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The potential role of miRNA therapies in spinal muscle atrophy

Gandhi G, Abdullah S, Foead AI, Yeo WWY

J Neurol Sci, 2021 08 15;427:117485.
PMID: 34015517 DOI: 10.1016/j.jns.2021.117485

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by low levels of full-length survival motor neuron (SMN) protein due to the loss of the survival motor neuron 1 (SMN1) gene and inefficient splicing of the survival motor neuron 2 (SMN2) gene, which mostly affects alpha motor neurons of the lower spinal cord. Despite the U.S. Food and Drug Administration (FDA) approved SMN-dependent therapies including Nusinersen, Zolgensma® and Evrysdi™, SMA is still a devastating disease as these existing expensive drugs may not be sufficient and thus, remains a need for additional therapies. The involvement of microRNAs (miRNAs) in SMA is expanding because miRNAs are important mediators of gene expression as each miRNA could target a number of genes. Hence, miRNA-based therapy could be utilized in treating this genetic disorder. However, the delivery of miRNAs into the target cells remains an obstacle in SMA, as there is no effective delivery system to date. This review highlights the potential strategies for intracellular miRNA delivery into target cells and current challenges in miRNA delivery. Furthermore, we provide the future prospects of miRNA-based therapeutic strategies in SMA.
Fulltext Opportunities and challenges of 5G network technology toward precision medicine

Kang CC, Lee TY, Lim WF, Yeo WWY

Clin Transl Sci, 2023 Nov;16(11):2078-2094.
PMID: 37702288 DOI: 10.1111/cts.13640

Moving away from traditional "one-size-fits-all" treatment to precision-based medicine has tremendously improved disease prognosis, accuracy of diagnosis, disease progression prediction, and targeted-treatment. The current cutting-edge of 5G network technology is enabling a growing trend in precision medicine to extend its utility and value to the smart healthcare system. The 5G network technology will bring together big data, artificial intelligence, and machine learning to provide essential levels of connectivity to enable a new health ecosystem toward precision medicine. In the 5G-enabled health ecosystem, its applications involve predictive and preventative measurements which enable advances in patient personalization. This review aims to discuss the opportunities, challenges, and prospects posed to 5G network technology in moving forward to deliver personalized treatments and patient-centric care via a precision medicine approach.
Fulltext Drug Discovery of Spinal Muscular Atrophy (SMA) from the Computational Perspective: A Comprehensive Review

Chong LC, Gandhi G, Lee JM, Yeo WWY, Choi SB

Int J Mol Sci, 2021 Aug 20;22(16).
PMID: 34445667 DOI: 10.3390/ijms22168962

Spinal muscular atrophy (SMA), one of the leading inherited causes of child mortality, is a rare neuromuscular disease arising from loss-of-function mutations of the survival motor neuron 1 (SMN1) gene, which encodes the SMN protein. When lacking the SMN protein in neurons, patients suffer from muscle weakness and atrophy, and in the severe cases, respiratory failure and death. Several therapeutic approaches show promise with human testing and three medications have been approved by the U.S. Food and Drug Administration (FDA) to date. Despite the shown promise of these approved therapies, there are some crucial limitations, one of the most important being the cost. The FDA-approved drugs are high-priced and are shortlisted among the most expensive treatments in the world. The price is still far beyond affordable and may serve as a burden for patients. The blooming of the biomedical data and advancement of computational approaches have opened new possibilities for SMA therapeutic development. This article highlights the present status of computationally aided approaches, including in silico drug repurposing, network driven drug discovery as well as artificial intelligence (AI)-assisted drug discovery, and discusses the future prospects.
Fulltext Adult muscle-derived stem cells engraft and differentiate into insulin-expressing cells in pancreatic islets of diabetic mice

Mitutsova V, Yeo WWY, Davaze R, Franckhauser C, Hani EH, Abdullah S, et al.

Stem Cell Res Ther, 2017 04 18;8(1):86.
PMID: 28420418 DOI: 10.1186/s13287-017-0539-9

BACKGROUND: Pancreatic beta cells are unique effectors in the control of glucose homeostasis and their deficiency results in impaired insulin production leading to severe diabetic diseases. Here, we investigated the potential of a population of nonadherent muscle-derived stem cells (MDSC) from adult mouse muscle to differentiate in vitro into beta cells when transplanted as undifferentiated stem cells in vivo to compensate for beta-cell deficiency.
RESULTS: In vitro, cultured MDSC spontaneously differentiated into insulin-expressing islet-like cell clusters as revealed using MDSC from transgenic mice expressing GFP or mCherry under the control of an insulin promoter. Differentiated clusters of beta-like cells co-expressed insulin with the transcription factors Pdx1, Nkx2.2, Nkx6.1, and MafA, and secreted significant levels of insulin in response to glucose challenges. In vivo, undifferentiated MDSC injected into streptozotocin (STZ)-treated mice engrafted within 48 h specifically to damaged pancreatic islets and were shown to differentiate and express insulin 10-12 days after injection. In addition, injection of MDSC into hyperglycemic diabetic mice reduced their blood glucose levels for 2-4 weeks.
CONCLUSION: These data show that MDSC are capable of differentiating into mature pancreatic beta islet-like cells, not only upon culture in vitro, but also in vivo after systemic injection in STZ-induced diabetic mouse models. Being nonteratogenic, MDSC can be used directly by systemic injection, and this potential reveals a promising alternative avenue in stem cell-based treatment of beta-cell deficiencies.
Photoactivated riboflavin inhibits planktonic and biofilm growth of Candida albicans and non-albicans Candida species

Farah N, Lim CW, Chin VK, Chong PP, Basir R, Yeo WWY, et al.

Microb Pathog, 2024 Apr 27;191:106665.
PMID: 38685359 DOI: 10.1016/j.micpath.2024.106665

Fungal infections caused by Candida species pose a serious threat to humankind. Antibiotics abuse and the ability of Candida species to form biofilm have escalated the emergence of drug resistance in clinical settings and hence, rendered it more difficult to treat Candida-related diseases. Lethal effects of Candida infection are often due to inefficacy of antimicrobial treatments and failure of host immune response to clear infections. Previous studies have shown that a combination of riboflavin with UVA (riboflavin/UVA) light demonstrate candidacidal activity albeit its mechanism of actions remain elusive. Thus, this study sought to investigate antifungal and antibiofilm properties by combining riboflavin with UVA against Candida albicans and non-albicans Candida species. The MIC20 for the fluconazole and riboflavin/UVA against the Candida species tested was within the range of 0.125-2 μg/mL while the SMIC50 was 32 μg/mL. Present findings indicate that the inhibitory activities exerted by riboflavin/UVA towards planktonic cells are slightly less effective as compared to controls. However, the efficacy of the combination towards Candida species biofilms showed otherwise. Inhibitory effects exerted by riboflavin/UVA towards most of the tested Candida species biofilms points towards a variation in mode of action that could make it an ideal alternative therapeutic for biofilm-related infections.