AMPK Signaling Research Articles

The differentiation of human induced pluripotent stem cells (hiPSCs) into sinoatrial node-like cells (SANLCs) remains challenged by complex differentiation protocols and low efficiency. This study aims to reveal the role of AMPK signaling in the differentiation process of hiPSCs into SANLCs, providing new strategies for obtaining SANLCs in vitro. Cells from the cardiac mesodermal stage, cardiac progenitor cell stage and cardiomyocyte stage during differentiation of hiPSCs to cardiomyocytes (hiPSC-CMs) were taken for transcriptome sequencing and analyses. PCR, immunostaining, Western blot, FACS and patch clamp techniques were employed for the analyses of differentiated hiPSC-CMs. KEGG analysis identified that the AMPK signaling pathway is significantly enriched with the expression of NKX2.5 (sinus node cell development-related transcription factor). The early activation and late inhibition of AMPK signaling were both effective in the upregulation of SANLCs markers. In addition, the combined manipulation of both stages further enhanced the differentiation efficiency reflected by higher SANLCs marker expression, which was also confirmed at the protein level by immunofluorescence, Western blot, flow cytometry analyses. SANLCs obtained from the differentiation with combined modulation of AMPK signaling displayed typical features of native pacemaker cells in the heart, including ion channel currents (IKAch, ICaT, ICaL, If), action potentials and robust autonomic responsiveness to both β-adrenergic and muscarinic stimulation. Early activation and then inhibition of the AMPK signaling pathway during the differentiation process can promote hiPSCs differentiation to SANLCs, which may provide a novel strategy for obtaining SANLCs for studies on sinoatrial node diseases.

Food is a crucial component affecting the health of individuals, which may have the potential to expand lifespan. It has been shown that a long lifespan may be related to fine-tuned autophagy. In general, suitable autophagy could play a significant role in the anti-aging biological exertion of the host. AMPK, a member of serine and threonine kinases, could play vital roles within the autophagy signaling pathway in various cells. In addition, alterations in the kinase activity of AMPK have been shown to be connected to several pathologies of aging-related diseases. Therefore, autophagy could control the lifespan-related homeostasis within the host from cells to a body via the modification of AMPK. The design of the diet and/or nutrition targeting the AMPK would be a possibility to expand the lifespan. Some analyses of the molecular biology underlying the autophagy suggest that supplementation of accurate nutraceuticals, as well as dietary restriction, mild fasting, and/or appropriate physical exercise, could modulate AMPK signaling, which may be advantageous for life extension with the alteration of autophagy. Remarkably, it has been revealed that several non-coding RNAs (ncRNAs) might also play significant roles in the regulation of autophagy. In addition, the production of some ncRNAs may be associated with the alteration of gut microbiota with certain diets. Therefore, the modulation of AMPK action with ncRNAs through choosing the relevant diet could be a therapeutic tactic for promoting longevity, which is also accompanied by a reduced risk for several aging-related diseases.

Objective: Dilated Cardiomyopathy (DCM) and Hypertrophic Cardiomyopathy (HCM) are two major forms of heart diseases characterized by different pathological mechanisms. DCM is often marked by ventricular dilation and impaired contractility, while HCM involves abnormal thickening of the heart muscle, leading to compromised cardiac function. Despite the significant differences in these two conditions, their underlying molecular mechanisms are not fully understood. This study aims to use Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to identify and compare the key biological processes and signaling pathways involved in DCM and HCM. Methods: We performed GO and KEGG pathway analysis on gene expression data from DCM and HCM patient samples in two published RNA-seq datasets (GSE116250 and GSE89714). Differential gene expression analysis was performed using DESeq2 with a statistical cutoff of FDR (False discovery rate) < 0.05 and fold change > 1.5. The enrichment analysis was performed using R package “clusterProfiler” and “org.Hs.eg.db”. Results: The analysis identified 3599 and 711 differentially expressed genes (DEGs) between DCM versus HCM. Interestingly, both DCM and HCM shared several overlapping genes and pathways, exhibiting a significantly common enrichment in cytoskeleton in muscle cells, suggesting common pathophysiological mechanisms despite the distinct phenotypes of these diseases (A). The GO analysis for DCM revealed significant alterations in processes related to sarcomere/myofibril organization. However, GO analysis for HCM suggests a crucial role of mitochondrial function alternations. The KEGG analysis also demonstrated that AMPK signaling pathway, citrate cycle, focal adhesion and insulin signaling pathway were highly enriched in DCM patients (B, C). While the same analysis for HCM patients demonstrated that chemical carcinogenesis − reactive oxygen species, diabetic cardiomyopathy, non−alcoholic fatty liver disease and oxidative phosphorylation were dramatically affected in HCM (D, E). Conclusion: This study provides a profound understanding of DCM and HCM, helping provide new insights into the pathogenesis of two diseases. DCM exhibited a more pronounced structural disorders of cardiomyocytes whereas HCM was predominantly affected in mitochondria and metabolism disorders. These findings may give novel insights into the discovery of potential therapeutic targets for treating various types of heart failure.

Dyslipidemia contributes to oxidative stress, inflammation, and the dedifferentiation, migration, and proliferation of vascular smooth muscle cells (SMCs), ultimately promoting the development and progression of atherosclerosis. Bempedoic acid (BA), an FDA-approved medication for managing dyslipidemia, particularly in patients with statin intolerance, acts by inhibiting adenosine triphosphate-citrate lyase (ACLY), a key enzyme in fatty acid biosynthesis. Recent evidence indicates that BA also exerts lipid-independent, pleiotropic effects by reducing oxidative stress and inflammation. Based on this, we hypothesized that BA could inhibit oxidized low-density lipoprotein (oxLDL)-induced migration, proliferation, and proinflammatory phenotype switching in SMCs by targeting oxidative stress and inflammation. To test this, human coronary artery SMCs were exposed to varying concentrations of oxLDL, and inflammatory responses were assessed. OxLDL induced a dose- and time-dependent increase in the mRNA and protein expression of a proinflammatory signaling molecule, TRAF3IP2, over a 6-hour period. Pre-treatment with 100 µM BA significantly reduced both TRAF3IP2 mRNA and protein levels. This oxLDL-induced TRAF3IP2 upregulation was found to be reactive oxygen species (ROS)-dependent, driven by NADPH oxidase activity, accompanied by downregulation of antioxidant enzymes superoxide dismutase 1 (SOD1) and catalase (CAT). Notably, BA reversed the suppression of SOD1 and CAT, thereby reducing ROS levels and subsequently decreasing TRAF3IP2 expression. Moreover, BA inhibited oxLDL-induced phenotypic switching of SMCs toward a proinflammatory state, as evidenced by downregulation of inflammatory markers (LGALS3, OLR1, IL-6, IL-8, ICAM1, VCAM1, and TNF) and restoration of contractile SMC markers (ACTA2 and MYH11). BA also suppressed oxLDL-induced activation of matrix metalloproteinases MMP2 and MMP9, as well as SMC migration and proliferation, without compromising cell viability. Importantly, inhibition of ACLY or AMPK signaling blunted the anti-inflammatory, anti-proliferative, and anti-migratory effects of BA. Collectively, these findings demonstrate that BA, through ACLY and AMPK pathways, mitigates oxLDL-induced oxidative stress and inflammation, thereby preventing the transition of SMCs to a proinflammatory, pro-migratory, and proliferative phenotype. These results support the potential therapeutic application of BA in vascular atherosclerotic diseases.

ObjectiveTo analyze the lipidomic profile of ESCC patients, link changes in cancer lipid metabolism to gene expression changes, and provide new insights into the diagnosis and treatment of ESCC patients in the Kazakh Xinjiang ethnic group.MethodsBy integrating the lipidome and transcriptome results, genes related to differential lipid metabolites in Kazakh ESCC patients were identified, and the effects of the key gene AMPK on lipid metabolism in ESCC cells were investigated by ultra-performance liquid chromatography/tandem mass spectrometry (UPLC‒MS/MS).ResultThrough absolute lipid quantification analysis of two serum samples, 13 classes of lipids were detected, with triglycerides (TAGs) being the most abundant. Phosphatidylcholine (LPC), phosphatidylethanolamine (PE), and ceramide (Cer) were the lipid categories with significant differences between the two groups. Transcriptome analysis revealed that genes related to fatty acid synthesis, carnitine biosynthesis, and other lipid metabolism pathways were enriched in the tumor tissue. Integrative analysis of the two groups suggested that fatty acid synthesis, fatty acid metabolism, lipid degradation, cholesterol metabolism, and the AMPK signaling pathway were enriched in tumor tissue. UPLC‒MS/MS was used to perform targeted lipidomic analysis of AMPK-knockdown esophageal squamous cell carcinoma cells, suggesting that AMPK may be involved in the reprogramming of lipid metabolism in Kazakh ESCC patients.ConclusionsLipid metabolic reprogramming occurs in the tumor tissue of Kazakh ESCC patients, and there is a correlation between AMPK activity and lipid metabolism, which suggests a potential therapeutic target for the treatment of Kazakh ESCC.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12885-025-14858-7.

Regulatory mechanism of quercitrin on oxidative stress and histone acetylation changes in PRV infected 3D4/2cells.

DEHP promotes psoriasis via immune modulation and direct molecular interactions: Evidence from epidemiology, multi-omics, and structural simulation.

Potential saviour of pulmonary fibrosis: multi-pathway treatment of natural products.

Therapeutic extracellular vesicles enriched with SNHG5 reprogram autophagy and macrophage polarization in osteoarthritis.

SIRT3 mitigates osteoarthritis by suppressing ferroptosis through activating AMPK signaling pathway.

HSQC-guided discovery and structural optimization of antiadipogenic indole diterpenoids from endophytic fungus Penicillium janthinellum H-6.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent joint inflammation and progressive structural damage, with early diagnosis remaining a significant clinical challenge. Circulating microRNAs (miRNAs) have emerged as promising biomarkers for disease diagnosis, prognosis, and therapeutic response due to their critical roles in gene regulation. However, the specific miRNAs causally involved in RA pathogenesis remain largely unidentified. We conducted a 2-sample Mendelian randomization (MR) analysis using summary-level data from the largest available genome-wide association study of circulating cis-miRNA expression quantitative trait loci (cis-miR-eQTLs) and RA genome-wide association study summary statistics. The inverse variance weighted method served as the primary analytical approach, supplemented by comprehensive sensitivity analyses including Cochran Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis to ensure result robustness. Additionally, we performed target gene prediction, gene ontology and kyoto encyclopedia of genes and genomes enrichment analyses, and druggable analysis to explore the underlying biological mechanisms and therapeutic potential of the causal miRNAs. Our MR analysis identified 8 circulating miRNAs with significant causal associations with RA risk. Notably, hsa-miR-130a-3p (P = 6.5332 × 10−5, OR = 1.0720, 95% CI = 1.0360–1.1092) emerged as a key risk factor, while hsa-miR-204-5p (P = 6.2123 × 10−4, OR = 0.9707, 95% CI = 0.9543–0.9874) demonstrated a protective effect. Bioinformatics analyses revealed that hsa-miR-130a-3p may modulate the TGF-β, Hippo, and mTOR signaling pathways by interacting with competing endogenous RNAs (ceRNAs) such as H19 and regulating hub proteins including TNF, UBB, PPARG, and TGFBR1. Resveratrol and flufenamic acid were identified as candidate therapeutic agents targeting its downstream pathways. Conversely, hsa-miR-204-5p was predicted to influence the AMPK, cGMP-PKG, and cAMP signaling pathways via ceRNAs like NEAT1 and NORAD, affecting key proteins such as BCL2, SIRT1, and HMGA2, with cilostazol, melatonin, and curcumin identified as potential modulators. This study provides novel causal evidence implicating hsa-miR-130a-3p and hsa-miR-204-5p in RA pathogenesis. These findings highlight their potential as circulating biomarkers for early diagnosis and risk assessment, as well as therapeutic targets for miRNA-based intervention strategies, thereby offering valuable insights for advancing precision medicine in RA management.

Natural products in the treatment of autoimmune hepatitis: A comprehensive review of therapeutic potential and mechanisms.

Background/AimType 2 diabetes mellitus (T2DM) is a prevalent disorder characterized by an increased concentration of blood glucose and impaired insulin function. Throughout the course of the disease, β-cell function fails and insulin production decreases. Studying the molecular systems responsible for insulin production, release, and action is crucial for the management and treatment of the disease. Thus, this study aimed to scrutinize the therapeutic efficacies of oxytocin (OXT) on nicotinamide (NA)/streptozotocin (STZ)-induced diabetes in rats and elucidate the underlying mechanisms.Materials and MethodsWistar rats were supplied a single intraperitoneal (i.p.) dose of NA (120 mg/kg) 15 min before an i.p. injection of STZ (60 mg/kg) after fasting for 16 h. Ten days later, the diabetic rats were orally administered OXT every day for eight weeks at dose levels 0.5, 1, and 2 IU/kg.ResultsThe treatment of diabetic rats with OXT significantly improved oral glucose tolerance, serum insulin and C-peptide concentrations, and pancreatic islets’ structure and function. Furthermore, the activities of liver glucose-6-phospatase and glycogen phosphorylase significantly decreased. OXT treatment also resulted in an increase in serum adiponectin levels, while the levels of serum resistin, omentin, vaspin, and free fatty acids significantly decreased. Additionally, OXT significantly alleviated the mRNA levels of components of the PI3K-AKT and AMPK signaling pathways as well as their effectors including PPARγ, insulin receptor (IR), IR substrates 1 and 2 (IRS1 & IRS2), PI3K, AKT, AMPK, and glucose transporter 4 (GLUT4) in visceral adipose tissues of diabetic rats.ConclusionOXT can exert antidiabetic effects and may be useful for developing multiple targeted therapeutic strategies for diabetes treatment. The effects may be mediated via improvement in β-cell function, insulin secretory response, and insulin sensitivity.

A 56-day feeding trial was performed to investigate the effects of the dietary protein-to-energy (P/E) ratio on the growth performance, body composition, and health status of large-sized grass carp, Ctenopharyngodon idella . The fish (initial body weight 2,200.4 ± 79.3 g) were randomly fed one of the six isolipidic and isoenergetic diets (gross energy 10 kJ/g), which were formulated with various P/E ratios (21.7 mg/kJ, 23.7 mg/kJ, 24.9 mg/kJ, 27.1 mg/kJ, 29.2 mg/kJ, and 31.5 mg/kJ) and named P/E 21.7, P/E 23.7, P/E 24.9, P/E 27.1, P/E 29.2 mg/kJ and P/E 31.5, respectively. After the feeding trial, the best growth performance was observed in the P/E 29.2 group, which had the highest weight gain. In addition, fish fed the optimal P/E diet exhibited a superior health status in terms of tissue histology and biochemical analyses of serum and liver. The liver transcriptome assay revealed that a suitable P/E ratio potentially enhances growth performance and immune function by modulating the AMPK signaling pathway, the Ras signaling pathway, and arachidonic acid metabolism, along with affecting rRNA synthesis by regulating ribosome biogenesis gene expression in eukaryotes. Based on the second-order polynomial regression analysis of the growth performance and health status against P/E, the optimal P/E range was found to be 27.36–28.93.

Abstract Disclosure: R. Fang: None. R.S. Carroll: None. U.B. Kaiser: None. Background and Objective: The prevalence of male hypogonadism and infertility are increasing in association with the pandemic of obesity and type 2 diabetes (T2D). A bidirectional relationship between kisspeptin (Kiss1) neurons in the hypothalamic arcuate nucleus (ARC) and metabolism is emerging. Kiss1 neuron dysfunction has been reported in male mice fed a high-fat diet (HFD), a model of metabolic disorder-induced hypogonadism. However, the mechanism is not well understood. 5-hydroxymethylcytosine (5hmC), an oxidation product of 5-methylcytosine (5mC) generated by the Ten-Eleven Translocation (TET) family of α-ketoglutarate-dependent dioxygenases, is down-regulated by hyperglycemia via AMPK signaling and glucose oxidation intermediates such as succinate and fumarate. We hypothesize that the porous blood-brain barrier in the median eminence exposes Kiss1 neurons to metabolite changes in the peripheral blood that directly impact the Kiss1 neuron 5hmC methylome and metabolism. Methods: Six-week-old male C57BL6 mice were fed ad libitum standard chow (Purina 5053, 13.2% fat) or high-fat diet (HFD; Research Diets D12492, 60% fat) for 3 months. ARC tissue was collected from chow- and HFD-fed mice and analyzed by RNA-seq and hydroxymethylated DNA immunoprecipitation sequencing (hMeDIP-seq). Results: Mice fed HFD developed obesity (48.3 ± 0.8 vs 29.3 ± 0.7 g, p<0.001) and hyperglycemia (fasting glucose 186.4 ± 4.7 vs 125.8 ± 4.3 mg/dL, p<0.001). Glucose clearance was significantly slower in glucose tolerance and insulin tolerance tests, demonstrating glucose intolerance and insulin resistance. HFD mice had lower T levels (2.1 ± 0.6 vs 6.1 ± 2.0 ng/ml, p<0.05) and sperm counts (0.63 ± 0.04 vs 0.41 ± 0.03 million, p<0.05). LH secretion in response to ip senktide stimulation – but not to ip kisspeptin-10 – was significantly reduced (AUC 51.4 ± 3.3 vs 63.1 ± 7.2, p<0.05). Differentially expressed genes detected by RNA-seq in HFD ARC (676 in total, 1.5 fold change & p<0.05) were enriched in KEGG pathways important for fatty acid metabolism, neuron projection, and synapse formation and maintenance. hMeDIP-seq revealed widespread 5hmC alterations that correlated with gene expression changes. Ectopic TET expression in immortalized ARC Kiss1 neuron cell line restored 5hmC and expression of key metabolic and neuronal genes (Fabp7, Foxo1, Rxra, Dusp1, Fos) that were suppressed in HFD ARC, demonstrating functional importance. Conclusions: Our study demonstrates that Kiss1 neurons are sensitive to diet and metabolic changes, and are key targets of the effects of metabolic disorders. Hyperglycemia-induced 5hmC changes play a key role in regulating Kiss1 neuron metabolism and function, thereby affecting reproduction. These findings provide a new mechanism underlying the cross-talk of Kiss1 neurons and metabolism, independent of upstream inputs from POMC and AgRP neurons. Presentation: Monday, July 14, 2025

Small breast epithelial mucin (SBEM) is upregulated in primary breast tumors and metastatic lymph nodes and has been implicated in chemoresistance. While it has been identified as a potential biomarker for monitoring hematogenous micrometastasis in patients with breast cancer undergoing adjuvant chemotherapy, the molecular mechanisms by which SBEM confers this resistance remain unclear. Therefore, the present study aimed to elucidate the mechanisms by which SBEM regulates paclitaxel (PTX) resistance in breast cancer. To this aim, breast cancer cell lines with SBEM overexpression and knockdown were developed from parental drug-resistant strains. Additionally, AMPK activator 13 was used to investigate the involvement of the AMPK pathway in the SBEM-mediated effects. The results indicated that SBEM overexpression promoted cell viability and enhanced resistance to PTX in breast cancer cells. Conversely, SBEM knockdown significantly increased apoptosis, with a three-fold increase compared with the controls, and restored PTX sensitivity in drug-resistant cells. Mechanistically, SBEM was found to interact with dual-specificity phosphatase 16 (DUSP16) and upregulate its expression. Additionally, SBEM downregulation inhibited AMPK signaling activity, thereby suppressing cancer cell viability. In conclusion, abnormal activation of the AMPK signaling pathway was shown to contribute to PTX resistance in breast cancer. SBEM enhanced DUSP16 expression and activated the AMPK signaling pathway, thereby conferring resistance to PTX.

BackgroundThe global prevalence of adult obesity has increased significantly, affecting over 890 million adults worldwide. Wumeishanzhayin (WMSZY), a formulation derived from four medicinal and edible botanical drugs, has shown efficacy in alleviating obesity and lipid metabolism disorders induced by high-fat and high-fructose (HFHF) diets. However, its underlying therapeutic mechanisms remain unclear.ObjectiveThis study aims to investigate the therapeutic effects and mechanisms of WMSZY in ameliorating obesity induced by a HFHF diet.MethodsUPLC-MS/MS was used to characterize the metabolites of WMSZY. The effects of WMSZY on body weight gain, lipid metabolism, and glucose dysfunction were evaluated in a HFHF diet-induced murine model. Targeted lipidomics and transcriptomics analyses were performed to identify differentially altered lipids (DALs) and differentially expressed genes (DEGs). Computational approaches, including molecular docking simulation and dynamics simulations, were used to predict bioactive compound-target interactions. Key findings were validated through RT-qPCR and Western blot. Integrated transcriptomic and lipidomic analyses identified potential therapeutic targets.ResultsSixteen metabolites were identified in WMSZY. Animal studies showed that WMSZY reduced body weight gain, improved lipid and glucose metabolism, and alleviated inflammation in HFHF diet-induced mice. Targeted lipidomics indicated that WMSZY’s anti-obesity effect may be linked to cholesterol metabolism, adipocyte lipolysis, lipid digestion, insulin resistance, and glycerolipid metabolism. Transcriptomic analysis suggested involvement of AMPK, MAPK, and PPAR signaling pathways. Molecular docking simulation revealed strong binding of WMSZY metabolites with AMPK, and simulations showed that cryptochlorogenic acid had notable binding affinity. The data from Western blot and RT-qPCR showed changes associated with the activation of the AMPK/CPT-1 pathway and the inhibition of lipid metabolism-related genes following WMSZY treatment.ConclusionWMSZY significantly reduces body weight gain and ameliorates glucose and lipid metabolic disorders in HFHF diet-induced mice. Its anti-obesity effect is likely due to the regulation of lipid metabolism via the AMPK/CPT-1 signaling pathway.

BackgroundAlveolar echinococcosis (AE) is a globally widespread zoonotic disease caused by the larval stage of the tapeworm Echinococcus multilocularis, posing a high fatality rate and poor prognosis if not properly managed. Currently, effective vaccines or drugs for echinococcosis remain elusive. MicroRNAs (miRNAs) play crucial roles in various biological processes and are closely linked with parasite infection and pathogenicity. To date, there is limited knowledge about host miRNA profiles in E. multilocularis infection at different stages. Hence, exploring host miRNA expression patterns at different infection stages is vital for understanding miRNA transcriptional regulation mechanisms.MethodsThis study employs small RNA sequencing to depict the temporal dynamics of miRNAs in mice liver at 40, 80, and 120 dpi with E. multilocularis. Additionally, Short Time-series Expression Miner, Gene ontology, KEGG pathway, and miRNA-target gene-pathway network analysis were conducted to elucidate each miRNA’s changing trends, focusing on the hub miRNAs during infection. Subsequently, miRNA altering patterns at 40, 80, and 120 dpi were confirmed via quantitative real-time PCR.ResultsThe findings reveal time-dependent miRNA expression profiles, categorized into three distinct patterns specific to early, middle, and late infection stages. Overall, 61 miRNAs were stage-differentially expressed in the livers of infected mice compared to uninfected mice, with 29 miRNAs up-regulated and 32 miRNAs down-regulated. Notably, in the early phase, 23 miRNAs showed differential expression, with 18 up-regulated and 5 down-regulated (|log₂FC| >1, P < 0.05). Moreover, genes regulated during this phase primarily involved in Th17 cell differentiation, AMPK signaling pathway, and Calcium signaling pathway. Subsequently, during the middle infection stage, a total of 16 miRNAs exhibited differential expression, with 8 up-regulated and 8 down-regulated (|log₂FC| >1, P < 0.05). These miRNAs are involved in prolactin signaling pathway, aldosterone synthesis secretion, and Cushing’s syndrome. In the late infection stage, 22 differentially expressed miRNAs were identified, with 3 up-regulated and 19 down-regulated (|log₂FC| >1, P < 0.05). Furthermore, the identified target genes primarily participated in ECM-receptor interaction, TGF-β signaling pathway, and human papillomavirus infection pathway. Also, through network interaction analysis, it was speculated that Src, Jag1, and Mapk1 exhibited the most hub signaling genes during the early, middle, and late infection stages, respectively, while the Srf was dynamically expressed hub signaling gene throughout the whole infection stage. As the disease progresses, several hub networks have been identified around target genes, including the mmu-miR-1247-5p-Src-Rap1 signaling pathway, mmu-miR-149-5p-Jag1-Notch signaling pathway, mmu-miR-299a-5p-Mapk1-human papillomavirus infection pathway in the early, middle and late stages, respectively. Additionally, the mmu-miR-122-3p-Srf-MAPK signaling pathway was predicted to be the hub network in the whole infection stage.ConclusionsOverall, our investigation elucidates the temporal dynamic changes in host miRNAs and their potential target genes at the early, middle and late stages of E. multilocularis infection, which allows us to understand the roles of miRNAs in host-parasite interactions throughout infection and provides a reference for further studies of molecular pathogenesis and new drug or vaccine targets for control of AE.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12864-025-12049-z.

ABSTRACTPleural Mesothelioma (PM) is an aggressive tumor with a poor prognosis and limited therapeutic options. Despite the notion that resveratrol (RSV) significantly inhibits the growth of PM cancer cells, it is necessary to evaluate the effects of this stilbene as a tumor suppressor agent. In this work, the effects of the natural polyphenol were investigated on PM cell lines (MSTO‐211H and IST‐MES 2) to evaluate its action as a potential adjuvant agent, together with chemotherapy. Our results showed that RSV treatment was effective in PM cell lines, in particular in MSTO‐211H. RES treatment decreases the viability evaluated with the MTT assay and Live/Dead staining. RSV stimulates the apoptotic process with positive staining for Annexin V‐PI and Caspase‐3/7 and inhibits the migration ability of both PM cell lines. In IST‐MES 2, RSV causes a reduction in mitochondrial and cytoplasmic calcium levels. Moreover, RSV affects cellular morphology, E‐cadherin protein expression, and decreased nuclear localization of β‐catenin, attenuating Wnt/β‐catenin signaling, which regulates tumor cell proliferation. At the molecular level, RSV modulated the expression of key genes that play an important role in cellular adhesion, proliferation, and metabolic activity, as well as AMPK signaling. RSV seems to be a promising therapeutic adjuvant agent for PM treatment.