A novel biting rod model for assessing aggressive behavior in restraint-stressed rats: Role of 5-HT3 receptor and NF-κB-kynurenine pathways.

Preclinical models are essential for understanding the pathophysiology of intermittent explosive disorder (IED) in rodents. However, current models fail to fully uncover the molecular mechanisms behind restraint stress-induced aggression. We introduced a restrainer combined with a biting rod to measure IED-associated symptoms in stressed rats.

Thiopentone in Combination with Xylazine: An Experimental Investigation for Induction of Surgical Anesthesia and Safe Recovery in Experimental Rats.

Introduction: Achieving reliable anesthesia induction and rapid postoperative recovery are crucial aspects of animal research, particularly in small experimental animals. Thiopentone is still a widely used anesthetic drug, but its safety is a primary concern in delivering a safe dose to experimental animals. However, the use of thiopentone in combination with xylazine for surgical procedures in small experimental animals remains underexplored.

Naringenin prevents ethanol-induced reward behavior in adolescent rats through inhibition of TRPM3-dependent inflammation in the pVTA.

Ethanol intake activates the posterior ventral tegmental area (pVTA), enhancing dopamine synthesis in the nucleus accumbens shell (AcbSh) and contributing to Alcohol Use Disorder (AUD). Chronic adolescent ethanol exposure promotes neuroinflammation and disrupts reward pathways, increasing susceptibility to addiction. While transient receptor potential melastatin 3 (TRPM3) activation promotes inflammation and contributes to psychiatric disorders, its role in reward mechanisms remains unclear.

Recent Advances in Molecular Docking Techniques: Transforming Perspectives in Distinct Drug Targeting and Drug Discovery Approaches.

Introduction: Drug targeting and drug discovery methodologies are advancing rapidly due to recent developments in molecular docking techniques. Molecular docking forecasts the interactions between a small molecule, such as a potential medicine, and a target protein or receptor.

Objectives: This comprehensive review focuses on significant advances in molecular docking algorithms such as Vina, Glide, and AutoDock, including their enhanced accuracy and efficiency in predicting drug-target interactions.

In-vivo Pharmacokinetic Assessment and In-vitro Characterization of Strategically Optimized Perphenazine-loaded Nanostructured Lipid Carriers for Nose-to-brain Targeting.

Background: Perphenazine (PPZ) is a prevalent antipsychotic medication used to treat schizophrenia. After oral treatment, however, it shows substantial first-pass metabolism and decreased bioavailability.

Objective: The goal of this research was to incorporate PPZ into nanostructured lipid carriers and thereby improve its bioavailability and brain targeting (PPZ-NLCs).

Inhibition of TRPM3 channels in the medial prefrontal cortex mitigates OCD symptoms following traumatic brain injury.

Although tumor necrosis factor-alpha (TNF-α) plays an important role in the development of obsessive-compulsive disorder (OCD), the pathogenesis remains unclear. Since transient receptor potential melastatin 3 (TRPM3) channels are activated during inflammatory conditions, crosstalk with TNF-α in the progression of OCD has not been investigated yet. We hypothesize that mild traumatic brain injury (mTBI) stimulates TRPM3 channels, thereby enhancing the level of TNF-α in the medial prefrontal cortex (mPFC), a key brain region implicated in OCD pathogenesis.

Targeted nanoliposomes for precision rheumatoid arthritis therapy: a review on mechanisms and potential.

Rheumatoid arthritis (RA) is an inflammatory immune-triggered disease that causes synovitis, cartilage degradation, and joint injury. In nanotechnology, conventional liposomes were extensively investigated for RA. However, they frequently undergo rapid clearance, reducing circulation time and therapeutic efficacy.

Repurposing Nano Curcumin: Unveiling its Therapeutic Potential in Diabetic Nephropathy.

Currently, Diabetic Nephropathy (DN) stands as the predominant global cause of endstage renal disease. Many scientists believe that diabetes will eventually spread to pandemic levels due to the rising prevalence of the disease. While the primary factor leading to diabetic nephropathy is vascular dysfunction induced by hyperglycemia, several other pathological elements, such as fibrosis, inflammation, and oxidative stress, also contribute to the progression of the disease.

Identifying Novel Inhibitors for Dengue NS2B-NS3 Protease by Combining Topological similarity, Molecular Dynamics, MMGBSA and SiteMap Analysis.

Introduction: DENV NS2B-NS3 protease inhibitors were designed based upon the reference molecule, 4-(1,3-dioxoisoindolin-2-yl)-N-(4-ethylphenyl) benzenesulfonamide, reported by our team with the aim to optimize lead compound via rational approach. Top five best scoring molecules with zinc ids ZINC23504872, ZINC48412318, ZINC00413269, ZINC13998032 and ZINC75249613 bearing 'pyrimidin-4(3H)-one' basic scaffold have been identified as a promising candidate against DENV protease enzyme.

Methods: The shape and electrostatic complementary between identified HITs and reference molecules were found to be Tanimotoshape 0.

Lycopene alleviates BCG-induced depressive phenotypes in mice by disrupting 5-HT3 receptor - IDO1 interplay in the brain.

The 5-HT3 receptor and indoleamine 2,3-dioxygenase 1 (IDO1) enzyme play a crucial role in the pathogenesis of depression as their activation reduces serotonin contents in the brain. Since molecular docking analysis revealed lycopene as a potent 5-HT3 receptor antagonist and IDO1 inhibitor, we hypothesized that lycopene might disrupt the interplay between the 5-HT3 receptor and IDO1 to mitigate depression. In mice, the depression-like phenotypes were induced by inoculating Bacillus Calmette-Guerin (BCG).

Potentially active aspirin derivative to release nitric oxide: , and approaches.

The series of newer salicylate derivatives incorporating nitroxy functionality were synthesized and evaluated for their potential effect in gastrointestinal (GI) related toxicity produced by aspirin. The synthesized compounds (5a-j) were subjected to %NO (nitric oxide) release study, anti-inflammatory potential, % inhibition of carrageenan-induced paw edema and the obtained results were validated by studies including molecular docking, MD simulations and ADME (absorption, distribution, metabolism, and elimination) calculations. Compounds 5a (20.

CB2 Cannabinoid Receptor as a Potential Target in Myocardial Infarction: Exploration of Molecular Pathogenesis and Therapeutic Strategies.

The lipid endocannabinoid system has recently emerged as a novel therapeutic target for several inflammatory and tissue-damaging diseases, including those affecting the cardiovascular system. The primary targets of cannabinoids are cannabinoid type 1 (CB1) and 2 (CB2) receptors. The CB2 receptor is expressed in the cardiomyocytes.

Pathophysiological and therapeutic implications of neuropeptide S system in neurological disorders.

Neuropeptide S (NPS) is a 20 amino acids-containing neuroactive molecule discovered by the reverse pharmacology method. NPS is detected in specific brain regions like the brainstem, amygdala, and hypothalamus, while its receptor (NPSR) is ubiquitously expressed in the central nervous system (CNS). Besides CNS, NPS and NPSR are also expressed in the peripheral nervous system.

Neuroinflammation in the Central Nervous System: Exploring the Evolving Influence of Endocannabinoid System.

Neuroinflammation is a complex biological process that typically originates as a protective response in the brain. This inflammatory process is triggered by the release of pro-inflammatory substances like cytokines, prostaglandins, and reactive oxygen and nitrogen species from stimulated endothelial and glial cells, including those with pro-inflammatory functions, in the outer regions. While neuronal inflammation is common in various central nervous system disorders, the specific inflammatory pathways linked with different immune-mediated cell types and the various factors influencing the blood-brain barrier significantly contribute to disease-specific characteristics.

Mechanisms of emerging resistance associated with non-antibiotic antimicrobial agents: a state-of-the-art review.

Although the development of resistance by microorganisms to antimicrobial drugs has been recognized as a global public health concern, the contribution of various non-antibiotic antimicrobial agents to the development of antimicrobial resistance (AMR) remains largely neglected. The present review discusses various chemical substances and factors other than typical antibiotics, such as preservatives, disinfectants, biocides, heavy metals and improper chemical sterilization that contribute to the development of AMR. Furthermore, it encompasses the mechanisms like co-resistance and co-selection, horizontal gene transfer, changes in the composition and permeability of cell membrane, efflux pumps, transposons, biofilm formation and enzymatic degradation of antimicrobial chemicals which underlie the development of resistance to various non-antibiotic antimicrobial agents.

Recent Advancements in Topical Anti-Psoriatic Nanostructured Lipid Carrier-Based Drug Delivery.

Psoriasis is linked with unusual differentiation and hyperproliferation of epidermal keratinocytes that significantly impair the quality of life (QoL) of patients. The present treatment options only provide symptomatic relief and are surrounded by various adverse effects. Recently, nanostructured lipid carriers (NLCs) have emerged as next-generation nanocarriers with better physicochemical characteristics.

Ghrelin alleviates depression-like behaviour in rats subjected to high-fat diet and diurnal rhythm disturbance.

Objectives: In the era of globalization, a sedentary lifestyle is highly linked with obesity and neurobehavioral complications such as depression. While depression is associated with dopamine dysfunction in the ventral tegmental area (VTA), ghrelin enhances the dopaminergic activity in the VTA. Therefore, the present study aimed to assess the effect of ghrelin on depression-like behaviour in rats subjected to a high-fat diet (HFD) and disturbed diurnal rhythm (DDR) for 45 days.

Therapeutic Potential and Pharmaceutical Development of a Multitargeted Flavonoid Phloretin.

Phloretin is a flavonoid of the dihydrogen chalcone class, present abundantly in apples and strawberries. The beneficial effects of phloretin are mainly associated with its potent antioxidant properties. Phloretin modulates several signaling pathways and molecular mechanisms to exhibit therapeutic benefits against various diseases including cancers, diabetes, liver injury, kidney injury, encephalomyelitis, ulcerative colitis, asthma, arthritis, and cognitive impairment.

Verapamil hydrochloride loaded solid lipid nanoparticles: Preparation, optimization, characterisation, and assessment of cardioprotective effect in experimental model of myocardial infarcted rats.

Verapamil, a calcium channel blocker has poor bioavailability (20-30%) owing to extensive hepatic first-pass metabolism. Hence, the major objective of this research was to improve the oral bioavailability of Verapamil by Solid Lipid Nanoparticles (V-SLNs) using high shear homogenization and ultrasonication technology. A 3 factorial design was employed to statistically optimize the formulation to get minimum particle size with maximum entrapment efficiency.

Thymoquinone Produces Cardioprotective Effect in β-Receptor Stimulated Myocardial Infarcted Rats via Subsiding Oxidative Stress and Inflammation.

Earlier studies reported that long-term treatment with thymoquinone (TQ) at a high dose (20 mg/kg) exerts a cardioprotective effect against isoproterenol (ISO)-triggered myocardial infarction (MI) in rats. In the present study, we tested the hypothesis that TQ, as a potent molecule, can exhibit cardioprotective effects at the lower dose for a short-term regimen. The rats were administered with TQ (5 mg/kg, intraperitoneal) at the 4 h interval for 2 days.

Curcumin Protects Diabetic Mice against Isoproterenol-Induced Myocardial Infarction by Modulating CB2 Cannabinoid Receptors.

Molecular docking revealed curcumin as a potent CB2 cannabinoid receptor (CB2R) agonist. Since CB2R is involved in cardioprotective functions, we explored its role in ameliorative actions of curcumin against myocardial damage triggered by isoproterenol in diabetic animals. Mice were kept on a high-fat diet (HFD) throughout the experiment (30 days).

Health Benefits, Pharmacological Effects, Molecular Mechanisms, and Therapeutic Potential of α-Bisabolol.

α-Bisabolol is one of the important monocyclic sesquiterpenes, derived naturally from essential oils of many edible and ornamental plants. It was first obtained from , commonly known as chamomile or German chamomile. The available literature indicates that this plant along with other α-Bisabolol containing plants is popularly used in traditional medicine for potential health benefits and general wellbeing.

and characterization of Entacapone-loaded nanostructured lipid carriers developed by quality-by-design approach.

Entacapone, a reversible catechol-o-methyl transferase inhibitor, is used to enhance the action of dopamine agonists by reducing their metabolism and the 'Wearing-off' effects associated with long-term use in the treatment of Parkinson's disease. It is used as an adjunct to levodopa/Carbidopa therapy. Due to limited dissolution and first-pass clearance, it suffers low and variable bioavailability issues.