Resveratrol-Based Carbamates as Selective Butyrylcholinesterase Inhibitors: Design, Synthesis, Computational Study and Biometal Complexation Capability.

Considering our previous experience in the design of new cholinesterase inhibitors, especially resveratrol analogs, in this research, the basic stilbene skeleton was used as a structural unit for new carbamates designed as potentially highly selective butyrylcholinesterase (BChE) inhibitors with excellent absorption, distribution, metabolism, excretion and toxicity ADMET properties. The inhibitory activity of newly prepared carbamates - was tested toward the enzymes acetylcholinesterase (AChE) and BChE. In the tested group of compounds, the leading inhibitors were and , which achieved excellent selective inhibitory activity for BChE with IC values of 0.

Synthesis, Antimalarial Activity and Molecular Dynamics Studies of Pipecolisporin: A Novel Cyclic Hexapeptide with Potent Therapeutic Potential.

Malaria, caused by species and transmitted by mosquitoes, continues to pose a significant global health threat. Pipecolisporin, a cyclic hexapeptide isolated from , has emerged as a promising antimalarial candidate due to its potent biological activity and stability. This study explores the synthesis, antimalarial activity, and computational studies of pipecolisporin, aiming to better understand its therapeutic potential.

Enhancing HDAC Inhibitor Screening: Addressing Zinc Parameterization and Ligand Protonation in Docking Studies.

Precise binding free-energy predictions for ligands targeting metalloproteins, especially zinc-containing histone deacetylase (HDAC) enzymes, require specialized computational approaches due to the unique interactions at metal-binding sites. This study evaluates a docking algorithm optimized for zinc coordination to determine whether it could accurately differentiate between protonated and deprotonated states of hydroxamic acid ligands, a key functional group in HDAC inhibitors (HDACi). By systematically analyzing both protonation states, we sought to identify which state produces docking poses and binding energy estimates most closely aligned with experimental values.

Proteins and DNA Sequences Interacting with Tanshinones and Tanshinone Derivatives.

Tanshinones, biologically active diterpene compounds derived from , interact with specific proteins and DNA sequences, influencing signaling pathways in animals and humans. This study highlights tanshinone-protein interactions observed at concentrations achievable in vivo, ensuring greater physiological relevance compared to in vitro studies that often employ supraphysiological ligand levels. Experimental data suggest that while tanshinones interact with multiple proteomic targets, only a few enzymes are significantly affected at biologically relevant concentrations.

Single-Cell RNA-Seq Uncovers Robust Glial Cell Transcriptional Changes in Methamphetamine-Administered Mice.

Methamphetamine is a highly addictive stimulant known to cause neurotoxicity, cognitive deficits, and immune dysregulation in the brain. Despite significant research, the molecular mechanisms driving methamphetamine-induced neurotoxicity and glial cell dysfunction remain poorly understood. This study investigates how methamphetamine disrupts glial cell function and contributes to neurodevelopmental and neurodegenerative processes.

Onvansertib and Navitoclax Combination as a New Therapeutic Option for Mucinous Ovarian Carcinoma.

Mucinous epithelial ovarian cancer (mEOC) is a rare subtype of epithelial ovarian cancer, characterized by poor responses to standard platinum-based chemotherapy. Polo-like kinase 1 (PLK1) is a key regulator of mitosis and cell cycle progression and its inhibition has been recently identified as a target in mEOC. In this study, we aimed to identify further therapeutic targets in mEOC using a CRISPR/Cas9 library targeting 3015 genes, with and without treatment with onvansertib, a PLK1 inhibitor.

Importance of Modulating Kynurenic Acid Metabolism-Approaches for the Treatment of Dementia.

In this article, we focus on kynurenic acid metabolism in neuropsychiatric disorders and the biochemical processes involved in memory and cognitive impairment, followed by different approaches in the fight against dementia. Kynurenic acid-a biochemical part of L-tryptophan catabolism-is synthesized from L-kynurenine by kynurenine aminotransferases. Experimental pharmacological studies have shown that elevated levels of kynurenic acid in the brain are associated with impaired learning and that lowering kynurenic acid levels can improve these symptoms.

The Intersection of Epigenetics and Senolytics in Mechanisms of Aging and Therapeutic Approaches.

The biological process of aging is influenced by a complex interplay of genetic, environmental, and epigenetic factors. Recent advancements in the fields of epigenetics and senolytics offer promising avenues for understanding and addressing age-related diseases. Epigenetics refers to heritable changes in gene expression without altering the DNA sequence, with mechanisms like DNA methylation, histone modification, and non-coding RNA regulation playing critical roles in aging.

Angiotensin IV Receptors in the Rat Prefrontal Cortex: Neuronal Expression and NMDA Inhibition.

Background: N-methyl-D-aspartate type glutamate receptors (NMDARs) are fundamental to neuronal physiology and pathophysiology. The prefrontal cortex (PFC), a key region for cognitive function, is heavily implicated in neuropsychiatric disorders, positioning the modulation of its glutamatergic neurotransmission as a promising therapeutic target. Our recently published findings indicate that AT receptor activation enhances NMDAR activity in layer V pyramidal neurons of the rat PFC.

In vivo and in silico study of europinidin against streptozotocin-isoproterenol-induced myocardial damage via alteration of hs-CRP/CPK-MB/Caspase-3/Bcl-2 pathways.

Europinidin is a novel anthocyanidin found in the petals of Plumbago europea that exhibits several physiological effects. Research was conducted to assess europinidin's cardioprotective efficacy in a diabetic and myocardial infarction (MI) experimental model. Rat was injected through the intraperitoneal administration of 45 mg/kg of streptozotocin (STZ), while MI was induced by subcutaneously administering 85 mg/kg of isoproterenol (ISP) at 24 and 48 h prior to the sacrifice procedure.

siRNA-mediated inhibition of hTERT enhances the effects of curcumin in promoting cell death in precursor-B acute lymphoblastic leukemia cells: an in silico and in vitro study.

This study investigates the interrelationship between human telomerase reverse transcriptase (hTERT) and ferroptosis in precursor-B (pre-B) acute lymphoblastic leukemia (ALL), specifically examining how hTERT modulation affects ferroptotic cell death pathways. Given that hTERT overexpression characterizes various cancer phenotypes and elevated telomerase activity is observed in early-stage and relapsed ALL, we investigated the molecular mechanisms linking hTERT regulation and ferroptosis in leukemia cells. The experimental design employed Nalm-6 and REH cell lines under three distinct conditions: curcumin treatment, hTERT siRNA knockdown, and their combination.

Corticolimbic circuitry as a druggable target in schizophrenia spectrum disorders: a narrative review.

Schizophrenia spectrum disorders (SSD) involve disturbances in the integration of perception, emotion and cognition. The corticolimbic system is an interacting set of cortical and subcortical brain regions critically involved in this process. Understanding how neural circuitry and molecular mechanisms within this corticolimbic system may contribute to the development of not only positive symptoms but also negative and cognitive deficits in SSD has been a recent focus of intense research, as the latter are not adequately treated by current antipsychotic medications and are more strongly associated with poorer functioning and long-term outcomes.

Secondary metabolites of Alternaria alternate appraisal of their SARS-CoV-2 inhibitory and anti-inflammatory potentials.

This study identifies the secondary metabolites from Alternaria alternate and evaluates their ACE-2: Spike RBD (SARS-CoV-2) inhibitory activity confirmed via immunoblotting in human lung microvascular endothelial cells. In addition, their in vitro anti-inflammatory potential was assessed using a cell-based assay in LPS-treated RAW 264.7 macrophage cells.

Indole-3-Lactic Acid Inhibits Doxorubicin-Induced Ferroptosis Through Activating Aryl Hydrocarbon Receptor/Nrf2 Signalling Pathway.

The clinical application of doxorubicin (DOX) is limited due to its cardiotoxicity, which is primarily attributed to its interaction with iron in mitochondria, leading to lipid peroxidation and myocardial ferroptosis. This study aimed to investigate the role of the gut microbiota-derived metabolite, indole-3-lactic acid (ILA), in mitigating DOX-induced cardiotoxicity (DIC). Cardiac function, pathological changes, and myocardial ferroptosis were assessed in vivo.

Influence of Bee Venom on Nociception and Inflammatory Cytokine Profiles in Experimental Hyperalgesia.

Hyperalgesia is a condition marked by an abnormal increase in pain sensitivity, often occurring in response to tissue injury, inflammation, or prolonged exposure to certain medications. Inflammatory mediators, such as cytokines IL-1β, IL-6, and TNF-α, play a central role in this process, amplifying pain perception. Developing effective treatments that address the underlying mechanisms of hyperalgesia is an active field of research.

Silymarin as a Therapeutic Agent for Hepatocellular Carcinoma: A Multi-Approach Computational Study.

Background: Hepatocellular carcinoma (HCC) is a prevalent and lethal form of liver cancer with limited treatment options. Silymarin, a flavonoid complex derived from milk thistle, has shown promise in liver disease treatment due to its antioxidant, anti-inflammatory, and anticancer properties. This study aims to explore the therapeutic potential of silymarin in HCC through a comprehensive in silico approach.

A Novel, Cell-Compatible Hyaluronidase Activity Assay Identifies Dextran Sulfates and Other Sulfated Polymeric Hydrocarbons as Potent Inhibitors for CEMIP.

Hyaluronan (HA) levels are dynamically regulated homeostatically through biosynthesis and degradation. HA homeostasis is often perturbed under disease conditions. HA degradation products are thought to contribute to disease pathology.

810-nm Photobiomodulation Evokes Glutamate Release in Normal and Rotenone-Dysfunctional Cortical Nerve Terminals by Modulating Mitochondrial Energy Metabolism.

The dysfunction of mitochondria, the primary source of cellular energy and producer of reactive oxygen species (ROS), is associated with brain aging and neurodegenerative diseases. Scientific evidence indicates that light in the visible and near-infrared spectrum can modulate mitochondrial activity, a phenomenon known in medicine as photobiomodulation therapy (PBM-t). The beneficial effects of PBM-t on dementia and neurodegeneration have been reviewed in the literature.

Exploring the Mechanism of Shi-San-Wei-He-Zhong-Wan in the Treatment of Functional Dyspepsia Based on Network Pharmacology and Experimental Validation.

Purpose: The incidence of Functional Dyspepsia (FD) is gradually increasing, yet there are currently no effective treatment methods available. This study explored the effective components, potential targets, and pathways of Shi-San-Wei-He-Zhong-Wan (SSWHZW) in the treatment of FD, aiming to provide new insights into its treatment.

Methods: First, the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) and GeneCards databases were utilized to identify the major active components of SSWHZW and potential therapeutic targets of FD.

Modified Gegen Qinlian Decoction Ameliorates DSS-Induced Colitis in Mice via the Modulation of NF-B and Nrf2/HO-1 Pathways.

This study aims to reveal the potential molecular mechanisms of modified Gegen Qinlian decoction (MGQD) in relieving ulcerative colitis (UC). C57BL/6J mice were used to establish experimental colitis via dextran sodium sulfate (DSS). Body weight, disease activity index (DAI), spleen weight, colon length, and histopathologic features were measured to evaluate the therapeutic effects of MGQD on mice with UC.

Exploring the ROS-mediated anti-cancer potential in human triple-negative breast cancer by garlic bulb extract: A source of therapeutically active compounds.

Background And Aim: L. has been used medicinally and traditionally since antiquity. This study sought to examine the ethanolic extract (ASEE) in inducing apoptosis in human triple-negative breast cancer (TNBC) MDA-MB-231 cells and the molecular interactions of the identified components with cell death markers using method.

Integrated analysis of bioinformatics, mendelian randomization, and experimental validation reveals novel diagnostic and therapeutic targets for osteoarthritis: progesterone as a potential therapeutic agent.

Background: Osteoarthritis (OA), characterized by progressive degeneration of cartilage and reactive proliferation of subchondral bone, stands as a prevalent condition in orthopedic clinics. However, the precise mechanisms underlying OA pathogenesis remain inadequately explored.

Methods: In this study, Random Forest (RF), Least Absolute Shrinkage and Selection Operator (LASSO), and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) machine learning techniques were employed to identify hub genes.

Huaier inhibits the proliferation and migration of gastrointestinal stromal tumors by regulating the JAK2 / STAT3 signaling pathway.

Ethnopharmacological Relevance: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the digestive tract, often accompanied by a high risk of recurrence and drug resistance. Huaier (Trametes robiniophila Murr), a traditional Chinese medicinal fungus, has demonstrated potent anticancer properties and is widely used as an adjuvant treatment for liver, breast, gastric, colon, and non-small cell lung cancers. However, its effects and molecular mechanisms in GIST remain unclear.

The interplay between chromatin remodeling and DNA double-strand break repair: Implications for cancer biology and therapeutics.

Proper chromatin remodeling is crucial for many cellular physiological processes, including the repair of DNA double-strand break (DSB). While the mechanism of DSB repair is well understood, the connection between chromatin remodeling and DSB repair remains incompletely elucidated. In this review, we aim to highlight recent studies demonstrating the close relationship between chromatin remodeling and DSB repair.

Single-Cell Multi-Omics Profiling of Immune Cells Isolated from Atherosclerotic Plaques in Male ApoE Knockout Mice Exposed to Arsenic.

Background: Millions worldwide are exposed to elevated levels of arsenic that significantly increase their risk of developing atherosclerosis, a pathology primarily driven by immune cells. While the impact of arsenic on immune cell populations in atherosclerotic plaques has been broadly characterized, cellular heterogeneity is a substantial barrier to in-depth examinations of the cellular dynamics for varying immune cell populations.

Objectives: This study aimed to conduct single-cell multi-omics profiling of atherosclerotic plaques in apolipoprotein E knockout () mice to elucidate transcriptomic and epigenetic changes in immune cells induced by arsenic exposure.