Insulin-Like Growth Factor-1 (IGF-1) Reduces ischemic changes and increases circulating angiogenic factors in experimentally - induced myocardial infarction in rats

Background: Coronary artery disease is a global health concern in the present day with limited therapies. Extensive efforts have been devoted to find molecular therapies to enhance perfusion and function of the ischemic myocardium. Aim of the present study was to look into the effects of insulin like growth factor -1 (IGF-1) on circulating angiogenic factors after myocardial ischemia in rats.\ud \ud \ud Methods: Adult male Sprague-Dawley rats were randomly divided into 10-days control, myocardial infarction, IGF-1 alone (2 μg/rat/day) and ISO+IGF-1 groups. Isoproterenol (ISO), a synthetic catecholamine was used to induce myocardial infarction. Serum transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) levels were checked after 10-days of IGF-1 administration.\ud \ud \ud Results: There was a significant increase in heart weight after IGF-1 treatment. A significant increase in cardiac enzyme level (CK-MB and LDH) was seen in isoproterenol treated rats when compared to control group. IGF-1treatment induced a significant increase in serum angiogenic factors, IGF-1, VEGF and TGF beta levels. IGF-1 also reduced the ischemic changes in the myocardium when compared to the isoproterenol alone treated group.\ud \ud \ud Conclusions: In conclusion, treatment with insulin-like growth factor-1 (IGF-1) in myocardial infarction significantly increased circulating angiogenic growth factors like IGF-1, VEGF and TGF beta thus, protecting against myocardial ischemia.\u

The therapeutic potential of plant flavonoids on rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune condition that mainly affects peripheral joints. Although immunosuppressive drugs and non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat this condition, these drugs have severe side effects. Flavonoids are the most abundant phenolic compounds which exhibit antioxidant, anti-inflammatory and immunomodulatory properties. Many bioactive flavonoids have powerful anti-inflammatory effects. However, a very few have reached clinical use. Dietary flavonoids have been reported to control joint inflammation and alleviate arthritis symptoms in both human RA and animal models of arthritis. There is little scientific evidence about their mechanism of actions in RA. We review the therapeutic effects of different groups of flavonoids belonging to the most common and abundant groups on RA. In particular, the probable mechanisms of major flavonoids on cells and chemical messengers involved in the inflammatory signalling components of RA are discussed in detail

Current concepts of neurodegenerative mechanisms in Alzheimer's disease

Neurodegenerative diseases are hereditary or sporadic conditions that result in the progressive loss of the structure and function of neurons as well as neuronal death. Although a range of diseases lie under this umbrella term, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases that affect a large population around the globe. Alzheimer's disease is characterized by the abnormal accumulation of extracellular amyloid-beta plaques and intraneuronal neurofibrillary tangles in brain regions and manifests as a type of dementia in aged individuals that results in memory loss, multiple cognitive abnormalities, and intellectual disabilities that interfere with quality of life. Since the discovery of AD, a wealth of new information has emerged that delineates the causes, mechanisms of disease, and potential therapeutic agents, but an effective remedy to cure the diseases has not been identified yet. This could be because of the complexity of the disease process, as it involves various contributing factors that include environmental factors and genetic predispositions. This review summarizes the current understanding on neurodegenerative mechanisms that lead to the emergence of the pathology of AD

Quercetin glycosides induced neuroprotection by changes in the gene expression in a cellular model of Parkinson's disease

Quercetin glycosides, rutin and isoquercitrin, are potent antioxidants that have been found to possess neuroprotective effect in diseases like Parkinson's and Alzheimer's disease. In the present study, we have examined the gene expression changes with rutin and isoquercitrin pretreatment on 6-hydroxydopamine (6-OHDA)-treated toxicity in rat pheochromocytoma (PC12) cells. PC12 cells were pretreated with rutin or isoquercitrin and subsequently exposed to 6-OHDA. Rutin-pretreated PC12 attenuated the Park2, Park5, Park7, Casp3, and Casp7 genes which were expressed significantly in the 6-OHDA-treated PC12 cells. Rutin upregulated the TH gene which is important in dopamine biosynthesis, but isoquercitrin pretreatment did not affect the expression of this gene. Both rutin and isoquercitrin pretreatments upregulated the ion transport and antiapoptotic genes (NSF and Opa1). The qPCR array data were further validated by qRT-PCR using four primers, Park5, Park7, Casp3, and TH. This finding suggests that changes in the expression levels of transcripts encoded by genes that participate in ubiquitin pathway and dopamine biosynthesis may be involved in Parkinson's disease

Neuroprotective Effects of Alpha Lipoic Acid on Haloperidol-Induced Oxidative Stress in the Rat Brain

Haloperidol is an antipsychotic drug that exerts its' antipsychotic effects by inhibiting dopaminergic neurons. Although the exact pathophysiology of haloperidol extrapyramidal symptoms are not known, the role of reactive oxygen species in inducing oxidative stress has been proposed as one of the mechanisms of prolonged haloperidol-induced neurotoxicity. In the present study, we evaluate the protective effect of alpha lipoic acid against haloperidol-induced oxidative stress in the rat brain. Sprague Dawley rats were divided into control, alpha lipoic acid alone (100 mg/kg p.o for 21 days), haloperidol alone (2 mg/kg i.p for 21 days), and haloperidol with alpha lipoic acid groups (for 21 days). Haloperidol treatment significantly decreased levels of the brain antioxidant enzymes super oxide dismutase and glutathione peroxidase and concurrent treatment with alpha lipoic acid significantly reversed the oxidative effects of haloperidol. Histopathological changes revealed significant haloperidol-induced damage in the cerebral cortex, internal capsule, and substantia nigra. Alpha lipoic acid significantly reduced this damage and there were very little neuronal atrophy. Areas of angiogenesis were also seen in the alpha lipoic acid-treated group. In conclusion, the study proves that alpha lipoic acid treatment significantly reduces haloperidol-induced neuronal damage

Tocotrienols ameliorate neurodegeneration and motor deficits in the 6-ohda-induced rat model of parkinsonism: Behavioural and immunohistochemistry analysis

Parkinson’s disease (PD) is a debilitating neurodegenerative disease, which progresses over time, causing pathological depigmentation of the substantia nigra (SN) in the midbrain due to loss of dopaminergic neurons. Emerging studies revealed the promising effects of some nutrient compounds in reducing the risk of PD. One such nutrient compound that possess neuroprotective effects and prevents neurodegeneration is tocotrienol (T3), a vitamin E family member. In the present study, a single dose intracisternal injection of 250 µg 6-hydroxydopamine (6-OHDA) was used to induce parkinsonism in male Sprague Dawley (SD) rats. Forty-eight hours post injection, the SD rats were orally supplemented with alpha (α)-and gamma (γ)-T3 for 28 days. The neuroprotective effects of α-and γ-T3 were evaluated using behavioural studies and immunohistochemistry (IHC). The findings from this study revealed that supplementation of α-and γ-T3 was able to ameliorate the motor deficits induced by 6-OHDA and improve the neuronal functions by reducing inflammation, reversing the neuronal degradation, and preventing further reduction of dopaminergic neurons in the SN and striatum (STR) fibre density

Therapeutic effect of quercetin in collagen-induced arthritis

Quercetin, a bioactive flavonoid with anti-inflammatory, immunosuppressive, and protective properties, is a potential agent for the treatment of rheumatoid arthritis (RA). Collagen-induced arthritis (CIA) is the most commonly used animal model for studying the pathogenesis of RA. This study analysed the therapeutic role of quercetin in collagen-induced arthritis in C57BL/6 mice. The animals were allocated into five groups that were subjected to the following treatments: negative (untreated) control, positive control (arthritis-induced), arthritis + methotrexate, arthritis + quercetin, and arthritis + methotrexate + quercetin. Assessments of weight, oedema, joint damage, and cytokine production were used to determine the therapeutic effect of quercetin. This study demonstrated for the first time the anti-inflammatory and protective effects of quercetin in vivo in CIA. The results also showed that the concurrent administration of quercetin and methotrexate did not offer greater protection than the administration of a single agent. The use of quercetin as a monotherapeutic agent resulted in the lowest degree of joint inflammation and the highest protection. The reduced severity of the disease in animals treated with quercetin was associated with decreased levels of TNF-α, IL-1β, IL-17, and MCP-1. In conclusion, this study determined that quercetin, which was non-toxic, produced better results than methotrexate for the protection of joints from arthritic inflammation in mice. Quercetin may be an alternative treatment for RA because it modulates the main pathogenic pathways of RA

Unravelling the neuroprotective mechanisms of carotenes in differentiated human neural cells: biochemical and proteomic approaches

Carotenoids, fat-soluble pigments found ubiquitously in plants and fruits, have been reported to exert significant neuroprotective effects against free radicals. However, the neuroprotective effects of total mixed carotenes complex (TMC) derived from virgin crude palm oil have not been studied extensively. Therefore, the present study was designed to establish the neuroprotective role of TMC on differentiated human neural cells against 6-hydroxydopamine (6-OHDA)-induced cytotoxicity. The human neural cells were differentiated using retinoic acid for six days. Then, the differentiated neural cells were pre-treated for 24 hr with TMC before exposure to 6-OHDA. TMC pre-treated neurons showed significant alleviation of 6-OHDA-induced cytotoxicity as evidenced by enhanced activity of the superoxide dismutase (SOD) and catalase (CAT) enzymes. Furthermore, TMC elevated the levels of intra-neuronal dopamine and tyrosine hydroxylase (TH) in differentiated neural cells. The 6-OHDA induced overexpression of α-synuclein was significantly hindered in neural cells pre-treated with TMC. In proteomic analysis, TMC altered the expression of ribosomal proteins, α/β isotypes of tubulins, protein disulphide isomerases (PDI) and heat shock proteins (HSP) in differentiated human neural cells. The natural palm phytonutrient TMC is a potent antioxidant with significant neuroprotective effects against free radical-induced oxidative stress

Factors influencing medical students’ experiences and satisfaction with blended integrated e-learning

Objectives: Blended learning has been presented as a promising learner-centred model that emphasises the learning outcome rather than the process of education, but it can negatively affect learners’ engagement with learning. Subject and Methods: Using a mixed-methods approach, this study aimed to determine the significant predictors of learning satisfaction and to evaluate the experiences of medical students with the different domains of an introduced blended integrated learning approach. Results: The survey was administered to 92 respondents with a mean age of 20.5 years. Male students had significantly higher computer self-efficacy and overall learner satisfaction ratings than their female counterparts. Multiple regression analysis showed that gender (student characteristics), performance expectations (cognitive factors), and learning climate (social environment) were predictors of the perceived satisfaction of learners. Conclusion: Wider integration of blended learning into pre-clinical undergraduate medical education could enhance the shift towards competency-based education and life-long learning among medical students. However, effective implementation would depend largely on student characteristics, as well as environmental and cognitive components of the delivery method