20 results on '"Ling APK"'
Search Results
2. Mesenchymal stem cells as future treatment for cardiovascular regeneration and its challenges.
- Author
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Seow KS and Ling APK
- Abstract
Cardiovascular diseases (CVDs), particularly stroke and myocardial infarction (MI) contributed to the leading cause of death annually among the chronic diseases globally. Despite the advancement of technology, the current available treatments mainly served as palliative care but not treating the diseases. However, the discovery of mesenchymal stem cells (MSCs) had gained a consideration to serve as promising strategy in treating CVDs. Recent evidence also showed that MSCs are the strong candidate to be used as stem cell therapy involving cardiovascular regeneration due to its cardiomyogenesis, anti-inflammatory and immunomodulatory properties, antifibrotic effects and neovascularization capacity. Besides, MSCs could be used for cellular cardiomyoplasty with its transdifferentiation of MSCs into cardiomyocytes, paracrine effects, microvesicles and exosomes as well as mitochondrial transfer. The safety and efficacy of utilizing MSCs have been described in well-established preclinical and clinical studies in which the accomplishment of MSCs transplantation resulted in further improvement of the cardiac function. Tissue engineering could enhance the desired properties and therapeutic effects of MSCs in cardiovascular regeneration by genome-editing, facilitating the cell delivery and retention, biomaterials-based scaffold, and three-dimensional (3D)-bioprinting. However, there are still obstacles in the use of MSCs due to the complexity and versatility of MSCs, low retention rate, route of administration and the ethical and safety issues of the use of MSCs. The aim of this review is to highlight the details of therapeutic properties of MSCs in treating CVDs, strategies to facilitate the therapeutic effects of MSCs through tissue engineering and the challenges faced using MSCs. A comprehensive review has been done through PubMed and National Center for Biotechnology Information (NCBI) from the year of 2010 to 2021 based on some specific key terms such as 'mesenchymal stem cells in cardiovascular disease', 'mesenchymal stem cells in cardiac regeneration', 'mesenchymal stem cells facilitate cardiac repairs', 'tissue engineering of MSCs' to include relevant literature in this review., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-23-1936/coif). The authors have no conflicts of interest to declare., (2024 Annals of Translational Medicine. All rights reserved.)
- Published
- 2024
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3. How Do Abnormalities in the Cerebrospinal Fluid Impact Neuropsychology with Progressing Age?
- Author
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Joshi G, Ling APK, Chye SM, and Koh RY
- Subjects
- Adult, Adolescent, Child, Infant, Newborn, Humans, Aged, Central Nervous System physiology, Brain, Aging, Neuropsychology, Alzheimer Disease
- Abstract
The behavior of an individual changes from neonate to elderly due to the development of the central nervous system (CNS). One of the important components of the CNS is the cerebrospinal fluid (CSF), which bathes the brain and spinal cord. CSF has changing properties throughout life, including composition and volume imbalance. However, a specific age group that shows prevailing abnormality- corresponding behavior remains unclear. The objective of this article is to explore how such changes reflect on one's psychological as well as physical processing. Production of CSF could be affected by many factors, including its flow, absorption, volume, and composition. Prenatally, congenital malformations and infections hold the greatest risk of impacting the child's physical and mental growth. In adolescents, transmission of external substances like alcohol or drugs in the cerebrospinal fluid is known to impact severe mood changes that potentially result in suicide and depression. In the adult working population, the influence of stress levels on CSF composition causes anxiety and sleep disorders. Finally, the reduced production of CSF was found to be associated with memory deficits and Alzheimer's disease in the aging group. From the collected evidence, it can be observed that CSF played an important role in behavioral changes and may be associated with neurodegenerations. By linking the CSF abnormalities to the clinical symptoms at different stages of life, it may provide additional information in the diagnosis of diseases that are associated with neuropsychological changes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2023
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4. The Role of Monoamine Oxidase B Inhibitors in the Treatment of Parkinson's Disease - An Update.
- Author
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Chew ZX, Lim CL, Ng KY, Chye SM, Ling APK, and Koh RY
- Subjects
- Humans, Selegiline pharmacology, Antiparkinson Agents therapeutic use, Antiparkinson Agents pharmacology, Monoamine Oxidase Inhibitors therapeutic use, Monoamine Oxidase Inhibitors pharmacology, Dopamine Agents, Monoamine Oxidase metabolism, Dopamine, Parkinson Disease drug therapy, Neurodegenerative Diseases
- Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disease characterised by reduced dopamine levels in the substantial nigra. This may lead to typical motor features such as bradykinesia, resting tremors and rigid muscles, as well as non-motor symptoms such as neuropsychiatric symptoms, sleep disorders, autonomic dysfunction, and sensory disturbances. Inhibitors of monoamine oxidase B (MAO-B) are used to alleviate symptoms by reducing monoamine oxidase-catalysed degradation of dopamine; hence, preserving functional levels of dopamine. The very first MAO-B inhibitor used therapeutically was selegiline, followed by rasagiline, its indane derivative which has superior efficacy and selectivity. Both inhibitors can be used as monotherapy or in combination with other anti- Parkinson drugs. Safinamide, a reversible MAO-B inhibitor that utilises both dopaminergic and non-dopaminergic mechanisms, was recently approved by the European Medicines Agency (EMA) (2015) and U.S. FDA (2017) as an add-on therapy for patients with mid- or late-stage Parkinson's disease. Furthermore, MAO-B inhibitors were found to be associated with potential neuroprotective and disease modifying effects. However, evidence of their efficacy and role in PD models is scarce and warrants further investigation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2023
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5. Applying stem cell therapy in intractable diseases: a narrative review of decades of progress and challenges.
- Author
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Brianna, Ling APK, and Wong YP
- Abstract
Background and Objective: Stem cell therapy (SCT) is one of the vastly researched branches of regenerative medicine as a therapeutic tool to treat incurable diseases. With the use of human stem cells such as embryonic stem cells (ESCs), adult stem cells (ASCs) and induced pluripotent stem cells (iPSCs), stem cell therapy aims to regenerate or repair damaged tissues and congenital defects. As stem cells are able to undergo infinite self-renewal, differentiate into various types of cells and secrete protective paracrine factors, many researchers have investigated the potential of SCT in regenerative medicine. Therefore, this review aims to provide a comprehensive review on the recent application of SCT in various intractable diseases, namely, haematological diseases, neurological diseases, diabetes mellitus, retinal degenerative disorders and COVID-19 infections along with the challenges faced in the clinical translation of SCT., Methods: An extensive search was conducted on Google scholar, PubMed and Clinicaltrials.gov using related keywords. Latest articles on stem cell therapy application in selected diseases along with their challenges in clinical applications were selected., Key Content and Findings: In vitro and in vivo studies involving SCT are shown to be safe and efficacious in treating various diseases covered in this review. There are also a number of small-scale clinical trials that validated the positive therapeutic outcomes of SCT. Nevertheless, the effectiveness of SCT are highly variable as some SCT works best in patients with early-stage diseases while in other diseases, SCT is more likely to work in patients in late stages of illnesses. Among the challenges identified in SCT translation are uncertainty in the underlying stem cell mechanism, ethical issues, genetic instability and immune rejection., Conclusions: SCT will be a revolutionary treatment in the future that will provide hope to patients with intractable diseases. Therefore, studies ought to be done to ascertain the long-term effects of SCT while addressing the challenges faced in validating SCT for clinical use. Moreover, as there are many studies investigating the safety and efficacy of SCT, future studies should look into elucidating the regenerative and reparative capabilities of stem cells which largely remains unknown., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://sci.amegroups.com/article/view/10.21037/sci-2022-021/coif). The authors have no conflicts of interest to declare., (2022 Stem Cell Investigation. All rights reserved.)
- Published
- 2022
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6. Bioinformatics approaches and applications in plant biotechnology.
- Author
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Tan YC, Kumar AU, Wong YP, and Ling APK
- Abstract
Background: In recent years, major advance in molecular biology and genomic technologies have led to an exponential growth in biological information. As the deluge of genomic information, there is a parallel growth in the demands of tools in the storage and management of data, and the development of software for analysis, visualization, modelling, and prediction of large data set., Main Body: Particularly in plant biotechnology, the amount of information has multiplied exponentially with a large number of databases available from many individual plant species. Efficient bioinformatics tools and methodologies are also developed to allow rapid genome sequence and the study of plant genome in the 'omics' approach. This review focuses on the various bioinformatic applications in plant biotechnology, and their advantages in improving the outcome in agriculture. The challenges or limitations faced in plant biotechnology in the aspect of bioinformatics approach that explained the low progression in plant genomics than in animal genomics are also reviewed and assessed., Conclusion: There is a critical need for effective bioinformatic tools, which are able to provide longer reads with unbiased coverage in order to overcome the complexity of the plant's genome. The advancement in bioinformatics is not only beneficial to the field of plant biotechnology and agriculture sectors, but will also contribute enormously to the future of humanity., (© 2022. The Author(s).)
- Published
- 2022
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7. Anti-neuroinflammatory of Chloroform Extract of Panax ginseng Root Culture on Lipopolysaccharide-stimulated BV2 Microglia Cells.
- Author
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Cheah CH, Ling APK, Wong YP, Koh RY, and Hussein S
- Abstract
Background: It is believed that activation of microglia in the central nervous system upon detection of stimulus like lipopolysaccharides provokes neuroinflammation via the production of pro-inflammatory mediators and cytokines. The cytoprotective and anti-inflammatory properties of various folk medicine has been gaining attention as a strategy to combat various disease. This study aimed to assess the anti-neuroinflammatory properties of chloroform extract of in vitro Panax ginseng root culture based on nitric oxide and cytokines production., Methods: The study was initiated with the determination of maximum non-toxic dose (MNTD) of P. ginseng root culture chloroform extract using the MTT assay. The lipopolysaccharides-stimulated BV2 microglia cells were treated with MNTD and ½MNTD of the extract and its anti-neuroinflammatory properties were assessed by measuring the production of nitric oxide (NO) via Griess assay, as well as TNF-α, IL-6 and IL-10 using Quantikine ELISA., Results: It was found that the MNTD and ½MNTD of the extract did not play a significant role in the production of pro-inflammatory cytokines such as NO, TNF-α and IL-6. However, the MNTD and ½MNTD of chloroform extract significantly increased the anti-inflammatory IL-10 compared to the untreated cells., Conclusion: With this, the chloroform extract of P. ginseng root culture potentially exerts anti-neuroinflammatory properties.
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- 2022
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8. CRISPR/Cas9 in plant biotechnology: applications and challenges.
- Author
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Gan WC and Ling APK
- Abstract
The application of plant biotechnology to enhance beneficial traits in crops is now indispensable because of food insecurity due to increasing global population and climate change. The recent biotechnological development of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated system 9 (Cas9) allows for a more simple and precise method of gene editing, which is now preferred compared to Zinc Finger Nucleases (ZFNs) and Transcription Activator-like Effector Nucleases (TALENs). In this review, recent progress in utilizing CRISPR/Cas9-mediated gene editing in plants to enhance certain traits in beneficial crops, including rice, soybean, and oilseed rape, is discussed. In addition, novel methods of applying the CRISPR/Cas9 system in live cell imaging are also extensively reviewed. Despite all the applications, the existing delivery methods of CRISPR/Cas9 fail to provide consistent results and are inefficient for in planta transformation. Hence, research should be focused on improving current delivery methods or developing novel ones to facilitate CRISPR/Cas9-based gene editing studies. Strict regulations on the sale and commercial growth of gene-edited crops have restricted more efforts in applying CRISPR/Cas9 technology in plant species. Therefore, a shift in public viewpoint toward gene editing would help to propel scientific progress rapidly., Competing Interests: The authors declare that there is no conflict of interest., (© 2022 Institute of Bioorganic Chemistry, Polish Academy of Sciences.)
- Published
- 2022
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9. Gene introduction approaches in chloroplast transformation and its applications.
- Author
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Kumar AU and Ling APK
- Abstract
Background: Chloroplast is a type of plastid that is believed to be originated from ancestral cyanobacteria. Chloroplast besides being a major component for photosynthesis, also takes part in another major plant metabolism, making it one of the major components of plants., Main Body: Chloroplast transformation is an alternative and better genetic engineering approach compared to the nuclear transformation that has been widely applied in plant genetic engineering. Chloroplast transformation has exhibited various positive effects as compared to nuclear transformation. This is a more preferred technique by researchers. To carry out chloroplast transformation, the vector design must be performed, and a selectable marker needs to be incorporated before the chloroplast could uptake the construct. The common way of introducing a gene into the host, which is the chloroplast, involves the biolistic, PEG-mediated, carbon nanotubes carriers, UV-laser microbeam, and Agrobacterium-mediated transformation approaches. Apart from discussing the processes involved in introducing the gene into the chloroplast, this review also focuses on the various applications brought about by chloroplast transformation, particularly in the field of agriculture and environmental science., Conclusion: Chloroplast transformation has shown a lot of advantages and proven to be a better alternative compared to nuclear genome transformation. Further studies must be conducted to uncover new knowledge regarding chloroplast transformation as well as to discover its additional applications in the fields of biotechnology., (© 2021. The Author(s).)
- Published
- 2021
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10. COVID-19 and its effects on neurological functions.
- Author
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Yew MMT, Lip JQ, and Ling APK
- Subjects
- Angiotensin-Converting Enzyme 2 metabolism, Anosmia virology, Central Nervous System virology, Dysgeusia virology, Encephalitis, Viral virology, Humans, Meningitis, Viral virology, Nervous System Diseases pathology, Peripheral Nervous System virology, SARS-CoV-2, Seizures virology, COVID-19 pathology, Central Nervous System pathology, Nervous System Diseases virology, Peripheral Nervous System pathology
- Abstract
Ever since the first reported case series on SARS-CoV-2-induced neurological manifestation in Wuhan, China in April 2020, various studies reporting similar as well as diverse symptoms of COVID-19 infection relating to the nervous system were published. Since then, scientists started to uncover the mechanism as well as pathophysiological impacts it has on the current understanding of the disease. SARS-CoV-2 binds to the ACE2 receptor which is present in certain parts of the body which are responsible for regulating blood pressure and inflammation in a healthy system. Presence of the receptor in the nasal and oral cavity, brain, and blood allows entry of the virus into the body and cause neurological complications. The peripheral and central nervous system could also be invaded directly in the neurogenic or hematogenous pathways, or indirectly through overstimulation of the immune system by cytokines which may lead to autoimmune diseases. Other neurological implications such as hypoxia, anosmia, dysgeusia, meningitis, encephalitis, and seizures are important symptoms presented clinically in COVID-19 patients with or without the common symptoms of the disease. Further, patients with higher severity of the SARS-CoV-2 infection are also at risk of retaining some neurological complications in the long-run. Treatment of such severe hyperinflammatory conditions will also be discussed, as well as the risks they may pose to the progression of the disease. For this review, articles pertaining information on the neurological manifestation of SARS-CoV-2 infection were gathered from PubMed and Google Scholar using the search keywords "SARS-CoV-2", "COVID-19", and "neurological dysfunction". The findings of the search were filtered, and relevant information were included.
- Published
- 2021
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11. Immunotherapies for Parkinson's Disease: Progression of Clinical Development.
- Author
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Teng JS, Ooi YY, Chye SM, Ling APK, and Koh RY
- Subjects
- Animals, Antibodies, Monoclonal therapeutic use, Humans, Neurons drug effects, Substantia Nigra drug effects, Immunotherapy methods, Parkinson Disease therapy
- Abstract
Parkinson's disease is a common neurodegenerative disease affecting the movement and well-being of most elderly. The manifestations of Parkinson's disease often include resting tremor, stiffness, bradykinesia, and muscular rigidity. The typical hallmark of Parkinson's disease is the destruction of neurons in the substantia nigra and the presence of Lewy bodies in different compartments of the central nervous system. Due to various limitations to the currently available treatments, immunotherapies have emerged to be the new approach to Parkinson's disease treatment. This approach shows some positive outcomes on the efficacy by removing the aggregated species of alpha-synuclein, which is believed to be one of the causes of Parkinson's disease. In this review, an overview of how alpha-synuclein contributes to Parkinson's disease and the effects of a few new immunotherapeutic treatments, including BIIB054 (cinpanemab), MEDI1341, AFFITOPE, and PRX002 (prasinezumab) that are currently under clinical development, will be discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2021
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12. Current updates and research on plant-based vaccines for coronavirus disease 2019.
- Author
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Uthaya Kumar A, Kadiresen K, Gan WC, and Ling APK
- Abstract
The primary outbreak of severe acute respiratory syndrome coronavirus 2, causing pneumonia-like symptoms in patients named coronavirus disease 2019 (COVID-19) had evolved into a global pandemic. COVID-19 has surpassed Middle East respiratory syndrome and severe acute respiratory syndrome in terms of rate and scale causing more than one million deaths. Development of an effective vaccine to fight against the spread of COVID-19 is the main goal of many countries around the world and plant-based vaccines are one of the available methods in vaccine developments. Plant-based vaccine has gained its reputation among researchers for its known effective manufacturing process and cost effectiveness. Many companies around the world are participating in the race to develop an effective vaccine by using the plant system. This review discusses different approaches used as well as highlights the challenges faced by various companies and research groups in developing the plant-based COVID-19 vaccine., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Korean Vaccine Society.)
- Published
- 2021
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13. The Mechanism of Action of Salsolinol in Brain: Implications in Parkinson's Disease.
- Author
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Voon SM, Ng KY, Chye SM, Ling APK, Voon KGL, Yap YJ, and Koh RY
- Subjects
- Animals, Apoptosis, Humans, Mice, Neurotoxins, Rats, Brain pathology, Isoquinolines metabolism, Parkinson Disease pathology
- Abstract
1-Methyl-1,2,3,4-tetrahydroisoquinoline-6,7-diol, commonly known as salsolinol, is a compound derived from dopamine. It was first discovered in 1973 and has gained attention for its role in Parkinson's disease. Salsolinol and its derivatives were claimed to play a role in the pathogenesis of Parkinson's disease as a neurotoxin that induces apoptosis of dopaminergic neurons due to its structural similarity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its ability to induce Parkinsonism. In this article, we discussed the biosynthesis, distribution and blood-brain barrier permeability of salsolinol. The roles of salsolinol in a healthy brain, particularly the interactions with enzymes, hormone and catecholamine, were reviewed. Finally, we discussed the involvement of salsolinol and its derivatives in the pathogenesis of Parkinson's disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2020
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14. Mechanisms of action of amyloid-beta and its precursor protein in neuronal cell death.
- Author
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Leong YQ, Ng KY, Chye SM, Ling APK, and Koh RY
- Subjects
- Alzheimer Disease genetics, Alzheimer Disease pathology, Amyloid beta-Peptides genetics, Amyloid beta-Protein Precursor genetics, Animals, Cell Death physiology, Humans, Neurofibrillary Tangles genetics, Neurofibrillary Tangles pathology, Neurons pathology, Alzheimer Disease metabolism, Amyloid beta-Peptides metabolism, Amyloid beta-Protein Precursor metabolism, Neurofibrillary Tangles metabolism, Neurons metabolism
- Abstract
Extracellular senile plaques and intracellular neurofibrillary tangles are the neuropathological findings of the Alzheimer's disease (AD). Based on the amyloid cascade hypothesis, the main component of senile plaques, the amyloid-beta (Aβ) peptide, and its derivative called amyloid precursor protein (APP) both have been found to place their central roles in AD development for years. However, the recent therapeutics have yet to reverse or halt this disease. Previous evidence demonstrates that the accumulation of Aβ peptides and APP can exert neurotoxicity and ultimately neuronal cell death. Hence, we discuss the mechanisms of excessive production of Aβ peptides and APP serving as pathophysiologic stimuli for the initiation of various cell signalling pathways including apoptosis, necrosis, necroptosis and autophagy which lead to neuronal cell death. Conversely, the activation of such pathways could also result in the abnormal generation of APP and Aβ peptides. An elucidation of actions of APP and its metabolite, Aβ, could be vital in suggesting novel therapeutic opportunities.
- Published
- 2020
- Full Text
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15. Anticancer Potential of Syzygium Species: a Review.
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Chua LK, Lim CL, Ling APK, Chye SM, and Koh RY
- Subjects
- Chalcones pharmacology, Humans, Oleanolic Acid pharmacology, Pentacyclic Triterpenes, Phenols pharmacology, Plants, Medicinal, Triterpenes pharmacology, Betulinic Acid, Antineoplastic Agents, Phytogenic pharmacology, Phytochemicals pharmacology, Syzygium chemistry
- Abstract
Cancer is a preventable and treatable disease, however, the incidence rates are on the rise. Classical treatment modalities for cancer include surgery, radiotherapy and chemotherapy. However, these are associated with detrimental side effects such as nausea and emesis. Therefore, researchers currently vest interest in complementary and alternative medicines for cancer treatment and prevention. Plants such as Syzygium sp. are a common basis of complementary medicines due to its abundance of bioactive phytochemicals. Numerous natural compounds derived from Syzygium sp., such as phenolics, oleanolic acids, and betulinic acids, and dimethyl cardamonins, were reported to have anticancer effects. Many possess the ability to inhibit cell proliferation and induce apoptosis. In this review, we discuss the vast potential Syzygium sp. harbours as a source of anticancer natural compounds due to its abundance, easy acceptability, affordability and safety for regular consumption.
- Published
- 2019
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16. Harnessing neuroplasticity: modern approaches and clinical future.
- Author
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Sasmita AO, Kuruvilla J, and Ling APK
- Subjects
- Animals, Forecasting, Humans, Nervous System Diseases diagnosis, Neuronal Plasticity drug effects, Neurons drug effects, Neurons pathology, Neuroprotective Agents pharmacology, Neuroprotective Agents therapeutic use, Nervous System Diseases metabolism, Nervous System Diseases therapy, Neuronal Plasticity physiology, Neurons metabolism
- Abstract
Background and purpose : Neurological diseases and injuries to the nervous system may cause inadvertent damage to neuronal and synaptic structures. Such phenomenon would lead to the development of neurological and neurodegenerative disorders which might affect memory, cognition and motoric functions. The body has various negative feedback systems which can induce beneficial neuroplastic changes in mediating some neuronal damage; however, such efforts are often not enough to ameliorate the derogatory changes. Materials and methods: Articles discussing studies to induce beneficial neuroplastic changes were retrieved from the databases, National Center for Biotechnology Information (NCBI) and MEDLINE, and reviewed. Results: This review highlights the significance of neuroplasticity in restoring neuronal functions and current advances in research to employ this positive cellular event by inducing synaptogenesis, neurogenesis, clearance of toxic amyloid beta (Aβ) and tau protein aggregates, or by providing neuroprotection. Compounds ranging from natural products (e.g. bilobalides, curcumin) to novel vaccines (e.g. AADvac1, RG7345) have been reported to induce long-lasting neuroplasticity in vitro and in vitro . Activity-dependent neuroplasticity is also inducible by regimens of exercises and therapies with instances in human studies proving major successes. Lastly, mechanical stimulation of brain regions through therapeutic hypothermia or deep brain stimulation has given insight on the larger scale of neuroplasticity within the nervous system. Conclusion: Harnessing neuroplasticity may not only offer an arm in the vast arsenal of approaches being taken to tackle neurological disorders, such as neurodegenerative diseases, but from ample evidence, it also has major implications in neuropsychological disorders.
- Published
- 2018
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17. Therapeutic potential of combined viral transduction and CRISPR/Cas9 gene editing in treating neurodegenerative diseases.
- Author
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Kuruvilla J, Sasmita AO, and Ling APK
- Subjects
- Animals, Genetic Vectors, Humans, CRISPR-Cas Systems physiology, Gene Editing methods, Genetic Therapy methods, Neurodegenerative Diseases genetics, Neurodegenerative Diseases therapy
- Abstract
Background and Purpose: The central nervous system (CNS) faces unique difficulties in attaining permanent therapy for neurodegenerative disorder (ND). Genomic level forms of therapy have garnered interest in the recent decade, with the novel CRISPR/Cas9 gene editing tool continuing to be explored due to its efficiency, safety, and adaptability to varying conditions. With the aid of viral vectors as transport vectors, the gene editing tool has produced promising in vitro and in vivo findings in study models. Thus, this review focuses on the recent advancements and update of CRISPR/Cas9 to combat neurodegenerative diseases., Methods: Articles detailing potential applications of CRISPR/Cas9 in neurodegenerative settings were retrieved from PubMed and Google Scholar with the keywords "CRISPR," "gene editing," and "neurodegenerative diseases." Relevant information was collected and critically reviewed., Results: The utility of CRISPR/Cas9 coupled with viral transduction ranges from the disruption of amyloid precursor protein (APP) production at a genomic level in Alzheimer's disease (AD) to the deletion of varying exon portions of the Dmd gene in Duchenne muscular dystrophy (DMD) which would increase dystrophin expression. This usage of CRISPR/Cas9 also extends to experimentally ameliorate the neurodegenerative effects caused by viral infections., Conclusion: The CRISPR/Cas9 gene editing tool is a powerful arsenal in the field of gene therapy and molecular medicine; hence, more research should be called to focus on the ample potential this tool has to offer in the field of neurodegenerative diseases.
- Published
- 2018
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18. Madecassoside activates anti‑neuroinflammatory mechanisms by inhibiting lipopolysaccharide‑induced microglial inflammation.
- Author
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Sasmita AO, Ling APK, Voon KGL, Koh RY, and Wong YP
- Subjects
- Animals, Cell Line, Inflammation immunology, Inflammation pathology, Mice, Microglia immunology, Microglia pathology, Reactive Oxygen Species analysis, Reactive Oxygen Species immunology, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Inflammation drug therapy, Lipopolysaccharides immunology, Microglia drug effects, Triterpenes pharmacology
- Abstract
Neurodegeneration is typically preceded by neuroinflammation generated by the nervous system to protect itself from tissue damage, however, excess neuroinflammation may inadvertently cause more harm to the surrounding tissues. Attenuating neuroinflammation with non‑steroidal anti‑inflammatory drugs can inhibit neurodegeneration. However, such treatments induce chronic side effects, including stomach ulcers. Madecassoside, a triterpene derived from Centella asiatica, is considered to be an alternative treatment of inflammation. In the present study, the anti‑neuroinflammatory properties of madecassoside were assessed in BV2 microglia cells, which were pre‑treated with madecassoside at a maximum non‑toxic dose (MNTD) of 9.50 µg/ml and a ½ MNTD of 4.75 µg/ml for 3 h and stimulated with 0.1 µg/ml lipopolysaccharide (LPS). The effect of madecassoside was assessed by determining reactive oxygen species (ROS) levels in all groups. Furthermore, the expression of pro‑ and anti‑neuroinflammatory genes and proteins were analyzed using reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that ROS levels in cells treated with the MNTD of madecassoside were significantly reduced compared with cells treated with LPS alone (P<0.05). The expression of pro‑neuroinflammatory genes, including inducible nitric oxide synthase, cyclooxygenase‑2, signal transducer and activator of transcription 1 and nuclear factor‑κB, were significantly downregulated in a dose‑independent manner following treatment with madecassoside. Conversely, the anti‑neuroinflammatory component heme oxygenase 1 was significantly upregulated by 175.22% in the MNTD‑treated group, compared with cells treated with LPS alone (P<0.05). The gene expression profiles of pro‑ and anti‑inflammatory genes were also consistent with the results of western blotting. The results of the present study suggest that madecassoside may be a potent anti‑neuroinflammatory agent. The antioxidative properties of madecassoside, which serve a major role in anti‑neuroinflammation, indicate that this compound may be a functional natural anti‑neuroinflammatory agent, therefore, further in vivo or molecular studies are required.
- Published
- 2018
- Full Text
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19. Biomarkers and therapeutic advances in glioblastoma multiforme.
- Author
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Sasmita AO, Wong YP, and Ling APK
- Subjects
- Brain Neoplasms pathology, Glioblastoma pathology, Humans, Male, Biomarkers, Tumor analysis, Brain Neoplasms diagnosis, Brain Neoplasms therapy, Glioblastoma diagnosis, Glioblastoma therapy
- Abstract
Glioblastoma multiforme (GBM) is a malignant tumor within the brain. Generally classified as primary and secondary with several different subtypes, ample molecular biomarkers have risen throughout the years which have garnered the attention of researchers. The advancements in genomics and proteomics have allowed researchers to gather prominent molecular biomarkers. All these biomarkers are gathered by means of biopsy or bodily fluid sample collection and are quantitatively analyzed by polymerase chain reaction coupled with other computational technologies. This review highlights the significance, regulation and prevalence of molecular biomarkers such as O
6 -methylguanine-DNA methyltransferase, epidermal growth factor receptor vIII, isocitrate dehydrogenase mutation and several others which expressed differently in different types and molecular subtypes of GBM. The discoveries and roles of GBM-specific microRNAs including miR-21 and miR-10b as biomarkers with promising prognostic values were also delineated. The role and mechanism of biomarkers in GBM tumorigenesis are essential in the development of therapy for patients suffering from the disease itself. Thus, this review also discusses the mechanisms, effects and limitations of therapy such as temozolomide, viral gene transfer, biomarker-based vaccines or even engineered T cells for more specific responses. Biomarkers have displayed a high value and could eventually be utilized as drug targets. It is hoped that by combining different aspects of the disease which present with different biomarkers could lead to the development of a robust, effective and innovative take on GBM therapy., (© 2017 John Wiley & Sons Australia, Ltd.)- Published
- 2018
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20. Anticancer mechanisms of Strobilanthes crispa Blume hexane extract on liver and breast cancer cell lines.
- Author
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Koh RY, Lim FP, Ling LSY, Ng CPL, Liew SF, Yew MY, Tiong YL, Ling APK, Chye SM, and Ng KY
- Abstract
Cancer is a major public health concern not only in developed countries, but also in developing countries. It is one of the leading causes of mortality worldwide. However, current treatments may cause severe side effects and harm. Therefore, recent research has been focused on identifying alternative therapeutic agents extracted from plant-based sources in order to develop novel treatment options for cancer. Strobilanthes crispa Blume is a plant native to countries including Madagascar and Indonesia. It has been used as an anti-diabetic, diuretic and laxative in traditional folk medicine. Furthermore, S. crispa has potential in treating cancer, as evidenced in previous studies. In the present study, the cytotoxic and apoptotic activities of S. crispa crude extracts were investigated in liver and breast cancer cell lines. Hexane, ethyl acetate, chloroform, methanol and water extracts prepared from the leaves, and stems of S. crispa were evaluated for their cytotoxicity on HepG-2 and MDA-MB-231 cells using an MTT assay. The anti-proliferative properties of stem hexane (SH) extract on both cell lines were analysed using cell doubling time determination and cell cycle analysis, while the apoptogenic properties was determined through the detection of caspase-8. Among the extracts tested, SH extract exhibited the lowest half maximal inhibitory concentrations in both the cell lines. The SH extract induced morphological changes in HepG-2 and MDA-MB-231 cells, and significantly delayed cell population doubling time. Furthermore, it altered cell cycle profile and significantly increased caspase-8 activity in HepG-2 cells, but not in MDA-MB-231 cells. In conclusion, the SH extract of S. crispa possesses potent anticancer properties and may be a suitable chemotherapeutic target.
- Published
- 2017
- Full Text
- View/download PDF
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