Search Results (6,821)

The purpose of this study was to offer a theoretical foundation for the use of curcumin in poultry systems for anti-stress responses. Fourteen-day-old SPF Leghorn embryonic eggs were isolated and digested to produce primary cultured cardiomyocytes for this investigation. The primary cultured cardiomyocytes were divided into three groups: the CK group, serving as the control check; the HS group, which underwent a heat stress challenge; and the HS_Cur group, which was pre-treated with curcumin prior to experiencing heat stress. Twenty hours prior to the heat stress phase, the HS_Cur group received 15 μmol/L of curcumin. The culture medium’s cells and supernatant were extracted. Curcumin has been shown to protect cells against heat stress by drastically inhibiting the release of CK-MB and LDH, reducing the generation of MDA, and improving the potential of the mitochondrial membrane. Heat stress may alter cell proliferation, the base repair process, and cause proteotoxic stress, according to pathway enrichment analysis. Several iron metabolism-related pathways were both shown in CK vs. HS and HS vs. HS_Cur comparisons. Curcumin can promote heme synthesis and improve iron storage and antioxidant capacity by suppressing the expression of FTL, MAP1LC3C, and FXN and increasing the expression of SLC7A11, FTH1, FECH, SQSTM1, and NQO1, according to our subsequent analysis of iron metabolism-related DEGs. Curcumin may protect cells from the toxicity of LIP by inhibiting the expression of ferritinophagy-related genes and increasing the expression of heme production, iron storage, and antioxidant-related genes. Full article

Background: As a novel drug delivery vehicle, transfersomes (TFSs) have great deformability, good biocompatibility, and biodegradability, which can significantly improve drug delivery efficiency. However, their application is limited by their poor stability and vulnerability to leaks. Methods: This paper prepared and assessed the stability of transfersomes co-loaded with Pueraria total flavonoids (PTFs) and tanshinone (TAN), known as PTF/TAN-TFSs, in order to overcome this constraint. Results: The findings showed that the co-loaded system (PTF/TAN-TFSs) had better structural stability than the single-loaded systems (PTF-TFSs and TAN-TFSs), with drug leakage rates decreased by roughly 5% and 7%, respectively, and a more uniform size distribution with a particle size of 44.52 ± 0.47 nm and a PDI of 0.22, while the single-loaded systems had PDI values larger than 0.3. The co-loaded system showed a better sustained-release profile than the suspension with a 15.28% decrease in the maximum cumulative release of the poorly soluble component Tan IIA. Additionally, the co-loaded system demonstrated enhanced solubilization capability, making the poorly soluble component TAN more soluble by 89.52 times compared to the free medication and by 1.97 times compared to the single-loaded system. Furthermore, the co-loaded system significantly improved the intestinal absorption of Tan IIA, increasing the Papp and Ka values in the ileum segment by 2.02-fold and 1.80-fold, respectively. Conclusions: The stability of the system was successfully improved by co-loading many components with varying hydrophobicities. This method provides a fresh way to enhance transferosome stability, broadening their application in the field of drug delivery. Full article

Astragalus membranaceus is an important medicinal plant with considerable pharmacological and economic value; however, its growth and productivity are frequently threatened by drought stress. Basic leucine zipper (bZIP) transcription factors play crucial roles in plant growth, development, and abiotic stress responses, yet a comprehensive investigation of the bZIP gene family in A. membranaceus remains unavailable. In this study, 74 bZIP genes (AmbZIPs) were identified in the A. membranaceus genome and classified into 12 subfamilies based on phylogenetic relationships with Arabidopsis thaliana. Analyses of gene structure, conserved motifs, chromosomal distribution, and duplication events revealed high conservation within subfamilies and indicated that segmental duplication was the major driver of AmbZIP family expansion. Codon usage analysis showed that AmbZIP genes exhibited relatively weak codon usage bias, with codon preference predominantly shaped by natural selection rather than mutation pressure. A total of 23 optimal codons were identified, of which 91.3% were A/T-ending codons. Codon adaptability analysis further demonstrated that tobacco possessed the highest codon compatibility among five tested hosts, whereas Escherichia coli exhibited the lowest adaptability, suggesting that plant expression systems may be more suitable for functional studies of AmbZIP genes. Promoter analysis identified numerous cis-acting elements associated with phytohormone signaling and abiotic stress responses, particularly those related to abscisic acid, methyl jasmonate, salicylic acid, and drought responsiveness. Transcriptome analysis and quantitative real-time polymerase chain reaction (qRT-PCR) validation revealed that several AmbZIP genes were significantly induced under drought stress. Among them, AmbZIP46 displayed strong drought-responsive expression, transcriptional activation activity, and exclusive nuclear localization. These findings provide the first comprehensive characterization of the bZIP gene family in A. membranaceus and establish a valuable foundation for elucidating drought-tolerance mechanisms and facilitating molecular breeding in this medicinal plant. Full article

Leptin is the oldest studied adipokine, and its mechanism of action in the regulation of energy metabolism remains a hot topic of current research. In this paper, we systematically review the progress of clinical and basic research on leptin and energy metabolism from 1994 to 2026. It is shown that leptin can regulate the energy metabolism homeostasis through autocrine, paracrine and neurohumoral pathways (e.g., hypothalamic–leptin–melanocortin axis). In addition, the effects of mainstream weight loss strategies such as dietary control, pharmacological interventions and exercise on leptin levels, and their underlying mechanisms were investigated in this paper, with the aim of providing a theoretical basis for the clinical application of leptin in metabolic diseases (e.g., obesity, diabetes mellitus). Future studies need to further clarify the molecular mechanisms of leptin resistance and explore precise intervention strategies based on the leptin signaling pathway. Full article

Lung cancer is the most common malignant tumor worldwide in terms of both incidence and mortality, and the development of highly effective, low-toxicity therapeutic strategies remains an urgent clinical challenge. Here, we report that Salvianolic acid A (SAA), a natural compound extracted from Salvia miltiorrhiza Bunge, inhibits the proliferation of non-small cell lung cancer (NSCLC) cells and induces ferroptosis. Mechanistically, SAA acts as an SRC kinase inhibitor, blocking SRC autophosphorylation at Tyr416, thereby disrupting the SRC-YAP interaction and preventing YAP nuclear translocation. This leads to GPX4 downregulation and subsequently triggers ferroptosis, characterized by increased reactive oxygen species (ROS), Fe²⁺ accumulation, and lipid peroxidation. Overexpression of YAP abrogates the effects of SAA, while inhibiting SRC or YAP enhances its activity. SAA inhibits tumor growth and downregulates key effector molecules in vivo. In summary, this study reveals a novel mechanism by which SAA induces ferroptosis via the SRC/YAP/GPX4 axis, supporting its further development as a candidate therapeutic agent for NSCLC. Full article

Ethnopharmacological relevance: Dioscorea nipponica Makino is a traditional medicinal plant widely used in East Asia for the treatment of rheumatic disorders, inflammatory diseases, and cardiovascular conditions. Its rhizome has long been applied in clinical practice for relieving pain, promoting blood circulation, and reducing swelling. Aim of the study: This narrative review aims to provide a comprehensive and critical overview of the phytochemical constituents, pharmacological activities, and underlying mechanisms of D. nipponica and to identify current research gaps and future perspectives. Materials and methods: The literature was searched in PubMed, Web of Science, ScienceDirect, CNKI and Wanfang Data from database inception to December 2025. The combined retrieval keywords were set as: (Dioscorea nipponica Makino OR Chuanshanlong) AND (chemical constituents OR steroidal saponins OR flavonoids OR phenols) AND (biological activity OR anti-inflammatory OR cardioprotective OR hepatotoxicity OR clinical application). Both English and Chinese publications were retrieved, and studies written in other languages were excluded. Results: Phytochemical studies have identified diverse secondary metabolites, particularly steroidal saponins, along with diarylheptanoids and phenanthrenes. These compounds exhibit multiple pharmacological activities, including anti-inflammatory, anti-tumor, immunomodulatory, and cardioprotective effects. Mechanistic studies indicate that these activities are mediated through the modulation of key signaling pathways such as NF-κB, PI3K/Akt, AMPK, and the NLRP3 inflammasome. However, current research remains fragmented, with limited integration of chemical composition, molecular targets, and therapeutic outcomes. Conclusions: D. nipponica represents a promising source of bioactive natural products, with steroidal saponins as the major contributors to its pharmacological effects. Future studies should focus on multi-component interactions, pharmacokinetics, quality control, and clinical validation to support its rational development and sustainable utilization. Full article

Bovine mastitis caused by multidrug-resistant (MDR) Escherichia coli remains a major challenge in the dairy industry due to recurrent infection, excessive lipopolysaccharide (LPS) release, and persistent mammary inflammation. Whole-genome sequencing (WGS) revealed that the clinical isolate was resistant to seven classes of antibiotics and exhibited a marked enrichment of iron uptake systems, which accounted for 27.14% of the 140 virulence genes identified. Upon this, we developed a targeted combination therapy using the iron mimetic gallium nitrate and the antimicrobial peptide thanatin (Tn). A rat model of mastitis was established to evaluate the in vivo therapeutic efficacy of the Tn-gallium nitrate combination. Our results demonstrated that the combination of gallium nitrate and Tn exerted a potent enhanced therapeutic effect in the rat mastitis model. This regimen significantly inhibited bacterial proliferation, neutralized endotoxin activity, and downregulated the expression of pro-inflammatory cytokines. Histopathological evaluation confirmed that the combination therapy effectively protected the alveolar structure and alleviated tissue damage, with a protective effect superior to that of ceftiofur (CEF), the first-line clinical drug. Collectively, our findings demonstrate the therapeutic potential of the combination of thanatin and gallium nitrate in a rat model of mastitis and provide experimental evidence supporting the development of a novel non-antibiotic therapeutic strategy for bovine mastitis caused by multidrug-resistant E. coli. Full article

Objective: This study aimed to analyze risk factors for post-stroke dysphagia during the recovery phase of acute ischemic stroke and to construct a preliminary risk prediction model for patients who were eligible for bedside swallowing assessment. Methods: A retrospective analysis was performed for patients with ischemic stroke who were continuously admitted to Shanghai Fourth People’s Hospital. Swallowing function was assessed using the water swallowing test. Univariate and multivariate analyses were used to screen variables, and a predictive model was constructed using binary logistic regression. The model was visualized using a nomogram. Calibration curves and receiver operating characteristic curves were employed to assess the model’s accuracy and predictive value, while decision curve analysis was used to examine the model’s clinical relevance. Results: Overall, 209 ischemic stroke patients were included in the analysis. Univariate and multivariate logistic regression analyses identified higher NIHSS score and lower triglyceride level as independent factors associated with swallowing dysfunction (p-value < 0.05); the full model (NIHSS + TG) yielded AUCs of 0.685 (95% CI: 0.523–0.783) in the training set and 0.679 (95% CI: 0.606–0.700) in the test set, with corresponding sensitivities of 0.52 and 0.61, and specificities of 0.78 and 0.70, respectively. Compared with NIHSS alone (AUC 0.652, 95% CI: 0.518–0.746), the AUC improvement was not significant (DeLong p = 0.09), but the net reclassification improvement was 0.26 (95% CI: 0.02–0.49). Conclusions: This preliminary derivation model, based on NIHSS and triglyceride levels, demonstrates modest discrimination but provides incremental reclassification value over NIHSS alone for estimating the risk of PSD in cooperative patients. The model should be considered exploratory, and external validation is required before any clinical application. Full article

Background: Knee osteoarthritis (KOA) affects over 300 million people globally, yet current therapies face limitations in efficacy and safety. Chitosan, a natural polysaccharide, has shown conflicting evidence in KOA management. This systematic review evaluates chitosan’s clinical effectiveness and defines its optimal application scenarios. Methods: Randomized controlled trials (RCTs) published before the end of November 2024 on chitosan and knee osteoarthritis were systematically retrieved from PubMed, Web of Science, Cochrane Library, EBSCO, PsycINFO, ClinicalTrials.gov, SINOMED, Chinese Medical Journal Network, CNKI, VIP, Wanfang Data, Embase, and SCOPUS. After screening the references, publications meeting the inclusion and exclusion criteria was selected. RevMan5.4 software was used to perform the meta-analysis of the data. Results: A total of 231 articles were retrieved, and 14 RCTs involving 1504 participants were included. For the primary efficacy outcome, pooled analysis of 10 RCTs showed a significantly higher overall clinical response rate in the chitosan group compared with the control group (OR = 5.43, 95% CI = 3.21, 9.18, p < 0.001), with no observed heterogeneity (I² = 0%). Additionally, meta-analysis of 12 RCTs demonstrated a significant reduction in visual analog scale (VAS) pain scores (MD = −1.06, 95% CI = −1.38, −0.73, p < 0.001) in patients receiving intra-articular chitosan injection. Subgroup analysis of VAS scores showed that pain reduction varied significantly by follow-up duration (I² for subgroup differences = 62.5%, p = 0.03). Conclusions: Intra-articular injection of medical chitosan shows potential benefits for pain relief and clinical efficacy in patients with knee osteoarthritis, with a low incidence of adverse reactions. Nevertheless, the evidence remains promising but preliminary. Full article

Coronary heart disease (CHD) is a global cardiovascular disease with high morbidity and mortality, and its complex pathological mechanism poses great challenges to clinical prevention and treatment. Paeoniflorin (PA), a monoterpene glycoside active ingredient from Ranunculaceae plants, has shown potential in cardiovascular protection, but its specific anti-CHD molecular targets and systematic regulatory networks remain unclear. In this study, a mouse model of CHD was established, and a multi-omics strategy combining label-free quantitative proteomics and metabolomics was adopted to explore the mechanism of PA in treating CHD. The results showed that PA significantly improved cardiac function, alleviated myocardial pathological injury and fibrosis, and regulated lipid metabolism in CHD model mice, with the high-dose group showing the optimal effect. Proteomic analysis identified 51 key differentially expressed proteins (DEPs) reversed by PA, which were mainly enriched in complement and coagulation cascades, and neutrophil extracellular trap formation pathways, with the C3-Cfd-C3aR signaling axis as the core hub. Further verification confirmed that PA could downregulate the expression of C3, Cfd, C3aR, and their downstream molecule BTK, thereby inhibiting myocardial inflammatory response and cardiomyocyte apoptosis. In addition, PA downregulated the expression of platelet activation markers ITGA2B/ITGB3. Metabolomic analysis revealed that PA reversed 57 abnormal metabolites in CHD mice, which were enriched in GABAergic synapse, retrograde endocannabinoid signaling and other pathways. Molecular docking confirmed that PA could stably bind to C3, Cfd, C3aR, BTK, and ITGA2B/ITGB3 with strong binding activity. In conclusion, PA exerts anti-CHD effects through a multi-target and multi-pathway synergism, mainly by targeting the C3-Cfd-C3aR axis to inhibit inflammation, apoptosis and platelet activation, and regulating metabolic disorders. This study provides experimental evidence and theoretical support for the clinical application of PA as a multi-target therapeutic drug for CHD. Full article

Background: The rising global prevalence of hyperlipidemia is closely linked to current dietary patterns, sparking interest in “medicine-food homology” (MFH) plants as natural resources that provide both nutritional benefits and therapeutic effects. This study reviews MFH plants used to treat hyperlipidemia, incorporating changes in regulatory mechanisms, the impact of processing on bioavailability, and evidence of their lipid-lowering effects. Methods: This narrative review, supported by a structured literature search, summarizes the practical applications of MFH plant species with both medicinal and edible properties and discusses their bioactive components and lipid-regulating mechanisms. Results: MFH plants not only contain anti-lipid active ingredients but also have improved bioavailability after processing through processing technology and function through lipid metabolism pathways and the gut-liver axis. Conclusions: The development and application of MFH plants face several challenges, including incomplete and inconsistent international regulatory frameworks, difficulties in quality control, and limited clinical evidence for lipid-lowering mechanisms. Nevertheless, MFH plants hold promise for development into functional foods or nutraceuticals aimed at supporting lipid regulation. Full article

Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal and heterogeneous primary liver malignancy with a dismal prognosis. Approximately 70% of patients are diagnosed at locally advanced or metastatic stages, therefore missing the opportunity for curative surgery, and conventional chemotherapy offers limited survival benefits. Immunotherapy, especially immune checkpoint blockade, represents a promising strategy, yet its efficacy as monotherapy in iCCA remains modest primarily due to the profoundly immunosuppressive and desmoplastic tumor microenvironment. This review examines the immune cell infiltration landscape of iCCA, focusing on the distinct roles of lymphoid cells and myeloid cells in shaping immune evasion. We then analyze key factors affecting immune responses, such as tumor-intrinsic driver mutations, immune regulatory mechanisms, and acquired resistance. Furthermore, we summarize current clinical advances in iCCA immunotherapy, including immune checkpoint inhibitor monotherapy, bispecific antibodies, combination strategies with chemotherapy or targeted therapy, cancer vaccines, and adoptive cell therapy. Despite some progress, the overall response to immunotherapy remains suboptimal, and future strategies need to focus on deciphering context-specific resistance mechanisms and enhancing the tumor-specific immune response. Full article

The dried rhizome of Atractylodes lancea (RAL) is a widely used traditional Chinese medicine (TCM). Its quality evaluation and origin authentication have long relied on time-consuming chromatographic methods, which are poorly suited for rapid, on-site decisions in commercial supply chains, and existing studies generally focus on isolated morphological indicators without systematic digital characterization and practical on-site grading tools. Guided by the traditional empirical knowledge of “Bianzhuang Lunzhi”, which holds that external morphological traits can reflect the internal quality of TCM, this study presents the first systematic multi-dimensional digital characterization of RAL morphological traits using an integrated multi-sensor approach and quantitatively explores the underlying correlations between digital traits and key bioactive constituent contents. Nighty samples from three major producing regions were analyzed. Significant correlations were observed between odor indices, color parameters, density, oil cavity area ratio and bioactive component contents in the authentic Maoshan-sourced RAL (p < 0.01 or p < 0.05). Such associations were absent in the emerging regions (Dabie and Qin−Ba Mountains). A three-grade quality classification system based on density thresholds (Grade A: ≥0.73 g/cm³; B: 0.58–0.73 g/cm³; C: <0.58 g/cm³) was established specifically for Maoshan RAL. Additionally, an electronic nose-based classification model was constructed for geographical origin discrimination, which delivered reliable and robust classification performance in external validation with independent blind test samples. This work provides practical, low-cost tools for rapid quality grading and origin identification of RAL. The proposed trait-driven analytical strategy offers a generalizable framework for the quality control of other complex herbal medicines. Full article

Background/Objectives: Metabolic-dysfunction-associated steatotic liver disease (MASLD) and metabolic-dysfunction-associated steatohepatitis (MASH) arise in the setting of obesity, insulin resistance, type 2 diabetes, and metabolic syndrome. This review examines how mitochondrial dysfunction participates in the transition from lipid accumulation to hepatocyte injury, inflammation, and fibrosis, and how evidence from human, animal, and in vitro studies should be interpreted. Methods: We provide a narrative synthesis of mechanistic, translational, and clinical studies on hepatic mitochondrial metabolism, fatty acid oxidation, oxidative phosphorylation, redox stress, organelle crosstalk, mitophagy, mitochondrial biogenesis and proteostasis, mitochondrial danger signals, the gut-liver-mitochondria axis, and mitochondria-related therapeutic strategies. Results: In early metabolic overload, mitochondrial oxidation may increase as an adaptive response. With persistent substrate pressure, this adaptation can become inefficient, with impaired fatty acid disposal, less efficient oxidative phosphorylation, reactive oxygen species production, redox imbalance, defective mitochondrial quality control, altered mitochondrial biogenesis, mitochondrial unfolded protein response (UPRmt)-related proteostatic stress and mtDNA instability. Mitochondrial DNA and RNA released from damaged organelles may also activate cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING), inflammasome, and RNA-sensing pathways, linking hepatocyte stress to macrophage activation, stellate cell activation, extracellular matrix deposition, and fibrosis. Conclusions: The current evidence supports mitochondria as a stage-dependent amplifier of metabolic liver injury rather than a uniform initiating event. Clinically, the strongest evidence remains with upstream metabolic unloading and liver-directed metabolic therapy, whereas direct mitochondrial restoration and quality-control targeting remain promising but less mature. Full article

Cardiac glycosides from Periplocae Cortex are bioactive constituents, but isolating and structurally confirming their trace in vivo metabolites remains challenging because authentic standards are often unavailable. We developed a steroid-core fragment-guided strategy based on the diagnostic ion at m/z 355.2270 that integrates metabolite screening, targeted purification, and structural characterization. Periplocin-related analytes were detected in rat urine and plasma after oral periplocin administration using HPLC-QQQ-MS/MS and UPLC-Q-TOF-MS/MS. Guided by the diagnostic ion, 13 L of rat urine was fractionated using macroporous resin, Sephadex LH-20, ODS chromatography, and preparative HPLC. Two trace metabolites were isolated and identified as gomphogenin (M1, 4 mg) and 17α-asclepioside (M2, 8 mg) by HR-MS and NMR spectroscopy. Periplocin, periplogenin, and periplocymarin were confirmed using reference standards. Structural comparison supported a putative transformation pathway involving deglycosylation and steroid-core modification. In a hypoxia/reoxygenation-injured H9c2 cell model, M1 and M2 increased cell viability at 50 μM, supporting further evaluation using complementary cellular endpoints. This diagnostic-ion-guided workflow enables the targeted isolation of trace cardenolide metabolites from biological matrices and provides reference compounds for future pharmacokinetic and pharmacological studies. Full article