Danshensu and atorvastatin are employed in the management of cardiovascular diseases (CVDs) to lower blood lipid levels and dilate blood vessels. Therefore, this study aimed to examine the potential pharmacokinetic interaction between danshensu and atorvastatin in rats.
Chromatography was performed using a CORTECST UPLC C18 column (2.1 × 1.5 mm, 1.6 μm) at a temperature of 40 °C. Acetonitrile and water were combined in the mobile phase at a rate of 0.4 mL/min via gradient elution. The methodology was validated under the guidance of the FDA and EMA literature. A total of 12 Sprague-Dawley (SD) rats were randomly assigned into two groups: the experimental group (treated with 150 mg/kg/day danshensu) and the control group (treated with 0.5% CMC-Na). Atorvastatin 10 mg/kg was administered after two weeks. The proposed method meets all the standards of bioanalysis technology verification.
Compared to the control group, the experimental group exhibited significant differences in the area under the curve (AUC), t1/2, CLz/F, and Cmax (p < 0.05). The AUC, Cmax, and t1/2 of the experimental group were higher, yet the clearance rate was significantly slowed.
This technique was effectively utilized to investigate the pharmacokinetic interaction between danshensu and atorvastatin in rats, which may be of significant clinical importance and contribute to the rationalization of clinical medicine, ultimately facilitating individualized administration.
This investigation was driven by the growing interest in natural cancer therapeutics, which aim to minimize the side effects of chemical treatments and enhance immunity. Thus, this study aimed to assess the impacts of a carrageenan/soy protein mixture on Human Colorectal Tumor Cells (HCT-116) colon cancer cells through pathway regulation and cell death assessment.
This experiment compared the treated HCT (THCT) cells exposed to a carrageenan/soy protein mixture (0.25/0.05 mg/mL) with the untreated control cells (UNT) over the experimental durations of 24, 48, and 72 hours.
The treatment triggered sophisticated cell death dynamics, characterized by progressive morphological changes. Viability displayed a fascinating pattern—decreasing to 78.8% at 24 h (p < 0.001) before partially recovering to 86.86% by 72 h (p = 0.018). Death mechanisms showed remarkable temporal organization: early apoptosis appeared exclusively at HCT 24 h (p = 0.0056), late apoptosis peaked early then declined, while necrosis followed a wavelike progression: initially high, dropping at 48 h (p = 0.0183), then dramatically surging by 72 h (p < 0.0001) to become the dominant death mode. Gene expression correlations analysis underwent striking temporal reconfiguration: 24 h showed BAX expression correlating with Bcl-2 and NF-kB (p < 0.01) and a strong association with Notch-1/2 (p < 0.0001); by 48 h, the correlations for BAX had weakened while NF-kB formed negative relationships with Bcl-2 (p < 0.001) and positive ones with Notch-1 and HSE-1 (p < 0.001); at 72 h, Bcl-2/Notch-1 aligned powerfully (p < 0.001) while HSE-1 developed significant negative correlations with most genes, particularly Notch-2 (p < 0.0001) and NF-kB (p < 0.001).
The natural carrageenan–soy mixture triggered a three-stage death process in colon cancer cells, with a surprising 72-hour phase where cells looked healthier but were dying. This pattern altered key gene activity, disrupting the cancer cell survival process and offering a promising new approach to target the metabolism of stubborn cancers.
Severe heart failure (HF) is accompanied by cardiac cachexia (CC), defined as significant weight loss, muscle atrophy, and metabolic abnormalities. Muscle wasting in patients with CC is closely associated with hormonal changes. Previous studies on the pathogenesis of CC have focused on the imbalance between catabolic and anabolic processes. Thus, this review focused on the role of endothelial dysfunction in CC. We summarized how inflammatory cytokines and neurohormonal factors cause vascular dysfunction, leading to reduced nutrient delivery and perfusion. Furthermore, we discuss both conventional and emerging therapeutic strategies that may ameliorate CC by targeting the vasculature. These include ghrelin, the vascular benefits of foundational HF drugs (angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor-neprilysin inhibitors (ARNIs), and beta-blockers), and the promise of novel agents, such as BTB and CNC homology 1 (BACH1) inhibitors and fibroblast growth factor 21 (FGF21) agonists. We also summarize the existing animal models of CC and discuss advanced imaging and omics technologies for future research. This review provides a novel perspective on CC pathogenesis and highlights promising avenues for therapeutic intervention.
Diabetic cardiomyopathy (DbCM) is a serious complication of diabetes. Adropin (ADR), a 76-amino acid peptide encoded by the Energy homeostasis associated (Enho) gene, plays a crucial role in energy homeostasis. However, the effects of (Enho) on cardiomyocytes (CMs) apoptosis under hyperglycemic conditions and the associated mechanisms remain poorly understood. Thus, this study aimed to investigate the protective effects of ADR against high glucose-induced CM apoptosis and elucidate the underlying mechanisms involving mitophagy and mitochondrial dynamics.
Neonatal rat CMs were cultured in vitro and divided into three groups: control (CMs), high glucose condition (HGLc; CMs + HGLc), and HGLc with ADR treatment (CMs + HGLc + ADR). Cell viability was assessed using the MTT assay, while apoptosis was quantified by flow cytometry. Lysosomal activity was evaluated via fluorescent probes, and autophagic flux was measured using the monomeric Red Fluorescent Protein-enhanced Green Fluorescent Protein-Microtubule-associated protein 1 light chain 3 (mRFP-eGFP-LC3) dual-fluorescence system. The expression of Proteins invoved in mitophagy and mitochondrial dynamics was analyzed by Western blotting.
High glucose exposure significantly reduced CM viability, increased apoptosis, and impaired mitochondrial membrane potential and autophagy (p < 0.05 vs. the controls group). These effects were accompanied by downregulation of sequestosome 1 (p62), PTEN-induced kinase 1 (PINK1), Parkin, Mitofusin 1 (Mfn1), and Mitofusin 2 (Mfn2), and upregulation of Dynamin-related protein 1 (Drp1) . ADR treatment attenuated these abnormalities, restoring viability, reducing apoptosis, and improving mitochondrial function and autophagy (p < 0.05 vs. CMs + HGLc group). Notably, ADR upregulated p62, PINK1, Parkin, Mfn1 and Mfn2 while suppressing Drp1 expression (p < 0.05 vs CMs + HGLc group).
ADR mitigates high glucose-induced CMs apoptosis by enhancing mitophagy and restoring mitochondrial dynamics, suggesting that ADR treatment offers therapeutic potential for DbCM.
The local inhibition of the gastric renin angiotensin system (RAS) has emerged as a pivotal therapeutic target in treating gastric ulcers. Rosmarinic acid (RA), a medically significant herb belonging to the category of water-soluble polyphenolic compounds, exhibits notable antiulcer properties. Our previous research has demonstrated that the anti-ferroptosis effect of RA in lipopolysaccharide (LPS)-induced septic acute respiratory distress syndrome (ARDS) depends on the RAS. Therefore, this study aimed to assess the underlying mechanism through which RA mitigates ethanol-induced gastric ulcers in mice.
Gastric tissue samples were collected from patients with gastric ulcers to perform RNA sequencing (RNA-seq) and bioinformatics analyses. Moreover, the gastric ulcer mouse model was induced through a single gavage of absolute ethanol at a dose of 0.1 mL/10 g. Before induction, mice were orally administered RA at doses of 4 and 20 mg/kg, or esomeprazole 3.03 mg/kg (as a reference drug), for a duration of 5 days. The anti-gastric ulcer effects were assessed through histopathological evaluations and Western blot analysis.
The RNA-seq data and bioinformatic insights revealed that the angiotensin-converting enzyme (ACE)/angiotensin (Ang) 2 converting enzyme (ACE2) balance may constitute a novel mechanism in alcohol-related gastric ulcer, which RA modulates. A total of six overlapping targets related to both RA and gastric ulcers were identified. Among them, matrix metalloproteinase-1 (MMP1), matrix metalloproteinase-3 (MMP3), and A Disintegrin and Metalloproteinase with a Thrombospondin type 1 motif, type 4 (ADAMTS4) presented low binding energy with RA and formed a protein-protein interaction (PPI) network with ACE and ACE2. In vivo experiments further substantiated that RA conferred gastric protection by restoring the ACE/ACE2 balance and upregulating GPX4 expression.
RA might be a potential gastroprotective agent by suppressing RAS-related ferroptosis in the gastric tissues.
Platelet-rich plasma has emerged as a widely used regenerative therapy across multiple medical specialties, yet fundamental quality-control and standardization challenges have limited the associated clinical evidence base. Induced pluripotent stem cell-derived artificial platelets represent a next-generation approach that addresses these limitations through standardized, scalable manufacturing under good manufacturing practice conditions. This review examines the pharmacological properties of induced pluripotent stem cell (iPSC)-derived artificial platelets, with an emphasis on the associated pharmacokinetics, pharmacodynamics, and safety profiles in regenerative medicine applications. Unlike donor-derived platelet concentrates, which exhibit substantial batch-to-batch variability in platelet counts, leukocyte content, and growth factor concentrations, iPSC-derived platforms enable precise control over product composition and functional characteristics. Moreover, preclinical studies have demonstrated therapeutic efficacy in osteoarthritis models by modulating anabolic and catabolic pathways, with emerging clinical data supporting acceptable safety profiles. The transition from transfusion-focused applications to regenerative medicine represents a paradigm shift in artificial platelet development, requiring novel pharmacological characterization frameworks distinct from traditional hematology endpoints. Therefore, manufacturing standardization, quantifiable pharmacokinetic parameters, and reproducible pharmacodynamic effects position iPSC-derived artificial platelets as promising candidates for regenerative applications, where current platelet-rich plasma therapies often yield inconsistent outcomes.
Continuous exposure to a range of environmental conditions can induce the production of primary and secondary metabolites in plants. Thus, this study aimed to examine variations in phytochemical compounds and antimicrobial activity of crude extracts from Bidens pilosa plants across various Egyptian habitats.
Plants were gathered from 10 habitats across five Southern and Middle Nile Delta Governorates. The phytochemical components of B. pilosa extracts were estimated both qualitatively and quantitatively.
The plant was found to contain terpenoids, flavonoids, phenols, tannins, alkaloids, sterols, saponins, carbohydrates, and amino acids, which are mainly concentrated in shoots. Citrus, guava, and mango orchards and wasteland habitats contained the highest contents of total flavonoids, phenols, tannins, and alkaloids. Fifty compounds were identified in the ethanol extract; the most dominant groups were aromatic and aliphatic compounds (22 and 17 compounds, respectively) with the highest peak area % recorded for nonadecane (9.58%), 14α-H-pregna (7.15%), pentane, 3-methyl (3.40%), and dodecane (4.20%). While 30 compounds were recorded in the chloroform:methanol extract with the dominance of organosilicons (30.00% of the total compounds), dicarboxylic acids (16.67%) and carboxylic acids (13.33%), in addition to the highest peak area % was recorded for cyclononasiloxane, octadecamethyl (10.98%), (Z)-5-ethylidene-3-hydroxy-4-(3'-methylbutanoyl)-2(5H)-furanone (9.55%), and silicone oil (7.95%). The raw extract of the B. pilosa shoots exhibited antimicrobial activity against many bacterial and fungal isolates. Most of the identified secondary metabolites exhibited physiological and ecological roles in plants and play roles in adverse environmental stressors. Many of the identified compounds possessed nutritional value and therapeutic effects. In addition, the methanol extract had a beneficial impact on these bioactive phyto-organic constituents, which can be harnessed and used in the food and pharmaceutical industries to produce drugs and raw materials for industrial purposes.