Both Alzheimer's disease (AD) and Type 2 diabetes mellitus (T2DM) share the presence of systemic and neuro-inflammation, enhanced production and accumulation of β -amyloid peptide and abnormal levels ...of the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Altered levels of AChE and BuChE both in AD as well as in T2DM imply that those two enzymes may be playing a pivotal role in the pathogenesis of the two disorders. AD and T2DM are both characterized by elevated levels of AChE and BuChE in the plasma. On the other hand, in AD the brain levels of AChE go down while those of BuChE go up, resulting in deregulation in balance between AChE and BuChE. This imbalance and change in the AChE/BuChE ratio causes cholinergic deficit in the brain, i.e. deficiency in the brain neurotransmitter acetylcholine. With better understanding of the inter-relationship of AChE and BuChE levels in normality as well as abnormality, AD and T2DM can be effectively treated. Thus, general cholinesterase inhibitors that inhibit both AChE and BuChE as well as highly selective BuChE inhibitors may have potential therapeutic benefits in the treatment of AD and other related dementias.
Dengue virus is a potential source of propagating dengue hemorrhagic fever. This virus leads to dengue hemorrhagic fever/dengue shock syndrome, benign syndrome, and severe syndrome and due to its ...infection, there occurs alterations at multiple levels such as gene expression and pathway levels. So, it is critical to understand the pathogenesis of dengue infection in terms of gene expression and the associated functions.
For this purpose, here, we have analyzed the temporal gene expression profiling for the dengue hemorrhagic fever dataset at 12, 24, and 48 hours.
The outcome appears that the dengue hemorrhagic fever evolves differently at different time periods or stages.
The change in the gene expression pattern increases exponentially from 12 hours to 48 hours and the number of altered functions (pathways) also increases. Wnt, apoptosis, and transcription signaling are among the critical pathways which are dominantly altered. In the initial phase (first 12 hours), only two pathways are altered due to dengue infection, while in the next 12 hours, eight pathways are altered, and finally, in the next 24 hours, 11 pathways are altered and most of these 11 pathways are very critical in terms of biological pathways and functions.
Heavy metals constitute some of the most significant environmental contaminants today. The abundance of naturally growing Tetraena qataranse around Ras Laffan oil and gas facilities in the state of ...Qatar reflects its toxitolerant character. This study examined the desert plant's tolerance to Ba, Cd, Cr, Cu, Ni and Pb relative to soil concentration. Analysis by inductively coupled plasma - optical emission spectroscopy (ICP-OES) showed that the plant biomass accumulates higher Cd, Cr, Cu and Ni concentration than the soil, particularly in the root. The bioconcentration factor (BCF) of all metals in the root and shoot indicates the plant's capacity to accumulate these metals. Cd had a translocation factor (TF) greater than one; however, it is less than one for all other metals, suggesting that the plant remediate Cd by phytoextraction, where it accumulates in the shoot and Cr, Cu and Ni through phytostabilization, concentrating the metals in the root. Metals phytostabilization restrict transport, shield animals from toxic species ingestion, and consequently prevent transmission across the food chain. Fourier Transform Infrared Spectroscopy (FTIR) analysis further corroborates ICP-OES quantitative data. Our results suggest that T. qataranse is tolerant of Cd, Cr, Cu, and Ni. Potentially, these metals can accumulate at higher concentration than shown here; hence, T. qataranse is a suitable candidate for toxic metals phytostabilization.
In general, proteins can only execute their various biological functions when they are appropriately folded. Their amino acid sequence encodes the relevant information required for correct ...three-dimensional folding, with or without the assistance of chaperones. The challenge associated with understanding protein folding is currently one of the most important aspects of the biological sciences. Misfolded protein intermediates form large polymers of unwanted aggregates and are involved in the pathogenesis of many human diseases, including Alzheimer's disease (AD) and Type 2 diabetes mellitus (T2DM). AD is one of the most prevalent neurological disorders and has worldwide impact; whereas T2DM is considered a metabolic disease that detrementally influences numerous organs, afflicts some 8% of the adult population, and shares many risk factors with AD. Research data indicates that there is a widespread conformational change in the proteins involved in AD and T2DM that form β-sheet like motifs. Although conformation of these β-sheets is common to many functional proteins, the transition from α-helix to β-sheet is a typical characteristic of amyloid deposits. Any abnormality in this transition results in protein aggregation and generation of insoluble fibrils. The abnormal and toxic proteins can interact with other native proteins and consequently catalyze their transition into the toxic state. Both AD and T2DM are prevalent in the aged population. AD is characterized by the accumulation of amyloid-β (Aβ) in brain, while T2DM is characterized by the deposition of islet amyloid polypeptide (IAPP, also known as amylin) within beta-cells of the pancreas. T2DM increases pathological angiogenesis and immature vascularisation. This also leads to chronic cerebral hypoperfusion, which results in dysfunction and degeneration of neuroglial cells. With an abundance of common mechanisms underpinning both disorders, a significant question that can be posed is whether T2DM leads to AD in aged individuals and the associations between other protein misfolding diseases.
Alzheimer's disease (AD) is the most frequent cause of dementia, especially in the elderly. AD is the most common progressive neurodegenerative disorder, which involves the loss of structure and ...function of cholinergic neurons. Moreover, if these neuronal changes cannot be compensated, this may ultimately lead to neurodegenerative processes. Therefore, most of the drug therapies are based on the cholinergic hypothesis, which suggests that AD begins as a deficiency in the production of the neurotransmitter acetylcholine. In this context, many inhibitors play an important role in AD treatment among which acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have more potential in the treatment process of AD. In this study, we selected tea polyphenols of green tea which are reported as AChE and BChE inhibitors used in the treatment of AD. The molecular docking results revealed that polyphenols exhibit interactions and inhibit by binding with AChE and BChE. The amount of energy to bind with AChE and BChE needed by Epigallocatechin-3-gallate was lowest at about -14.45 and -13.30 kcal/mol, respectively. All compounds showed binding energy values ranging between -14.45 to -9.75 kcal/mol for both types of enzymes. The present docking study suggests that tea polyphenols inhibit AChE as well as BChE and enhance the cholinergic neurotransmission by prolonging the time. However, AChE molecules remain in the synaptic cleft. In consideration to these findings, cholinesterase inhibitors are suggested as the standard drugs for the treatment of AD.
Essential oils are liquid extracts from aromatic plants, which have numerous applications in multiple industries. There are a variety of methods used for the extraction of essential oils, with each ...method exhibiting certain advantages and determining the biological and physicochemical properties of the extracted oils. Essential oils from different plant species contain more than 200 constituents which are comprised of volatile and non-volatile components. The application of essential oils as antimicrobial, anticancer, anti-inflammatory and anti-viral agents is due to their effective and efficient properties, inter alia.
Several advanced (supercritical fluid extraction, subcritical extraction liquid, solvent-free microwave extraction) and conventional (hydrodistillation, steam distillation, hydrodiffusion, solvent extraction) methods have been discussed for the extraction of essential oils. Advanced methods are considered as the most promising extraction techniques due to less extraction time, low energy consumption, low solvent used and less carbon dioxide emission.
This manuscript reviewed the major research studies in the field and discussed several research findings on the chemical composition of essential oils, methods of oil extraction, and application of these oils in pharmaceutical and therapeutic fields. These essential oils can be used as anticancer, antimicrobial, antiviral, and as skin permeation enhancer agents.
Nanotechnology is the process of modulating shape and size at the nanoscale to design and manufacture structures, devices, and systems. Nanotechnology's prospective breakthroughs are incredible, and ...some cannot even be comprehended right now. The blood-brain barrier, which is a prominent physiological barrier in the brain, limits the adequate elimination of malignant cells by changing the concentration of therapeutic agents at the target tissue. Nanotechnology has sparked interest in recent years as a way to solve these issues and improve drug delivery. Inorganic and organic nanomaterials have been found to be beneficial for bioimaging approaches and controlled drug delivery systems. Brain cancer (BC) and Alzheimer's disease (AD) are two of the prominent disorders of the brain. Even though the pathophysiology and pathways for both disorders are different, nanotechnology with common features can deliver drugs over the BBB, advancing the treatment of both disorders. This innovative technology could provide a foundation for combining diagnostics, treatments, and delivery of targeted drugs to the tumour site, further supervising the response and designing and delivering materials by employing atomic and molecular elements. There is currently limited treatment for Alzheimer's disease, and reversing further progression is difficult. Recently, various nanocarriers have been investigated to improve the bioavailability and efficacy of many AD treatment drugs. Nanotechnology-assisted drugs can penetrate the BBB and reach the target tissue. However, further research is required in this field to ensure the safety and efficacy of drug-loaded nanoparticles. The application of nanotechnology in the diagnosis and treatment of brain tumours and Alzheimer's disease is briefly discussed in this review.
Molecules containing triazolopyrimidine core showed diverse biological activities, including anti-Alzheimer's, anti-diabetes, anti-cancer, anti-microbial, anti-tuberculosis, anti-viral, ...anti-malarial, anti-inflammatory, anti-parkinsonism, and anti-glaucoma activities. Triazolopyrimidines have 8 isomeric structures, including the most stable 1,2,4-triazolo1,5- a pyrimidine ones. Triazolopyrimidines were obtained by using various chemical reactions, including a) 1,2,4-triazole nucleus annulation to pyrimidine, b) pyrimidines annulation to 1,2,4-triazole structure, c) 1,2,4-triazolol,5-a pyrimidines rearrangement, and d) pyrimidotetrazine rearrangement. This review discusses synthetic methods, recent pharmacological actions and drug delivery perspectives of triazolopyrimidines.
Diabetes Mellitus (DM) is now a well-known factor which initiates many metabolic derangements in various tissues and organs including liver, muscle, pancreas, adipose tissue, cardiovascular and ...nervous system. Cardiovascular complications are the most crucial , and their effects are so intensive that their derangement leads to cardiac failure even in the absence of ischemic heart diseases. This entity of cardiac pathology in DM is often regarded as diabetic cardiomyopathy (DCM). Recently, many plant-derived drugs have been tested to control and alleviate DCM. Wogonin is one of the drugs the characteristics of which have been deeply studied. Wogonin is a flavonoid having yellow color pigment in their leaves and is obtained from the roots of plant Scutellaria Baicalensis Georgi. Wogonin has long been used as an active anti-cancer drug in Chinese medicine practice. In recent past wogonin has shown to possess notable anti-inflammatory, and anti-allergic properties. Wogonin has demonstrated to possess anti-oxidant, anti-viral, anti-inflammatory and also anti-thrombotic properties. Wogonin has shown to alleviate apoptosis, and ER stress in the cells and this property can also be used in the treatment of cardiovascular diseases. Notably, wogonin has been documented to have an extensive margin of safety as well as displays little or no organ toxicity following extended intravenous administration. In this review, we discuss recently discovered therapeutic potential of wogonin in the treatment of DCM.
Application of nanotechnologies to cancer therapy might increase solubility and/or bioavailability of bioactive compounds of natural or synthetic origin and offers other potential benefits in cancer ...therapy, including selective targeting. In the present review we aim to evaluate in vivo studies on the anticancer activity of nanoparticles (NPs) obtained from food-derived flavonoids. From a systematic search a total of 60 studies were identified. Most of the studies involved the flavanol epigallocatechin-3-O-gallate and the flavonol quercetin, in both delivery and co-delivery (with anti-cancer drugs) systems. Moreover, some studies investigated the effects of other flavonoids, such as anthocyanins aglycones anthocyanidins, flavanones, flavones and isoflavonoids. NPs inhibited tumor growth in both xenograft and chemical-induced animal models of cancerogenesis.
Encapsulation improved bioavailability and/or reduced toxicity of both flavonoids and/or co-delivered drugs, such as doxorubicin, docetaxel, paclitaxel, honokiol and vincristine. Moreover, flavonoids have been successfully applied in molecular targeted nanosystems. Selectivity for cancer cells involves pH- and/or reactive oxygen species-mediated mechanisms. Furthermore, flavonoids are good candidates as drug delivery for anticancer drugs in green synthesis systems. In conclusion, although human studies are needed, NPs obtained from food-derived flavonoids have promising anticancer effects in vivo.
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