Chapters authored
Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning-Impaired Rat Model of Alzheimer’s Disease By Saima Khan and Kaneez Fatima Shad
The purpose of this study was to find out the beneficial effects of curcumin and vitamin D3 in rats treated with scopolamine as to generate animal model of tauopathies, i.e., neurodegenerative disorders, including Alzheimer’s disease (AD). Abnormal phosphorylation of tau results in the transformation of normal adult tau into paired-helical-filament (PHF) tau and neurofibrillary tangles (NFTs). Our results indicated that scopolamine-treated rats exhibit increased levels of hyperphosphorylated tau protein along with PHF, and curcumin and vitamin D3 lowered the levels of PHF better than donepezil. The effect of abnormal hyperphosphorylation of tau was also detected in the hematoxylin and eosin staining of brain tissues as well as in the western blot analyses in our experimental rat models of AD. This abnormal level of hyperphosphorylated tau probably causes cognitive and memory deficit as observed in different behavioral tests on exploratory groups. Hyperphosphorylated tau may have disrupted the microtubule network in experimental rats. Signs of temporal region dementia noted during behavioral studies may be linked to the neurodegeneration and abnormal hyperphosphorylation of tau observed in our experimental animal model of AD. The curcumin and vitamin D3-treated group presented lower levels of hyperphosphorylated tau and a better behavioral response. Thus, inhibition of abnormal hyperphosphorylation of tau offers a promising therapeutic target for AD and related tauopathies.
Part of the book: Neurological and Mental Disorders
Early Predictive Biomarkers for Hypertension Using Human Fetal Astrocytes By Fahmida Abdi, Ann M. Simpson, Sara Lal and Kaneez Fatima Shad
Hypertension is a major risk factor for cardiovascular and cerebrovascular diseases, causing high numbers of deaths and /or disabilities worldwide. Previous studies have reported numerous biomolecules, such as, triglycerides and fibrinogen as biomarkers of hypertension (HTN), but none of these biomolecules could be considered as ‘true’ predictive biomarkers as they were produced after the establishment of HTN. Therefore, there is an urgent need for identifying and monitoring molecules that are linked to early pre-HTN stages, that is, prior to the onset of HTN. Astrocytes are the most abundant cells in the nervous system and through their long processes, astrocytes can communicate with both neuronal and non-neuronal cells such as endothelial cells lining blood vessels. Thus, any biochemical changes in astrocytes will affect both blood vessels and neurons. We are using human fetal astrocytes (HFAs) to investigate the molecules which may possibly act as early predictive biomarkers for hypertension. Astrocytic processes are mostly supported by the intermediate filaments, an example is the glial fibrillary acidic protein (GFAP) which is a type III intermediate filament. Elevated GFAP levels are being considered as a marker of astroglial injury, indicating the conversion of non-reactive (A2) into reactive (A1) astrocytes. Our initial immunohistochemistry studies using anti-GFAP antibodies on astrocytes from spontaneous hypertensive rats (SHRs) and their normal counter parts (WKY) rats showed a similar profile to that of reactive (A1) and non-reactive (A2) HFAs, respectively. Numerous studies point to a significant role of calcium ion channel proteins in hypertension, and calcium channel blockers such as Amlodipine (Norvasc) Diltiazem (Cardizem) are commonly used as antihypertensive drugs. By using liquid chromatography–tandem mass spectrometry (LC–MS/MS) we observed that reactive (A1) astrocytes, contain more calcium-activated proteins such as calpain, calpastatin, cathepsin and mitogen activated protein kinase (MAPK) as compare to normal (A2) HFAs, suggesting their possible link to the future onset of HTN. Hence these proteins could be considered as potential early predictive biomarkers of HTN.
Part of the book: Erythrocyte
Are ABO Gene Alleles Responsible for Cardiovascular Diseases and Venous Thromboembolism and Do They Play a Role in COVID? By Dennis J. Cordato, Wissam Soubra, Sameer Saleem and Kaneez Fatima Shad
Cardiovascular diseases (CVD) including coronary heart disease and stroke are leading causes of death and disability globally. Studies of the association between ABO blood groups and CVD have consistently demonstrated an increased risk of coronary heart disease, myocardial infarction, cerebral ischaemic stroke, peripheral arterial disease and venous thromboembolism (VTE) including deep vein thrombosis and pulmonary thromboembolism in patients who possess a non-O blood group type. The most likely mechanism is thought to be the increase in von Willebrand Factor (vWF) and factor VIII levels seen in patients with a non-O blood group. Other postulated mechanisms include elevations in circulating inflammatory markers such as endothelial cell and platelet adhesion molecules in subjects with a non-O blood group. More recently, it has also been recognised that individuals with a non-O blood group type carry a higher risk of SARS-C0V-2 infection and COVID-19 related complications. The increased levels in vWF and factor VIII amongst individuals with a non-O blood group who have contracted SARS-CoV-2 infection may result in an additive thrombophilic effect to that caused by the SARS-CoV-2 virus. Another postulated mechanism is that individuals with an O-blood group are protected by anti-A and B antibodies which possibly inhibit the binding of the SARS-CoV-2 spike protein to lung epithelium angiotensin converting enzyme-2 receptors. There are over 35 minor blood groups on red blood cells, some of which such as Kidd, Lewis and Duffy have been associated with CVD either alone or in combination with a non-O blood group allele(s). However, their role in SARS-CoV-2 infection and mechanism of action for an association with CVD remain unknown. This review explores the relationship between ABO and minor blood groups with CVD and VTE, with a focus on potential mechanisms underlying this relationship and the potential role of ABO blood group types in COVID.
Part of the book: Blood Groups
Unlocking the Mysteries: Serotonin Receptor Networks Explored By Javeria Tanveer, Ammarah Baig, Rukhsana Rubeen, Shahana Rasheed Qureshi, Nosheen Bashir, Kanza Khan and Kaneez Fatima-Shad
Serotonin affects immunological regulation, hemostasis, vasoconstriction, gut motility, and is linked to several diseases. During peristalsis, serotonin (5-HT) is released from the gut mucosa and is largely generated by enterochromaffin cells (ECs) rather than gut microbes. Gut bacteria can stimulate the production of 5-HT. Serotonin in the blood that is retained within the platelets contributes to the production of clots and platelet aggregation. It binds to receptors such as 5HT2A, producing platelet aggregation and neuronal excitement. It regulates vasoconstriction via 5HT1D in cranial blood arteries. Atherosclerosis, thrombosis, and hypertension are some cardiovascular conditions liked to serotonin dysregulation. Serotonin imbalances in the gut influence gut motility and absorption, leading to conditions such as irritable bowel syndrome (IBS). 5-HT receptor subsets (5-HT1, 5HT2B, 5-HT3, 5-HT4, and 5-HT7) in gut are promising therapeutic targets. Serotonin in the Central Nervous System (CNS) controls a variety of behavioral and cognitive activities. 5-HTRs, including 5-HT1A and 5-HT2A, can have conflicting effects on pyramidal neuron firing. The chapter comprehends 5HTRs’ involvement in the blood, gut, and brain, emphasizing its significance in modulating a variety of biological activities. Further investigation must be conducted to better comprehend the complexity of serotonin signaling to develop innovative treatment techniques that target serotonin receptor networking.
Part of the book: Serotonin [Working title]
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