Non-coding RNAs in Regulation of Protein Aggregation and Clearance Pathways: Current Perspectives Towards Alzheimer's Research and Therapy.

Alzheimer's disease (AD) is the leading cause of dementia, affecting approximately 45.0 million people worldwide and ranking as the fifth leading cause of mortality. AD is identified by neurofibrillary tangles (NFTs), which include abnormally phosphorylated tau-protein and amyloid protein (amyloid plaques). Peptide dysregulation is caused by an imbalance between the production and clearance of the amyloid-beta (Aß) and NFT. AD begins to develop when these peptides are not cleared from the body. As a result, understanding the processes that control both normal and pathological protein recycling in neuronal cells is critical. Insufficient Aß and NFT clearance are important factors in the development of AD. Autophagy, lysosomal dysfunction, and ubiquitin-proteasome dysfunction have potential roles in the pathogenesis of many neurodegenerative disorders, particularly in AD. Modulation of these pathways may provide a novel treatment strategy for AD. Non-coding RNAs (ncRNAs) have recently emerged as important biological regulators, with particular relevance to the emergence and development of neurodegenerative disorders such as AD. ncRNAs can be used as potential therapeutic targets and diagnostic biomarkers due to their critical regulatory functions in several biological processes involved in disease development, such as the aggregation and accumulation of Aß and NFT. It is evident that ncRNAs play a role in the pathophysiology of AD. In this communication, we explored the link between ncRNAs and AD and their regulatory mechanisms that may help in finding new therapeutic targets and AD medications.

Synthesis of Novel Acrylamide Graft Copolymer of Acacia nilotica Gum for the Stabilization of Melatonin Nanoparticles for Improved Therapeutic Effect: Optimization Using (3)2 Factorial Design.

The objective of the present study was to optimize the microwave-assisted synthesis of the acrylamide graft copolymer of Acacia nilotica gum (AM-co-ANG). Furthermore, graft copolymer was used for the formulation of a nanoparticulate system using a novel top to bottom solvent antisolvent technique for the delivery of melatonin. Grafting of ANG was optimized by using 32 factorial design, where concentrations of polymer and monomer (acrylamide) were used as independent variables and swelling index in acidic (0.1 N HCl) and basic (1 N NaOH) pH. Grafted polymers were further used to develop and optimize nanoparticulate system using concentration of the graft copolymer and concentration of drug as independent variables. The size of the nanoformulation and entrapment efficiency were selected as dependent variables. Difference in infrared spectrum and absorbance maxima in the ultraviolet region confirm that grafting has taken place. Porous structure and a higher contact angle confirmed hydrophobic nature of AM-co-ANG as compared with the native polymer. Acrylamide graft copolymers show more swelling in 1 N NaOH as compared with 0.1 N HCl. In vitro toxicity studies in hepatic (HepG2 cell line), brain (SHSY5Y cell line), and skin (HaCaT cell line) cells easily predict that synthesized polymer have no cytotoxicity. The entrapment efficiency ranged from 55.24 ± 1.35% to 73.21 ± 1.83%. A nonlinear correlation was observed between independent and dependent variables, as confirmed by multivariate analysis of variance, surface regression, and the correlation report. The prepared formulations were able to release drug up to 12 h. The regression coefficient easily predicted that most of the formulations followed Baker-Lonsdale drug release kinetics.

Herbal Components Inspiring Current Lifestyle Disease Treatment: Role of Nutraceuticals.

Nutraceuticals are the foods that are used to prevent and cure diseases. Food and nutrients are essential for the body's normal function and aid in the maintenance of an individual's health and prevent various diseases. Nutraceuticals are medicinal foods that aid in the maintenance of health, the enhancement of immunity, and the prevention and treatment of specific diseases. The markets of nutraceuticals are one of the fastest-growing industry segments. The prime reason for this accelerated market growth lies in the fact that nutraceuticals are low cost, can prevent diseases to occur, hence, can save the health care cost, have more nutritional value, and many others. Nutraceuticals can be classified on different foundations based on what they promise, natural sources, and nutraceutical food available in the market. This article will discuss those classifications in detail along with the role of nutraceuticals in lifestyle diseases, regulations, market trends, and prospects of nutraceuticals. The article will also highlight the concern areas which play as the limiting factor in the nutraceuticals industry growth like lack of quality control, lack of data on its working, and many other things.

Human-derived Biomaterials for Biomedical and Tissue Engineering Applications.

Biomaterials have been utilised since the dawn of time to aid wound healing and to try to restore damaged tissues and organs. Many different materials are now commercially accessible for maintaining and restoring biological functioning, and many more are being researched. New biomaterials have to be developed to meet growing clinical demands. The aim of this study is to propose innovative biomaterials of human origin and their recent applications in tissue engineering and the biomedical field. Recent trends in tissue engineering are summarized in this review highlighting the use of stem cells, 3D printing techniques, and the most recent application of biomaterials to produce a dynamic scaffold resembling natural tissue. Various literature survey was carried out using PubMed, Scopus, Elsevier, google scholar, and others and it was summarized from the study that the extracellular matrix (ECM) offers the opportunity to create a biomaterial consisting of a microenvironment with interesting biological and biophysical properties for improving and regulating cell functions. Based on the literature study, biomaterials have become increasingly important to the development of tissue engineering, which aims to unlock the regeneration capacity of human tissues/organs in a state of degeneration and restore or reestablish normal biological function. Biomaterials have also become increasingly important to the success of biomedical devices. Hence, it can be concluded from the finding of the study that the advances in the understanding of biomaterials and their role in new tissue formation can open new prospects in the field of tissue engineering and regenerative medicine.

Chimeric Antigen Receptor (CAR) T-cell Therapy: A New Genetically Engineered Method of Immunotherapy for Cancer.

Chimeric antigen receptor (CAR T) cell treatment for solid tumours faces significant challenges. CAR T cells are unable to pass the vascular barrier in tumours due to a lack of endothelial leukocyte adhesion molecules. The invasion, activity, and durability of CAR T cells may be hampered by additional immunosuppressive mechanisms present in the solid tumour environment. The use of CAR T cells to attack cancer vascular endothelial metabolic targets from within the blood may simplify the fight against cancer. These are the principles that govern our examination of CAR T cell treatment for tumor cells, with a specific eye toward tumour venous delivery. CAR T cells may also be designed such that they can be readily, safely, and successfully transferred.

Genetic Causes of Alzheimer's Disease and the Neuroprotective Role of Melatonin in its Management.

Dementia is a global health concern owing to its complexity, which also poses a great challenge to pharmaceutical scientists and neuroscientists. The global dementia prevalence is approximately 47 million, which may increase by three times by 2050. Alzheimer's disease (AD) is the most common cause of dementia. AD is a severe age-related neurodegenerative disorder characterized by short-term memory loss, aphasia, mood imbalance, and executive function. The etiology of AD is still unknown, and the exact origin of the disease is still under investigation. Aggregation of Amyloid ß (Aß) plaques or neurotoxic Aßo oligomers outside the neuron is the most common cause of AD development. Amyloid precursor protein (APP) processing by ß secretase and γ secretase produces abnormal Aß monomers. This aggregation of Aß and NFT is promoted by various genes like BACE1, ADAM10, PIN1, GSK-3, APOE, PPARα, etc. Identification of these genes can discover several therapeutic targets that can be useful in studying pathogenesis and underlying treatments. Melatonin modulates the activities of these genes, thereby reducing Aß production and increasing its clearance. Melatonin also reduces the expression of APP by attenuating cAMP, thereby enhancing the non-amyloidogenic process. Present communication explored and discussed the neuroprotective role of melatonin against Aß-dependent AD pathogenesis. The manuscript also discussed potential molecular and genetic mechanisms of melatonin in the production and clearance of Aß that could ameliorate neurotoxicity.

Advancement and Strategies for the Development of Peptide-drug Conjugates: Pharmacokinetic Modulation, Role and Clinical Evidence against Cancer Management.

Currently, many new treatment strategies are being used for the management of cancer. Among them, chemotherapy based on peptides has been of great interest due to the unique features of peptides. This review discusses the role of peptide and peptides analogues in the treatment of cancer, with special emphasis on their pharmacokinetic modulation and research progress. Low molecular weight, targeted drug delivery, enhanced permeability, etc., of the peptide-linked drug conjugates, lead to an increase in the effectiveness of cancer therapy. Various peptides have recently been developed as drugs and vaccines with an altered pharmacokinetic parameter which has subsequently been assessed in different phases of the clinical study. Peptides have made a great impact in the area of cancer therapy and diagnosis. Targeted chemotherapy and drug delivery techniques using peptides are emerging as excellent tools in minimizing problems with conventional chemotherapy. It can be concluded that new advances in using peptides to treat different types of cancer have been shown by different clinical studies indicating that peptides could be used as an ideal therapeutic method in treating cancer due to the novel advantages of peptides. The development of identifying and synthesizing novel peptides could provide a promising choice to patients with cancer.

Characterization of Microwave-Controlled Polyacrylamide Graft Copolymer of Tamarind Seed Polysaccharide.

The main objective of the study was to prepare tamarind seed polysaccharide grafted copolymers of polyacrylamide (TSP-g-Am) using a 32 factorial design. Tamarind seed polysaccharide (TSP) was extracted, and grafted copolymer of TSP was prepared using polyacrylamide as copolymer and ceric ammonium nitrate as initiator. Various batches (F1-F9) of TSP-g-Am were prepared, among which F1 showed highest grafting efficiency; hence, the prepared TSP-g-Am (F1) was evaluated for grafting efficiency, conversion, effect of initiator and further characterized using SEM analysis, contact angle determination, DSC analysis, swelling index, swelling and deswelling, and chemical resistance. The contact angle of TSP was found to be 81 ± 2, and that of TSP-g-Am (F1) was found to be 74 ± 2, which indicates that the wetting ability of the grafted copolymer was less than that of the native polymer. The results of thermal analysis indicated that TSP-g-Am had a more stable molecular structure than TSP. The morphology of the grafted polymer was observed from SEM images, and it was observed that the particles was asymmetrical. Antimicrobial activity was also found in the grafted copolymer. The present study concludes that the TSP-g-Am showed an excellent performance in thermal stability and swelling capacity compared with TSP. The detailed structural characteristics, as well as the excellent thermal stability and swelling capacities, will make it beneficial to use the synthesised copolymer as a precursor for the production of large-scale eco-friendly advanced materials with a wide range of applications, acting as a stabiliser, thickener, binder, release retardant, modifier, suspending agent, viscosity enhancer, emulsifying agent, or carrier for novel drug delivery systems in oral, buccal, colon, and ocular systems, and in nanofabrication and wound dressing, and it is also becoming an important part of food, cosmetics, confectionery, and bakery.

Fabrication and Characterization of Chitosan-Tamarind Seed Polysaccharide Composite Film for Transdermal Delivery of Protein/Peptide.

Transdermal drug delivery is used to deliver a drug by eliminating the first-pass metabolism, which increases the bioavailability of the drug. The present study aims to formulate the chitosan-tamarind seed polysaccharide composite films and evaluate for the delivery of protein/peptide molecules. Nine formulations were prepared and evaluated by using different parameters, such as physical appearance, folding endurance, thickness of film, surface pH, weight variation, drug content, surface morphology, percentage moisture intake and uptake, drug release kinetics, and drug permeability. The film weight variance was observed between 0.34 ± 0.002 to 0.47 ± 0.003 g. The drug level of the prepared films was found to be between 96 ± 1.21 and 98 ± 1.33µg. Their intake of moisture ranged between 2.83 ± 0.002 and 3.76 ± 0.001 (%). The moisture absorption of the films ranged from 5.33 ± 0.22 to 10.02 ± 0.61 (%). SEM images revealed a smooth film surface, while minor cracks were found in the film after permeation tests. During the first 4 days, drug release was between 13.75 ± 1.64% and 22.54 ± 1.34% and from day 5 to day 6, it was between 72.67 ± 2.13% and 78.33 ± 3.13%. Drug permeation during the first 4 days was 15.78 ± 1.23 %. Drug permeation (%) during the first 4 days was between 15.78 ± 1.23 and 22.49 ± 1.29 and from day 5 to day 6, it was between 71.49 ± 3.21 and 77.93 ± 3.20.

Evaluation and Characterization of Tamarind Gum Polysaccharide: The Biopolymer.

Polymers from natural sources are widely used as excipients in the formulation of pharmaceutical dosage forms. The objective of this study was to extract and further characterize the tamarind gum polysaccharide (TGP) obtained from Tamarindus indica as an excipient for biomedical applications. Double distilled water was used as a solvent for the extraction of gum while Ethyl alcohol was used as an antisolvent for the precipitation. The results of the Hausner ratio, Carr's index and angle of repose were found to be 0.94, 6.25, and 0.14, respectively, which revealed that the powder is free-flowing with good flowability. The gum was investigated for purity by carrying out chemical tests for different phytochemical constituents and only carbohydrates were found to be present. The swelling index was found to be 87 ± 1%, which shows that TGP has good water intake capacity. The pH of the 1% gum solution was found to be neutral, approximately 6.70 ± 0.01. The ash values such as total ash, sulphated ash, acid insoluble ash, and water-soluble ash were found to be 14.00 ± 1.00%, 13.00 ± 0.05%, 14.04 ± 0.57% and 7.29 ± 0.06%, respectively. The IR spectra confirmed the presence of alcohol, amines, ketones, anhydrides groups. The contact angle was <90°, indicating favorable wetting and good spreading of liquid over the surface The scanning electron micrograph (SEM) revealed that the particle is spherical in shape and irregular. DSC analysis shows a sharp exothermic peak at 350 °C that shows its crystalline nature. The results of the evaluated properties showed that TGP has acceptable properties and can be used as a excipient to formulate dosage forms for biomedical applications.