Displaying publications 1 - 20 of 137 in total

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  1. Kuek CY, A/P Gurmukh Singh SK
    Asian Bioeth Rev, 2022 Oct;14(4):363-377.
    PMID: 36203711 DOI: 10.1007/s41649-022-00216-3
    The advancement of human reproductive technology has made it possible for parents with a child affected by a haematological disorder to select and bring into being, a prospective child who can act as a matched stem cell donor. This can be done through the use of preimplantation genetic diagnosis (PGD) coupled with human leukocyte antigen (HLA) typing (PGD-HLA typing), or HLA tying as a standalone procedure, where a healthy embryo, which is an HLA match to the existing sick sibling, is chosen for implantation. The creation of such a sibling (saviour sibling) is normally taken as a last resort when there is no related or unrelated matched donor. While the conception of a saviour sibling may serve as a reliable and realistic treatment option for the ailing child, it also poses new moral questions that challenge a religiously pluralistic society such as Malaysia. The use of PGD-HLA typing may be controversial as it involves creating a life to save a life, selection of compatible human embryos and destruction of the unselected embryos. At present, there is no legal framework regulating the conception of saviour siblings. The development of ethically sound and appropriate local laws and policies should consider the views of religious communities, especially when it involves a controversial subject such as the conception of saviour siblings. This article seeks to explore the perceptions of religious scholars and representatives of the major religions professed and practised in Malaysia, namely Islam, Buddhism, Christianity and Hinduism, through qualitative interviews.
  2. Singhal D, Kanodia N, Singh R, Singh SK, Agrawal S
    Malays Orthop J, 2021 Nov;15(3):71-77.
    PMID: 34966498 DOI: 10.5704/MOJ.2111.011
    Introduction: Pre-operative identification of patients with inadequate hamstring graft for anterior cruciate ligament reconstruction is still a subject of interest. The purpose of this study is to correlate dimension of a harvested dimensions graft with patient physical anthropometric variables.

    Materials and methods: This cohort study included 280 patients (male = 226, female = 54) scheduled for primary anterior cruciate ligament (ACL) reconstruction. Interrelationships between quadruple semitendinosus (ST) graft and anthropometric parameters (age, sex, height, weight, and BMI) were assessed using Pearson Correlation test and regression analysis. Difference among gender was analysed using Mann Whitney and t test. The observed graft diameter was also compared with the literature using Bland - Altman plot.

    Results: Mean age of cohort was 29 years (range, 17-50 years), mean height was 1.69m (range, 1.6-1.9m), mean weight was 75 kg (range, 50-116kg) and mean BMI was 26kg/m2 (range 16.65-40.40kg/m2). Mean quadruple length of harvested ST graft was 7cm (7.1±0.6 cm, range, 5.6-8.8cm) and mean diameter was 8mm (8.2±0.8mm, range, 6.5-10mm). Only height and weight were significantly correlated with graft length and diameter in both sex (p value <0.05). Female, compared to male, had significantly smaller (p<0.0001) and thinner graft (p<0.0001). There was a strong agreement between the literature and our observed graft diameter, but with an overestimated graft diameter in 18.5% of the cases.

    Conclusion: Among anthropometric parameter, only height and weight had moderate positive correlation with graft diameter. Males had longer and wider ST graft in contrast to age-matched female group.

  3. Nhu VH, Shirzadi A, Shahabi H, Singh SK, Al-Ansari N, Clague JJ, et al.
    PMID: 32316191 DOI: 10.3390/ijerph17082749
    Shallow landslides damage buildings and other infrastructure, disrupt agriculture practices, and can cause social upheaval and loss of life. As a result, many scientists study the phenomenon, and some of them have focused on producing landslide susceptibility maps that can be used by land-use managers to reduce injury and damage. This paper contributes to this effort by comparing the power and effectiveness of five machine learning, benchmark algorithms-Logistic Model Tree, Logistic Regression, Naïve Bayes Tree, Artificial Neural Network, and Support Vector Machine-in creating a reliable shallow landslide susceptibility map for Bijar City in Kurdistan province, Iran. Twenty conditioning factors were applied to 111 shallow landslides and tested using the One-R attribute evaluation (ORAE) technique for modeling and validation processes. The performance of the models was assessed by statistical-based indexes including sensitivity, specificity, accuracy, mean absolute error (MAE), root mean square error (RMSE), and area under the receiver operatic characteristic curve (AUC). Results indicate that all the five machine learning models performed well for shallow landslide susceptibility assessment, but the Logistic Model Tree model (AUC = 0.932) had the highest goodness-of-fit and prediction accuracy, followed by the Logistic Regression (AUC = 0.932), Naïve Bayes Tree (AUC = 0.864), ANN (AUC = 0.860), and Support Vector Machine (AUC = 0.834) models. Therefore, we recommend the use of the Logistic Model Tree model in shallow landslide mapping programs in semi-arid regions to help decision makers, planners, land-use managers, and government agencies mitigate the hazard and risk.
  4. Firoz A, Malik A, Singh SK, Jha V, Ali A
    Gene, 2015 Dec 15;574(2):235-46.
    PMID: 26260015 DOI: 10.1016/j.gene.2015.08.012
    Glycogenes regulate a large number of biological processes such as cancer and development. In this work, we created an interaction network of 923 glycogenes to detect potential hubs from different mouse tissues using RNA-Seq data. DAVID functional cluster analysis revealed enrichment of immune response, glycoprotein and cholesterol metabolic processes. We also explored nsSNPs that may modify the expression and function of identified hubs using computational methods. We observe that the number of nsSNPs predicted by any two methods to affect protein function is 4, 7 and 2 for FLT1, NID2 and TNFRSF1B. Residues in the native and mutant proteins were analyzed for solvent accessibility and secondary structure change. Analysis of hubs can help in determining their degree of conservation and understanding their functions in biological processes. The nsSNPs proposed in this work may be further targeted through experimental methods for understanding structural and functional relationships of hub mutants.
  5. Singh SK, Enzhong L, Reidpath DD, Allotey P
    Public Health, 2017 Mar;144:78-85.
    PMID: 28274388 DOI: 10.1016/j.puhe.2016.11.022
    OBJECTIVE: To explore the initiating factors of waterpipe tobacco smoking (WTS) among youth.

    STUDY DESIGN: The analytic framework for this scoping review was performed using the methodology outlined by Arksey and O'Malley, which includes identification of the research question, study selection, charting the data, collating, summarizing and reporting the results that were primarily guided by the research question; 'what is known about the initiation of shisha smoking among youth?'

    METHODS: Electronic databases such as Cochrane, MEDLINE and PsycINFO were used to search for relevant articles. Articles included were all in English and published within the year of 2006 to 2015. Inclusion criteria; i) age range of 10 to 29 years; ii) examined the reasons why youth started or tried WTS; iii) in full text. Therefore, 26 articles were included in this scoping review.

    RESULTS: This review has identified and classified the initiating factors of WTS among youth in four subtopics: individual factors, interpersonal influences, cigarettes and alcohol use, and media influences. Individual factors and interpersonal influences played an important role in initiation factors of WTS among youth.

    CONCLUSION: This study concludes that public health professionals within the Southeast Asia region need to promote innovative preventive measures through peer-to-peer led interventions that are also easily assessable on social media platforms. The public health messages need to address the misconceptions of risk associated to WTS use.
  6. Tan YY, Yap PK, Xin Lim GL, Mehta M, Chan Y, Ng SW, et al.
    Chem Biol Interact, 2020 Sep 25;329:109221.
    PMID: 32768398 DOI: 10.1016/j.cbi.2020.109221
    Cancer continues to be one of the most challenging diseases to be treated and is one of the leading causes of deaths around the globe. Cancers account for 13% of all deaths each year, with cancer-related mortality expected to rise to 13.1 million by the year 2030. Although, we now have a large library of chemotherapeutic agents, the problem of non-selectivity remains the biggest drawback, as these substances are toxic not only to cancerous cells, but also to other healthy cells in the body. The limitations with chemotherapy and radiation have led to the discovery and development of novel strategies for safe and effective treatment strategies to manage the menace of cancer. Researchers have long justified and have shed light on the emergence of nanotechnology as a potential area for cancer therapy and diagnostics, whereby, nanomaterials are used primarily as nanocarriers or as delivery agents for anticancer drugs due to their tumor targeting properties. Furthermore, nanocarriers loaded with chemotherapeutic agents also overcome biological barriers such as renal and hepatic clearances, thus improving therapeutic efficacy with lowered morbidity. Theranostics, which is the combination of rationally designed nanomaterials with cancer-targeting moieties, along with protective polymers and imaging agents has become one of the core keywords in cancer research. In this review, we have highlighted the potential of various nanomaterials for their application in cancer therapy and imaging, including their current state and clinical prospects. Theranostics has successfully paved a path to a new era of drug design and development, in which nanomaterials and imaging contribute to a large variety of cancer therapies and provide a promising future in the effective management of various cancers. However, in order to meet the therapeutic needs, theranostic nanomaterials must be designed in such a way, that take into account the pharmacokinetic and pharmacodynamics properties of the drug for the development of effective carcinogenic therapy.
  7. Tan CL, Chan Y, Candasamy M, Chellian J, Madheswaran T, Sakthivel LP, et al.
    Eur J Pharmacol, 2022 Feb 11;919:174821.
    PMID: 35151643 DOI: 10.1016/j.ejphar.2022.174821
    Chronic respiratory diseases have collectively become a major public health concern and have now taken form as one of the leading causes of mortality worldwide. Most chronic respiratory diseases primarily occur due to prolonged airway inflammation. In addition, critical environmental factors such as cigarette smoke, industrial pollutants, farm dust, and pollens may also exacerbate such diseases. Moreover, alterations in the genetic sequence of an individual, abnormalities in the chromosomes or immunosuppression resulting from bacterial, fungal, and viral infections may also play a key role in the pathogenesis of respiratory diseases. Over the years, multiple in vitro models have been employed as the basis of existing as well as emerging advancements in chronic respiratory disease research. These include cell lines, gene expression techniques, single cell RNA sequencing, cytometry, culture techniques, as well as serum/sputum biomarkers that can be used to elucidate the molecular mechanisms underlying these diseases, and to identify novel diagnostic and management options for these diseases. This review summarizes the current understanding of the pathogenesis of various chronic respiratory diseases derived through in vitro experimental models, where the knowledge obtained from these studies can greatly benefit researchers in the discovery and development of novel screening techniques and advanced therapeutic strategies that could be translated into clinical use in the future.
  8. Alnuqaydan AM, Almutary AG, Sukamaran A, Yang BTW, Lee XT, Lim WX, et al.
    AAPS PharmSciTech, 2021 Jun 08;22(5):173.
    PMID: 34105037 DOI: 10.1208/s12249-021-02062-2
    Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health.
  9. Lee JY, Bhandare RR, Boddu SHS, Shaik AB, Saktivel LP, Gupta G, et al.
    Biomed Pharmacother, 2024 Apr;173:116275.
    PMID: 38394846 DOI: 10.1016/j.biopha.2024.116275
    Tumour suppressor genes play a cardinal role in the development of a large array of human cancers, including lung cancer, which is one of the most frequently diagnosed cancers worldwide. Therefore, extensive studies have been committed to deciphering the underlying mechanisms of alterations of tumour suppressor genes in governing tumourigenesis, as well as resistance to cancer therapies. In spite of the encouraging clinical outcomes demonstrated by lung cancer patients on initial treatment, the subsequent unresponsiveness to first-line treatments manifested by virtually all the patients is inherently a contentious issue. In light of the aforementioned concerns, this review compiles the current knowledge on the molecular mechanisms of some of the tumour suppressor genes implicated in lung cancer that are either frequently mutated and/or are located on the chromosomal arms having high LOH rates (1p, 3p, 9p, 10q, 13q, and 17p). Our study identifies specific genomic loci prone to LOH, revealing a recurrent pattern in lung cancer cases. These loci, including 3p14.2 (FHIT), 9p21.3 (p16INK4a), 10q23 (PTEN), 17p13 (TP53), exhibit a higher susceptibility to LOH due to environmental factors such as exposure to DNA-damaging agents (carcinogens in cigarette smoke) and genetic factors such as chromosomal instability, genetic mutations, DNA replication errors, and genetic predisposition. Furthermore, this review summarizes the current treatment landscape and advancements for lung cancers, including the challenges and endeavours to overcome it. This review envisages inspired researchers to embark on a journey of discovery to add to the list of what was known in hopes of prompting the development of effective therapeutic strategies for lung cancer.
  10. Sakharkar MK, Kashmir Singh SK, Rajamanickam K, Mohamed Essa M, Yang J, Chidambaram SB
    PLoS One, 2019;14(9):e0220995.
    PMID: 31487305 DOI: 10.1371/journal.pone.0220995
    Parkinson's disease (PD) is an irreversible and incurable multigenic neurodegenerative disorder. It involves progressive loss of mid brain dopaminergic neurons in the substantia nigra pars compacta (SN). We compared brain gene expression profiles with those from the peripheral blood cells of a separate sample of PD patients to identify disease-associated genes. Here, we demonstrate the use of gene expression profiling of brain and blood for detecting valid targets and identifying early PD biomarkers. Implementing this systematic approach, we discovered putative PD risk genes in brain, delineated biological processes and molecular functions that may be particularly disrupted in PD and also identified several putative PD biomarkers in blood. 20 of the differentially expressed genes in SN were also found to be differentially expressed in the blood. Further application of this methodology to other brain regions and neurological disorders should facilitate the discovery of highly reliable and reproducible candidate risk genes and biomarkers for PD. The identification of valid peripheral biomarkers for PD may ultimately facilitate early identification, intervention, and prevention efforts as well.
  11. Anand K, Abdul NS, Ghazi T, Ramesh M, Gupta G, Tambuwala MM, et al.
    ACS Omega, 2021 Jan 12;6(1):265-277.
    PMID: 33458478 DOI: 10.1021/acsomega.0c04461
    In this study, novel self-assembled carbazole-thiooctanoic acid nanoparticles (CTNs) were synthesized from amino carbazole (a mutagen) and thiooctanoic acid (an antioxidant). The nanoparticles were characterized using hyperspectral techniques. Then, the antiproliferative potential of CTNs was determined in HepG2 liver carcinoma cells. This study employed a solvent-antisolvent interaction method to synthesize a spherical CTN of size less than 50 nm. Moreover, CT was subsequently capped to gold nanoparticles (AuNPs) in the additional comparative studies. The CT derivative was synthesized from carbazole and lipoic acid by the amide bond formation reaction using a coupling agent. Furthermore, it was characterized using infrared (IR), 1H nuclear magnetic resonance, dynamic light scattering (DLS), and transmission electron microscopy techniques. The CT-capped gold nanoparticles (CTAuNPs) were prepared from CT, chloroauric acid, and NaBH4. The CTAuNPs were characterized using ultraviolet-visible, high-resolution TEM, DLS, and Fourier transform IR techniques. The cytotoxicity and apoptosis-inducing ability of both nanoparticles were determined in HepG2 cells. The results demonstrate that CTNs exhibit antiproliferative activity in the cancerous HepG2 cells. Moreover, molecular docking and molecular dynamics studies were conducted to explore the therapeutic potential of CT against human EGFR suppressor protein to gain more insights into the binding mode of the CT, which may show a significant role in anticancer therapy.
  12. Datsyuk JK, Paudel KR, Rajput R, Kokkinis S, El Sherkawi T, Singh SK, et al.
    Chem Biol Interact, 2023 Nov 01;385:110737.
    PMID: 37774998 DOI: 10.1016/j.cbi.2023.110737
    Chronic respiratory diseases like asthma and Chronic Obstructive Pulmonary Disease (COPD) have been a burden to society for an extended period. Currently, there are only preventative treatments in the form of mono- or multiple-drug therapy available to patients who need to utilize it daily. Hence, throughout the years there has been a substantial amount of research in understanding what causes inflammation in the context of these diseases. For example, the transcription factor NFκB has a pivotal role in causing chronic inflammation. Subsequent research has been exploring ways to block the activation of NFκB as a potential therapeutic strategy for many inflammatory diseases. One of the possible ways through which this is probable is the utilisation of decoy oligodeoxynucleotides, which are synthetic, short, single-stranded DNA fragments that mimic the consensus binding site of a targeted transcription factor, thereby functionally inactivating it. However, limitations to the implementation of decoy oligodeoxynucleotides include their rapid degradation by intracellular nucleases and the lack of targeted tissue specificity. An advantageous approach to overcome these limitations involves using nanoparticles as a vessel for drug delivery. In this review, all of those key elements will be explored as to how they come together as an application to treat chronic inflammation in respiratory diseases.
  13. Byrne I, William T, Chua TH, Patterson C, Hall T, Tan M, et al.
    Sci Rep, 2023 Aug 10;13(1):12998.
    PMID: 37563178 DOI: 10.1038/s41598-023-39670-w
    Malaysia has reported no indigenous cases of P. falciparum and P. vivax for over 3 years. When transmission reaches such low levels, it is important to understand the individuals and locations where exposure risks are high, as they may be at greater risk in the case of a resurgence of transmission. Serology is a useful tool in low transmission settings, providing insight into exposure over longer durations than PCR or RDT. We ran blood samples from a 2015 population-based survey in northern Sabah, Malaysian Borneo on a multiplex bead assay. Using supervised machine learning methods, we characterised recent and historic exposure to Plasmodium falciparum and P. vivax and found recent exposure to P. falciparum to be very low, with exposure to both species increasing with age. We performed a risk-factor assessment on environmental, behavioural, demographic and household factors, and identified forest activity and longer travel times to healthcare as common risk-factors for exposure to P. falciparum and P. vivax. In addition, we used remote-sensing derived data and geostatistical models to assess environmental and spatial associations with exposure. We created predictive maps of exposure to recent P. falciparum in the study area and showed 3 clear foci of exposure. This study provides useful insight into the environmental, spatial and demographic risk factors for P. falciparum and P. vivax at a period of low transmission in Malaysian Borneo. The findings would be valuable in the case of resurgence of human malarias in the region.
  14. Lee LY, Hew GSY, Mehta M, Shukla SD, Satija S, Khurana N, et al.
    Life Sci, 2021 Feb 15;267:118973.
    PMID: 33400932 DOI: 10.1016/j.lfs.2020.118973
    Eosinophils are bi-lobed, multi-functional innate immune cells with diverse cell surface receptors that regulate local immune and inflammatory responses. Several inflammatory and infectious diseases are triggered with their build up in the blood and tissues. The mobilization of eosinophils into the lungs is regulated by a cascade of processes guided by Th2 cytokine generating T-cells. Recruitment of eosinophils essentially leads to a characteristic immune response followed by airway hyperresponsiveness and remodeling, which are hallmarks of chronic respiratory diseases. By analysing the dynamic interactions of eosinophils with their extracellular environment, which also involve signaling molecules and tissues, various therapies have been invented and developed to target respiratory diseases. Having entered clinical testing, several eosinophil targeting therapeutic agents have shown much promise and have further bridged the gap between theory and practice. Moreover, researchers now have a clearer understanding of the roles and mechanisms of eosinophils. These factors have successfully assisted molecular biologists to block specific pathways in the growth, migration and activation of eosinophils. The primary purpose of this review is to provide an overview of the eosinophil biology with a special emphasis on potential pharmacotherapeutic targets. The review also summarizes promising eosinophil-targeting agents, along with their mechanisms and rationale for use, including those in developmental pipeline, in clinical trials, or approved for other respiratory disorders.
  15. Mehta M, Paudel KR, Shukla SD, Shastri MD, Singh SK, Gulati M, et al.
    EXCLI J, 2020;19:1477-1480.
    PMID: 33312108 DOI: 10.17179/excli2020-2997
  16. Paudel KR, Wadhwa R, Tew XN, Lau NJX, Madheswaran T, Panneerselvam J, et al.
    Life Sci, 2021 Jul 01;276:119436.
    PMID: 33789146 DOI: 10.1016/j.lfs.2021.119436
    Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality globally. Despite the availability of therapeutic options, the improvement in patient survival is yet to be achieved. Recent advances in natural product (e.g., Rutin) research, therapeutic nanotechnology and especially the combination of both could aid in achieving significant improvements in the treatment or management of NSCLC. In this study, we explore the anti-cancer activity of Rutin-loaded liquid crystalline nanoparticles (LCNs) in an in vitro model where we have employed the A549 human lung epithelial carcinoma cell line. The anti-proliferative activity was determined by MTT and Trypan blue assays, whereas, the anti-migratory activity was evaluated by the scratch wound healing assay and a modified Boyden chamber assay. We also evaluated the anti-apoptotic activity by Annexin V-FITC staining, and the colony formation activity was studied using crystal violet staining. Here, we report that Rutin-LCNs showed promising anti-proliferative and anti-migratory activities. Furthermore, Rutin-LCNs also induced apoptosis in the A549 cells and inhibited colony formation. The findings warrant further detailed and in-depth anti-cancer mechanistic studies of Rutin-LCNs with a focus towards a potential therapeutic option for NSCLC. LCNs may help to enhance the solubility of Rutin used in the treatment of lung cancer and hence enhance the anticancer effect of Rutin.
  17. Allam VSRR, Chellappan DK, Jha NK, Shastri MD, Gupta G, Shukla SD, et al.
    PMID: 33977840 DOI: 10.1080/10408398.2021.1915744
    Respiratory diseases, both acute and chronic, are reported to be the leading cause of morbidity and mortality, affecting millions of people globally, leading to high socio-economic burden for the society in the recent decades. Chronic inflammation and decline in lung function are the common symptoms of respiratory diseases. The current treatment strategies revolve around using appropriate anti-inflammatory agents and bronchodilators. A range of anti-inflammatory agents and bronchodilators are currently available in the market; however, the usage of such medications is limited due to the potential for various adverse effects. To cope with this issue, researchers have been exploring various novel, alternative therapeutic strategies that are safe and effective to treat respiratory diseases. Several studies have been reported on the possible links between food and food-derived products in combating various chronic inflammatory diseases. Nutraceuticals are examples of such food-derived products which are gaining much interest in terms of its usage for the well-being and better human health. As a consequence, intensive research is currently aimed at identifying novel nutraceuticals, and there is an emerging notion that nutraceuticals can have a positive impact in various respiratory diseases. In this review, we discuss the efficacy of nutraceuticals in altering the various cellular and molecular mechanisms involved in mitigating the symptoms of respiratory diseases.
  18. Mehta M, Paudel KR, Shukla SD, Shastri MD, Satija S, Singh SK, et al.
    Future Med Chem, 2021 03;13(6):543-549.
    PMID: 33538615 DOI: 10.4155/fmc-2020-0297
    Aim: In the present study, the inhibitory potential of rutin-loaded liquid crystalline nanoparticles (LCNs) on oxidative stress was determined in human bronchial epithelial cells (BEAS-2B) by analysing the expression levels of different antioxidant (NADPH quinine oxidoreductase-1 (NQO1); γ-glutamyl cysteine synthetase catalytic subunit (GCLC)) and pro-oxidant (NADPH oxidase (Nox)-4; Nox2B) genes. Results: Our findings revealed that the rutin-loaded LCNs inhibited the genes, namely Nox2B and Nox4, which caused oxidative stress. In addition, these nanoparticles demonstrated an upregulation in the expression of the antioxidant genes Gclc and Nqo-1 in a dose-dependent manner. Conclusion: The study indicates the promising potential of rutin-loaded LCNs as an effective treatment strategy in patients with high oxidant loads in various respiratory diseases.
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