Nanogels are highly recognized as adaptable drug delivery systems that significantly contribute to improving various therapies and diagnostic examinations for different human diseases. These three-dimensional, hydrophilic cross-linked polymers have the ability to absorb large amounts of water or biological fluids. Due to the growing demand for enhancing current therapies, nanogels have emerged as the next-generation drug delivery system. They effectively address the limitations of conventional drug therapy, such as poor stability, large particle size, and low drug loading efficiency. Nanogels find extensive use in the controlled delivery of therapeutic agents, reducing adverse drug effects and enabling lower therapeutic doses while maintaining enhanced efficacy and patient compliance. They are considered an innovative drug delivery system that highlights the shortcomings of traditional methods. This article covers several topics, including the involvement of nanogels in the nanomedicine sector, their advantages and limitations, ideal properties like biocompatibility, biodegradability, drug loading capacity, particle size, permeability, non-immunological response, and colloidal stability. Additionally, it provides information on nanogel classification, synthesis, drug release mechanisms, and various biological applications. The article also discusses barriers associated with brain targeting and the progress of nanogels as nanocarriers for delivering therapeutic agents to the central nervous system.

The primary and considerable weakening event affecting elderly individuals is age-dependent cognitive decline and dementia. Alzheimer’s disease (AD) is the chief cause of progressive dementia, and it is characterized by irreparable loss of cognitive abilities, forming senile plaques having Amyloid Beta (Aβ) aggregates and neurofibrillary tangles with considerable amounts of tau in affected hippocampus and cortex regions of human brains. AD affects millions of people worldwide, and the count is showing an increasing trend. Therefore, it is crucial to understand the underlying mechanisms at molecular levels to generate novel insights into the pathogenesis of AD and other cognitive deficits. A growing body of evidence elicits the regulatory relationship between the mammalian target of rapamycin (mTOR) signaling pathway and AD. In addition, the role of autophagy, a systematic degradation, and recycling of cellular components like accumulated proteins and damaged organelles in AD, is also pivotal. The present review describes different mechanisms and signaling regulations highlighting the trilateral association of autophagy, the mTOR pathway, and AD with a description of inhibiting drugs/molecules of mTOR, a strategic target in AD. Downregulation of mTOR signaling triggers autophagy activation, degrading the misfolded proteins and preventing the further accumulation of misfolded proteins that inhibit the progression of AD. Other target mechanisms such as autophagosome maturation, and autophagy-lysosomal pathway, may initiate a faulty autophagy process resulting in senile plaques due to defective lysosomal acidification and alteration in lysosomal pH. Hence, the strong link between mTOR and autophagy can be explored further as a potential mechanism for AD therapy.

Background: Non-healing diabetic wounds represent a significant clinical challenge globally, necessitating innovative approaches in drug delivery to enhance wound healing. Understanding the pathogenesis of these wounds is crucial for developing effective treatments. Bioactive dressings and polymeric nanofibers have emerged as promising modalities, with silk biomaterials gaining attention for their unique properties in diabetic wound healing. Purpose of Review: The purpose of this review is to examine the challenges and innovations in treating non-healing diabetic wounds, emphasizing the global burden and the need for effective solutions. This review explores the complex mechanisms of wound healing in diabetes and evaluates the therapeutic potential of bioactive dressings and polymeric nanofibers. Special focus is given to the application of silk biomaterials, particularly silk fibroin, for wound healing, detailing their properties, mechanisms, and clinical translation. This review also describes various nanofiber fabrication methods, especially electrospinning technology, and presents existing evidence on the effectiveness of electrospun silk fibroin formulations. Recent Findings: Recent advancements highlight the potential of silk biomaterials in diabetic wound healing, owing to their biocompatibility, mechanical strength, and controlled drug release properties. Electrospun silk fibroin-based formulations have shown promising results in preclinical and clinical studies, demonstrating accelerated wound closure and tissue regeneration. Summary: Non-healing diabetic wounds present a significant healthcare burden globally, necessitating innovative therapeutic strategies. Bioactive dressings and polymeric nanofibers, particularly silk-based formulations fabricated through electrospinning, offer promising avenues for enhancing diabetic wound healing. Further research is warranted to optimize formulation parameters and validate efficacy in larger clinical trials.

Obesity is a complex disease caused by various factors, and synthetic drugs used to treat it can have side effects. Natural compounds, such as olivetol, could be a promising alternative. Olivetol is a substance found in certain lichen species and has anti-inflammatory and anti-cancer properties. In this study, researchers conducted in-silico molecular docking studies and found that olivetol had significant binding affinity with receptors involved in obesity. They also investigated the effects of olivetol on a diet-induced obese zebrafish model and found that high doses of olivetol reduced excessive fat accumulation and triglyceride and lipid accumulation. The low dose of olivetol showed a significant reduction in liver enzymes' levels. However, the high dose of olivetol resulted in a significant increase in HMG-CoA levels. These results suggest that olivetol may be a promising anti-obesity agent for the treatment of hyperlipidemia-related disorders, but further research is necessary to understand its full effects on the body.

Excitotoxicity is a condition in which neurons are damaged/injured by the over-activation of glutamate receptors. Excitotoxins play a crucial part in the progression of several neurological diseases. Marsilea quadrifolia Linn (M. quadrifolia) is a very popular aquatic medicinal plant that has been utilised for a variety of therapeutic benefits since ancient times. Its chemical composition is diverse and includes phenolic compounds, tannins, saponins, flavonoids, steroids, terpenoids, alkaloids, carbohydrates and several others that possess antioxidant properties. The objective of the present study was to investigate the neuroprotective potential of M. quadrifolia against monosodium glutamate (MSG)-induced excitotoxicity in rats. For this purpose, a high-performance thin-layer chromatography (HPTLC) analysis of chloroform extract of M. quadrifolia (CEMQ) was conducted to identify the major constituents. Further, the in-silico docking analysis was carried out on selected ligands. To confirm CEMQ's neuroprotective effects, the locomotor activity, non-spatial memory, and learning were assessed. The present study confirmed that CMEQ contains quercetin and its derivatives in large. The in-silico findings indicated that quercetin has a better binding affinity (-7.9 kcal/mol) towards the protein target 5EWJ. Animals treated with MSG had 1) a greater reduction in the locomotor score and impairment in memory and learning 2) a greater increase in the blood levels of calcium and sodium and 3) neuronal disorganization, along with cerebral edema and neuronal degeneration in the brain tissues as compared to normal control animals. The changes were however, significantly improved in animals which received standard drug memantine (20 mg/kg) and CEMQ (200 and 400 mg/kg) as compared to the negative control. It is plausible that the changes seen with CEMQ may be attributed to the N-methyl-D-aspartate (NMDA) antagonistic properties. Overall, this study indicated that M. quadrifolia ameliorated MSGinduced neurotoxicity. Future investigations are required to explore the neuroprotective mechanism of M. quadrifolia and its active constituents, which will provide exciting insights in the therapeutic management of neurological disorders.

Alzheimer's disease (AD) is a major cause of disability and one of the top causes of mortality globally. AD remains a major public health challenge due to its prevalence, impact on patients and caregivers, and the current lack of a cure. In recent years, polyphenols have garnered attention for their potential therapeutic effects on AD. The objective of the study was to establish network pharmacology between selected polyphenols of plant origin and AD. Insilico tools such as SwissADME, ProTox3.0, pkCSM, Swiss Target Prediction, DisGeNET, InterActiVenn, DAVID database, STRING database, Cytoscape/CytoHubba were employed to establish the multi-target potential of the polyphenolic compounds. The present study revealed that out of 17 polyphenols, 10 ligands were found to possess a drug-likeness nature along with desirable pharmacokinetic parameters and a lesser toxicity profile. Also, the results highlighted the possible interactions between the polyphenols and the disease targets involved in AD. Further, this study has shed light on the mTOR pathway and its impact on AD through the autophagic mechanism. Overall, this study indicated that polyphenols could be a better therapeutic option for treating AD. Hence, the consumption of polyphenolic cocktails as a part of the diet could produce more effective outcomes against the disease. Additional studies are warranted in the future to explore additional pathways and genes to provide a comprehensive understanding regarding the usage of the shortlisted polyphenols and their derivatives for the prevention and treatment of AD.