Search Results (110,236)

Background/Objectives: Rumex obtusifolius L. (Polygonaceae) has been traditionally used to treat various disorders, including hepatic and gastrointestinal diseases. However, the phytochemical constituents of its roots and their potential protective effects against skeletal muscle atrophy remain poorly understood. This study aimed to isolate and characterize bioactive constituents from R. obtusifolius roots and evaluate their protective effects against dexamethasone (DEX)-induced muscle atrophy in C2C12 myotubes. Methods: LC–MS-guided phytochemical investigation of the ethanol extract of R. obtusifolius roots, followed by successive column chromatography and HPLC purification, resulted in the isolation of four naphthalene-type glycosides. Their structures were elucidated using 1D and 2D NMR spectroscopy, HR-ESIMS, and chemical transformation. The protective effects of compounds 1 and 4 against dexamethasone (DEX)-induced muscle atrophy were evaluated by assessing myotube morphology, myogenic and atrophy-related protein expression, and PI3K/Akt/mTOR signaling. Results: A new naphthalene malonylglucoside, nepodin-8-O-β-D-(6′-O-malonyl)-glucopyranoside (1), together with three known glycosides (2–4), was identified. Among the isolated compounds, compound 1 significantly attenuated DEX-induced muscle atrophy in a concentration-dependent manner by increasing myotube diameter and improving myotube morphology. It restored the expression of the myogenic markers MyoD and myogenin while suppressing the atrophy-related proteins MuRF1 and MAFBX. Furthermore, compound 1 reversed DEX-induced suppression of the PI3K/Akt/mTOR signaling pathway, indicating recovery of anabolic signaling. Conclusions: This study reports a new naphthalene malonylglucoside (1) from R. obtusifolius roots and demonstrates that compound 1 protects against DEX-induced skeletal muscle atrophy through restoration of myogenic differentiation and activation of the PI3K/Akt/mTOR pathway. These findings suggest that compound 1 is a promising natural lead compound for the development of therapeutics targeting muscle wasting disorders. Full article

Dendrobium officinale polysaccharide (DOP) shows efficacy against type 2 diabetes (T2D), but its mechanisms remain unclear. The present investigation aimed to identify potential biomarkers associated with DOP-mediated therapeutic interventions in T2D. Datasets related to T2D were excavated from the Gene Expression Omnibus (GEO) database. Candidate genes were acquired from the intersection of genes obtained from weighted gene co-expression network analysis (WGCNA) and differential analysis. Subsequently, Mendelian randomization (MR) identified causal biomarkers, validated by Receiver Operating Characteristic (ROC) curves and expression profiling. Then, a nomogram, immune infiltration, single-cell analysis, and molecular docking were performed. Among the 12 candidate genes, 7 with available eQTL instruments were included in MR analysis, while 5 lacking genome-wide significant IVs (p < 5 × 10⁻⁸) were excluded. Three genes demonstrated significant MR associations with T2D, and biomarkers GLI1 and LGALS9 showed strong diagnostic performance and were upregulated in T2D. The nomogram had good predictive value. Seventeen immune cells differed significantly between T2D and controls, with GLI1 and LGALS9 positively correlating with most and primarily expressed in stellate cells. Finally, D-Galacturonic acid, D-Mannose, and L-rhamnose monohydrate were compounds showing predicted binding potential with candidate biomarkers GLI1 and LGALS9 emerged as promising potential molecular candidates associated with DOP-mediated T2D regulation, offering novel mechanistic perspectives on DOP’s anti-diabetic properties. Full article

Traumatic spinal cord injury (SCI) is a severe medical condition, often resulting in permanent disability, with significant impacts on patients’ quality of life and burden on healthcare systems. Current therapeutic approaches for SCI are insufficient, advocating for the development of more effective treatments. As changes in transcriptome post-SCI can provide clues for novel treatment strategies and targets, substantial efforts have been made recently to characterize such transcriptional changes and their spatiotemporal features. This narrative review focuses on how transcriptomics, alone or in combination with other omics data, can contribute to understanding SCI pathobiology and the mechanisms of post-SCI regeneration and guide the development of novel SCI therapies. It covers an arsenal of tools for transcriptomics studies and provides a concise summary of findings from the latest relevant studies (predominantly from 2020 to 2025), representing the major directions in the field. Full article

Mucopolysaccharidoses (MPS) are severe, inherited metabolic diseases, classified among lysosomal storage diseases (LSDs). The presence of pathological variants of genes coding for enzymes involved in the degradation of glycosaminoglycans (GAGs) is a primary cause of each MPS type, and accumulation of these compounds is a characteristic feature of MPS. Depending on the kind of defective enzyme and the type of stored GAG(s), 12 classical types are distinguished, and a few other related diseases, whose classification is unclear. Although there is no fully effective cure for MPS, several kinds of therapeutic approaches have been proposed to treat these diseases, and some of them have been introduced into clinical practice. In this review article, we present and discuss very recent advances in developing various therapies for MPS, also indicating problems and limitations. This paper focuses on enzyme replacement therapy (ERT), cell- and gene-based therapies (including hematopoietic stem cell transplantation and gene therapy), inhibition of GAG synthesis, and some other newly developed therapeutic approaches. Perspectives on MPS therapies are also discussed. Full article

Myocardial ischemia–reperfusion injury (MIRI) represents a major contributor to morbidity and mortality in patients undergoing reperfusion therapy after acute myocardial infarction. Although timely restoration of coronary blood flow is essential for myocardial salvage, reperfusion paradoxically initiates a complex cascade of molecular and cellular events that may aggravate myocardial injury. Oxidative stress is considered one of the central mechanisms underlying MIRI, primarily through excessive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), leading to mitochondrial dysfunction, calcium overload, endothelial injury, inflammatory activation, and cardiomyocyte death. This review summarizes the current understanding of the pathophysiological mechanisms involved in oxidative stress-mediated reperfusion injury, with emphasis on mitochondrial permeability transition pore opening, inflammasome activation, cytokine release, neutrophil extracellular trap formation, macrophage polarization, and interconnected cell death pathways including PANoptosis. Emerging evidence regarding immunometabolic regulation and epigenetic modulation in MIRI is also discussed. In addition, current pharmacological and non-pharmacological cardioprotective strategies targeting oxidative stress, mitochondrial dysfunction, and inflammatory signaling are reviewed, highlighting both promising experimental findings and the persistent challenges in clinical translation. A deeper understanding of the molecular interplay between oxidative stress and inflammatory pathways may facilitate the development of integrated therapeutic approaches aimed at improving myocardial recovery and long-term cardiovascular outcomes following reperfusion therapy. Full article

Ferroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation and is mechanistically distinct from apoptosis, necrosis and pyroptosis. Increasing evidence indicates that ferroptosis plays a critical role in cancer biology, including lymphoproliferative disorders, where chronic redox imbalance, dysregulated iron metabolism, and metabolic rewiring create a permissive environment for ferroptotic vulnerability. In these malignancies, altered iron handling, elevated reactive oxygen species, and a strong reliance on antioxidant systems such as glutathione and glutathione peroxidase 4 tightly control ferroptotic sensitivity. Dysregulation of key components, including SLC7A11, lipid metabolism pathways, and intracellular iron homeostasis, further shapes the susceptibility of malignant lymphoid cells to ferroptosis. Importantly, emerging preclinical studies suggest that therapeutic targeting of ferroptosis may overcome resistance to conventional chemotherapy, targeted agents, and immunotherapy, offering novel opportunities particularly in relapsed or refractory disease. This review provides a comprehensive overview of the molecular mechanisms governing ferroptosis in lymphoproliferative disorders, highlights the interplay between ferroptosis and major cellular and metabolic pathways, and discusses current and emerging strategies to pharmacologically induce ferroptosis, with an emphasis on biomarker-driven clinical translation. Full article

Background: Neuroinflammation contributes to the etiopathology and symptom severity of neurodegenerative and neuropsychiatric disorders. Glial cells, especially microglia and astrocytes, play a crucial role in neuroinflammation. It has been reported that ginseng (Panax ginseng) and its bioactive component ginsenoside Rg1 exhibit anti-inflammatory effects and can improve cognitive performance in various models. However, the exact underlying mechanisms remain unclear. Methods: Astrocyte–microglia co-culture models simulating physiological (M5, 5–10% microglia) and pathological/inflammatory (M30, 30–40% microglia) conditions were treated with different concentrations of ginsenoside Rg1 (15, 30, 45 µM) or ginseng extract (derived from Korean red ginseng) at low (12.5, 25, 37.5 µg/mL) or high doses (125, 250, 375 µg/mL) for 24 h. Cell viability was assessed using the MTT assay while microglial reactivity was examined using immunocytochemistry. Astrocytic gap-junctional coupling was investigated using the scrape-loading method, and connexin 43 (Cx43) expression was analyzed using immunocytochemistry and Western blot. Results: Both Rg1 and low-dose ginseng extract reduced microglial activation under inflammatory conditions by promoting a shift in microglia from an activated to homeostatic (resting) phenotype. Rg1 preserved astrocytic gap-junctional function by preventing the inflammation-induced downregulation of Cx43 expression and enhancing Cx43-mediated gap-junctional intercellular communication. Rg1 caused a significant reduction in glial cell viability, but only at high concentrations (30 and 45 µM), under inflammatory conditions. High-dose ginseng extract showed a significant concentration-dependent reduction in glial cell viability under physiological and pathological conditions, without comparable anti-inflammatory benefits. Conclusions: This study demonstrates that low-dose ginseng and its active compound Rg1 exert anti-inflammatory effects by modulating astrocytic coupling and microglial reactivity. These results provide a novel therapeutic perspective for the use of ginseng in the treatment of neurodegenerative and neuropsychiatric diseases related to neuroinflammation. Full article

The complex genus Achillea L. comprises more than 140 species distributed widely throughout the Northern Hemisphere. Several species are widely used in traditional medicine for their therapeutic properties, yet few studies have correlated their biological properties with the plant’s phytochemical composition. Among these, Achillea setacea Waldst. & Kit. is a perennial species traditionally used to treat digestive and inflammatory disorders. In this study, the essential oil of A. setacea, collected wild in North Macedonia, was analyzed spectrometrically and spectroscopically by GC-MS and NMR, respectively. A total of nineteen compounds were identified, with camphor (31.3%), 4-terpineol (11.3%), and eucalyptol (10.6%) being the main constituents. Furthermore, the biological activities of pure oil were evaluated, showing notable antioxidant properties, as well as antimicrobial effects against a panel of clinically relevant microorganisms, including Gram-positive and Gram-negative bacteria. Furthermore, its impact on human intestinal epithelial (Caco-2) cells was assessed, highlighting its potential relevance for gastrointestinal applications, in agreement with the traditional use of Achillea species for digestive disorders. Full article

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder characterized by hyperandrogenism, insulin resistance, oxidative stress, and chronic low-grade inflammation, while conventional therapies are often limited by adverse effects and suboptimal adherence. This narrative review aims to evaluate the chemical composition and mechanistic effects of bioactive compounds derived from Allium species in the context of PCOS. A comprehensive analysis of the literature was performed, focusing on organosulfur compounds and polyphenols, with emphasis on their structure, reactivity, transformation pathways, and biological activity, integrating findings from preclinical and clinical studies. The evidence indicates that key compounds, including allicin, ajoene, and diallyl sulfides, exert biological effects through modulation of redox balance, inhibition of inflammation-related signaling, and regulation of insulin signaling pathways, while also influencing steroidogenesis and androgen synthesis. Polyphenolic compounds contribute primarily through antioxidant mechanisms related to their structural features. However, the current evidence remains limited by the scarcity of large-scale, long-term human clinical trials, particularly in women with PCOS, which restricts definitive conclusions regarding clinical efficacy, optimal dosing, safety, and long-term therapeutic applicability. Overall, Allium species represent a promising source of multitarget bioactive compounds for PCOS management, and understanding the chemical basis of their activity is essential for optimizing their therapeutic potential and guiding future research. Full article

Pancreatic ductal adenocarcinoma is highly malignant with poor prognosis. Its dense tumor microenvironment severely limits the efficacy of conventional chemotherapy and causes severe side-effects. Herein, we adopt the established Schiff-base crosslinked thermoresponsive injectable self-healing poly(2-(2-methoxyethoxy)ethyl methacrylate-co-oligo(ethylene glycol) methyl ether methacrylate-co-aldehyde 2-hydroxyethyl methacrylate)/carboxymethyl chitosan (APMOH/CMCS) hydrogel as the delivery scaffold. By regulating monomer composition, the volume phase transition temperature (T_VPT) of the hydrogel was tuned to around 43 °C to match the therapeutic temperature requirement. Subsequently, copper–metal organic framework (Cu-MOF) nanoparticles co-loaded with 2,2′-azobis(2-methylimidazoline) dihydrochloride (AIPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) cationic radicals (ABTS·⁺) (denoted as AB@Cu-MOF) were uniformly incorporated into the hydrogel network. Under near-infrared (NIR) irradiation, ABTS·⁺ acts as a photothermal agent to generate hyperthermia for tumor ablation; the elevated temperature further activates AIPH to produce alkyl radicals, which can oxidize inactivated ABTS back to ABTS·⁺ and construct a sustainable photothermal therapy–thermodynamic therapy (PTT-TDT) circulation. Meanwhile, Cu-MOF can consume intracellular glutathione (GSH) to protect active components from deactivation and initiate chemodynamic therapy (CDT) via Fenton-like reactions to produce toxic reactive oxygen species. Benefiting from the thermoresponsive characteristic, the hydrogel undergoes volume shrinkage upon heating, achieving NIR-triggered on-demand drug release with a cumulative release rate of 81.1%. In vitro and in vivo experiments verified that this integrated platform realizes remarkable triple synergistic efficacy of PTT, TDT, and CDT. The tumor volume of the treatment group was merely 13.3% of the control group, and the system also exhibited excellent biocompatibility. Collectively, it offers a feasible and promising intelligent platform for precise local treatment of pancreatic cancer. Full article

Pomegranate (Punica granatum), a shrub belonging to the Lythraceae family, has long been recognized for its diverse pharmacological benefits, including potential roles in managing inflammation and diabetes. The present study explored the insulin-secretory and β-cell proliferative properties of the ethanol extract of P. granatum fruit peel (EEPG) and assessed its influence on glucose regulation in high-fat-fed diet-induced obese mice (HFDi-OM) through in vivo and in silico studies. In vitro, EEPG was found to activate cAMP-dependent pathways and regulate K_ATP channels, thereby enhancing glucose-stimulated insulin secretion from BRIN-BD11 β-cells, with partial reliance on extracellular calcium. EEPG promoted β-cell proliferation, as indicated by an increase in Ki-67 positive cells, and displayed inhibitory effects on glucose diffusion and starch hydrolysis, suggesting a capacity to delay carbohydrate digestion and absorption. Furthermore, EEPG demonstrated antioxidant activity by neutralizing free radicals. In an acute test, EEPG (at doses of 150 and 250 mg/5 mL/kg) improved oral glucose tolerance and elevated plasma insulin levels. Long-term oral treatment for 21 days to HFDi-OM led to a significant reduction in fasting blood glucose, body weight, and food and fluid intake. It also enhanced gastrointestinal motility and improved lipid profiles by increasing HDL and lowering total cholesterol, LDL, and triglycerides. The therapeutic properties of EEPG are likely attributed to its rich bioactive components, including flavonoids (quercetin, kaempferol, catechin, and epicatechin) and phenolic acids (ellagic acid), which exhibited strong multi-target binding affinities in in silico molecular docking studies toward SUR1, PDE4, PI3K, and α-amylase, thereby supporting enhanced insulin secretion, β-cell function and glucose homeostasis. Full article

Emerging evidence shows long non-coding RNAs (lncRNAs) as critical regulators of osteoarthritis (OA) progression, often acting in complex networks with microRNAs (miRNAs). In our study, we investigated the potential regulatory function of the lncRNA MEG3/miR-21-5p axis in the OA phenotype of chondrocytes. Differential gene expression analysis in damaged vs. intact cartilage was performed, re-analyzing existing public RNA-seq data. MiRTarBase, LncRNADisease, and Open Targets databases were utilized to identify miR-21-5p target genes and OA-associated lncRNAs and genes. Functional enrichment analysis and protein–protein interaction (PPI) network construction were performed using the DAVID and STRING databases, respectively. MEG3, miR-21-5p, SOX5, COL2A1 and ACAN mRNA expressions were assessed by qRT-PCR. The role of the MEG3/miR-21-5p axis in OA chondrocytes was examined using transfection experiments. Eighty-one lncRNAs displayed significant differences in expression between damaged and intact cartilage, including MEG3. Bioinformatic analysis indicated that MEG3 interacts with miR-21-5p, while SOX5 was identified to be a putative target of miR-21-5p. MEG3 and SOX5 expression levels were significantly downregulated in OA chondrocytes, whereas miR-21-5p expression was upregulated. Silencing of MEG3 resulted in increased miR-21-5p levels in chondrocytes. Conversely, inhibition of miR-21-5p led to increased SOX5 expression and anabolic markers COL2A1 and ACAN. Notably, MEG3 silencing significantly reduced SOX5 expression, an effect that was reversed upon miR-21-5p inhibition. Our findings highlight a potential regulatory role of the dysregulated MEG3/miR-21-5p axis in modulating the anabolic phenotype of chondrocytes through regulation of SOX5 expression. This novel lncRNA/miRNA/mRNA regulatory network may represent a candidate therapeutic axis for knee osteoarthritis. Full article

Lactylation, a recently identified post-translational modification, has been associated with multiple cancer types, including neuroblastoma (NB). The present study aimed to investigate the prognostic significance of lactylation-related genes and to develop a prognostic model to enhance patient risk stratification and guide targeted therapy for NB. In the present bioinformatics study, single-cell RNA sequencing data (GSE137804) were analyzed to quantify lactylation activity in NB cells using the AddModuleScore algorithm based on 371 lactylation-related genes. A total of 142 differentially expressed lactylation-related genes (DELGs) were identified between high- and low-lactylation tumor cells, and these genes were mainly enriched in cell cycle-related pathways. A 14-gene lactylation-related prognostic model was then constructed using the identified DELGs in a training cohort (GSE49710, n = 349) via Cox and LASSO regression, and validated in internal (GSE49710, n = 149) and external (E-MTAB-8248, n = 223) cohorts. The model effectively stratified patients into high- and low-risk groups with significantly different overall survival (OS) outcomes, and its robust predictive performance was confirmed across both validation cohorts. The present study reveals the significant prognostic role of lactylation in NB, and the 14-gene model serves as a novel molecular tool for risk stratification and provides a reference for developing targeted therapeutic strategies for NB. Full article

Hydrogels have gained prominence as a class of biomaterials in biomedicine due to their excellent biocompatibility, biodegradability, and high water retention. Among them, hydrogels derived from natural polysaccharides sourced from plants, animals, and microbes are attracting growing interest due to their renewable nature, low toxicity, low immunogenicity, and diverse functional properties. While several recent reviews have addressed polysaccharide-based hydrogels, they have largely focused on isolated aspects—such as 3D bioprinting formulations, double-network mechanical reinforcement, rheological behavior, or single-source polysaccharides—without establishing an integrated framework that links raw material selection, structural diversity, chemical modification, and crosslinking design to clinical translation. This review distinguishes itself by providing a systematic, end-to-end perspective that spans from the structural diversity of plant- and microbe-derived polysaccharides through recent advances in chemical modification and novel cross-linking strategies, to the fine-tuning of physicochemical properties for enhanced therapeutic outcomes. This article provides an overview of the progress made in the emerging biomedical applications and material design of natural polysaccharide hydrogels in terms of raw material selection, chemical modification, cross-linking mechanisms, and functional utilization. It aims to fully explore the potential of these materials and promote integration into advanced biomedical practices. Full article

The Kidney Disease: Improving Global Outcomes (KDIGO) CGA framework remains the essential basis for chronic kidney disease (CKD) classification, risk stratification, and guideline-based therapy. However, eGFR and albuminuria do not always explain the physiological mechanism maintaining the current filtration level or the heterogeneity of treatment responses. This narrative review proposes a hypothesis-generating functional–hemodynamic extension of KDIGO CGA that incorporates renal functional reserve (RFR), blood pressure, volume status, proteinuria phenotype, and selected tubular markers. RFR is discussed as a dynamic stress test of nephron reserve rather than as a replacement for eGFR or albuminuria. A low, zero, or negative RFR may suggest reserve exhaustion or relative hyperfiltration, but its interpretation depends on standardized testing conditions and clinical context. We distinguish established evidence-based therapy—RAAS blockade in albuminuric or hypertensive CKD, SGLT2 inhibition for kidney and cardiorenal protection, and non-steroidal MRA therapy in selected patients—from conceptual sequencing hypotheses such as RAASi-prioritized, SGLT2i-prioritized, early dual, or staged triple renoprotection. The review also summarizes albuminuria as a two-compartment phenomenon involving both glomerular passage and proximal tubular handling of filtered proteins. The proposed framework is not a validated treatment algorithm. It is intended to support physiological phenotyping, interpretation of early eGFR changes, and the design of prospective studies that test whether RFR adds independent prognostic or therapeutic value beyond KDIGO CGA. Full article