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.

Alcohol Consumption and Autoimmune Diseases.

Alcohol is the second-most misused substance after tobacco. It has been identified as a causal factor in more than 200 diseases and 5.3% of all deaths and is associated with significant behavioral, social, and economic difficulties.

MK-8776 and Olaparib Combination Acts Synergistically in Hepatocellular Carcinoma Cells, Demonstrating Lack of Adverse Effects on Liver Tissues in Ovarian Cancer PDX Model.

Hepatocellular carcinoma (HCC) cells critically depend on PARP1 and CHK1 activation for survival. Combining the PARP inhibitor (PARPi) olaparib with a CHK1 inhibitor (MK-8776, CHK1i) produced a synergistic effect, reducing cell viability and inducing marked oxidative stress and DNA damage, particularly in the HepG2 cells. This dual treatment significantly increased apoptosis markers, including γH2AX and caspase-3/7 activity.

Resilience of Spontaneously Hypertensive Rats to Secondary Insults After Traumatic Brain Injury: Immediate Seizures, Survival, and Stress Response.

Traumatic brain injury (TBI) is one of the primary causes of mortality and disability, with arterial blood pressure being an important factor in the clinical management of TBI. Spontaneously hypertensive rats (SHRs), widely used as a model of essential hypertension and vascular dementia, demonstrate dysfunction of the hypothalamic-pituitary-adrenal axis, which may contribute to glucocorticoid-mediated hippocampal damage. The aim of this study was to assess acute post-TBI seizures, delayed mortality, and hippocampal pathology in SHRs and normotensive Sprague Dawley rats (SDRs).

The Role of Nutrition, Oxidative Stress, and Trace Elements in the Pathophysiology of Autism Spectrum Disorders.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction, alongside repetitive behaviors, and atypical sensory-motor patterns. The growing prevalence of ASD has driven substantial advancements in research aimed at understanding its etiology, preventing its onset, and mitigating its impact. This ongoing effort necessitates continuous updates to the body of knowledge and the identification of previously unexplored factors.

Re-Sensitization of Resistant Ovarian Cancer SKOV3/CDDP Cells to Cisplatin by Curcumin Pre-Treatment.

A major challenging problem facing effective ovarian cancer therapy is cisplatin resistance. Re-sensitization of cisplatin-resistant ovarian cancer cells to cisplatin (CDDP) has become a critical issue. Curcumin (CUR), the most abundant dietary polyphenolic curcuminoids derived from turmeric (), has achieved previously significant anti-cancer effects against human ovarian adenocarcinoma SKOV-3/CDDP cisplatin-resistant cells by inhibition the gene expression of the antioxidant enzymes (, , , and ), transcription factor and signaling pathway (//).

A Senescent Cluster in Aged Human Hematopoietic Stem Cell Compartment as Target for Senotherapy.

To identify the differences between aged and young human hematopoiesis, we performed a direct comparison of aged and young human hematopoietic stem and progenitor cells (HSPCs). Alterations in transcriptome profiles upon aging between humans and mice were then compared. Human specimens consist of CD34+ cells from bone marrow, and mouse specimens of hematopoietic stem cells (HSCs; Lin- Kit+ Sca1+ CD150+).

Charge Reversal of the Uppermost Arginine in Sliding Helix S4-I Affects Gating of Cardiac Sodium Channel.

Several mutations of the uppermost arginine, R219, in the voltage-sensing sliding helix S4 of cardiac sodium channel Nav1.5 are reported in the ClinVar databases, but the clinical significance of the respective variants is unknown (VUSs). AlphaFold 3 models predicted a significant downshift of S4 in the R219C VUS.

Effect of a Low-Molecular-Weight Allosteric Agonist of the Thyroid-Stimulating Hormone Receptor on Basal and Thyroliberin-Stimulated Activity of Thyroid System in Diabetic Rats.

The approaches to correct thyroid deficiency include replacement therapy with thyroid hormones (THs), but such therapy causes a number of side effects. A possible alternative is thyroid-stimulating hormone (TSH) receptor activators, including allosteric agonists. The aim of this work was to study the effect of ethyl-2-(4-(4-(5-amino-6-(-butylcarbamoyl)-2-(methylthio)thieno[2,3-d]pyrimidin-4-yl)phenyl)--1,2,3-triazol-1-yl) acetate (TPY3m), a TSH receptor allosteric agonist developed by us, on basal and thyroliberin (TRH)-stimulated TH levels and the hypothalamic-pituitary-thyroid (HPT) axis in male rats with high-fat diet/low-dose streptozotocin-induced type 2 diabetes mellitus (T2DM).

Olaparib Combined with DDR Inhibitors Effectively Prevents EMT and Affects miRNA Regulation in -Mutated Epithelial Ovarian Cancer Cell Lines.

Epithelial ovarian cancer (EOC) remains a leading cause of gynecologic cancer mortality. Despite advances in treatment, metastatic progression and resistance to standard therapies significantly worsen patient outcomes. Epithelial-mesenchymal transition (EMT) is a critical process in metastasis, enabling cancer cells to gain invasive and migratory capabilities, often driven by changing miRNA expression involved in the regulation of pathological processes like drug resistance.

Tinostamustine (EDO-S101) and Its Combination with Celecoxib or Temozolomide as a Therapeutic Option for Adult-Type Diffuse Gliomas.

Adult-type diffuse gliomas are characterized by inevitable recurrence and very poor prognosis. Novel treatment options, including multimodal drugs or effective drug combinations, are therefore eagerly awaited. Tinostamustine is an alkylating and histone deacetylase inhibiting molecule with great potential in cancer treatment.

The Modulatory Effect of Selol (Se IV) on Pro-Inflammatory Pathways in RAW 264.7 Macrophages.

Selol is a semi-synthetic mixture of selenized triglycerides. The results of biological studies revealed that Selol exhibits several anticancer effects. However, studies on its potential anti-inflammatory activity are scarce, and underlying signaling pathways are unknown.

Ecometabolomics of Loggerhead Sea Turtles (): The Impact of Age on Metabolomic Profiles.

To investigate the impact of age on the metabolomic profile of loggerhead sea turtles (), this study analyzed 100 plasma samples of individuals across two age groups-50 post-hatchlings and 50 juveniles-from various locations along the Mediterranean coastline. Both targeted and untargeted metabolomic analyses were performed on the samples. Our results demonstrated a significant age-related effect on the metabolomic profiles in both analyses.

Pharmacodynamic Mechanisms of Cicadae Periostracum in Parkinson's Disease: A Metabolomics-Based Study.

Cicadae Periostracum (CP) is a traditional Chinese animal-derived medicine with the potential to treat Parkinson's disease (PD). This study aims to explore the pharmacodynamic mechanisms of CP against PD-based on metabolomics technology and provide a theoretical basis for developing new anti-PD medicine. First, MPP-induced SH-SY5Y cells were used to evaluate the anti-PD activity of CP.

and Variant Alleles Affect Susceptibility to Infection and Severity of -Associated Clinical Manifestations.

Considering the mutual relationship between redox disbalance and inflammation in (HP) infection, we aimed to evaluate whether the polymorphisms in antioxidant glutathione transferases genes ( rs1695, rs1138272, rs4925 and rs156697) modify susceptibility to HP infection, as well as the severity of HP-associated gastric manifestation development. Therefore, GST gene polymorphisms were determined via the appropriate PCR in 101 HP-positive and 107 HP-negative patients. Our results show that carriers of the variant genotype (rs1695) or at least one variant allele (rs1138272) were more prone to the development of HP-positive gastritis compared with reference allele carriers (OR = 3.

Predictive Factors Associated with Inappropriate Intravenous Proton Pump Inhibitors Use in Hospitalized Patients: A Case-Control Study.

: Proton Pump Inhibitors (PPIs) are the most effective agents for treating acid-related gastrointestinal disorders. The prescription of an intravenous (IV) formulation of PPIs has increased dramatically. The aims of this study were to assess the appropriateness of IV PPI use and to define the risk factors and outcomes associated with its inappropriate use.

Biodegradation of Phenol at High Initial Concentration by 3D Strain: Biochemical and Genetic Aspects.

Phenolic compounds are an extensive group of natural and anthropogenic organic substances of the aromatic series containing one or more hydroxyl groups. The main sources of phenols entering the environment are waste from metallurgy and coke plants, enterprises of the leather, furniture, and pulp and paper industries, as well as wastewater from the production of phenol-formaldehyde resins, adhesives, plastics, and pesticides. Among this group of compounds, phenol is the most common environmental pollutant.

Characterization and Probiotic Potential of DPL5: A Novel Strain Isolated from Human Breast Milk with Antimicrobial Properties Against Biofilm-Forming .

Lactobacillus is a key genus of probiotics commonly utilized for the treatment of oral infections The primary aim of our research was to investigate the probiotic potential of the newly isolated DPL5 strain from human breast milk, focusing on its ability to combat biofilm-forming pathogens such as . Employing in vitro approaches, we demonstrate DPL5's ability to endure at pH 3 with survival rates above 30%, and withstand the osmotic stress often found during industrial processes like fermentation and freeze drying, retaining over 90% viability. The lyophilized cell-free supernatant of DPL5 had a significant antagonistic effect against biofilm-producing nasal strains of , and it completely eradicated biofilms at subinhibitory concentrations of 20 mg·mL.

Studying the Oncolytic Activity of Strains Against Hepatoma, Glioma, and Pancreatic Cancer and .

Background: Cancer remains a leading cause of mortality globally. Conventional treatment modalities, including radiation and chemotherapy, often fall short of achieving complete remission, highlighting the critical need for novel therapeutic strategies. One promising approach involves the oncolytic potential of Group A (GAS) strains for tumor treatment.

Atypical Leber Hereditary Optic Neuropathy (LHON) Associated with a Novel MT-CYB:m.15309T>C(Ile188Thr) Variant.

The study presents a detailed examination and follow-up of a Slovenian patient with an Leber Hereditary Optic Neuropathy (LHON)-like phenotype and bilateral optic neuropathy in whom genetic analysis identified a novel variant :m.15309T>C (Ile188Thr). We provide detailed analysis of the clinical examinations of a male patient with bilateral optic neuropathy from the acute stage to 8 years of follow-up.

Sickle Cell Disease in the Islands of Zanzibar: Patients' Characteristics, Management, and Clinical Outcomes.

Background: This study aimed to describe Sickle Cell Disease (SCD) phenotypes, sociodemographic characteristics, healthcare, and clinical outcomes of patients with SCD attending Mnazi Mmoja Hospital (MMH) in Zanzibar.

Methods: Individuals who visited MMH between September 2021 and December 2022 and were known or suspected to have SCD were enrolled in the clinic. Sociodemographic characteristics and clinical features were documented, and laboratory tests were performed.

Polygenic Score Approach to Predicting Risk of Metabolic Syndrome.

Background/objectives: Metabolic syndrome (MetS) is a complex condition linking obesity, diabetes, and hypertension, representing a major challenge in clinical care. Its rising global prevalence, driven by urbanization, sedentary lifestyles, and dietary changes, underscores the need for effective management. This study aims to explore the genetic mechanisms behind MetS, including adiposity, inflammation, neurotransmitters, and β-cell function, to develop a prognostic tool for MetS risk.

Metabolomics and WGCNA Analyses Reveal the Underlying Mechanisms of Resistance to in Hazelnut.

Background: Hazelnut (), a significant woody oil tree species in economic forests, faces production constraints due to biotic stresses, with Hazelnut Husk Brown Rot, caused by the pathogenic necrotrophic fungus (), being the most severe. To date, limited information is available regarding the resistance of hazelnuts to . To better understand the mechanisms of resistance to .

Endometrial Receptivity-Lessons from "Omics".

The window of implantation (WOI) is a critical phase of the menstrual cycle during which the endometrial lining becomes receptive and facilitates embryo implantation. Drawing on findings from various branches of "omics", including genomics, epigenomics, transcriptomics, proteomics, lipidomics, metabolomics, and microbiomics, this narrative review aims to (1) discuss mechanistic insights on endometrial receptivity and its implication in infertility; (2) highlight advances in investigations for endometrial receptivity; and (3) discuss novel diagnostic and therapeutic strategies that may improve reproductive outcomes.

Functional Characterization of the SHIP1-Domains Regarding Their Contribution to Inositol 5-Phosphatase Activity.

The Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1) is a multidomain protein consisting of two protein-protein interaction domains, the Src homology 2 (SH2) domain, and the proline-rich region (PRR), as well as three phosphoinositide-binding domains, the pleckstrin homology-like (PHL) domain, the 5-phosphatase (5PPase) domain, and the C2 domain. SHIP1 is commonly known for its involvement in the regulation of the PI3K/AKT signaling pathway by dephosphorylation of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P) at the D5 position of the inositol ring. However, the functional role of each domain of SHIP1 for the regulation of its enzymatic activity is not well understood.