Biochanin-A co-crystal formulation improves bioavailability and ameliorates cerulein-induced pancreatitis by attenuating the inflammation.

Co-crystallization of a therapeutic ingredient with an appropriate co-former is a powerful technique to augment the physicochemical and pharmacokinetic properties and the effectiveness of Active Pharmaceutical Ingredients (APIs). Biochanin A (BCA), a flavonoid with medicinal potential, is limited by poor solubility and low oral bioavailability. This study aimed to design and develop a novel BCA-nicotinamide cocrystal as BCC to enhance BCA's oral bioavailability and explore its therapeutic potential for ameliorating cerulein-induced acute pancreatitis (CIAP) by elucidating the target identification utilizing tissue/serum metabolite profiles.

Mechanism of Nucleic Acid Phosphodiester Bond Cleavage by Human Endonuclease V: MD and QM/MM Calculations Reveal a Versatile Metal Dependence.

Human endonuclease V (EndoV) catalytically removes deaminated nucleobases by cleaving the phosphodiester bond as part of RNA metabolism. Despite being implicated in several diseases (cancers, cardiovascular diseases, and neurological disorders) and potentially being a useful tool in biotechnology, details of the human EndoV catalytic pathway remain unclear due to limited experimental information beyond a crystal structure of the apoenzyme and select mutational data. Since a mechanistic understanding is critical for further deciphering the central roles and expanding applications of human EndoV in medicine and biotechnology, molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations were used to unveil the atomistic details of the catalytic pathway.

Wormhole Mesoporous Silica Framework with Enhanced Thiol Loading for Improved Hg Sequestration.

Thiol-functionalized mesoporous silica and materials potentially dedicated to diverse applications of composite materials, metal colloids, and metal catalysts, etc. Here, we developed a new synthesis route for 3-methacryloxypropyl trimethoxy silane (MPTMS) functionalized mesoporous silica (KIT-6), achieving a 71.5 % enhancement in thiol functionalization on KIT-6 surfaces.

A QbD-Navigated Approach to the Development and Evaluation of Etodolac-Phospholipid Complex Containing Polymeric Films for Improved Anti-Inflammatory Effect.

The current study focuses on development of phospholipid complex-loaded films of etodolac for enhanced transdermal permeation and anti-inflammatory effect. An etodolac-phospholipid complex was developed using the solvent evaporation method and was characterized by DSC, XRD, FTIR, and H-NMR studies. The formation of the complex led to conversion of a crystalline drug to an amorphous form.

Electrochemical Charge Transfer Kinetics of Ferrocene in the Light of Different Working Electrodes.

Ferrocene is an accidentally discovered organometallic compound that serves as a crucial redox probe in investigating electrochemical charge transfer dynamics. Besides solution phase studies, ferrocene derivatives are well-explored in molecular thin films, including self-assembled monolayers on various electrodes for understanding on-surface redox behavior, molecular electronics, and charge storage applications. Heterogeneous charge transfer is an imperative parameter for efficient charge transport in spin-dependent electrochemistry, photoelectrochemistry, and molecular electronic devices.

Clinical Characteristics of Migraine and Their Association With the Retinal Nerve Fiber Layer Thickness.

Background: Migraine is characterized by recurrent episodes of unilateral, pulsating headaches. At the cerebral and ocular levels, it is recognized that the vascular narrowing and loss of blood flow are transient; however, the chronic nature of migraine may result in long-term functional and structural changes in these structures. It could result in axonal loss and an alteration in the thickness of the retinal nerve fiber layers (RNFL).

Yohimbine Treatment Alleviates Cardiac Inflammation/Injury and Improves Cardiac Hemodynamics by Modulating Pro-Inflammatory and Oxidative Stress Indicators.

Acute myocarditis, also known as myocardial inflammation, is a self-limited condition caused by systemic infection with cardiotropic pathogens, primarily viruses, bacteria, or fungi. Despite significant research, inflammatory cardiomyopathy exacerbated by heart failure, arrhythmia, or left ventricular dysfunction and it has a dismal prognosis. In this study, we aimed to evaluate the therapeutic effect of yohimbine against lipopolysaccharide (LPS) induced myocarditis in rat model.

Elucidation of the catalytic mechanism of a single-metal dependent homing endonuclease using QM and QM/MM approaches: the case study of I-I.

Homing endonucleases (HEs) are highly specific DNA cleaving enzymes, with I-I having been suggested to use a single metal to accelerate phosphodiester bond cleavage. Although an I-I mechanism has been proposed based on experimental structural data, no consensus has been reached regarding the roles of the metal or key active site amino acids. This study uses QM cluster and QM/MM calculations to provide atomic-level details of the I-I catalytic mechanism.

Nitrogen-containing heterocyclic compounds: A ray of hope in depression?

Depression is not similar to daily mood fluctuations and temporary emotional responses to day-to-day activities. Depression is not a passing problem; it is an ongoing problem. It deals with different episodes consisting of several symptoms that last for at least 2 weeks.

Exploration of oxadiazole clubbed benzhydrylpiperazine pharmacophoric features as structural feature for antidepressant activity: In vitro, in vivo and in silico analysis.

Arylpiperazine clubbed various heterocyclic molecules present potential pharmacophoric structural features for the development of psychoactive drugs. There are various CNS active molecules possessing arylpiperazine moiety in their pharmacophore approved by USFDA. In the current study, we have explored the benzhydrylpiperazine moiety clubbed with various substituted oxadiazole moieties (AP1-12) for their monoamine oxidase (MAO) inhibition and antidepressant potential.

Is Metal Stabilization of the Leaving Group Required or Can Lysine Facilitate Phosphodiester Bond Cleavage in Nucleic Acids? A Computational Study of EndoV.

Endonuclease V (EndoV) is a single-metal-dependent enzyme that repairs deaminated DNA nucleobases in cells by cleaving the phosphodiester bond, and this enzyme has proven to be a powerful tool in biotechnology and medicine. The catalytic mechanism used by EndoV must be understood to design new disease detection and therapeutic solutions and further exploit the enzyme in interdisciplinary applications. This study has used a mixed molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) approach to compare eight distinct catalytic pathways and provides the first proposed mechanism for bacterial EndoV.

Pesticides: An alarming detrimental to health and environment.

Pesticides are chemical substances of natural or synthetic origin that are used to eradicate pests and insects. These are indispensable in the agricultural processes for better crop production. Pesticide use aims to promote crop yield and protect the crops from diseases and damage.

Exploring the Therapeutic Potential of Alkaloids in Alzheimer's Disease Management.

Background: Alkaloids are important phytoconstituents obtained from various plant sources. The study's primary goal is to assess the anti-Alzheimer potential of alkaloids using a molecular docking study. Alzheimer's disease (AD) is considered a gradual decline in memory, reasoning, decision-making, orientation to one's physical surroundings, and language.

Nintedanib solid lipid nanoparticles improve oral bioavailability and ameliorate pulmonary fibrosis in vitro and in vivo models.

Nintedanib (NIN) and pirfenidone are the only approved drugs for the treatment of Idiopathic Pulmonary Fibrosis (IPF). However, NIN and pirfenidone have low oral bioavailability and limited therapeutic potential, requiring higher dosages to increase their efficacy, which causes significant liver and gastrointestinal toxicities. In this study, we aimed to develop nintedanib-loaded solid lipid nanoparticles (NIN-SLN) to improve the oral bioavailability and therapeutic potential against TGF-β-induced differentiation in IPF fibroblasts and bleomycin (BLM)-induced lung fibrosis in rat models.

Investigation of Ginseng Phytoconstituents as Novel Therapeutics Against MAO-A.

Background: Ginseng () is a herb of medicinal and nutritional importance. Ginseng has been used since ancient times for the treatment of numerous ailments as it has many therapeutic properties. Several phytoconstituents are present in that possess a variety of beneficial pharmacological properties.

Target protein degradation by protacs: A budding cancer treatment strategy.

Cancer is one of the most common causes of death. So, its lethal effect increases with time. Near about hundreds of cancers are known in humans.

Evolving Advances in the Cosmetic use of Probiotics and Postbiotics: Health, Regulatory and Marketing Aspects.

Ongoing development in cosmetics is increasingly making use of probiotics, which are defined as "live microorganisms with health-enhancing properties mediated through ingestion or topical application to the host". The observation that several bacterial strains augment normal processes of healthy tissue maintenance, particularly for the skin, has opened up new avenues for the use of bacterial strains in cosmetics. A principal feature of such "cosmeceuticals" is an application of increasing insight into the biochemical nature of the skin's normal microbial flora, also called its microbiome.

Alkaloids as Potential Anti-HIV Agents.

Background: Alkaloids are nitrogen-containing compounds that are naturally occurring and have a variety of biological activities, including antimicrobial properties. In this study, the authors used a molecular docking approach to evaluate the anti-HIV potential of 64 alkaloids.

Methods: The authors used the Molegro Virtual Docker software to dock the alkaloids into the active sites of three HIV enzymes: protease, integrase, and non-nucleoside reverse transcriptase (NNRT).

Combating Microbial Infections Using Metal-Based Nanoparticles as Potential Therapeutic Alternatives.

The nature of microorganisms and the efficiency of antimicrobials have witnessed a huge co-dependent change in their dynamics over the last few decades. On the other side, metals and metallic compounds have gained popularity owing to their effectiveness against various microbial strains. A structured search of both research and review papers was conducted via different electronic databases, such as PubMed, Bentham, Springer, and Science Direct, among others, for the present review.

A novel multistage ensemble approach for prediction and classification of diabetes.

Diabetes mellitus is a metabolic syndrome affecting millions of people worldwide. Every year, the rate of occurrence rises drastically. Diabetes-related problems across several vital organs of the body can be fatal if left untreated.

The Impact of DFT Functional, Cluster Model Size, and Implicit Solvation on the Structural Description of Single-Metal-Mediated DNA Phosphodiester Bond Cleavage: The Case Study of APE1.

Phosphodiester bond hydrolysis in nucleic acids is a ubiquitous reaction that can be facilitated by enzymes called nucleases, which often use metal ions to achieve catalytic function. While a two-metal-mediated pathway has been well established for many enzymes, there is growing support that some enzymes require only one metal for the catalytic step. Using human apurinic/apyrimidinic endonuclease (APE1) as a prototypical example and cluster models, this study clarifies the impact of DFT functional, cluster model size, and implicit solvation on single-metal-mediated phosphodiester bond cleavage and provides insight into how to efficiently model this chemistry.

The metal dependence of single-metal mediated phosphodiester bond cleavage: a QM/MM study of a multifaceted human enzyme.

Nucleases catalyze the cleavage of phosphodiester bonds in nucleic acids using a range of metal cofactors. Although it is well accepted that many nucleases rely on two metal ions, the one-metal mediated pathway is debated. Furthermore, one-metal mediated nucleases maintain activity in the presence of many different metals, but the underlying reasons for this broad metal specificity are unknown.