Search Results (19)

Aspartame is a widely used artificial sweetener, but its possible relationship with rheumatoid arthritis (RA) remains insufficiently understood. This study aimed to explore, rather than prove, potential molecular links between aspartame-related targets and RA-associated gene networks. Three public RA transcriptomic datasets (GSE55235, GSE55457, and GSE77298) from the Gene Expression Omnibus (GEO) database were integrated as discovery/training data. Because these datasets included different tissue origins, batch correction was used to reduce dataset-level technical variation, whereas tissue-origin-related biological variation was not assumed to be fully removable. After differential expression analysis, RA-associated differentially expressed genes (DEGs) were identified. The single-cell dataset GSE200815 was used for cell annotation and cellular expression visualization; because its comparator group consists of psoriatic arthritis (PsA) samples rather than healthy controls, single-cell results were interpreted as RA-vs-PsA observations and were not treated as disease-versus-healthy-control evidence. Potential targets of aspartame were retrieved from ChEMBL, SwissTargetPrediction, and the Similarity Ensemble Approach (SEA), and were intersected with RA-related DEGs to construct an aspartame-gene-RA regulatory network. Diagnostic models were developed using 113 machine-learning algorithm combinations to determine an optimal multigene model and its core genes. HLA-DRB1 was selected for exploratory scTenifoldKnk-based virtual knockout mainly because it was included in the optimal model and has a well-established role in RA immunogenetics; the single-cell analysis was used only to describe cellular distribution in the RA/PsA dataset. Molecular docking was then used to evaluate the possible interaction between aspartame and HLA-DRB1. Forty-four intersected genes linked the predicted aspartame targets with RA DEGs. The random forest plus partial least-squares generalized linear model (RF + plsRglm) identified 16 core genes. Network-level interpretation indicated that these genes were distributed across immune/antigen-processing, inflammatory-signaling, protease/extracellular-matrix-remodeling, adhesion, metabolic, and proliferation-related modules; therefore, HLA-DRB1 was treated as a prioritized immune-module candidate rather than as the sole driver of the network. Following virtual knockout of HLA-DRB1, affected genes were enriched in extracellular matrix organization, extracellular structure organization, extracellular matrix, collagen trimer, extracellular matrix structural constituent, and collagen binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included integrin signaling, focal adhesion, proteoglycans in cancer, cytoskeleton in muscle, and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling. Molecular docking showed a minimum binding energy of −6.7 kcal/mol, which was more negative than the preset stability criterion of −5.0 kcal/mol, and the docking pose suggested contacts around ARG-146. This integrative analysis suggests a hypothesis-generating association between aspartame-related predicted targets and RA-relevant molecular networks involving HLA-DRB1 and other core genes. The findings do not establish causality and require experimental, epidemiological, biophysical, and tissue-stratified validation before any causal or clinical inference can be made. Full article

Preeclampsia, affecting 3–8% of pregnancies worldwide, remains a leading cause of maternal and perinatal morbidity and mortality. This review synthesizes current molecular, immunological, and hemodynamic evidence to clarify the central role of oxidative stress in the pathogenesis of preeclampsia. Placental oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) generation and antioxidant defenses, secondary to placental hypoxia due to various etiologies especially impaired spiral artery remodeling, drives mitochondrial dysfunction in trophoblasts, ischemia–reperfusion injury, inflammatory pathway activation, and disruption of angiogenic homeostasis, thereby promoting systemic inflammation. Key regulatory pathways, including Nrf2/HO-1, NF-κB, PI3K/Akt, and HIF-1α, together with biomarkers such as malondialdehyde, 8-isoprostane, and the sFlt-1/PlGF ratio, characterize this redox imbalance. Although experimental studies demonstrate promising effects of targeted antioxidants, mitochondria-directed agents, and pathway-specific modulators, clinical translation remains limited, as non-specific antioxidants such as vitamins C and E have failed to prevent preeclampsia. Future advances will likely depend on mechanism-based therapies initiated early in pregnancy and tailored to the disease subtype and biomarker profiles. Collectively, this review provides an integrated mechanistic framework and highlights critical knowledge gaps that must be addressed to enable the development of effective preventive and therapeutic interventions for preeclampsia. Full article

This study systematically analyzed the multidimensional effects of Lactobacillus fermentation on Pueraria lobata (PL) and investigated the potential mechanisms underlying its hypolipidemic activity. Results indicated that fermentation significantly increased the total acid content from 1.02 to 3.48 g·L⁻¹, representing a 2.41-fold increase. Although slight reductions were observed in total flavonoids (8.67%) and total phenolics (6.72%), the majority of bioactive components were well preserved. Other antioxidant capacities were retained at >74.71% of baseline, except hydroxyl radical scavenging. Flavor profiling showed increased sourness and astringency, accompanied by reduced bitterness, with volatile compounds such as β-pinene and trans-2-hexenyl butyrate contributing to a distinct aromatic profile. Untargeted metabolomics analysis revealed that fermentation specifically enhanced the abundance of low-concentration isoflavone aglycones, including daidzein and genistein, suggesting a compositional shift that may improve hypolipidemic efficacy. Integrated network pharmacology and computational modeling predicted that eight key components, including genistein, could stably bind to ten core targets (e.g., AKT1 and MMP9) primarily through hydrogen bonding and hydrophobic interactions, potentially regulating lipid metabolism via the PI3K-AKT, PPAR, and estrogen signaling pathways. This study reveals the role of Lactobacillus fermentation in promoting the conversion of isoflavone glycosides to aglycones in PL and constructs a multi-dimensional “components-targets-pathways-disease” network, providing both experimental evidence and a theoretical foundation for further research on the lipid-lowering mechanisms of fermented PL and the development of related functional products. Full article

Background: Metabolic flexibility, the ability to efficiently switch between fuel sources in response to changing nutrient availability and energy demands, is recognized as a key determinant of metabolic health. In a recent randomized controlled human feeding trial, overweight individuals receiving American black elderberry juice (EBJ) demonstrated improvements in multiple clinical indices of metabolic flexibility, but the mechanisms of action were unexplored. The objective of this study was to utilize RNA sequencing to examine how EBJ modulates the transcriptional response to fasting and feeding, focusing on pathways related to metabolic flexibility. Methods: Overweight or obese adults (BMI > 25 kg/m²) without chronic illnesses were randomized to a 5-week crossover study protocol with two 1-week periods of twice-daily EBJ or placebo (PL) separated by a washout period. RNA sequencing was performed on peripheral blood mononuclear cells from 10 participants to assess transcriptomic responses collected at fasting (pre-meal) and postprandial (120 min post-meal) states during a meal-challenge test. Results: The fasted-to-fed transition for EBJ showed 234 differentially expressed genes following EBJ consumption compared to 59 genes following PL, with 44 genes shared between interventions. EBJ supplementation showed significantly higher enrichment of several metabolic pathways including insulin, FoxO, and PI3K–Akt signaling. KEGG pathway analysis showed 27 significant pathways related to metabolic flexibility compared to 7 for PL. Conclusions: Our findings indicate that short-term elderberry juice consumption may promote metabolic flexibility in overweight adults. Full article

The popularity of bioactive compounds extracted from sea cucumbers is growing due to their wide application in the pharmaceutical industry, particularly in the development of drugs for neurological disorders. Different types of compounds, such as saponins, phenolic compounds, cerebrosides, and glucocerebrosides, are being studied intensively for their efficacy in assessing the treatment of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and brain tumors, among others. Positive results have been observed in the upregulation in the content of p-CREB, p-PL3K, BDNF, SOD, and MDA. Furthermore, the neuroprotective mechanism of the compounds against Alzheimer’s disease revealed that suppressing the phosphorylation of tau protein by the PI3K/Akt/GSK3β pathway leads to improved synaptic plasticity and reduced nerve fiber tangles. This comprehensive review explores recent findings on the therapeutic potential of sea cucumber bioactives in the treatment of brain-related disorders. Full article

Background: Chronic atrophic gastritis precancerous lesions (PL-CAG) are characterized by the atrophy of gastric mucosal glands, often accompanied by intestinal metaplasia or dysplasia. Timely intervention and treatment can effectively reverse its malignant progression and prevent the onset of gastric cancer. Bombyx Batryticatus (BB) exhibits a range of pharmacological effects, including anticoagulation, antiepileptic properties, anticancer activity, and antibacterial effects. However, the pharmacological basis and mechanisms underlying BB’s efficacy in treating PL-CAG remain unclear. Methods: A three-factor modeling approach was implemented to develop a rat PL-CAG model, while the MNNG-induced PLGC (precancerous lesions of gastric cancer) cell model was served as a cell PL-CAG model. UPLC-QE-Orbitrap-MS/MS (Ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry) was utilized to perform an in-depth analysis of the components in the plasma extract of BB. Leveraging network pharmacology, molecular docking analyses, and experimental validation, we initially elucidated the potential mechanisms through which BB mediates its therapeutic effects on PL-CAG at both in vivo and in vitro levels. Results: Prototype compounds of 42 blood-entering components were identified by UPLC-QE-Orbitrap-MS/MS analysis. Network pharmacology analysis and molecular docking studies indicate that the core targets are primarily enriched in the PI3K-Akt signaling pathway, and the key components, including Nepitrin, Quercetin 3-O-neohesperidoside, Rutin, and others, exhibited stable docking conformations with the first eleven pivotal targets. Both in vivo and in vitro experiments validated that BB may effectively treat PL-CAG via modulation of the PI3K-Akt signaling pathway. Conclusions: The therapeutic efficacy of BB in the management of PL-CAG may be achieved through the synergistic interaction of multiple components and targets, which may be more closely related to the inhibition of the PI3K/AKT signaling pathway. This approach will establish a solid experimental foundation and provide essential data for the clinical application of BB in treating PL-CAG, while also facilitating further research initiatives. Full article

Curcumin, a polyphenol found in turmeric, demonstrates multifaceted anti-cancer activity against glioblastoma. Its therapeutic potential stems from its ability to modulate various molecular pathways implicated in glioblastoma development and progression, enhance the effectiveness of radiation therapy, and induce cancer cell death through diverse mechanisms, including apoptosis, autophagy, and cell cycle arrest. These combined actions make curcumin a promising candidate for glioblastoma treatment, warranting further investigation into its clinical application. In this review, we summarize the latest research on curcumin and its analogs’ potential in glioblastoma therapy. Full article

The onset of SARS-CoV-2 infection in 2019 sparked a global COVID-19 pandemic. This infection is marked by a significant rise in both viral and host kinase activity. Our primary objective was to identify a pivotal host kinase essential for COVID-19 infection and the associated phenomenon of the cytokine storm, which may lead to long-term COVID-19 complications irrespective of viral genetic variations. To achieve this, our study tracked kinase phosphorylation dynamics in RAW264.7 macrophages following SPIKE transfection over time. Among the kinases surveyed, p70S6K (RPS6KB1) exhibited a 3.5-fold increase in phosphorylation at S418. This significant change prompted the selection of p70S6K for in silico investigation, utilizing its structure bound to M2698 (PDB: 7N93). M2698, an oral dual Akt/p70S6K inhibitor with an IC₅₀ of 1.1 nM, exhibited psychosis side effects in phase I clinical trials, potentially linked to its interaction with Akt2. Our secondary objective was to discover a small-molecule analogue of M2698 that exhibits a distinct binding preference for p70S6K over Akt2 through computational modeling and analysis. The in silico part of our project began with validating the prediction accuracy of the docking algorithm, followed by an OCA analysis pinpointing specific atoms on M2698 that could be modified to enhance selectivity. Subsequently, our investigation led to the identification of an analog of M2698, designated as S34, that showed a superior docking score towards p70S6K compared to Akt2. To further assess the stability of S34 in its protein–ligand (PL) complexes with p70S6K and Akt2, MD simulations were conducted. These simulations suggest that S34, on average, forms two hydrogen bond interactions with p70S6K, whereas it only forms one hydrogen bond interaction with Akt2. This difference in hydrogen bond interactions likely contributed to the observed larger root mean square deviation (RMSD) of 0.3 nm in the S34-Akt2 complex, compared to 0.1 nm in the S34-p70S6K complex. Additionally, we calculated free binding energy to predict the strength of the binding interactions of S34 to p70S6K and Akt2, which showed ~2-fold favorable binding affinity of S34 in the p70S6K binding pocket compared to that in the Akt2 binding pocket. These observations may suggest that the S34-p70S6K complex is more stable than the S34-Akt2 complex. Our work focused on identifying a host kinase target and predicting the binding affinity of a novel small molecule to accelerate the development of effective treatments. The wet bench results specifically highlight p70S6K as a compelling anti-COVID-19 target. Meanwhile, our in silico investigations address the known off-target effects associated with M2698 by identifying a close analog called S34. In conclusion, this study presents novel and intriguing findings that could potentially lead to clinical applications with further investigations. Full article

Placenta accreta spectrum (PAS) disorders are characterized by abnormal trophoblastic invasion into the myometrium, leading to significant maternal health risks. PAS includes placenta accreta (invasion < 50% of the myometrium), increta (invasion > 50%), and percreta (invasion through the entire myometrium). The condition is most associated with previous cesarean deliveries and increases in chance with the number of prior cesarians. The increasing global cesarean rates heighten the importance of early PAS diagnosis and management. This review explores genetic expression and key regulatory processes, such as apoptosis, cell proliferation, invasion, and inflammation, focusing on signaling pathways, genetic expression, biomarkers, and non-coding RNAs involved in trophoblastic invasion. It compiles the recent scientific literature (2014–2024) from the Scopus, PubMed, Google Scholar, and Web of Science databases. Identifying new biomarkers like AFP, sFlt-1, β-hCG, PlGF, and PAPP-A aids in early detection and management. Understanding genetic expression and non-coding RNAs is crucial for unraveling PAS complexities. In addition, aberrant signaling pathways like Notch, PI3K/Akt, STAT3, and TGF-β offer potential therapeutic targets to modulate trophoblastic invasion. This review underscores the need for interdisciplinary care, early diagnosis, and ongoing research into PAS biomarkers and molecular mechanisms to improve prognosis and quality of life for affected women. Full article

Aralia elata, a renowned medicinal plant with a rich history in traditional medicine, has gained attention for its potential therapeutic applications. However, the leaves of this plant have been largely overlooked and discarded due to limited knowledge of their biological activity and chemical composition. To bridge this gap, a comprehensive study was conducted to explore the therapeutic potential of the 70% ethanol extract derived from Aralia elata leaves (LAE) for the treatment of cardiovascular disease (CVD). Initially, the cytotoxic effects of LAE on human umbilical vein endothelial cells (HUVECs) were assessed, revealing no toxicity within concentrations up to 5 μg/mL. This suggests that LAE could serve as a safe raw material for the development of health supplements and drugs aimed at promoting cardiovascular well-being. Furthermore, the study found that LAE extract demonstrated anti-inflammatory properties in HUVECs by modulating the PI3K/Akt and MAPK signaling pathways. These findings are particularly significant as inflammation plays a crucial role in the progression of CVD. Moreover, LAE extract exhibited the ability to suppress the expression of adhesion molecules VCAM-1 and ICAM-1, which are pivotal in leukocyte migration to inflamed blood vessels observed in various pathological conditions. In conjunction with the investigation on therapeutic potential, the study also established an optimal HPLC–PDA–ESI–MS/MS method to identify and confirm the chemical constituents present in 24 samples collected from distinct regions in South Korea. Tentative identification revealed the presence of 14 saponins and nine phenolic compounds, while further analysis using PCA and PLS-DA allowed for the differentiation of samples based on their geographical origins. Notably, specific compounds such as chlorogenic acid, isochlorogenic acid A, and quercitrin emerged as marker compounds responsible for distinguishing samples from different regions. Overall, by unraveling its endothelial protective activity and identifying key chemical constituents, this research not only offers valuable insights for the development of novel treatments but also underscores the importance of utilizing and preserving natural resources efficiently. Full article

Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disease associated with recurrent thrombosis and/or obstetric morbidity with persistent antiphospholipid antibodies (aPL). Although these antibodies drive endothelial injury and thrombophilia, the underlying molecular mechanism is still unclear. Small extracellular vesicles (sEVs) contain miRNAs, key players in intercellular communication. To date, the effects of miRNA-derived sEVs in PAPS are not well understood. We characterised the quantity, cellular origin and miRNA profile of sEVs isolated from thrombotic APS patients (PAPS, n = 50), aPL-carrier patients (aPL, n = 30) and healthy donors (HD, n = 30). We found higher circulating sEVs mainly of activated platelet origin in PAPS and aPL patients compared to HD, that were highly engulfed by HUVECs and monocyte. Through miRNA-sequencing analysis, we identified miR-483-3p to be differentially upregulated in sEVs from patients with PAPS and aPL, and miR-326 to be downregulated only in PAPS sEVs. In vitro studies showed that miR-483-3p overexpression in endothelial cells induced an upregulation of the PI3K-AKT pathway that led to endothelial proliferation/dysfunction. MiR-326 downregulation induced NOTCH pathway activation in monocytes with the upregulation of NFKB1, tissue factor and cytokine production. These results provide evidence that miRNA-derived sEVs contribute to APS pathogenesis by producing endothelial cell proliferation, monocyte activation and adhesion/procoagulant factors. Full article

Necroptosis, pro-inflammatory programmed necrosis, has been reported to exert momentous roles in pancreatic cancer (PC). Herein, the objective of this study is to construct a necroptosis-related prognostic model for detecting pancreatic cancer. In this study, the intersection between necroptosis-related genes and differentially expressed genes (DEGs) of pancreatic ductal adenocarcinoma (PDAC) was obtained based on GeneCards database, GEO database (GSE28735 and GSE15471), and verified using The Cancer Genome Atlas (TCGA). Next, a prognostic model with Cox and LASSO regression analysis, and divided the patients into high-risk and low-risk groups. Subsequently, the Kaplan–Meier (KM) survival curve and the receiver operating characteristic (ROC) curves were generated to assess the predictive ability of overall survival (OS) of PC patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the potential biofunction and possible mechanical pathways. The EMTome database and an immune analysis were applied to further explore underlying mechanism. Finally, clinical samples of PDAC patients were utilized to verify the expression of model genes via immunohistochemistry (IHC), and the normal human pancreatic ductal cell line, hTERT-HPNE as well as human pancreatic ductal carcinoma cell lines, PANC-1 and PL45, were used to identify the levels of model genes by Western blot (WB) and immunofluorescence (IF) in vitro. The results showed that 13 necroptosis-related DEGs (NRDEGs) were screened based on GEO database, and finally four of five prognostic genes, including KRT7, KRT19, IGF2BP3, CXCL5, were further identified by TCGA to successfully construct a prognostic model. Univariate and multivariate Cox analysis ultimately confirmed that this prognostic model has independent prognostic significance, KM curve suggested that the OS of low-risk group was longer than high-risk group, and the area under receiver (AUC) of ROC for 1, 3, 5 years was 0.733, 0.749 and 0.667, respectively. A GO analysis illustrated that model genes may participate in cell–cell junction, cadherin binding, cell adhesion molecule binding, and neutrophil migration and chemotaxis, while KEGG showed involvement in PI3K-Akt signaling pathway, ECMreceptor interaction, IL-17 signaling pathway, TNF signaling pathway, etc. Moreover, our results showed KRT7 and KRT19 were closely related to EMT markers, and EMTome database manifested that KRT7 and KRT19 are highly expressed in both primary and metastatic pancreatic cancer, declaring that model genes promoted invasion and metastasis potential through EMT. In addition, four model genes were positively correlated with Th2, which has been reported to take part in promoting immune escape, while model genes except CXCL5 were negatively correlated with TFH cells, indicating that model genes may participate in immunity. Additionally, IHC results showed that model genes were higher expressed in PC tissues than that in adjacent tumor tissues, and WB and IF also suggested that model genes were more highly expressed in PANC-1 and PL45 than in hTERT-HPNE. Tracing of a necroptosis-related prognostic model for pancreatic carcinoma reveals its invasion and metastasis potential through EMT and immunity. The construction of this model and the possible mechanism of necroptosis in PDAC was preliminarily explored to provide reliable new biomarkers for the early diagnosis, treatment, and prognosis for pancreatic cancer patients. Full article

Nanotechnology has emerged as the most popular research topic with revolutionary applications across all scientific disciplines. Tin oxide (SnO₂) has been gaining considerable attention lately owing to its intriguing features, which can be enhanced by its synthesis in the nanoscale range. The establishment of a cost-efficient and ecologically friendly procedure for its production is the result of growing concerns about human well-being. The novelty and significance of this study lie in the fact that the synthesized SnO₂ nanoparticles have been tailored to have specific properties, such as size and morphology. These properties are crucial for their applications. Moreover, this study provides insights into the synthesis process of SnO₂ nanoparticles, which can be useful for developing efficient and cost-effective methods for large-scale production. In the current study, green Pluronic-coated SnO₂ nanoparticles (NPs) utilizing the root extracts of Polygonum cuspidatum have been formulated and characterized by several methods such as UV–visible, Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray (EDAX), transmission electron microscope (TEM), field emission-scanning electron microscope (FE-SEM), X-ray diffraction (XRD), photoluminescence (PL), and dynamic light scattering (DLS) studies. The crystallite size of SnO₂ NPs was estimated to be 45 nm, and a tetragonal rutile-type crystalline structure was observed. FESEM analysis validated the NPs’ spherical structure. The cytotoxic potential of the NPs against HepG2 cells was assessed using the in vitro MTT assay. The apoptotic efficiency of the NPs was evaluated using a dual-staining approach. The NPs revealed substantial cytotoxic effects against HepG2 cells but failed to exhibit cytotoxicity in different liver cell lines. Furthermore, dual staining and flow cytometry studies revealed higher apoptosis in NP-treated HepG2 cells. Nanoparticle treatment also inhibited the cell cycle at G0/G1 stage. It increased oxidative stress and promoted apoptosis by encouraging pro-apoptotic protein expression in HepG2 cells. NP treatment effectively blocked the PI3K/Akt/mTOR axis in HepG2 cells. Thus, green Pluronic-F-127-coated SnO₂ NPs exhibits enormous efficiency to be utilized as an talented anticancer agent. Full article

To understand how genes precisely regulate lactation physiological activity and the molecular genetic mechanisms underlying mammary gland involution, this study investigated the transcriptome characteristics of goat mammary gland tissues at the late gestation (LG), early lactation (EL), peak lactation (PL), late lactation (LL), dry period (DP), and involution (IN) stages. A total of 13,083 differentially expressed transcripts were identified by mutual comparison of mammary gland tissues at six developmental stages. Genes related to cell growth, apoptosis, immunity, nutrient transport, synthesis, and metabolism make adaptive transcriptional changes to meet the needs of mammary lactation. Notably, platelet derived growth factor receptor beta (PDGFRB) was screened as a hub gene of the mammary gland developmental network, which is highly expressed during the DP and IN. Overexpression of PDGFRB in vitro could slow down the G1/S phase arrest of goat mammary epithelial cell cycle and promote cell proliferation by regulating the PI3K/Akt signaling pathway. In addition, PDGFRB overexpression can also affect the expression of genes related to apoptosis, matrix metalloproteinase family, and vascular development, which is beneficial to the remodeling of mammary gland tissue during involution. These findings provide new insights into the molecular mechanisms involved in lactation and mammary gland involution. Full article

Hypertensive nephropathy is a chronic kidney disease caused by hypertension. Eicosapentaenoic acid (EPA) has been reported to possess an antihypertensive effect, and our previous study suggested that EPA-enriched phospholipid (EPA-PL) had more significant bioactivities compared with traditional EPA. However, the effect of dietary EPA-PL on hypertensive nephropathy has not been studied. The current study was designed to examine the protection of EPA-PL against kidney damage in spontaneously hypertensive rats (SHRs). Treatment with EPA-PL for three weeks significantly reduced blood pressure through regulating the renin–angiotensin system in SHRs. Moreover, dietary EPA-PL distinctly alleviated kidney dysfunction in SHRs, evidenced by reduced plasma creatinine, blood urea nitrogen, and 24 h proteinuria. Histology results revealed that treatment of SHRs with EPA-PL alleviated renal injury and reduced tubulointerstitial fibrosis. Further mechanistic studies indicated that dietary EPA-PL remarkably inhibited the activation of TGF-β and Smad 3, elevated the phosphorylation level of PI3K/AKT, suppressed the activation of NF-κB, reduced the expression of pro-inflammatory cytokines, including IL-1β and IL-6, and repressed the oxidative stress and the mitochondria-mediated apoptotic signaling pathway in the kidney. These results indicate that EPA-PL has potential value in the prevention and alleviation of hypertensive nephropathy. Full article