Design, Development of Pyrazole-Linked Spirocyclopropyl Oxindole-Carboxamides as Potential Cytotoxic Agents and Type III Allosteric VEGFR-2 Inhibitors.

Tumor progression depends on angiogenesis, which is stimulated by growth factors like VEGF, targeting VEGFR kinase with small molecules is an effective anti-angiogenic therapeutic approach. The rational modification of sunitinib (VEGFR-2 inhibitor) to spirocyclopropyloxindoline carboxamides have been performed and their in vitro cytotoxic profiling was evaluated. The molecular modelling studies enabled the screening of designed analogues and identifying the possible interactions within the type III allosteric inhibitor binding site of VEGFR-2.

Quercetin ameliorates neuroinflammatory and neurodegenerative biomarkers in the brain and improves neurobehavioral parameters in a repeated intranasal amyloid-beta exposed model of Alzheimer's disease.

: The aim of the present study was to study the potential therapeutic effects of quercetin in protection against repeated intranasal exposure of an amyloid-beta-induced mouse model. : Mice received intranasal Aβ (5 μg/10 μL) exposure once daily for seven consecutive days. Quercetin was orally administered to them at 30 mg kg and 100 mg kg doses for one week starting from day five following Aβ peptide administration.

Abolished frameshifting for predicted structure-stabilizing SARS-CoV-2 mutants: implications to alternative conformations and their statistical structural analyses.

The SARS-CoV-2 frameshifting element (FSE) has been intensely studied and explored as a therapeutic target for coronavirus diseases, including COVID-19. Besides the intriguing virology, this small RNA is known to adopt many length-dependent conformations, as verified by multiple experimental and computational approaches. However, the role these alternative conformations play in the frameshifting mechanism and how to quantify this structural abundance has been an ongoing challenge.

Corrigendum to "Nitrosamines crisis in pharmaceuticals - Insights on toxicological implications, root causes and risk assessment: A systematic review" [J. Pharm. Anal. 14 (2024) 100919].

[This corrects the article DOI: 10.1016/j.jpha.

Design, Synthesis, and Biological Evaluation of Ferulic Acid-Piperazine Derivatives Targeting Pathological Hallmarks of Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent cause of dementia and is characterized by low levels of acetyl and butyrylcholine, increased oxidative stress, inflammation, accumulation of metals, and aggregations of Aβ and tau proteins. Current treatments for AD provide only symptomatic relief without impacting the pathological hallmarks of the disease. In our ongoing efforts to develop naturally inspired novel multitarget molecules for AD, through extensive medicinal chemistry efforts, we have developed , harboring the key functional groups to provide not only symptomatic relief but also targeting oxidative stress, able to chelate iron, inhibiting NLRP3, and Aβ aggregation in various AD models.

Development and validation of stability indicating assay method for mitapivat: Identification of novel hydrolytic, photolytic, and oxidative forced degradation products employing quadrupole-time of flight mass spectrometry.

Mitapivat is a novel, first-in-class orally active pyruvate kinase activator approved by the US Food and Drug Administration in 2022 for the treatment of hemolytic anemia. There is no literature available regarding the identification of degradation impurities of mitapivat. The present study deals with the degradation behavior of mitapivat under various stress conditions such as hydrolytic, photolytic, thermal, and oxidative stress.

Computational-Based Polyphenol Therapy for Nonsmall Cell Lung Cancer: Naringin Coamorphous Systems for Solubility and Bioavailability Enhancement.

In this research, we utilized molecular simulations to create co-amorphous materials (CAMs) of ceritinib (CRT) with the objective of improving its solubility and bioavailability. We identified naringin (NRG) as a suitable co-former for CRT CAMs based on binding energy and intermolecular interactions through computational modeling. We used the solvent evaporation method to produce CAMs of CRT and NRG, expecting to enhance both solubility and bioavailability simultaneously.

In-vitro and in-vivo studies of two-drug cocktail therapy targeting chemobrain via the Nrf2/NF-κB signaling pathway.

Today, we critically need alternative therapeutic options for chemotherapy-induced cognitive impairment (CICI), often known as chemo brain. Mitochondrial dysfunction and oxidative stress are two of the primary processes that contribute to the development of chemobrain. Therefore, the purpose of this study was to investigate how CoQ10 and berberine shield neurons from chemotherapy-induced damage in in-vitro studies and memory loss in vivo studies.

Seeing the unseen: The role of bioimaging techniques for the diagnostic interventions in intervertebral disc degeneration.

Intervertebral Disc Degeneration is a pathophysiological condition that primarily affects the spinal discs, causing back pain and neurological deficits. It is caused by the contribution of several factors such as genetic predisposition, age-related degeneration, and lifestyle choices like obesity and physical activity. Even though there are medications to treat pain, there is a lack of medicines for a complete cure.

Gemini surfactants as next-generation drug carriers in cancer management.

Introduction: Gemini surfactants (GS) are an elite class of amphiphilic molecules that have shown up as a potential candidate in the field of drug delivery because of their exceptional physicochemical properties. They comprise two hydrophilic headgroups connected by an adaptable spacer and hydrophobic tails that has shown promising results in delivering different therapeutic agents to cancer cells at preclinical level. However further studies are in demand to unlock the full potential of GS in this field.

Unravelling the role of tumor microenvironment responsive nanobiomaterials in spatiotemporal controlled drug delivery for lung cancer therapy.

Design and development of efficient drug delivery technologies that impart site-specificity is the need of the hour for the effective treatment of lung cancer. The emergence of materials science and nanotechnology partially helped drug delivery scientists to achieve this objective. Various stimuli-responsive materials that undergo degradation at the pathological tumor microenvironment (TME) have been developed and explored for drug delivery applications using nanotechnological approaches.

Understanding the role of endothelial cells in brain tumor formation and metastasis: a proposition to be explored for better therapy.

Glioblastoma is one of the most devastating central nervous system disorders. Being a highly vascular brain tumor, it is distinguished by aberrant vessel architecture. This lends credence to the idea that endothelial cells (ECs) linked with glioblastoma vary fundamentally from ECs seen in the healthy human brain.

Navigating the future of health care with AI-driven digital therapeutics.

Digital therapeutics (DTx) is a recently conceived idea in health care that aims to cure ailments and modify patient behavior by employing a range of digital technologies. Notably, when traditional medication is not entirely efficacious, DTx offers an innovative avenue for treatments linked to dysfunctional behaviors and lifestyle management. DTx involves extremely adaptable therapeutic devices that empower greater patient engagement in treating illness, using algorithms to collect, transfer and analyze the patient's data.

Lipidic Nanosystem as State-of-the-Art Nanovehicle for Biomedical Applications.

Unlabelled: Lipids have tremendously transformed the biomedical field, especially in the last few decades. Nanosystems, especially Lipid nanocapsules (LNCs), have emerged as the most demanding nanovehicle systems for delivering drugs, genes, and other diagnostic agents. Unique attributes and characteristic features such as higher encapsulation efficiency, stealth effect, ability to solubilize a wide range of drugs, capability to inhibit P-gp efflux pumps, and higher stability play a vital role in engaging this nanosystem.

Amelioration of breast cancer therapies through normalization of tumor vessels and microenvironment: paradigm shift to improve drug perfusion and nanocarrier permeation.

Breast cancer (BC) is the most commonly diagnosed cancer among women. Chemo-, immune- and photothermal therapies are employed to manage BC. However, the tumor microenvironment (TME) prevents free drugs and nanocarriers (NCs) from entering the tumor premises.

Therapeutic Monoclonal Antibodies for Metabolic Disorders: Major Advancements and Future Perspectives.

Purpose Of Review: Globally, the prevalence of metabolic disorders is rising. Elevated low-density lipoprotein (LDL) cholesterol is a hallmark of familial hypercholesterolemia, one of the most prevalent hereditary metabolic disorders and another one is Diabetes mellitus (DM) that is more common globally, characterised by hyperglycemia with low insulin-directed glucose by target cells. It is still known that low-density lipoprotein cholesterol (LDL-C) increases the risk of cardiovascular disease (CVD).

Achieving Endo/Lysosomal Escape Using Smart Nanosystems for Efficient Cellular Delivery.

The delivery of therapeutic agents faces significant hurdles posed by the endo-lysosomal pathway, a bottleneck that hampers clinical effectiveness. This comprehensive review addresses the urgent need to enhance cellular delivery mechanisms to overcome these obstacles. It focuses on the potential of smart nanomaterials, delving into their unique characteristics and mechanisms in detail.

Exploration of Abiraterone acetate loaded Nanostructured lipid carriers for bioavailability improvement and circumvention of fast-fed variability.

Abiraterone acetate (ABA), a biopharmaceutical class IV drug suffers from solubility and permeability pitfalls resulting in limited oral bioavailability and positive food effect, i.e. multi-fold enhancement in drug absorption in the presence of food.

Molecular Mechanisms Underlying Single Nucleotide Polymorphism-Induced Reactivity Decrease in CYP2D6.

Cytochrome P450 2D6 (CYP2D6) is one of the most important enzymes involved in drug metabolism. Genetic polymorphism can influence drug metabolism by CYP2D6 such that a therapy is seriously affected by under- or overdosing of drugs. However, a general explanation at the atomistic level for poor activity is missing so far.

Investigating the Variability among Indicators for Quantifying Antimicrobial Use in the Intensive Care Units: Analysis of Real-world Evidence.

Unlabelled: This study investigated variability among four indicators for quantifying antimicrobial use in intensive care units (ICUs): defined daily doses (DDD), prescribed daily doses (PDD), duration of therapy (DOT), and length of therapy (LOT) and recommended the most clinically relevant approach. Retrospective data from patients who had received at least one antimicrobial was analyzed. Patients whose records were incomplete or expired were excluded.