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Fulltext Development of tissue microarray (TMA) for translational research in colorectal cancer

See, Wee Han, Shaik I., Rizwan F., Hassan H. A., Yaacob W. A. W., Rhodes, A.

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):14-14.
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Introduction: Colorectal cancer is the second most common cause of death in women, and the third most common cause in men. The main treatments available following surgery are chemotherapy and radiotherapy which are not always effective and have side effects. Modern medicine aims to develop targeted cancer therapies that are efficient and cause less side effects to patients. However, this approach requires a thorough understanding of the molecular events that cause cancer cell to grow and divide in order to identify suitable targets. The process of translating the findings into clinical studies can be high cost and technically demanding. However, development of a tissue microarray (TMA), allows immunohistochemical (IHC) staining of multiple cases simultaneously, thereby greatly reducing costs and time. Methods: A TMA was produced from approximately 400 cases of colorectal cancer, along with collection of associated clinical and pathological data. Sections from the TMA were tested for quality by staining with haematoxylin and eosin (H & E), in addition to IHC markers to molecularly classify the colon cancers. Results: The cores from the 384 cases of cancer were successfully transferred to 18 recipient TMA blocks. H & E staining showed good morphological preservation of the cases, reflecting the tumour in the donor blocks. IHC testing was able to successfully classify cases into distinct molecular groupings. Conclusions: The development of a TMA of colorectal cancers provides a valuable tool for the efficient and subsequent molecular classification of colorectal cancer using immunohistochemistry.
Fulltext An approach for developing integrated undergraduate medical curriculum

Akram A, Rizwan F, Sattar K, Hadi JIS, Meo SA

Pak J Med Sci, 2018 9 8;34(4):804-810.
PMID: 30190732 DOI: 10.12669/pjms.344.14565

Background and Objectives: Medical schools are to develop integrated medical curricula because the term 'integrated curriculum' has grown up and flourished globally and it has become mandatory to align the medical education with the global concept in Pakistan. This paper aims to present a guideline to design an undergraduate integrated medical curriculum.
Methods: Various themes are used to develop integrated curriculum which are basic medical science, simulation skills, clinical science, personality development, research, entrepreneurship and pre specialization. Each theme is subdivided, termed a module and its contents primarily focus on particular aspect.
Results: Knowledge, skill and attitude, embodied in themes or modules, are planted in specific way that they have horizontal as well as vertical integration. There is no boundary of various traditional disciplines in template of five years curriculum. For example, diagnosis is a theme which carries contents from medicine, surgery, orthopedics etc.
Conclusion: The blueprint introduced in this paper would help medical educators to draft integrated medical curricula for those institutions which intend to switch their medical programs from traditional to integrated one.
Fulltext Mechanism involved in insulin resistance via accumulation of β-amyloid and neurofibrillary tangles: link between type 2 diabetes and Alzheimer's disease

Rad SK, Arya A, Karimian H, Madhavan P, Rizwan F, Koshy S, et al.

Drug Des Devel Ther, 2018;12:3999-4021.
PMID: 30538427 DOI: 10.2147/DDDT.S173970

The pathophysiological link between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) has been suggested in several reports. Few findings suggest that T2DM has strong link in the development process of AD, and the complete mechanism is yet to be revealed. Formation of amyloid plaques (APs) and neurofibrillary tangles (NFTs) are two central hallmarks in the AD. APs are the dense composites of β-amyloid protein (Aβ) which accumulates around the nerve cells. Moreover, NFTs are the twisted fibers containing hyperphosphorylated tau proteins present in certain residues of Aβ that build up inside the brain cells. Certain factors contribute to the aetiogenesis of AD by regulating insulin signaling pathway in the brain and accelerating the formation of neurotoxic Aβ and NFTs via various mechanisms, including GSK3β, JNK, CamKII, CDK5, CK1, MARK4, PLK2, Syk, DYRK1A, PPP, and P70S6K. Progression to AD could be influenced by insulin signaling pathway that is affected due to T2DM. Interestingly, NFTs and APs lead to the impairment of several crucial cascades, such as synaptogenesis, neurotrophy, and apoptosis, which are regulated by insulin, cholesterol, and glucose metabolism. The investigation of the molecular cascades through insulin functions in brain contributes to probe and perceive progressions of diabetes to AD. This review elaborates the molecular insights that would help to further understand the potential mechanisms linking T2DM and AD.
Fulltext Bacopa monnieri, a Neuroprotective Lead in Alzheimer Disease: A Review on Its Properties, Mechanisms of Action, and Preclinical and Clinical Studies

Abdul Manap AS, Vijayabalan S, Madhavan P, Chia YY, Arya A, Wong EH, et al.

Drug Target Insights, 2019;13:1177392819866412.
PMID: 31391778 DOI: 10.1177/1177392819866412

Alzheimer disease is a neurodegenerative disease that is signified by cognitive decline, memory loss, and erratic behavior. Till date, no cure for Alzheimer exists and the current Alzheimer medications have limited effectiveness. However, herbal medicines may slow down the disease's progression, which may hopefully reduce the number of cases in the years to come. Numerous studies have been done on characterizing the neuroprotective properties from plants belonging to Scrophulariaceae family, particularly Bacopa monnieri and its polyphenolic compounds known as bacosides. This review presents the findings on bacosides in therapeutic plants and their impact on Alzheimer disease pathology. These reports present data on the clinical, cellular activities, phytochemistry, and biological applications that may be used in new drug treatment for Alzheimer disease.
Fulltext Synergistic Effects of Curcumin and Piperine as Potent Acetylcholine and Amyloidogenic Inhibitors With Significant Neuroprotective Activity in SH-SY5Y Cells via Computational Molecular Modeling and in vitro Assay

Abdul Manap AS, Wei Tan AC, Leong WH, Yin Chia AY, Vijayabalan S, Arya A, et al.

Front Aging Neurosci, 2019;11:206.
PMID: 31507403 DOI: 10.3389/fnagi.2019.00206

Hallmarks of Alzheimer's disease (AD) pathology include acetylcholine (ACh) deficiency and plaque deposition. Emerging studies suggest that acetylcholinesterase (AChE) may interact with amyloid β (Aβ) to promote aggregation of insoluble Aβ plaques in brains of patients. Current therapeutic options available for AD patients, such as AChE inhibitors, provide only symptomatic relief. In this study, we screened four natural compounds believed to harbor cognitive benefits-curcumin, piperine, bacoside A, and chebulinic acid. In the first section, preliminary screening through computational molecular docking simulations gauged the suitability of the compounds as novel AChE inhibitors. From here, only compounds that met the in silico selection criteria were selected for the second section through in vitro investigations, including AChE enzyme inhibition assay, 3-(4,5-dimenthylthiazol-2-yl)-2,5-dimethyltetrazolium bromide (MTT) assay, Thioflavin T (ThT) assay, and biochemical analysis via a neuronal cell line model. Of the four compounds screened, only curcumin (-9.6 kcal/mol) and piperine (-10.5 kcal/mol) showed favorable binding affinities and interactions towards AChE and were hence selected. In vitro AChE inhibition demonstrated that combination of curcumin and piperine showed greater AChE inhibition with an IC50 of 62.81 ± 0.01 μg/ml as compared to individual compounds, i.e., IC50 of curcumin at 134.5 ± 0.06 μg/ml and IC50 of piperine at 76.6 ± 0.08 μg/ml. In the SH-SY5Y cell model, this combination preserved cell viability up to 85%, indicating that the compounds protect against Aβ-induced neuronal damage (p < 0.01). Interestingly, our results also showed that curcumin and piperine achieved a synergistic effect at 35 μM with an synergism quotient (SQ) value of 1.824. Synergistic behavior indicates that the combination of these two compounds at lower concentrations may provide a better outcome than singularly used for Aβ proteins. Combined curcumin and piperine managed to inhibit aggregation (reduced ThT intensity at 0.432 a.u.; p < 0.01) as well as disaggregation (reduced ThT intensity at 0.532 a.u.; p < 0.01) of fibrillar Aβ42. Furthermore, combined curcumin and piperine reversed the Aβ-induced up-regulation of neuronal oxidative stress (p < 0.01). In conclusion, curcumin and piperine demonstrated promising neuroprotective effects, whereas bacoside A and chebulinic acid may not be suitable lead compounds. These results are hoped to advance the field of natural products research as potentially therapeutic and curative AD agents.