Mechanistic Insights into the Anticancer Potential of Methoxyflavones Analogs: A Review.

2-phenylchromen-4-one, commonly known as flavone, plays multifaceted roles in biological response that can be abundantly present in natural sources. The methoxy group in naturally occurring flavones promotes cytotoxic activity in various cancer cell lines by targeting protein markers, in facilitating ligand-protein binding mechanisms and activating cascading downstream signaling pathways leading to cell death. However, the lipophilic nature of these analogs is a key concern as it impacts drug membrane transfer.

Multivariate Statistical Analyses of the Temporal Variation in the Chemical Composition of the Essential Oil of in Cyprus.

The genus L'Hér., is native to Australia with 61 introduced taxa in Cyprus, including Luehm., which has a wide distribution on the island.

Quantitative Structure-Activity Relationship (QSAR) Modeling of Chiral CCR2 Antagonists with a Multidimensional Space of Novel Chirality Descriptors.

The development of chirality descriptors for quantitative chirality structure-activity relationship (QCSAR) modeling has always attracted attention, owing to the importance of chiral molecules in pharmaceutical, agriculture, food, and fragrance industries, and environmental toxicology. The utility of a multidimensional space of novel relative chirality indices (RCIs) in the QCSAR modeling of twenty CCR2 antagonists is reported upon in this paper. The numerical characterization of chirality by the RCI approach gives a large pool of chirality descriptors with different degrees of mutual correlation (the correlation coefficient among the computed descriptors varied from 0.

Insights into the Mode of Action of Novel Morpholinated Curcumin Derivatives Exhibiting Potent Antitumor Activity in Bladder Cancer Cells In Vitro.

Although curcumin is a well-known natural polyphenol with many biological activities, its clinical application has been limited by low aqueous solubility and stability. Therefore, curcumin derivatives have been proposed to overcome these limitations and increase anticancer activity. This study tested curcumin derivatives with modified feruloyl moieties ( and ) and the β-diketo moiety () to better understand their anticancer mechanism against human bladder cancer cells.

Uncovering the Metabolic Footprint of New Psychoactive Substances by Metabolomics: A Systematic Review.

New psychoactive substances (NPSs) emerged in the 2000s as legal alternatives to illicit drugs and quickly became a huge public health threat due to their easy accessibility online, limited information, and misleading labels. Synthetic cannabinoids and synthetic cathinones are the most reported groups of NPSs. Despite NPSs being widely studied, due to their structural diversity and the constant emergence of novel compounds with unknown properties, the development of new techniques is required to clarify their mode of action and evaluate their toxicological effects.

Multipotent Effect of Clozapine on Lipopolysaccharide-Induced Acetylcholinesterase, Cyclooxygenase-2,5-Lipoxygenase, and Caspase-3: In Vivo and Molecular Modeling Studies.

Dual inhibition of cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) is a recognized strategy for enhanced anti-inflammatory effects in small molecules, offering potential therapeutic benefits for individuals at risk of dementia, particularly those with neurodegenerative diseases, common cancers, and diabetes type. Alzheimer's disease (AD) is the most common cause of dementia, and the inhibition of acetylcholinesterase (AChE) is a key approach in treating AD. Meanwhile, Caspase-3 catalyzes early events in apoptosis, contributing to neurodegeneration and subsequently AD.

A Novel Approach for In Vitro Testing and Hazard Evaluation of Nanoformulated RyR2-Targeting siRNA Drugs Using Human PBMCs.

Nucleic acid (NA)-based drugs are promising therapeutics agents. Beyond efficacy, addressing safety concerns-particularly those specific to this class of drugs-is crucial. Here, we propose an in vitro approach to screen for potential adverse off-target effects of NA-based drugs.

The Potential Effect of Bualuang (White Gaertn.) Extract on Sperm Quality and Metabolomic Profiles in Mancozeb-Induced Oxidative Stress in Male Rats.

Mancozeb (MZ), an EBDC fungicide, has been found to contaminate agricultural products and cause male reproductive toxicity. The phytochemical compounds of white petal extract (WNPE) and its effects on metabolomic profiles and reproductive function in male rats poisoned with MZ were investigated. Seventy-two mature male Wistar rats were divided into nine groups ( = 8) and, for 30 days, were gavaged with WNPE at doses of 0.

The Role of microRNA-22 in Metabolism.

microRNA-22 (miR-22) plays a pivotal role in the regulation of metabolic processes and has emerged as a therapeutic target in metabolic disorders, including obesity, type 2 diabetes, and metabolic-associated liver diseases. While miR-22 exhibits context-dependent effects, promoting or inhibiting metabolic pathways depending on tissue and condition, current research highlights its therapeutic potential, particularly through inhibition strategies using chemically modified antisense oligonucleotides. This review examines the dual regulatory functions of miR-22 across key metabolic pathways, offering perspectives on its integration into next-generation diagnostic and therapeutic approaches while acknowledging the complexities of its roles in metabolic homeostasis.

Toxicology Effects of Cadmium in : Accumulation, Oxidative Stress, Microbial Community, and Transcriptome Analysis.

Cadmium (Cd) pollution poses an important problem, but limited information is available about the toxicology effects of Cd on freshwater invertebrates. We investigated the accumulation, oxidative stress, microbial community changes, and transcriptomic alterations in apple snails ) under Cd stress. The snails were exposed to the 10 μg/L Cd solution for 16 days, followed by a 16-day elimination period.

Glucagon Can Increase Force of Contraction via Glucagon Receptors in the Isolated Human Atrium.

Glucagon can increase the force of contraction (FOC) in, for example, canine hearts. Currently, whether glucagon can also increase the FOC via cAMP-increasing receptors in the human atrium is controversial discussed. Glucagon alone did not (up to 1 µM) raise the FOC in human right atrial preparations (HAP).

Intermediates of Hydrogen Peroxide-Assisted Photooxidation of Salicylic Acid: Their Degradation Rates and Ecotoxicological Assessment.

Accelerated photooxidation of salicylic acid (SA) was performed using UV radiation and hydrogen peroxide. HPLC-MS analysis showed that the primary intermediates are 2,5-dihydroxybenzoic acid, 2,3-dihydroxybenzoic acid, pyrocatechol, and phenol. Deeper oxidation leads to low molecular weight aliphatic acids, such as maleic, fumaric, and glyoxylic.

AJCR4: A Potential Probiotic in the Fight Against Oral spp. Biofilms.

Oral candidiasis is one of the most common infections in the immunocompromised. Biofilms of species can make treatments difficult, leading to oral infection recurrence. This research aimed to isolate a with anti- effects from the oral cavity.

Ferroptosis Inducers Erastin and RSL3 Enhance Adriamycin and Topotecan Sensitivity in ABCB1/ABCG2-Expressing Tumor Cells.

Acquired resistance to chemotherapeutic drugs is the primary cause of treatment failure in the clinic. While multiple factors contribute to this resistance, increased expression of ABC transporters-such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance proteins-play significant roles in the development of resistance to various chemotherapeutics. We found that Erastin, a ferroptosis inducer, was significantly cytotoxic to NCI/ADR-RES, a P-gp-expressing human ovarian cancer cell line.

Impact of Larval Sertraline Exposure on Alternative Splicing in Neural Tissue of Adult .

Sertraline, a selective serotonin reuptake inhibitor (SSRI), is commonly used to treat various psychiatric disorders such as depression and anxiety due to its ability to increase serotonin availability in the brain. Recent findings suggest that sertraline may also influence the expression of genes related to synaptic plasticity and neuronal signaling pathways. Alternative splicing, a process that allows a single gene to produce multiple protein isoforms, plays a crucial role in the regulation of neuronal functions and plasticity.

The Rise of Fentanyl: Molecular Aspects and Forensic Investigations.

Fentanyl is a synthetic opioid widely used for its potent analgesic effects in chronic pain management and intraoperative anesthesia. However, its high potency, low cost, and accessibility have also made it a significant drug of abuse, contributing to the global opioid epidemic. This review aims to provide an in-depth analysis of fentanyl's medical applications, pharmacokinetics, metabolism, and pharmacogenetics while examining its adverse effects and forensic implications.

Alveolar Rhabdomyosarcoma of Nasopharynx and Paranasal Sinuses in Children Diagnosis and Treatment-Review of the Literature and Case Report.

Alveolar rhabdomyosarcoma (aRMS) is a rare pediatric malignant tumor with a poor prognosis, particularly when located in the rhinopharynx and sphenoidal floor, which complicates diagnosis and increases the risk of misclassification as benign growths. The specific genotype of aRMS is associated with a worse clinical outcome. In young children, especially those aged 4 to 12 years, rhinopharyngeal masses are often attributed to chronic adenoiditis; however, other benign (e.

The Impact of the Metabolic Syndrome Severity on the Appearance of Primary and Permanent DNA Damage.

The prevalence of metabolic syndrome (MetS) worldwide is rapid and significant on a global scale. A 2022 meta-analysis of data from 28 million individuals revealed a global prevalence of 45.1%, with notably higher rates in the Eastern Mediterranean Region and the Americas, particularly in high-income countries.

Development and Application of PSCPL13 Probiotics in Olive Flounder () Farming.

Aquaculture has grown significantly, contributing to global food security and sustainability; however, intensified fish farming has increased disease susceptibility and antibiotic resistance. This study assessed the probiotic potential of PSCPL13 (hereafter, PSCPL13), isolated from the intestines of Japanese eels, for enhancing the health of olive flounder. After screening 16 isolates, PSCPL13 was selected because of its potential broad-spectrum antibacterial activity against many pathogens, such as and .

Proteomic Profiling Towards a Better Understanding of Genetic Based Muscular Diseases: The Current Picture and a Look to the Future.

Proteomics accelerates diagnosis and research of muscular diseases by enabling the robust analysis of proteins relevant for the manifestation of neuromuscular diseases in the following aspects: (i) evaluation of the effect of genetic variants on the corresponding protein, (ii) prediction of the underlying genetic defect based on the proteomic signature of muscle biopsies, (iii) analysis of pathophysiologies underlying different entities of muscular diseases, key for the definition of new intervention concepts, and (iv) patient stratification according to biochemical fingerprints as well as (v) monitoring the success of therapeutic interventions. This review presents-also through exemplary case studies-the various advantages of mass proteomics in the investigation of genetic muscle diseases, discusses technical limitations, and provides an outlook on possible future application concepts. Hence, proteomics is an excellent large-scale analytical tool for the diagnostic workup of (hereditary) muscle diseases and warrants systematic profiling of underlying pathophysiological processes.

The Proapoptotic Effect of MB-653 Is Associated with the Modulation of Metastasis and Invasiveness-Related Signalling Pathways in Human Colorectal Cancer Cells.

Colorectal cancer is one of the most common cancers worldwide and has a high mortality rate. In this study, we investigated the cytotoxic, proapoptotic, and anti-invasive effects of the synthetic indole phytoalexin MB-653. The antiproliferative effect was determined using an MTT assay, showing IC values of 5.

Epigenetic Regulation of Stromal and Immune Cells and Therapeutic Targets in the Tumor Microenvironment.

The tumor microenvironment (TME) plays a pivotal role in neoplastic initiation and progression. Epigenetic machinery, governing the expression of core oncogenes and tumor suppressor genes in transformed cells, significantly contributes to tumor development at both primary and distant sites. Recent studies have illuminated how epigenetic mechanisms integrate external cues and downstream signals, altering the phenotype of stromal cells and immune cells.

Effects of Semaglutide Treatment on Psoriatic Lesions in Obese Patients with Type 2 Diabetes Mellitus: An Open-Label, Randomized Clinical Trial.

Psoriasis is a chronic inflammatory skin disease with relapsing nature. Estimates are that approximately 2-3% of the world's population suffers from this disease. More severe forms of psoriasis are conditions of high inflammation, which is confirmed by the clinical picture and numerous inflammatory parameters such as C-reactive protein (CRP), cytokines and homocysteine, which vary with disease activity.

G Protein-Coupled Receptor 17 Inhibits Glucagon-like Peptide-1 Secretion via a Gi/o-Dependent Mechanism in Enteroendocrine Cells.

Gut peptides, including glucagon-like peptide-1 (GLP-1), regulate metabolic homeostasis and have emerged as the basis for multiple state-of-the-art diabetes and obesity therapies. We previously showed that G protein-coupled receptor 17 (GPR17) is expressed in intestinal enteroendocrine cells (EECs) and modulates nutrient-induced GLP-1 secretion. However, the GPR17-mediated molecular signaling pathways in EECs have yet to be fully deciphered.

Antimicrobial Susceptibility Profiles of Commensal spp. Isolates from Chickens in Hungarian Poultry Farms Between 2022 and 2023.

Background: Antimicrobial resistance is one of the greatest challenges of our time, urging researchers in both veterinary and public health to engage in collaborative efforts, thereby fostering the One Health approach. Infections caused by species can not only lead to significant diseases in poultry but also pose serious threats to human life, particularly in hospital (nosocomial) infections; therefore, it is crucial to identify their antimicrobial resistance.

Methods: Our objective was to assess the susceptibility profile of commensal strains ( = 227) found in commercial chicken flocks in Hungary through the determination of minimum inhibitory concentration (MIC) values.