Harnessing the Power of Machine Learning Guided Discovery of NLRP3 Inhibitors Towards the Effective Treatment of Rheumatoid Arthritis.

The NLRP3 inflammasome, plays a critical role in the pathogenesis of rheumatoid arthritis (RA) by activating inflammatory cytokines such as IL1β and IL18. Targeting NLRP3 has emerged as a promising therapeutic strategy for RA. In this study, a multidisciplinary approach combining machine learning, quantitative structure-activity relationship (QSAR) modeling, structure-activity landscape index (SALI), docking, molecular dynamics (MD), and molecular mechanics Poisson-Boltzmann surface area MM/PBSA assays was employed to identify novel NLRP3 inhibitors.

In vivo antitumor activity of PHT-427 inhibitor-loaded polymeric nanoparticles in head and neck squamous cell carcinoma.

Recent studies on head and neck squamous cell carcinoma (HNSCC) tumorigenesis have revealed several dysregulated molecular pathways. The phosphatidylinositol-3-kinase (PI3K) signaling pathway is frequently activated in HNSCC, making it an attractive target for therapies. PHT-427 is a dual inhibitor of PI3K and the mammalian target of AKT/PDK1.

Combination of dapagliflozin and pioglitazone lacks superiority against monotherapy in streptozotocin-induced nephropathy.

Oxidative stress and apoptosis are highly engaged in development of diabetic nephropathy (DN). In monotherapy, dapagliflozin and pioglitazone positively modulate target organ damage even independently of their hypoglycaemic effect. This study evaluated whether a simultaneous PPARγ activation and SGLT cotransporter inhibition offer superior protection against DN-related oxidative and apoptotic processes in a T1DM rat model.

New insight into the protective effect of Citrullus colocynthis loaded with ZnONP cream on glutaraldehyde-induced dermatitis in health care workers.

Glutaraldehyde (GLU) is mainly used in medicine by healthcare workers during infection control as a chemical disinfectant. It has been linked to numerous health hazards that range from asthma to irritation of the eye to contact dermatitis. Citrullus colocynthis (C.

ACNO hydrogel enhances diabetic wound healing by modulating the Bcl-2/Bax/Caspase-3/PARP pathway.

Centella asiatica (L.) Urban, one of the authentic medicinal materials from Guizhou Province in China, has been traditionally applied for the treatment of contusions and fractures, as well as for promoting wound healing. Preliminary research suggests that asiaticoside-nitric oxide hydrogel (ACNO) exhibits the potential to enhance the healing of diabetic wounds (DWs); however, the underlying molecular mechanisms require further elucidation.

Exploration of the Mechanism of Tanre Qing Injection in Treating Acute Respiratory Distress Syndrome through Network Pharmacology, Molecular Docking, and Animal Experiments.

Objective: This study aimed to explore the active components and potential mechanism of Tanre Qing Injection (TRQI) in the treatment of Acute Respiratory Distress Syndrome (ARDS) using network pharmacology, molecular docking, and animal experiments.

Methods: The targets of active ingredients were identified using the TCMSP and Swiss Target Prediction databases. The targets associated with ARDS were obtained from the GeneCards database, Mala card database, and Open Targets Platform.

Functional evaluation and clinical classification of BRCA2 variants.

Germline BRCA2 loss-of function variants, which can be identified through clinical genetic testing, predispose to several cancers. However, variants of uncertain significance limit the clinical utility of test results. Thus, there is a need for functional characterization and clinical classification of all BRCA2 variants to facilitate the clinical management of individuals with these variants.

Network pharmacological mechanism and molecular experimental validation of artemisinin in the treatment of lung adenocarcinoma.

Background: Lung cancer is a medical ailment with high mortality and prevalence rates. Artemisinin (ART) and its derivatives exhibit anti-cancer properties against various malignancies, including lung cancer. However, further research is required to determine the precise anti-cancer mechanisms of ART.

Clinical and preclinical evidence of psilocybin as antidepressant. A narrative review.

In the rapidly growing field of psychedelic research, psilocybin (and active metabolite psilocin) has been proposed as a promising candidate in the search for novel treatments for neuropsychiatric disorders. Clinical trials have revealed that psilocybin has a large, rapid, and persistent effect in the improvement of symptoms of depression and anxiety. The safety profile is considered favourable, with low toxicity and good tolerance.

Aspirin-triggered resolvin D1 modulates pulmonary and neurological inflammation in an IL-22 knock-out organic dust exposure mouse model.

Agriculture dust contains many organic immunogenic compounds, and organic dust exposure is strongly associated with the development of immune-mediated chronic pulmonary diseases such as chronic obstructive pulmonary disease (COPD). Chronic organic dust exposure from agriculture sources induces chronic lung inflammatory diseases and organic dust exposure has recently been linked to an increased risk of developing dementia. The cytokine interleukin-22 (IL-22) has been established as an important mediator in the resolution and repair of lung tissues.

Targeting necroptosis in MCF-7 breast cancer cells: In Silico insights into 8,12-dimethoxysanguinarine from Eomecon Chionantha through molecular docking, dynamics, DFT, and MEP studies.

Breast cancer remains a significant challenge in oncology, highlighting the need for alternative therapeutic strategies that target necroptosis to overcome resistance to conventional therapies. Recent investigations into natural compounds have identified 8,12-dimethoxysanguinarine (SG-A) from Eomecon chionantha as a potential necroptosis inducer. This study presents the first computational exploration of SG-A interactions with key necroptotic proteins-RIPK1, RIPK3, and MLKL-through molecular docking, molecular dynamics (MD), density functional theory (DFT), and molecular electrostatic potential (MEP) analyses.

Aerobic exercise and metformin attenuate the cognitive impairment in an experimental model of type 2 diabetes mellitus: focus on neuroinflammation and adult hippocampal neurogenesis.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that increases the prevalence of cognitive impairment in the geriatric population. Aerobic exercise is an excellent non-pharmacological therapeutic strategy to prevent Alzheimer's disease, the most common form of dementia. The exact molecular mechanism of aerobic exercise (Exe) as an intervention to counter cognitive decline is far from clear.

Ligand and Residue Free Energy Perturbations Solve the Dual Binding Mode Proposal for an AAR Partial Agonist.

Adenosine receptors, particularly AAR, are gaining attention for their role in pathological conditions such as cancer immunotherapy, prompting the exploration for promising therapeutic applications. Despite numerous selective AAR antagonists, the lack of selective full agonists makes the partial agonist BAY60-6583 one of the most interesting activators of this receptor. Recent cryo-EM structures have univocally revealed the binding mode of nonselective ribosidic agonists such as adenosine and its derivative NECA to AAR; however, two independent structures with BAY60-6583 show alternative binding orientations, raising the question of which is the physiologically relevant binding mode.

Investigation into the Potential Mechanism of Radix Paeoniae Rubra Against Ischemic Stroke Based on Network Pharmacology.

Background: Radix Paeoniae Rubra (RPR), an edible and medicinal Traditional Chinese Medicine (TCM), is extensively employed in therapeutic interventions of cardiovascular and cerebrovascular diseases. However, the curative effect of RPR on ischemic stroke remains ambiguous. This work integrated network pharmacology, molecular docking, and experimental validation to explore the mechanisms of RPR in treating ischemic stroke.

From Tea to Functional Foods: Exploring Bunge for Anti-Rheumatoid Arthritis and Unraveling Its Potential Mechanisms.

Background: Bunge (CM) shows promising potential for managing rheumatoid arthritis (RA) and digestive disorders, attributed to its rich content of bioactive compounds such as polyphenols and flavonoids. Despite its common use in herbal tea, the specific mechanisms underlying CM's anti-inflammatory and joint-protective effects remain unclear, limiting its development as a functional food. This study investigated the effects of aqueous CM extract on RA in collagen-induced arthritis (CIA) rats and explored the underlying mechanisms.

The Effect of Quercetin on Non-Alcoholic Fatty Liver Disease (NAFLD) and the Role of Beclin1, P62, and LC3: An Experimental Study.

Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder with no established pharmacotherapy. Quercetin, a polyphenolic flavonoid, demonstrates potential hepatoprotective effects but has limited bioavailability. This study evaluates the impact of quercetin on NAFLD and assesses the roles of autophagy-related proteins in disease progression.

Phytochemical Profiling and Bioactivity Assessment of L. Essential Oil and Extracts: Experimental and In Silico Insights.

L., a member of the Lamiaceae family, is widely used in traditional medicine for its therapeutic properties. This study aims to analyze the chemical composition of its essential oil and extracts, evaluate their antimicrobial and antioxidant activities, and investigate the interactions of their bioactive compounds with biological targets using in silico methods to better understand their mechanisms of action.

Anti-Inflammatory Potential of 3-Hydroxy-β-Ionone from Decreased Transendothelial Migration of Monocytes Through an Inflamed Human Endothelial Cell Monolayer by Inhibiting the IκB-α/NF-κB Signaling Pathway.

Moringa leaves provide numerous health benefits due to their anti-inflammatory properties. This study presents the first evidence that endothelial cell inflammation can potentially be ameliorated by moringa leaf extract. Here, we established an experimental human blood vessel cell model of inflammation using EA.

Targeting EZH2 in Cancer: Mechanisms, Pathways, and Therapeutic Potential.

Enhancer of zeste homolog 2 (EZH2) is a methyltransferase involved in cell cycle regulation, cell differentiation, and cell death and plays a role in modulating the immune response. Although it mainly functions by catalyzing the tri-methylation of H3 histone on K27 (H3K27), to inhibit the transcription of target genes, EZH2 can directly methylate several transcription factors or form complexes with them, regulating their functions. EZH2 expression/activity is often dysregulated in cancer, contributing to carcinogenesis and immune escape, thereby representing an important target in anti-cancer therapy.

Molecular Docking and Experimental Analysis of Essential Oil-Based Preparations on Biofilm Formation on Orthodontic Archwires.

Good oral hygiene is crucial during treatment with fixed appliances, emphasising the need for additional or alternative oral health methods during orthodontic treatment. This study investigates the effect of essential oil (EO)-based preparations on biofilm adhesion to orthodontic archwires. Five identical-sized orthodontic archwires of different materials were tested using therapeutic and preventive applications of essential oils.

The Comparative Effects of Anakinra and Tocilizumab on Inflammation and Cerebral Vasospasm in an Experimental Subarachnoid Hemorrhage Model.

: Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular condition that triggers a robust inflammatory response and cerebral vasospasm. This study aimed to evaluate the effects of anakinra, an interleukin-1 receptor antagonist, and tocilizumab, an interleukin-6 receptor antagonist, on inflammation and vasospasm in an experimental rat SAH model. : Forty male Sprague Dawley rats (200-250 g) were randomly assigned to five groups: control, SAH, SAH + anakinra (ANA), SAH + tocilizumab (TCZ), and SAH + anakinra + tocilizumab (ANA+TCZ).

The Chemokine System as a Key Regulator of Pulmonary Fibrosis: Converging Pathways in Human Idiopathic Pulmonary Fibrosis (IPF) and the Bleomycin-Induced Lung Fibrosis Model in Mice.

Idiopathic pulmonary fibrosis (IPF) is a chronic and lethal interstitial lung disease (ILD) of unknown origin, characterized by limited treatment efficacy and a fibroproliferative nature. It is marked by excessive extracellular matrix deposition in the pulmonary parenchyma, leading to progressive lung volume decline and impaired gas exchange. The chemokine system, a network of proteins involved in cellular communication with diverse biological functions, plays a crucial role in various respiratory diseases.

Impact of Long-Term Cannabidiol (CBD) Treatment on Mouse Kidney Transcriptome.

Background: Cannabidiol, which is one of the main cannabinoids present in plants, has been shown to have therapeutic properties, including anti-inflammatory and antioxidant effects that may be useful for treatment of various kidney conditions.

Objectives: This article investigates the effect of long-term cannabidiol (CBD) treatment on changes in the renal transcriptome in a mouse model. The main hypothesis was that systematic CBD treatment would affect gene expression associated with those processes in the kidney.

Tumor-Infiltrating Immune Cells and HLA Expression as Potential Biomarkers Predicting Response to PD-1 Inhibitor Therapy in Stage IV Melanoma Patients.

PD-1 inhibitors are known to be effective in melanoma; however, a considerable proportion of patients fail to respond to therapy, necessitating the identification of predictive markers. We examined the predictive value of tumor cell HLA class I and II expression and immune cell infiltration in melanoma patients treated with PD-1 inhibitors. Pretreatment surgical samples from 40 stage IV melanoma patients were studied immunohistochemically for melanoma cell expression of HLA class I molecules (using four antibody clones with different specificities), HLA-II, and immune cell infiltration (using a panel of 10 markers).

Elucidating the mechanism of stigmasterol in acute pancreatitis treatment: insights from network pharmacology and / experiments.

Introduction: Acute pancreatitis (AP) is a severe inflammatory disease of the pancreas that could trigger a systemic inflammation and multi-organ dysfunction. Stigmasterol, a natural plant sterol found in various herbs and vegetables, exhibits a significant anti-inflammatory, antioxidant, and cholesterol-lowering effects. However, its therapeutic potential in AP have not been thoroughly investigated.