Unraveling APOE4's Role in Alzheimer's Disease: Pathologies and Therapeutic Strategies.

Alzheimer's disease (AD), the most common kind of dementia worldwide, is characterized by elevated levels of the amyloid-β (Aβ) peptide and hyperphosphorylated tau protein in the neurons. The complexity of AD makes the development of treatments infamously challenging. Apolipoprotein E (APOE) genes's ɛ4 allele is one of the main genetic risk factors for AD.

Exploring New Structures of Kinase Inhibitors and Multitarget Strategies in Alzheimer's Disease Treatment.

Alzheimer's disease (AD) treatments currently available have ineffective results. Previously employed Acetylcholine esterase inhibitors and memantine, an NMDA receptor antagonist, target a single target structure that plays a complex role in the multifactorial progression of disease. Memantine moderates the toxic effects of excessive glutamate activity by blocking NMDA receptors, which decreases neurotoxicity in AD, while acetylcholine esterase inhibitors function by blocking cholinergic receptors (muscarinic and nicotinic), preventing the breakdown of acetylcholine, thereby enhancing cholinergic transmission, thus improving cognitive functions in mild to moderate stages of AD.

Toxicity profile of standardized Krishna Vajra Abhraka bhasma made from biotite mica.

Introduction: The Bhasmas, herbo-minerals, are reported to produce adverse effects when used clinically. Therefore, the present study aimed to assess the safety of Krishna Vajra Abhraka Bhasma (KVB), through acute and subacute toxicity testing.

Materials And Methods: After ethics committee approval, total 66 Wistar albino rats weighing 180-200 gms were used.

Surface-modified liposomal nasal gel enhances brain targeting of berberine hydrochloride for Alzheimer's therapy: optimization and studies.

This work aimed to formulate surface-modified berberine hydrochloride (BER)-loaded liposomes containing nasal gel for bran targeting. The liposomes were prepared by ethanol-injection method and optimized following a 3 full-factorial design. Size, morphology, zeta potential, permeation, and release were estimated.

Unraveling the Mysteries of Alzheimer's Disease Using Artificial Intelligence.

Alzheimer's disease (AD) is a multidimensional, complex condition that affects individuals all over the world. Despite decades of experimental and clinical research that has revealed various processes, many concerns concerning the origin of Alzheimer's disease remain unresolved. Despite the notion that there isn't a complete set of jigsaw pieces, the growing number of public data-sharing initiatives that collect biological, clinical, and lifestyle data from those suffering from Alzheimer's disease has resulted in virtually endless volumes of knowledge about the disorder, far beyond what humans can comprehend.

Exploring the Therapeutic Potential of Noncoding RNAs in Alzheimer's Disease.

Despite significant research efforts, Alzheimer's disease (AD), the primary cause of dementia in older adults worldwide, remains a neurological challenge for which there are currently no effective therapies. There are substantial financial, medical, and personal costs associated with this condition.Important pathological features of AD include hyperphosphorylated microtubule-associated protein Tau, the formation of amyloid β (Aβ) peptides from amyloid precursor protein (APP), and continuous inflammation that ultimately results in neuronal death.

The implications of the EU ban on titanium dioxide: A comprehensive review of safety concerns and alternatives.

Titanium dioxide, a naturally occurring compound, has been extensively utilized across various industries such as food, pharmaceuticals, and cosmetics. In the food sector, it was commonly employed as a color and opacity enhancer under the designation E171. However, due to safety concerns, the EU has prohibited its use as a food additive, effective August 2022, following a six-month transition period.

Investigation of magnesium aluminometasilicate (Neusilin US2) based surface solid dispersion of sorafenib tosylate using QbD approach: and pharmacokinetic study.

Background And Purpose: Sorafenib tosylate (SFN), a potent multikinase inhibitor, is used for the treatment of various cancers. However, it shows limited therapeutic applications due to its poor biopharmaceutical properties. The aim of the present investigation is to develop surface solid dispersion (SSD) of SFN using adsorbent to improve its solubility, bioavailability and therapeutic efficacy.

W. Attenuates Inflammation and Oxidative Stress in Freund's Complete Adjuvant-Induced Rheumatoid Arthritis in Wistar Rats.

Rheumatoid arthritis (RA) is an autoimmune disease that causes distinctive inflammatory symptoms and affects over 21 million people worldwide. RA is characterized by severe discomfort, swelling, and degradation of the bone and cartilage, further impairing joint function. The current study investigates the antiarthritic effect of a methanolic extract of (methanolic extract of , MEAP), an aromatic herb.

Exploring intranasal drug delivery via nanocarriers: A promising glioblastoma therapy.

Glioblastoma is one of the most recurring types of glioma, having the highest mortality rate among all other gliomas. Traditionally, the standard course of treatment for glioblastoma involved maximum surgical resection, followed by chemotherapy and radiation therapy. Nanocarriers have recently focused on enhancing the chemotherapeutic administration to the brain to satisfy unmet therapeutic requirements for treating brain-related disorders.

In Silico Investigation of Suillin Derived from Suillus luteus Mushroom (Agaricomycetes) Targeting Acetylcholinesterase: Docking and Virtual Screening Study.

This study integrates bioinformatics and computer-aided drug discovery to assess suillin's therapeutic potential, particularly its interaction with acetylcholinesterase (AChE). Alzheimer's disease presents profound challenges, necessitating effective treatments to mitigate cognitive decline and improve patients' quality of life. Although current medications offer symptomatic relief, they often entail adverse effects and do not address the underlying disease progression.

Computational and ADMET Predictions of Novel Compounds as Dual Inhibitors of BuChE and GSK-3β to Combat Alzheimer's Disease.

Background: Alzheimer's disease is a serious and widespread neurodegenerative illness in the modern healthcare scenario. GSK-3β and BuChE are prominent enzymatic targets associated with Alzheimer's disease. Co-targeting GSK3β and BChE in Alzheimer's disease helps to modify disease progression and enhance cognitive function by addressing both tau pathology and cholinergic deficits.

Levothyroxine synthesis impurities are neither mutagenic nor genotoxic: Insilico, Ames test and micronucleus test studies.

In vitro and in silico tests were used to assess the possible genotoxicity and mutagenicity of five impurities that may be present in levothyroxine, a drug used for thyroid hormone replacement therapy. Neither ToxTree nor VEGA (Virtual Models for evaluating the properties of chemicals within a global architecture) identified cause for concern for any of the impurities. Ames test results (doses up to 1 mg per plate), with or without metabolic activation, were negative.

Mutagenic and genotoxic QSAR prediction of dimer impurity of gliflozins; canagliflozin, dapaglifozin, and emphagliflozin and evaluation by Ames and micronucleus test.

Canagliflozin, Dapagliflozin, and Empagliflozin, glucagon-like peptide-1 receptor agonists, are indicated for managing type II diabetes. Although the genotoxicity profiles of these drugs are well-explored, limited information exists regarding the genotoxic potential of their impurities. In this investigation, the dimer impurities of Canagliflozin, Dapagliflozin, and Empagliflozin underwent both and assessments for mutagenic potential.

Biological Cargo: Exosomes and their Role in Cancer Progression and Metastasis.

Cancer cells are among the many types of cells that release exosomes, which are nanovesicles. Because of their many potential applications, exosomes have recently garnered much attention from cancer researchers. The bioactive substances that exosomes release as cargo have been the subject of several investigations.

Lycopene potentiates wound healing in streptozotocin-induced diabetic rats.

Background: Diabetes is a growing metabolic disease that is characterized by high blood sugar levels with life-threatening results. Diabetic wounds are a major problem because they do not resolve in few days. Major problems affecting wound healing are infection, age, stress, etc.

Phytoconstituents Targeting the Serotonin 5-HT Receptor: Promising Therapeutic Strategies for Neurological Disorders.

The 5-hydroxytryptamine-3 receptor (5-HTR), a subtype of serotonin receptor, is a ligand-gated ion channel crucial in mediating fast synaptic transmission in the central and peripheral nervous systems. This receptor significantly influences various neurological activities, encompassing neurotransmission, mood regulation, and cognitive processing; hence, it may serve as an innovative target for neurological disorders. Multiple studies have revealed promising results regarding the beneficial effects of these phytoconstituents and extracts on conditions such as nausea, vomiting, neuropathic pain depression, anxiety, Alzheimer's disease, cognition, epilepsy, sleep, and dyskinesia via modulation of 5-HTR in the pathophysiology of neurological disorder.

Dual drug-loaded polymeric mixed micelles for ovarian cancer: Approach to enhanced therapeutic efficacy of albendazole and paclitaxel.

Chemotherapy resistance remains a significant challenge in treating ovarian cancer effectively. This study addresses this issue by utilizing a dual drug-loaded nanomicelle system comprising albendazole (ABZ) and paclitaxel (PTX), encapsulated in a novel carrier matrix of D-tocopheryl polyethylene glycol 1000 succinate vitamin E (TPGS), soluplus and folic acid. Our objective was to develop and optimize this nanoparticulate delivery system using solvent evaporation techniques to enhance the therapeutic efficacy against ovarian cancer.

Computational Investigation of Novel Compounds as Dual Inhibitors of AChE and GSK-3β for the Treatment of Alzheimer's Disease.

Background: Alzheimer's disease (AD) stands out as one of the most devastating and prevalent neurodegenerative disorders known today. Researchers have identified several enzymatic targets associated with AD among which Glycogen synthase kinase-3β (GSK-3β) and Acetylcholinesterase (AChE) are prominent ones. Unfortunately, the market offers very few drugs for treating or managing AD, and none have shown significant efficacy against it.

A current era in pulsatile drug delivery system: Drug journey based on chronobiology.

Almost all biological processes in the human body are regulated by circadian rhythm, which results in drastically different biochemical and physiological conditions throughout a 24 h period. Hence, suitable drug delivery systems should be efficiently monitored to attain the required therapeutic plasma concentration and therapeutic drug responses when needed as per chrono pharmacological concepts. "Chronotherapy" is the fast and transient release of a particular quantity of drug substance post a predetermined off-release period, termed as 'lag time'.

GLP-1/GIP Agonist as an Intriguing and Ultimate Remedy for Combating Alzheimer's Disease through its Supporting DPP4 Inhibitors: A Review.

Background: Alzheimer's disease (AD) is a widespread neurological illness in the elderly, which impacted about 50 million people globally in 2020. Type 2 diabetes has been identified as a risk factor. Insulin and incretins are substances that have various impacts on neurodegenerative processes.