltext SLC1A2 Gene Polymorphism Influences Methamphetamine-Induced Psychosis
    Yahya DN, Guad RM, Wu YS, Gan SH, Gopinath SCB, Zakariah HA, et al.
    J Pers Med, 2023 Jan 31;13(2).
    PMID: 36836504 DOI: 10.3390/jpm13020270
    SLC1A2 is a gene encoded for the excitatory amino acid transporter 2 which is responsible for glutamate reuptake from the synaptic cleft in the central nervous system. Recent studies have suggested that polymorphisms on glutamate transporters can affect drug dependence, leading to the development of neurological diseases and psychiatric disorders. Our study investigated the association of rs4755404 single nucleotide polymorphism (SNP) of the SLC1A2 gene with methamphetamine (METH) dependence and METH-induced psychosis and mania in a Malaysian population. The rs4755404 gene polymorphism was genotyped in METH-dependent male subjects (n = 285) and male control subjects (n = 251). The subjects consisted of the four ethnic groups in Malaysia (Malay, Chinese, Kadazan-Dusun, and Bajau). Interestingly, there was a significant association between rs4755404 polymorphism and METH-induced psychosis in the pooled METH-dependent subjects in terms of genotype frequency (p = 0.041). However, there was no significant association between rs4755404 polymorphism and METH dependence. Also, the rs455404 polymorphism was not significantly associated with METH-induced mania for both genotype frequencies and allele frequencies in the METH-dependent subjects, regardless of stratification into the different ethnicities. Our study suggests that the SLC1A2 rs4755404 gene polymorphism confers some susceptibility to METH-induced psychosis, especially for those who carry the GG homozygous genotype.
  2. Fulltext Long Noncoding RNA UCA1 in Gastrointestinal Cancers: Molecular Regulatory Roles and Patterns, Mechanisms, and Interactions
    Ramli S, Sim MS, Guad RM, Gopinath SCB, Subramaniyan V, Fuloria S, et al.
    J Oncol, 2021;2021:5519720.
    PMID: 33936199 DOI: 10.1155/2021/5519720
    The rising trend of gastrointestinal (GI) cancer has become a global burden due to its aggressive nature and poor prognosis. Long noncoding RNAs (lncRNAs) have recently been reported to be overexpressed in different GI cancers and may contribute to cancer progression and chemoresistance. They are featured with more than 200 nucleotides, commonly polyadenylated, and lacking an open reading frame. LncRNAs, particularly urothelial carcinoma-associated 1 (UCA1), are oncogenes involved in regulating cancer progression, such as cell proliferation, invasion, migration, and chemoresistance, particularly in GI cancer. This review was aimed to present an updated focus on the molecular regulatory roles and patterns of lncRNA UCA1 in progression and chemoresistance of different GI cancers, as well as deciphering the underlying mechanisms and its interactions with key molecules involved, together with a brief presentation on its diagnostic and prognostic values. The regulatory roles of lncRNA UCA1 are implicated in esophageal cancer, gastric cancer, pancreatic cancer, hepatobiliary cancer, and colorectal cancer, where they shared similar molecular mechanisms in regulating cancer phenotypes and chemoresistance. Comparatively, gastric cancer is the most intensively studied type in GI cancer. LncRNA UCA1 is implicated in biological roles of different GI cancers via interactions with various molecules, particularly microRNAs, and signaling pathways. In conclusion, lncRNA UCA1 is a potential molecular target for GI cancer, which may lead to the development of a novel chemotherapeutic agent. Hence, it also acts as a potential diagnostic and prognostic marker for GI cancer patients.
  3. Two birds with one stone: One-pot concurrent Ta-doping and -coating on Ni-rich LiNi0.92Co0.04Mn0.04O2 cathode materials with fiber-type microstructure and Li+-conducting layer formation
    Hendri YB, Kuo LY, Seenivasan M, Wu YS, Wu SH, Chang JK, et al.
    J Colloid Interface Sci, 2024 May;661:289-306.
    PMID: 38301467 DOI: 10.1016/j.jcis.2024.01.094
    A novel scalable Taylor-Couette reactor (TCR) synthesis method was employed to prepare Ta-modified LiNi0.92Co0.04Mn0.04O2 (T-NCM92) with different Ta contents. Through experiments and density functional theory (DFT) calculations, the phase and microstructure of Ta-modified NCM92 were analyzed, showing that Ta provides a bifunctional (doping and coating at one time) effect on LiNi0.92Co0.04Mn0.04O2 cathode material through a one-step synthesis process via a controlling suitable amount of Ta and Li-salt. Ta doping allows the tailoring of the microstructure, orientation, and morphology of the primary NCM92 particles, resulting in a needle-like shape with fine structures that considerably enhance Li+ ion diffusion and electrochemical charge/discharge stability. The Ta-based surface-coating layer effectively prevented microcrack formation and inhibited electrolyte decomposition and surface-side reactions during cycling, thereby significantly improving the electrochemical performance and long-term cycling stability of NCM92 cathodes. Our as-prepared NCM92 modified with 0.2 mol% Ta (i.e., T2-NCM92) exhibits outstanding cyclability, retaining 84.5 % capacity at 4.3 V, 78.3 % at 4.5 V, and 67.6 % at 45 ℃ after 200 cycles at 1C. Even under high-rate conditions (10C), T2-NCM92 demonstrated a remarkable capacity retention of 66.9 % after 100 cycles, with an initial discharge capacity of 157.6 mAh g-1. Thus, the Ta modification of Ni-rich NCM92 materials is a promising option for optimizing NCM cathode materials and enabling their use in real-world electric vehicle (EV) applications.
  4. Expression of LC3A, LC3B and p62/SQSTM1 autophagy proteins in hepatocellular carcinoma (HCC) tissues and the predicted microRNAs involved in the autophagy-related pathway
    Wong MM, Aziz NA, Ch'ng ES, Armon S, Chook JB, Bong JJ, et al.
    J Mol Histol, 2024 Apr 17.
    PMID: 38630414 DOI: 10.1007/s10735-024-10191-8
    BACKGROUND: Autophagy plays multifaceted roles in regulating hepatocellular carcinoma (HCC) and the mechanisms involved are under-explored. Regulatory microRNAs (miRNAs) have been reported to target autophagy proteins but their roles in HCC is not well studied. Using HCC patient tissues, this study aims to investigate the association of autophagy with several clinicopathological parameters as well as identifying the autophagy-related miRNAs and the possible pathways.

    METHODS AND RESULTS: Autophagy level in the HCC patient-derived cancer and non-cancer tissues was determined by immunohistochemistry (IHC) targeting SQSTM1, LC3A and LC3B proteins. Significance tests of clinicopathological variables were tested using the Fisher's exact or Chi-square tests. Gene and miRNA expression assays were carried out and analyzed using Nanostring platform and software followed by validation of other online bioinformatics tools, namely String and miRabel. Autophagy expression was significantly higher in cancerous tissues compared to adjacent non-cancer tissues. High LC3B expression was associated with advanced tumor histology grade and tumor location. Nanostring gene expression analysis revealed that SQSTM1, PARP1 and ATG9A genes were upregulated in HCC tissues compared to non-cancer tissues while SIRT1 gene was downregulated. These genes are closely related to an autophagy pathway in HCC. Further, using miRabel tool, three downregulated miRNAs (hsa-miR-16b-5p, hsa-miR-34a-5p, and hsa-miR-660-5p) and one upregulated miRNA (hsa-miR-539-5p) were found to closely interact with the abovementioned autophagy-related genes. We then mapped out the possible pathway involving the genes and miRNAs in HCC tissues.

    CONCLUSIONS: We conclude that autophagy events are more active in HCC tissues compared to the adjacent non-cancer tissues. We also reported the possible role of several miRNAs in regulating autophagy-related genes in the autophagy pathway in HCC. This may contribute to the development of potential therapeutic targets for improving HCC therapy. Future investigations are warranted to validate the target genes reported in this study using a larger sample size and more targeted molecular technique.

  5. Fulltext Lawsone Unleashed: A Comprehensive Review on Chemistry, Biosynthesis, and Therapeutic Potentials
    Nair AS, Sekar M, Gan SH, Kumarasamy V, Subramaniyan V, Wu YS, et al.
    Drug Des Devel Ther, 2024;18:3295-3313.
    PMID: 39081702 DOI: 10.2147/DDDT.S463545
    Lawsone, a naturally occurring organic compound also called hennotannic acid, obtained mainly from Lawsonia inermis (Henna). It is a potential drug-like molecule with unique chemical and biological characteristics. Traditionally, henna is used in hair and skin coloring and is also a medicinal herb for various diseases. It is also widely used as a starting material for the synthesis of various drug molecules. In this review, we investigate on the chemistry, biosynthesis, physical and biological properties of lawsone. The results showed that lawsone has potential antioxidant, anti-inflammatory, antimicrobial and antitumor properties. It also induces cell cycle inhibition and programmed cell death in cancer, making it a potential chemotherapeutic agent. Additionally, inhibition of pro-inflammatory cytokine production makes it an essential treatment for inflammatory diseases. Exploration of its biosynthetic pathway can pave the way for its development into targets for new drug development. In future, well-thought-out clinical studies should be made to verify its safety and efficacy.
  6. Fulltext Clinical and genetic risk factors for new-onset diabetes mellitus after transplantation (NODAT) in major transplant centres in Malaysia
    Guad RM, Taylor-Robinson AW, Wu YS, Gan SH, Zaharan NL, Basu RC, et al.
    BMC Nephrol, 2020 09 07;21(1):388.
    PMID: 32894076 DOI: 10.1186/s12882-020-02052-9
    BACKGROUND: New-onset diabetes after transplantation (NODAT) is associated with reduced patient and graft survival. This study examined the clinical and selected genetic factors associated with NODAT among renal-transplanted Malaysian patients.

    METHODS: This study included 168 non-diabetic patients (58% males, 69% of Chinese ethnicity) who received renal transplantation between 1st January 1994 to 31st December 2014, and were followed up in two major renal transplant centres in Malaysia. Fasting blood glucose levels were used to diagnose NODAT in patients who received renal transplantation within 1 year. Two single nucleotide polymorphisms (SNPs), namely; rs1494558 (interleukin-7 receptor, IL-7R) and rs2232365 (mannose-binding leptin-2, MBL2) were selected and genotyped using Sequenom MassArray platform. Cox proportional hazard regression analyses were used to examine the risk of developing NODAT according to the different demographics and clinical covariates, utilizing four time-points (one-month, three-months, six-months, one-year) post-transplant.

    RESULTS: Seventeen per cent of patients (n = 29, 55% males, 69% Chinese) were found to have developed NODAT within one-year of renal transplantation based on their fasting blood glucose levels. NODAT patients had renal transplantation at an older age compared to non-NODAT (39.3 ± 13.4 vs 33.9 ± 11.8 years, p = 0.03). In multivariate analysis, renal-transplanted patients who received a higher daily dose of cyclosporine (mg) were associated with increased risk of NODAT (Hazard ratio (HR) =1.01 per mg increase in dose, 95% confidence interval (CI) 1.00-1.01, p = 0.002). Other demographic (gender, ethnicities, age at transplant) and clinical factors (primary kidney disease, type of donor, place of transplant, type of calcineurin inhibitors, duration of dialysis pre-transplant, BMI, creatinine levels, and daily doses of tacrolimus and prednisolone) were not found to be significantly associated with risk of NODAT. GA genotype of rs1494558 (HR = 3.15 95% CI 1.26, 7.86) and AG genotype of rs2232365 (HR = 2.57 95% CI 1.07, 6.18) were associated with increased risk of NODAT as compared to AA genotypes.

    CONCLUSION: The daily dose of cyclosporine and SNPs of IL-7R (rs1494558) and MBL2 (rs2232365) genes are significantly associated with the development of NODAT in the Malaysian renal transplant population.

  7. Fulltext Mesenchymal Stem Cell-Derived Extracellular Vesicles: Regenerative Potential and Challenges
    Fuloria S, Subramaniyan V, Dahiya R, Dahiya S, Sudhakar K, Kumari U, et al.
    Biology (Basel), 2021 Feb 25;10(3).
    PMID: 33668707 DOI: 10.3390/biology10030172
    Evidence suggests that stem cells exert regenerative potential via the release of extracellular vesicles. Mesenchymal stem cell extracellular vesicles (MSCEVs) offer therapeutic benefits for various pathophysiological ailments by restoring tissues. Facts suggest that MSCEV action can be potentiated by modifying the mesenchymal stem cells culturing methodology and bioengineering EVs. Limited clinical trials of MSCEVs have questioned their superiority, culturing quality, production scale-up and isolation, and administration format. Translation of preclinically successful MSCEVs into a clinical platform requires paying attention to several critical matters, such as the production technique, quantification/characterization, pharmacokinetics/targeting/transfer to the target site, and the safety profile. Keeping these issues as a priority, the present review was designed to highlight the challenges in translating preclinical MSCEV research into clinical platforms and provide evidence for the regenerative potential of MSCEVs in various conditions of the liver, kidney, heart, nervous system, bone, muscle, cartilage, and other organs/tissues.
  8. Molecular Regulatory Roles of Long Non-coding RNA HOTTIP: An Overview in Gastrointestinal Cancer
    Hamid UZ, Sim MS, Guad RM, Subramaniyan V, Sekar M, Fuloria NK, et al.
    Curr Mol Med, 2021 Aug 06.
    PMID: 34365949 DOI: 10.2174/1566524021666210806162848
    Gastrointestinal (GI) cancers presented an alarmingly high number of new cancer cases worldwide and highly characterised with poor prognosis. The poor overall survival is mainly due to late detection and emerging challenges in treatment, particularly chemoresistance. Thus, the identification of novel molecular targets in GI cancer is highly regarded as the main focus. Recently, long non-coding RNAs (lncRNAs) have been discovered as a potential novel molecular target for combating cancer, as it is highly associated with carcinogenesis and has a great impact on cancer progression. Amongst lncRNAs, HOTIIP has demonstrated a prominent oncogenic regulation in cancer progression, particularly in GI cancers, including oesophageal cancer, gastric cancer, hepatocellular carcinoma, pancreatic cancer and colorectal cancer. This review aimed to present a focused update on the regulatory roles of HOTTIP in GI cancer progression and chemoresistance, as well as deciphering the associated molecular mechanisms underlying their impact on cancer phenotypes and chemoresistance and the key molecules involved. It has been reported that it regulates the expression of various genes and proteins in GI cancers that impacts on the cellular functions, including proliferation, adhesion, migration and invasion, apoptosis, chemosensitivity and tumour differentiation. Furthermore, HOTTIP was also discovered to have a higher diagnostic value as compared to existing diagnostic biomarkers. In overall, HOTTIP has presented itself as a novel therapeutic target and potential diagnostic biomarker in the development of GI cancer treatment.
  9. Fulltext Mangifera indica (Mango): A Promising Medicinal Plant for Breast Cancer Therapy and Understanding Its Potential Mechanisms of Action
    Yap KM, Sekar M, Seow LJ, Gan SH, Bonam SR, Mat Rani NNI, et al.
    Breast Cancer (Dove Med Press), 2021;13:471-503.
    PMID: 34548817 DOI: 10.2147/BCTT.S316667
    Globally, breast cancer is the most common cancer type and is one of the most significant causes of deaths in women. To date, multiple clinical interventions have been applied, including surgical resection, radiotherapy, endocrine therapy, targeted therapy and chemotherapy. However, 1) the lack of therapeutic options for metastatic breast cancer, 2) resistance to drug therapy and 3) the lack of more selective therapy for triple-negative breast cancer are some of the major challenges in tackling breast cancer. Given the safe nature of natural products, numerous studies have focused on their anti-cancer potentials. Mangifera indica, commonly known as mango, represents one of the most extensively investigated natural sources. In this review, we provide a comprehensive overview of M. indica extracts (bark, kernel, leaves, peel and pulp) and phytochemicals (mangiferin, norathyriol, gallotannins, gallic acid, pyrogallol, methyl gallate and quercetin) reported for in vitro and in vivo anti-breast cancer activities and their underlying mechanisms based on relevant literature from several scientific databases, including PubMed, Scopus and Google Scholar till date. Overall, the in vitro findings suggest that M. indica extracts and/or phytochemicals inhibit breast cancer cell growth, proliferation, migration and invasion as well as trigger apoptosis and cell cycle arrest. In vivo results demonstrated that there was a reduction in breast tumor xenograft growth. Several potential mechanisms underlying the anti-breast cancer activities have been reported, which include modulation of oxidative status, receptors, signalling pathways, miRNA expression, enzymes and cell cycle regulators. To further explore this medicinal plant against breast cancer, future research directions are addressed. The outcomes of the review revealed that M. indica extracts and their phytochemicals may have potential benefits in the management of breast cancer in women. However, to validate its utility in the creation of innovative and potent therapeutic agents to treat breast cancer, more dedicated research, especially clinical studies are needed to explore the anti-breast cancer potentials of M. indica extracts and their phytochemicals.
  10. Human Exfoliated Deciduous Teeth Stem Cells: Features and Therapeutic Effects on Neurogenerative and Hepatobiliary-pancreatic Diseases
    Wahab NWA, Guad RM, Subramaniyan V, Fareez IM, Choy KW, Bonam SR, et al.
    Curr Stem Cell Res Ther, 2021;16(5):563-576.
    PMID: 32957893 DOI: 10.2174/1574888X15999200918105623
    Stem cells can multiply into more cells with similar types in an undifferentiated form and differentiate into other types of cells. The great success and key essence of stem cell technology is the isolation of high-quality Mesenchymal Stem Cells (MSCs) with high potency, either with multipotent or pluripotent property. In this line, Stem cells from Human Exfoliated Deciduous teeth (SHEDs) are highly proliferative stem cells from dental pulp and have multipoint differentiation capacity. These cells play a pivotal role in regenerative medicine, such as cell repair associated with neurodegenerative, hepatobiliary, and pancreatic diseases. In addition, stem cell therapy has been widely used to regulate immune response and repair of tissue lesions. This overview captured the differential biological characteristics, and the potential role of stem cell technology and paid special attention to human welfare SHEDs in eliminating the above-mentioned diseases. This review provides further insights into stem cell technology by expanding the therapeutic potential of SHEDs in tissue engineering and cell organ repairs.
  11. Fulltext Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects
    Yap KM, Sekar M, Wu YS, Gan SH, Rani NNIM, Seow LJ, et al.
    Saudi J Biol Sci, 2021 Dec;28(12):6730-6747.
    PMID: 34866972 DOI: 10.1016/j.sjbs.2021.07.046
    Breast cancer (BC) has high incidence and mortality rates, making it a major global health issue. BC treatment has been challenging due to the presence of drug resistance and the limited availability of therapeutic options for triple-negative and metastatic BC, thereby urging the exploration of more effective anti-cancer agents. Hesperidin and its aglycone hesperetin, two flavonoids from citrus species, have been extensively evaluated for their anti-cancer potentials. In this review, available literatures on the chemotherapeutic and chemosensitising activities of hesperidin and hesperetin in preclinical BC models are reported. The safety and bioavailability of hesperidin and hesperetin as well as the strategies to enhance their bioavailability are also discussed. Overall, hesperidin and hesperetin can inhibit cell proliferation, migration and BC stem cells as well as induce apoptosis and cell cycle arrest in vitro. They can also inhibit tumour growth, metastasis and neoplastic changes in tissue architecture in vivo. Moreover, the co-administration of hesperidin or hesperetin with doxorubicin, letrozole or tamoxifen can enhance the efficacies of these clinically available agents. These chemotherapeutic and chemosensitising activities of hesperidin and hesperetin have been linked to several mechanisms, including the modulation of signalling pathways, glucose uptake, enzymes, miRNA expression, oxidative status, cell cycle regulatory proteins, tumour suppressor p53, plasma and liver lipid profiles as well as DNA repair mechanisms. However, poor water solubility, extensive phase II metabolism and apical efflux have posed limitations to the bioavailability of hesperidin and hesperetin. Various strategies for bioavailability enhancement have been studied, including the utilisation of nano-based drug delivery systems and the co-administration of hesperetin with other flavonoids. In particular, nanoformulated hesperidin and hesperetin possess greater chemotherapeutic and chemosensitising activities than free compounds. Despite promising preclinical results, further safety and efficacy evaluation of hesperidin and hesperetin as well as their nanoformulations in clinical trials is required to ascertain their potentials to be developed as clinically useful agents for BC treatment.
  12. Fulltext Different domains of dengue research in the Philippines: A systematic review and meta-analysis of questionnaire-based studies
    Guad RM, Carandang RR, Solidum JN, W Taylor-Robinson A, Wu YS, Aung YN, et al.
    PLoS One, 2021;16(12):e0261412.
    PMID: 34929011 DOI: 10.1371/journal.pone.0261412
    BACKGROUND: Dengue is the most rapidly spreading mosquito-borne viral disease of humans worldwide, including southeast Asia region. This review provides a comprehensive overview of questionnaire-related dengue studies conducted in the Philippines and evaluates their reliability and validity in these surveys.

    METHODS: A review protocol constructed by a panel of experienced academic reviewers was used to formulate the methodology, research design, search strategy and selection criteria. An extensive literature search was conducted between March-June 2020 in various major electronic biomedical databases including PubMed, EMBASE, MEDLINE and ScienceDirect. A systematic review and meta-analysis (PRISMA) were selected as the preferred item reporting method.

    RESULTS: Out of a total of 34 peer-reviewed dengue-related KAP studies that were identified, 15 published from 2000 to April 2020 met the inclusion criteria. Based on the meta-analysis, a poor mean score was obtained for each of knowledge (68.89), attitude (49.86) and preventive practice (64.69). Most respondents were equipped with a good knowledge of the major clinical signs of dengue. Worryingly, 95% of respondents showed several negative attitudes towards dengue prevention, claiming that this was not possible and that enacting preventive practices was not their responsibility. Interestingly, television or radio was claimed as the main source of gaining dengue information (range 50-95%). Lastly, only five articles (33.3%) piloted or pretested their questionnaire before surveying, of which three reported Cronbach's alpha coefficient (range 0.70 to 0.90).

    CONCLUSION: This review indicates that to combat the growing public health threat of dengue to the Philippines, we need the active participation of resident communities, full engagement of healthcare personnel, promotion of awareness campaigns, and access to safe complementary and alternative medicines. Importantly, the psychometric properties of each questionnaire should be assessed rigorously.

  13. Fulltext Neuroprotective potential of Marsilea quadrifolia Linn against monosodium glutamate-induced excitotoxicity in rats
    Subramanian A, Tamilanban T, Sekar M, Begum MY, Atiya A, Ramachawolran G, et al.
    Front Pharmacol, 2023;14:1212376.
    PMID: 37781695 DOI: 10.3389/fphar.2023.1212376
    Background: Excitotoxicity is a condition in which neurons are damaged/injured by the over-activation of glutamate receptors. Excitotoxins play a crucial part in the progression of several neurological diseases. Marsilea quadrifolia Linn (M. quadrifolia) is a very popular aquatic medicinal plant that has been utilised for a variety of therapeutic benefits since ancient times. Its chemical composition is diverse and includes phenolic compounds, tannins, saponins, flavonoids, steroids, terpenoids, alkaloids, carbohydrates and several others that possess antioxidant properties. Objective: The objective of the present study was to investigate the neuroprotective potential of M. quadrifolia against monosodium glutamate (MSG)-induced excitotoxicity in rats. Methods: A high-performance thin-layer chromatography (HPTLC) analysis of chloroform extract of M. quadrifolia (CEMQ) was conducted to identify the major constituents. Further, the in silico docking analysis was carried out on selected ligands. To confirm CEMQ's neuroprotective effects, the locomotor activity, non-spatial memory, and learning were assessed. Results and discussion: The present study confirmed that CMEQ contains quercetin and its derivatives in large. The in-silico findings indicated that quercetin has a better binding affinity (-7.9 kcal/mol) towards the protein target 5EWJ. Animals treated with MSG had 1) a greater reduction in the locomotor score and impairment in memory and learning 2) a greater increase in the blood levels of calcium and sodium and 3) neuronal disorganization, along with cerebral edema and neuronal degeneration in the brain tissues as compared to normal control animals. The changes were however, significantly improved in animals which received standard drug memantine (20 mg/kg) and CEMQ (200 and 400 mg/kg) as compared to the negative control. It is plausible that the changes seen with CEMQ may be attributed to the N-methyl-D-aspartate (NMDA) antagonistic properties. Conclusion: Overall, this study indicated that M. quadrifolia ameliorated MSG-induced neurotoxicity. Future investigations are required to explore the neuroprotective mechanism of M. quadrifolia and its active constituents, which will provide exciting insights in the therapeutic management of neurological disorders.
  14. Fulltext Promising Nutritional Fruits Against Cardiovascular Diseases: An Overview of Experimental Evidence and Understanding Their Mechanisms of Action
    Zuraini NZA, Sekar M, Wu YS, Gan SH, Bonam SR, Mat Rani NNI, et al.
    Vasc Health Risk Manag, 2021;17:739-769.
    PMID: 34858028 DOI: 10.2147/VHRM.S328096
    Cardiovascular diseases (CVDs) are one of the leading causes of morbidity and mortality in both developed and developing countries, affecting millions of individuals each year. Despite the fact that successful therapeutic drugs for the management and treatment of CVDs are available on the market, nutritional fruits appear to offer the greatest benefits to the heart and have been proved to alleviate CVDs. Experimental studies have also demonstrated that nutritional fruits have potential protective effects against CVDs. The aim of the review was to provide a comprehensive summary of scientific evidence on the effect of 10 of the most commonly available nutritional fruits reported against CVDs and describe the associated mechanisms of action. Relevant literatures were searched and collected from several scientific databases including PubMed, ScienceDirect, Google Scholar and Scopus. In the context of CVDs, 10 commonly consumed nutritious fruits including apple, avocado, grapes, mango, orange, kiwi, pomegranate, papaya, pineapple, and watermelon were analysed and addressed. The cardioprotective mechanisms of the 10 nutritional fruits were also compiled and highlighted. Overall, the present review found that the nutritious fruits and their constituents have significant benefits for the management and treatment of CVDs such as myocardial infarction, hypertension, peripheral artery disease, coronary artery disease, cardiomyopathies, dyslipidemias, ischemic stroke, aortic aneurysm, atherosclerosis, cardiac hypertrophy and heart failure, diabetic cardiovascular complications, drug-induced cardiotoxicity and cardiomyopathy. Among the 10 nutritional fruits, pomegranate and grapes have been well explored, and the mechanisms of action are well documented against CVDs. All of the nutritional fruits mentioned are edible and readily accessible on the market. Consuming these fruits, which may contain varying amounts of active constituents depending on the food source and season, the development of nutritious fruits-based health supplements would be more realistic for consistent CVD protection.
  15. Fulltext Promising Natural Products in New Drug Design, Development, and Therapy for Skin Disorders: An Overview of Scientific Evidence and Understanding Their Mechanism of Action
    Mohd Zaid NA, Sekar M, Bonam SR, Gan SH, Lum PT, Begum MY, et al.
    Drug Des Devel Ther, 2022;16:23-66.
    PMID: 35027818 DOI: 10.2147/DDDT.S326332
    The skin is the largest organ in the human body, composed of the epidermis and the dermis. It provides protection and acts as a barrier against external menaces like allergens, chemicals, systemic toxicity, and infectious organisms. Skin disorders like cancer, dermatitis, psoriasis, wounds, skin aging, acne, and skin infection occur frequently and can impact human life. According to a growing body of evidence, several studies have reported that natural products have the potential for treating skin disorders. Building on this information, this review provides brief information about the action of the most important in vitro and in vivo research on the use of ten selected natural products in inflammatory, neoplastic, and infectious skin disorders and their mechanisms that have been reported to date. The related studies and articles were searched from several databases, including PubMed, Google, Google Scholar, and ScienceDirect. Ten natural products that have been reported widely on skin disorders were reviewed in this study, with most showing anti-inflammatory, antioxidant, anti-microbial, and anti-cancer effects as the main therapeutic actions. Overall, most of the natural products reported in this review can reduce and suppress inflammatory markers, like tumor necrosis factor-alpha (TNF-α), scavenge reactive oxygen species (ROS), induce cancer cell death through apoptosis, and prevent bacteria, fungal, and virus infections indicating their potentials. This review also highlighted the challenges and opportunities of natural products in transdermal/topical delivery systems and their safety considerations for skin disorders. Our findings indicated that natural products might be a low-cost, well-tolerated, and safe treatment for skin diseases. However, a larger number of clinical trials are required to validate these findings. Natural products in combination with modern drugs, as well as the development of novel delivery mechanisms, represent a very promising area for future drug discovery of these natural leads against skin disorders.
  16. Fulltext Neuroprotective potency of mangiferin against 3-nitropropionic acid induced Huntington's disease-like symptoms in rats: possible antioxidant and anti-inflammatory mechanisms
    Lum PT, Sekar M, Seow LJ, Shaikh MF, Arulsamy A, Retinasamy T, et al.
    Front Pharmacol, 2023;14:1189957.
    PMID: 37521470 DOI: 10.3389/fphar.2023.1189957
    Huntington's disease (HD), a neurodegenerative disease, normally starts in the prime of adult life, followed by a gradual occurrence of psychiatric disturbances, cognitive and motor dysfunction. The daily performances and life quality of HD patients have been severely interfered by these clinical signs and symptoms until the last stage of neuronal cell death. To the best of our knowledge, no treatment is available to completely mitigate the progression of HD. Mangiferin, a naturally occurring potent glucoxilxanthone, is mainly isolated from the Mangifera indica plant. Considerable studies have confirmed the medicinal benefits of mangiferin against memory and cognitive impairment in neurodegenerative experimental models such as Alzheimer's and Parkinson's diseases. Therefore, this study aims to evaluate the neuroprotective effect of mangiferin against 3-nitropropionic acid (3-NP) induced HD in rat models. Adult Wistar rats (n = 32) were randomly allocated equally into four groups of eight rats each: normal control (Group I), disease control (Group II) and two treatment groups (Group III and Group IV). Treatment with mangiferin (10 and 20 mg/kg, p. o.) was given for 14 days, whereas 3-NP (15 mg/kg, i. p.) was given for 7 days to induce HD-like symptoms in rats. Rats were assessed for cognitive functions and motor coordination using open field test (OFT), novel object recognition (NOR) test, neurological assessment, rotarod and grip strength tests. Biochemical parameters such as oxidative stress markers and pro-inflammatory markers in brain hippocampus, striatum and cortex regions were evaluated. Histopathological study on brain tissue was also conducted using hematoxylin and eosin (H&E) staining. 3-NP triggered anxiety, decreased recognition memory, reduced locomotor activity, lower neurological scoring, declined rotarod performance and grip strength were alleviated by mangiferin treatment. Further, a significant depletion in brain malondialdehyde (MDA) level, an increase in reduced glutathione (GSH) level, succinate dehydrogenase (SDH), superoxide dismutase (SOD) and catalase (CAT) activities, and a decrease in tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) levels were observed in mangiferin treated groups. Mangiferin also mitigated 3-NP induced histopathological alteration in the brain hippocampus, striatum and cortex sections. It could be inferred that mangiferin protects the brain against oxidative damage and neuroinflammation, notably via antioxidant and anti-inflammatory activities. Mangiferin, which has a good safety profile, may be an alternate treatment option for treating HD and other neurodegenerative disorders. The results of the current research of mangiferin will open up new avenues for the development of safe and effective therapeutic agents in diminishing HD.
  17. Fulltext Molecular Targets of Aptamers in Gastrointestinal Cancers: Cancer Detection, Therapeutic Applications, and Associated Mechanisms
    Goh KW, Stephen A, Wu YS, Sim MS, Batumalaie K, Gopinath SCB, et al.
    J Cancer, 2023;14(13):2491-2516.
    PMID: 37670975 DOI: 10.7150/jca.85260
    Gastrointestinal (GI) cancers are among the most common cancers that impact the global population, with high mortality and low survival rates after breast and lung cancers. Identifying useful molecular targets in GI cancers are crucial for improving diagnosis, prognosis, and treatment outcomes, however, limited by poor targeting and drug delivery system. Aptamers are often utilized in the field of biomarkers identification, targeting, and as a drug/inhibitor delivery cargo. Their natural and chemically modifiable binding capability, high affinity, and specificity are favored over antibodies and potential early diagnostic imaging and drug delivery applications. Studies have demonstrated the use of different aptamers as drug delivery agents and early molecular diagnostic and detection probes for treating cancers. This review aims to first describe aptamers' generation, characteristics, and classifications, also providing insights into their recent applications in the diagnosis and medical imaging, prognosis, and anticancer drug delivery system of GI cancers. Besides, it mainly discussed the relevant molecular targets and associated molecular mechanisms involved, as well as their applications for potential treatments for GI cancers. In addition, the current applications of aptamers in a clinical setting to treat GI cancers are deciphered. In conclusion, aptamers are multifunctional molecules that could be effectively used as an anticancer agent or drug delivery system for treating GI cancers and deserve further investigations for clinical applications.
  18. Unveiling high-power and high-safety lithium-ion battery separator based on interlayer of ZIF-67/cellulose nanofiber with electrospun poly(vinyl alcohol)/melamine nonwoven membranes
    Wu XW, Karuppiah C, Wu YS, Zhang BR, Hsu LF, Shih JY, et al.
    J Colloid Interface Sci, 2024 Mar 15;658:699-713.
    PMID: 38141392 DOI: 10.1016/j.jcis.2023.12.098
    Due to the poor thermal stability of conventional separators, lithium-ion batteries require a suitable separator to maintain system safety for long-term cycling performance. It must have high porosity, superior electrolyte uptake ability, and good ion-conducting properties even at high temperatures. In this work, we demonstrate a novel composite membrane based on sandwiching of zeolitic imidazole frameworks-67 decorated cellulose acetate nanofibers (ZIF-67@CA) with electrospun poly(vinyl alcohol)/melamine (denoted as PVAM) nonwoven membranes. The as-prepared sandwich-type membranes are called PVAM/x%ZIF-67@CA/PVAM. The middle layer of composite membranes is primarily filled with different weight percentages of ZIF-67 nanoparticles (x = 5, 15, and 25 wt%), which both reduces the non-uniform porous structure of CA and increases its thermal stability. Therefore, our sandwich-type PVAM/x%ZIF-67@CA/PVAM membrane exhibits a higher thermal shrinkage effect at 200 °C than the commercial polyethylene (PE) separator. Due to its high electrolyte uptake (646.8%) and porosity (85.2%), PVAM/15%ZIF-67@CA/PVAM membrane achieved high ionic conductivity of 1.46 × 10-3 S cm-1 at 70 °C, as compared to the commercial PE separator (ca. 6.01 × 10-4 S cm-1 at 70 °C). Besides, the cell with PVAM/15%ZIF-67@CA/PVAM membrane shows an excellent discharge capacity of about 167.5 mAh g-1after 100 cycles at a 1C rate with a capacity retention of 90.3%. The ZIF-67 fillers in our sandwich-type composite membrane strongly attract anions (PF6-) through Lewis' acid-base interaction, allowing uniform Li+ ion transport and suppressing Li dendrites. As a result, we found that the PVAM/15%ZIF-67@CA/PVAM composite nonwoven membrane is applicable to high-power, high-safety lithium-ion battery systems that can be used in electric vehicles (EVs).
  19. Withanone as an Emerging Anticancer Agent and Understanding Its Molecular Mechanisms: Experimental and Computational Evidence
    Stephen A, Tune BXJ, Wu YS, Batumalaie K, Sekar M, Sarker MMR, et al.
    Curr Cancer Drug Targets, 2024 Mar 14.
    PMID: 38494932 DOI: 10.2174/0115680096290673240223043650
    Despite decades of research and effort, treating cancer is still a challenging task. Current conventional treatments are still unsatisfactory to fully eliminate and prevent re-emergence or relapses, and targeted or personalised therapy, which are more effective in managing cancer, may be unattainable or inaccessible for some. In the past, research in natural products have yielded some of the most commonly used cancer treatment drugs known today. Hence it is possible more are awaiting to be discovered. Withanone, a common withanolide found in the Ayurvedic herb Withania somnifera, has been claimed to possess multiple benefits capable of treating cancer. This review focuses on the potential of withanone as a safe cancer treatment drug based on the pharmacokinetic profile and molecular mechanisms of actions of withanone. Through these in silico and in vitro studies discussed in this review, withanone showspotent anticancer activities and interactions with molecular targets involved in cancer progression. Furthermore, some evidences also show the selective killing property of withanone, which highlights the safety and specificity of withanone in targeting cancer cell. By compiling these evidences, this review hopes to spark interest for future research to be conducted in more extensive studies involving withanone to generate more data, especially involving in vivo experiments and toxicity evaluation of withanone.
  20. Anti- COVID-19 drug discovery by flavonoid derivatives: an extensive computational drug design approach
    Banerjee S, Mukherjee S, Mohsin Kazi, Sen KK, Das A, Hasan R, et al.
    Cell Mol Biol (Noisy-le-grand), 2024 Sep 08;70(8):39-49.
    PMID: 39262264 DOI: 10.14715/cmb/2024.70.8.5
    The present study deals with the in-silico analyses of several flavonoid derivatives to explore COVID-19 through pharmacophore modelling, molecular docking, molecular dynamics, drug-likeness, and ADME properties. The initial literature study revealed that many flavonoids, including luteolin, quercetin, kaempferol, and baicalin may be useful against SARS β-coronaviruses, prompting the selection of their potential derivatives to investigate their abilities as inhibitors of COVID-19. The findings were streamlined using in silico molecular docking, which revealed promising energy-binding interactions between all flavonoid derivatives and the targeted protein. Notably, compounds 8, 9, 13, and 15 demonstrated higher potency against the coronavirus Mpro protein (PDB ID 6M2N). Compound 8 has a -7.2 Kcal/mol affinity for the protein and binds to it by hydrogen bonding with Gln192 and π-sulfur bonding with Met-165. Compound 9 exhibited a significant interaction with the main protease, demonstrating an affinity of -7.9 kcal/mol. Gln-192, Glu-189, Pro-168, and His-41 were the principle amino acid residues involved in this interaction. The docking score for compound 13 is -7.5 Kcal/mol, and it binds to the protease enzyme by making interactions with Leu-41, π-sigma, and Gln-189. These interactions include hydrogen bonding and π-sulfur. The major protease and compound 15 were found to bind with a favourable affinity of -6.8 Kcal/mol. This finding was further validated through molecular dynamic simulation for 1ns, analysing parameters such as RMSD, RMSF, and RoG profiles. The RoG values for all four of the compounds varied significantly (35.2-36.4). The results demonstrated the stability of the selected compounds during the simulation. After passing the stability testing, the compounds underwent screening for ADME and drug-likeness properties, fulfilling all the necessary criteria. The findings of the study may support further efforts for the discovery and development of safe drugs to treat COVID-19.
Related Terms
    Try searching for something
Filters
Contact Us

Please provide feedback to Administrator ([email protected])

External Links