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Metabolic Syndrome and Its Effect on the Brain: Possible Mechanism

Arshad N', Lin TS, Yahaya MF

CNS Neurol Disord Drug Targets, 2018;17(8):595-603.
PMID: 30047340 DOI: 10.2174/1871527317666180724143258

BACKGROUND & OBJECTIVE: Metabolic syndrome (MetS) is an interconnected group of physiological, biochemical, clinical and metabolic factors that directly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) and mortality. Rising evidence suggests that MetS plays a significant role in the progression of Alzheimer's disease and other neurodegenerative diseases. Nonetheless, the factors linking this association has not yet been elucidated. As we are facing an increasing incidence of obesity and T2DM in all stages of life, understanding the association of MetS and neurodegenerative diseases is crucial to lessen the burden of the disease.
CONCLUSION: In this review, we will discuss the possible mechanisms which may relate the association between MetS and cognitive decline which include vascular damages, elevation of reactive oxygen species (ROS), insulin resistance and low-grade inflammation.
Stingless Bee Honey Reduces Anxiety and Improves Memory of the Metabolic Disease-induced Rats

Arshad N', Lin TS, Yahaya MF

CNS Neurol Disord Drug Targets, 2020;19(2):115-126.
PMID: 31957619 DOI: 10.2174/1871527319666200117105133

BACKGROUND: Scientific studies support the evidence of the involvement of Metabolic Syndrome (MetS) in the progression of neurodegenerative diseases through oxidative stress. Consumption of antioxidant compounds was found to be beneficial for brain-health as it reduced the brain oxidative stress level and improved cognitive performance in animals. Stingless bee honey or locally known as Kelulut Honey (KH) has high phenolic content and is widely used as a food supplement.
OBJECTIVES: In this study, we aimed to investigate the effects of KH on the brain of MetS-induced rats.
METHODS: Forty male Wistar rats were divided into 5 groups; 8 weeks (C8) and 16 weeks control groups (C16), groups that received High-Carbohydrate High Fructose (HCHF) diet for 8 weeks (MS8) and 16 weeks (MS16), and a group that received HCHF for 16 weeks with KH supplemented for the last 35 days (KH).
RESULTS: Serum fasting blood glucose decreased in the KH group compared to the MS16 group. HDL levels were significantly decreased in MetS groups compared to control groups. Open field experiments showed that KH group exhibits less anxious behavior compared to the MetS group. Probe trial of Morris water maze demonstrated significant memory retention of KH group compared to the MS16 group. Nissl staining showed a significant decrease in the pyramidal hippocampal cells in the MS16 compared to the KH group.
CONCLUSION: KH has the ability to normalise blood glucose and reduce serum triglyceride and LDL levels in MetS rats, while behavior studies complement its effect on anxiety and memory. This shows a promising role of KH in attenuating neurodegenerative diseases through the antioxidant activity of its polyphenolic content.
Fulltext Role of microRNAs in Diagnosis, Prognosis and Management of Multiple Myeloma

Soliman AM, Lin TS, Mahakkanukrauh P, Das S

Int J Mol Sci, 2020 Oct 13;21(20).
PMID: 33066062 DOI: 10.3390/ijms21207539

Multiple myeloma (MM) is a cancerous bone disease characterized by malignant transformation of plasma cells in the bone marrow. MM is considered to be the second most common blood malignancy, with 20,000 new cases reported every year in the USA. Extensive research is currently enduring to validate diagnostic and therapeutic means to manage MM. microRNAs (miRNAs) were shown to be dysregulated in MM cases and to have a potential role in either progression or suppression of MM. Therefore, researchers investigated miRNAs levels in MM plasma cells and created tools to test their impact on tumor growth. In the present review, we discuss the most recently discovered miRNAs and their regulation in MM. Furthermore, we emphasized utilizing miRNAs as potential targets in the diagnosis, prognosis and treatment of MM, which can be useful for future clinical management.
Fulltext Histological changes in the heart and the proximal aorta in experimental diabetic rats fed with Piper sarmentsoum

Thent ZC, Lin TS, Das S, Zakaria Z

Afr J Tradit Complement Altern Med, 2012;9(3):396-404.
PMID: 23983373

Cardiovascular complications are one of the major causes of death in diabetes mellitus. Piper sarmentosum (P.s) is an herb that possesses antihyperglycaemic effects. The main aim of the study was to observe the histological changes in the heart and the proximal aorta of streptozotocin-induced diabetic rats following P.s administration. Twenty-four male Sprague-Dawley rats (n=24) were equally randomized into four groups: control group supplemented with normal saline (C); control group supplemented with P.s (CTx) ; diabetic group supplemented with normal saline (D) and, diabetic group supplemented with P.s (DTx). Diabetes was induced by STZ (50mg/kg body weight) intramuscularly. P.s extract (0.125g/kg) was administered orally for 28 days, following four weeks of STZ induction. The cardiac and aortic tissues were collected and processed under different stains: Haematoxylin and Eosin (H & E), Verhoeff-Van Gieson (VVG), Masson's Trichome (MT) and Periodic Acid- Schiff (PAS). There were abnormal cardiomyocytes nuclei, disarray of myofibres and increase in connective tissue deposits in cardiac tissues of the diabetic untreated group. The thickness of tunica media and ratio of tunica intima to media were found to be significantly increased in the aorta of diabetic untreated group (P < 0.05) compared to the control group. There were degenerative changes in the proximal aorta in diabetic untreated groups. All the histological damages of cardiac and aortic tissues were found to be lesser in the diabetic treated groups. Supplementation with P.s extract prevented the oxidative damage arising from diabetes mellitus, and reduced its complications.
Rituximab for refractory digital infarcts and ulcers in systemic sclerosis

Khor CG, Chen XL, Lin TS, Lu CH, Hsieh SC

Clin Rheumatol, 2014 Jul;33(7):1019-20.
PMID: 24722688 DOI: 10.1007/s10067-014-2579-1

Systemic sclerosis is an uncommon connective tissue disease characterised by excessive deposition of collagen and vasculopathy which affects the skin and multiple internal organs. It is associated with autoimmunity, inflammation, vasculopathy and fibrosis. Managing Raynaud's phenonemon, digital infarcts and ulcers in systemic sclerosis patients is often a challenge particularly among rheumatologists. We report a case of systemic sclerosis patient with refractory digital infarcts and ulcers responded successfully with rituximab.
Fulltext Natural Product-based Nanomedicine: Recent Advances and Issues for the Treatment of Alzheimer's Disease

Woon CK, Hui WK, Abas R, Haron MH, Das S, Lin TS

Curr Neuropharmacol, 2022;20(8):1498-1518.
PMID: 34923947 DOI: 10.2174/1570159X20666211217163540

Alzheimer's disease (AD) affects the elderly and is characterized by progressive neurodegeneration caused by different pathologies. The most significant challenges in treating AD include the inability of medications to reach the brain because of its poor solubility, low bioavailability, and the presence of the blood-brain barrier (BBB). Additionally, current evidence suggests the disruption of BBB plays an important role in the pathogenesis of AD. One of the critical challenges in treating AD is the ineffective treatments and their severe adverse effects. Nanotechnology offers an alternative approach to facilitate the treatment of AD by overcoming the challenges in drug transport across the BBB. Various nanoparticles (NP) loaded with natural products were reported to aid in drug delivery for the treatment of AD. The nano-sized entities of NP are great platforms for incorporating active materials from natural products into formulations that can be delivered effectively to the intended action site without compromising the material's bioactivity. The review highlights the applications of medicinal plants, their derived components, and various nanomedicinebased approaches for the treatment of AD. The combination of medicinal plants and nanotechnology may lead to new theragnostic solutions for the treatment of AD in the future.
Fulltext Evaluation of topical tocopherol cream on cutaneous wound healing in streptozotocin-induced diabetic rats

Lin TS, Abd Latiff A, Abd Hamid NA, Wan Ngah WZ, Mazlan M

Evid Based Complement Alternat Med, 2012;2012:491027.
PMID: 23097676 DOI: 10.1155/2012/491027

Diabetes is a common cause of delayed wound healing. The aim of the study was to determine the effect of topical administration of tocopherol cream on the wound healing process in diabetic rats. The study was conducted using 18 male Sprague Dawley rats which were divided into three groups: (I) diabetic rats receiving control cream (n = 6), (II) diabetic rats receiving 0.06% tocopherol cream (n = 6), and (III) diabetic rats receiving 0.29% tocopherol cream (n = 6). Four cutaneous wounds were created at the dorsal region of the rats. Wound healing was assessed by total protein content, rate of wound closure estimation, and histological studies on the tenth day after wounding. Tocopherol treatment enhanced the wound healing process by increasing rate of wound closure and total protein content significantly (P < 0.05) compared to the control group. Histological observation also showed better organized epithelium and more collagen fibers in the tocopherol treated groups. Application of tocopherol cream enhances wound healing process in diabetic condition which is known to cause delay in wound healing.