Journal of Cellular and Molecular Medicine最新文献

{"title":"EN2 Regulates Pancreatic Cancer Initiation, Progression, and Epithelial-Mesenchymal Transition Through the Notch Signalling Pathway.","authors":"Wei Yu, Raj K Varma, Yiming Ma, Varun Chandra Boinpelly, Areej Khatri, Emma Gombos, Rakesh K Srivastava, Sharmila Shankar","doi":"10.1111/jcmm.71158","DOIUrl":"10.1111/jcmm.71158","url":null,"abstract":"<p><p>The incidence and mortality of pancreatic cancer are steadily increasing worldwide, and the disease is projected to become the second leading cause of cancer-related deaths by 2030. Pancreatic tumorigenesis is driven by multiple genetic alterations, underscoring the need to elucidate the molecular mechanisms underlying pancreatic carcinogenesis. In this context, the present study is the first to identify a novel oncogenic role for Engrailed 2 (EN2) in the initiation and progression of pancreatic cancer and to characterise its underlying molecular pathogenesis. Immunohistochemical analysis of a pancreatic cancer tissue microarray revealed significantly elevated EN2 expression in tumour tissues compared with adjacent normal tissues. Consistent with these findings, EN2 was markedly upregulated in human pancreatic cancer cell lines, but absent in normal pancreatic epithelial cells, and functional studies demonstrated that EN2 expression is oncogenic in pancreatic cancer. TCGA data further corroborated the significantly higher EN2 expression in pancreatic cancer tissues and showed that elevated EN2 levels are associated with poor overall survival. To define the biological significance of EN2, we investigated its role in promoting pancreatic cancer initiation and progression. Gain- and loss-of-function studies revealed that EN2 regulates key target genes involved in pluripotency, cell survival, and cell-cycle progression, drug resistance, and epithelial-mesenchymal transition. Moreover, lentiviral-mediated shRNA knockdown of EN2 suppressed pancreatic cancer cell proliferation, invasion, and metastasis in vitro and significantly inhibited tumour growth in a xenograft mouse model, in part by inhibiting Notch signalling. Taken together, these findings identify EN2 as a critical driver of pancreatic cancer initiation, progression, and metastasis, representing the first report of its oncogenic function in this malignancy.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 9","pages":"e71158"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Endoplasmic Reticulum Stress by Empagliflozin in Doxorubicin-Induced Cardiotoxicity in Rats.","authors":"Akshi Malik, David C Y Cheung, D Allison Ledingham, Danielle Desautels, Joerg Herrmann, Pawan K Singal, Davinder S Jassal","doi":"10.1111/jcmm.71161","DOIUrl":"10.1111/jcmm.71161","url":null,"abstract":"<p><p>Although Doxorubicin (Dox) is an effective anticancer drug, it can cause severe cardiotoxicity. While several mechanisms have been proposed to explain Dox-induced cardiomyopathy (DIC), strategies to prevent it remain limited. In previous research on isolated cardiomyocytes, we identified that Empagliflozin (EMPA), an antidiabetic drug, mitigated Dox-induced ER stress and apoptosis. In this in vivo study using rats, we further investigated EMPA's potential in preventing and treating DIC. Rats administered a cumulative dose of 15 mg/kg Dox exhibited significant cardiovascular damage, including left ventricular cavity dilation, decreased left ventricular ejection fraction (LVEF), ER dilation, mitochondrial defects and vacuole formation. These structural changes were linked to the activation of ER-stress pathways (PERK, IRE1 and ATF6) and upregulation of apoptotic proteins initiated by ER stress. When EMPA (10 mg/kg/day) was administered either prophylactically or concurrently with Dox, it significantly attenuated adverse LV remodelling and preserved LVEF. Additionally, EMPA prevented ER stress and subsequent apoptosis in the myocardium of the Dox + EMPA-treated group. These findings suggest that EMPA offers cardioprotective benefits in DIC, likely through the inhibition of ER-stress-induced myocardial injury.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 9","pages":"e71161"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sialidase Neu3 Induced Sialic Acid Disorder and Promoted Vascular Endothelial Injury Through Transcription Factor SP3.","authors":"Yining Lu, Peng Xiang, Qingqiu Chen, Xianmin Wang, Le Chen, Tongchuan Wang, Rong Hu, Limei Ma, Chao Yu","doi":"10.1111/jcmm.71169","DOIUrl":"10.1111/jcmm.71169","url":null,"abstract":"<p><p>Atherosclerotic cardiovascular disease is still a major cause for the increasing mortality worldwide. The elevated metabolite N-acetylneuraminic acid (Neu5Ac) was considered one of the important risk factors responsible for the initiation of endothelial impairment, then participated in atherosclerosis progression. However, the reason for inducing Neu5Ac accumulation as well as its underlying mechanism remains unclear. Here, we applied human umbilical vein endothelial cells (HUVECs) and ApoE^-/- mice to investigate the key genes responsible for Neu5Ac accumulation as well as its regulation mechanism. We found that tumour necrosis factor alpha (TNF-α) could induce Neu5Ac metabolism disorder and increase Neu5Ac level, accompanied by the increasing levels of inflammatory markers in HUVECs. Further, we found that sialidase NEU3 was significantly up-regulated, accompanied by Neu5Ac accumulation. NEU3^siRNA in HUVECs could significantly reduce Neu5Ac levels and alleviate endothelial inflammation. In contrast, the addition of exogenous Neu5Ac reversed such phenomenon. Furthermore, we noted that NEU3 was highly expressed in atherosclerotic plaques from ApoE^-/- mice as well as atherosclerotic patient tissues. Mechanically, we found that the transcription factor specificity protein 3 (SP3) was activated in HUVECs, responsible for Neu5Ac metabolism disorder. While RNA interference of SP3 could decrease NEU3 mRNA level and reduce endothelial inflammatory injury, indicating that SP3 might be the upstream regulatory factor of NEU3. Together, these findings identified the key role of NEU3 in regulating Neu5Ac metabolism associated with endothelial function, as well as its potential regulation mechanism. Targeting SP3/NEU3 seems to be a potential therapeutic strategy for such diseases with Neu5Ac accumulation like atherosclerosis (AS).</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 9","pages":"e71169"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLA2 is Associated With Immune evasion and Exhaustion of CD8⁺ T Cells in Gastric Cancer.","authors":"Yujia Zhang, Xiaoyan Li, Rongchao Xiang","doi":"10.1111/jcmm.71164","DOIUrl":"10.1111/jcmm.71164","url":null,"abstract":"<p><p>The Src-like adaptor 2 (SLA2) functions as a negative regulator of T cell receptor signalling. However, its involvement in the tumour microenvironment (TME) of gastric cancer (GC) remains unexplored. In this study, we found that SLA2 expression was significantly elevated in GC tissues, and a high level of SLA2 was associated with poor prognosis in GC patients. Bioinformatics analyses revealed a close association between SLA2 and TME in GC. Single-cell RNA sequencing analysis indicated that SLA2 was significantly enriched in CD8⁺ T cells in GC tissues. Functional validation demonstrated that SLA2 overexpression contributed to the exhaustion of CD8⁺ T cells by suppressing their proliferation, upregulating the expression of exhaustion markers, reducing the secretion of effector cytokines (IFN-γ and TNF-α) and impairing cytotoxic function. SLA2 knockdown in in vitro-generated exhausted CD8 T cells significantly alleviated T cell exhaustion. Mechanistically, we found that inverse promoter methylation and active histone marks (H3K27ac, H3K4me3 and H3K4me1) may regulate SLA2 expression. Our findings suggest that SLA2 may modulate the TME and promote immune evasion via CD8⁺ T cell exhaustion in GC.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 9","pages":"e71164"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13158163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Analysis of Preeclamptic Cord Blood Mononuclear Cells Revealed Activation of Heme-Associated Signalling Pathways.","authors":"Polina Vishnyakova, Evgeny Karpulevich, Victoria Karyagina, Elena Gantsova, Yulia Trofimovich, Viktoriia Kiseleva, Miroslava Chirkova, Tatiana Gerashchenko, Anastasiya Lokhonina, Kamilla Muminova, Zulfiya Khodzhaeva, Evgeny Denisov, Andrey Elchaninov, Timur Fatkhudinov, Gennady Sukhikh","doi":"10.1111/jcmm.71150","DOIUrl":"10.1111/jcmm.71150","url":null,"abstract":"<p><p>Preeclampsia is a severe gestational complication whose molecular pathogenesis remains poorly understood despite extensive research. It is now recognized that both maternal and fetal cells contribute to disease progression. Notably, single-cell RNA sequencing of cord blood cells from preeclamptic pregnancies has not been previously investigated, and this became the focus of our study. In this work, we performed flow cytometry, single-cell RNA sequencing and bioinformatics analysis of cord blood mononuclear cells from preeclampsia and control groups. Bulk RNA-sequencing data of preeclamptic cord blood from open source was also analysed. We observed a significant decrease in the expression of the CD3, CD8 and CD4 markers in cord blood mononuclear cells in the preeclampsia group. Single-cell RNA sequencing revealed activation of iron- and heme-associated signalling pathways in various cell types (nonclassical monocytes, naive СD4⁺ and CD8⁺ T cells, T-helpers 2, NK cells and naive СD4⁺ regulatory T cells) in cord blood during preeclampsia. Analysis of open-source bulk RNA-sequencing data confirmed our findings of activation of heme-related signalling pathways in preeclamptic cord blood samples. These results may suggest the activation of compensatory mechanisms, potentially mediated by the proangiogenic heme degradation products carbon monoxide and biliverdin. Additionally, free heme may act as a proinflammatory damage-associated molecular pattern in preeclampsia. Further studies are needed to elucidate the direct relationship between these mechanisms and placental heme metabolism.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 9","pages":"e71150"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13125416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EIF2α-ATF4-CHAC1 Signalling Links ER Stress to Ferroptosis in Human Aortic Smooth Muscle Cells: Mechanistic Insights and Therapeutic Implications.","authors":"Changwen Fang, Xiaolong Du, Yadan Wang, Yiqi Jin, Wenbin Wang","doi":"10.1111/jcmm.71104","DOIUrl":"10.1111/jcmm.71104","url":null,"abstract":"<p><p>Ferroptosis-a regulated, iron-dependent cell death driven by lipid peroxidation-has been implicated in vascular pathology, yet how endoplasmic reticulum (ER) stress couples to ferroptotic execution in vascular smooth muscle cells (VSMCs) remains unclear. We investigated whether the PERK-EIF2α-ATF4-CHAC1 signalling axis links ER stress to ferroptosis in human aortic SMCs. Human aortic smooth muscle cells (HASMCs) and primary aortic smooth muscle cells (AoSMCs) were exposed to erastin (± ferrostatin-1), with pharmacologic modulation using buthionine sulfoximine (BSO; glutamate-cysteine ligase inhibitor) and salubrinal (selective EIF2α dephosphorylation inhibitor). Viability (CCK-8), ER-stress markers (p-PERK, p-EIF2α, GRP78, ATF4, CHAC1) and ferroptosis effectors (GPX4, ACSL4, ALOX15) were quantified by Western blotting and densitometry. Immunofluorescence assessed GPX4 and p-EIF2α/CHAC1 colocalization. Lipid peroxidation was evaluated by C11-BODIPY 581/591 imaging and malondialdehyde (MDA) content; labile Fe²⁺ was measured by calcein-AM quenching; apoptosis was examined by TUNEL. Statistics used t-tests or one-way ANOVA. Erastin reduced viability and activated the EIF2α-ATF4-CHAC1 pathway in both HASMCs and AoSMCs, as evidenced by increased p-EIF2α/ATF4/CHAC1 and decreased GPX4, with concomitant upregulation of ACSL4 and ALOX15. GPX4 immunofluorescence declined, while C11-BODIPY and MDA indicated robust lipid peroxidation, and calcein-AM revealed expansion of the labile Fe²⁺ pool; ferrostatin-1 mitigated these changes. BSO further amplified p-PERK→p-EIF2α → ATF4 → CHAC1 signalling and deepened GPX4 loss, whereas salubrinal sustained EIF2α phosphorylation, augmented ATF4/CHAC1, and further depressed GPX4. Across conditions, effects were consistent in both cell types and reached statistical significance (most p < 0.05 to < 0.01). ER-stress signalling via PERK-EIF2α-ATF4-CHAC1 constitutes a proximal driver of ferroptosis in human aortic SMCs by eroding glutathione tone and disabling GPX4, thereby promoting lipid peroxidation in an iron-rich milieu. Pharmacologic tuning of EIF2α phosphorylation and glutathione biosynthesis modulates ferroptotic susceptibility, nominating EIF2α-ATF4-CHAC1, GPX4/GSH homeostasis and iron handling as actionable nodes to preserve VSMC integrity in oxidizing vascular environments.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 9","pages":"e71104"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Pentamidine Niosomes Thwart S100B Effects in Human Colon Carcinoma Biopsies Favouring wtp53 Rescue\".","authors":"","doi":"10.1111/jcmm.71184","DOIUrl":"10.1111/jcmm.71184","url":null,"abstract":"","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 9","pages":"e71184"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13162343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathophysiology and Molecular Signalling in Osteoporosis: Linking Risk Factors to Bone Loss.","authors":"Pramoda G, Kamini Shivhare, Piyush Kumar Gupta, Amirhossein Sahebkar, Prashant Kesharwani, Rahul Shukla","doi":"10.1111/jcmm.71155","DOIUrl":"10.1111/jcmm.71155","url":null,"abstract":"<p><p>Osteoporosis is a prevalent skeletal disorder characterised by progressive reduction in bone mass, microarchitectural deterioration, and increased fracture susceptibility. In India, approximately one-third of the elderly population is affected by bone-related disorders, and the global burden of osteoporosis continues to rise. Despite its significant impact on morbidity, mortality, and quality of life, current diagnostic approaches and therapeutic strategies remain suboptimal due to limitations such as prolonged treatment duration, poor patient adherence, low oral bioavailability of first-line therapies, and potential cardiovascular risks associated with some anti-resorptive agents. Given these challenges, there is an urgent need to develop safer and more effective preventive and therapeutic interventions. However, rational drug design and targeted therapies require a comprehensive understanding of osteoporosis pathophysiology. In this review, we provide an integrated overview of normal bone remodelling, key cellular players, and the mechanisms underlying impaired bone homeostasis in osteoporosis. We discuss the roles of osteoblasts, osteoclasts, and their progenitor cells, along with critical regulatory factors governing their differentiation and function. Later, we have discussed the core mechanisms and pathways involved in the pathophysiology of osteoporosis, including the RANKL-OPG axis, Wnt/β-catenin signalling, Parathyroid hormone (PTH)/PTH1R (cAMP/PKA vs. sustained Ca²⁺/PKC) signalling, TGF-β/BMP-SMAD signalling, etc. Furthermore, we summarise the major risk factors, including ageing, sex hormones, nutritional deficiencies, lifestyle factors, and comorbidities and delineate their mechanistic links to bone loss. This comprehensive synthesis aims to enhance understanding of osteoporosis pathogenesis and to facilitate the identification of novel molecular targets for improved therapeutic strategies.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 9","pages":"e71155"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noninvasive Risk Stratification Based on Renal Tubular Injury Phenotypes: A Deep Learning Study for Predicting Vesicoureteral Reflux in Children.","authors":"Hongzhou Lin, Zeyu Cui, Zhantian Zhang, Yifan Luo, Jianwei Shuai, Kai Zhao, Yunlong Zhou, Dexuan Wang","doi":"10.1111/jcmm.71172","DOIUrl":"10.1111/jcmm.71172","url":null,"abstract":"<p><p>Vesicoureteral reflux (VUR) can cause retrograde urine flow under voiding pressure, facilitating ascending bacterial colonisation and recurrent inflammatory responses. These processes trigger a cascade of cellular and molecular events-innate immune activation, pro-inflammatory cytokine release, oxidative stress, apoptosis and extracellular matrix deposition-thereby promoting tubulointerstitial remodelling and increasing the risk of renal parenchymal injury and scarring. Static renal 99mTc-DMSA scintigraphy primarily reflects tracer uptake by proximal tubular cells in the renal cortex and can serve as an integrated phenotypic readout of tubular dysfunction and focal cortical involvement. However, its clinical interpretation remains experience-dependent and lacks reproducible quantitative criteria, while voiding cystourethrography (VCUG), the diagnostic and grading gold standard for VUR, is limited by invasiveness and procedural burden. In this study, we collected DMSA data from 346 children with febrile urinary tract infection treated at the Second Affiliated Hospital of Wenzhou Medical University between January 2019 and January 2023 and developed a deep learning model (MedSwinNet) for VUR risk stratification. Built on a Swin Transformer backbone and enhanced with multi-scale representation fusion, a convolutional block attention module and a gated selection strategy, MedSwinNet was designed to sensitively capture phenotypic signals such as reduced proximal tubular uptake and focal cortical defects while improving robustness. On the test set, the model achieved accuracies of 0.8290 under the severe-side input setting and 0.7997 under the bilateral-side input setting, demonstrating stable discriminative performance and favourable generalisation. Quality control analyses indicated broadly consistent distributions of key image quality metrics across data splits, mitigating potential bias from dataset shift. Collectively, deep learning-based decoding of tubular dysfunction-related phenotypic readouts enables noninvasive quantification of VUR-associated renal involvement, supports decision-making on whether VCUG is warranted and may reduce unnecessary invasive procedures while improving clinical risk-stratified management.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 9","pages":"e71172"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13158276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Network Pharmacology and Experimental Validation Strategy for Hypoglycemic Study of Lonicerae Japonicae Flos on Diabetes.","authors":"Zhang Nan, Liu Xiaolong, Li Chunyan, Ren Lu, Guo Chao, Xue Jintao","doi":"10.1111/jcmm.71167","DOIUrl":"10.1111/jcmm.71167","url":null,"abstract":"<p><p>As diabetes has become an important public health issue, Lonicerae Japonicae Flos (LJF) had gradually attracted increasing attention on diabetes. This study aimed to investigate the hypoglycemic ingredients and underlying mechanisms of LJF in diabetes using an integrated strategy of network pharmacology, molecular docking and experimental validation. Network pharmacology screened 73 active ingredients, 65 targets and 20 main signalling pathways. The results of molecular docking, protein-protein interaction and ingredient-target-pathway network indicated that four targets (PPARG, PPARD, MGAM, GAA) and three signalling pathways (PPAR signalling pathway, Starch and sucrose metabolism, Galactose metabolism) played essential roles. Subsequently, animal experiments and in vitro tests were performed to evaluate the anti-diabetic effect, antioxidant capacity and α-amylase inhibitory activity for the LJF extract. Animal studies indicated the LJF alcohol extract could significantly decrease blood glucose level and mitigate the weight loss compared to the model group (p < 0.05), respectively. Furthermore, both in vitro and in vivo tests confirmed that the LJF alcohol extract exhibited strong antioxidant capacity (p < 0.05 for MDA and SOD) and α-amylase inhibitory activity (maximum efficacy: 66.6% ± 4.6%). This strategy provided a promising approach to further elucidate the active ingredients and underlying mechanisms of LJF and other herbs.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 9","pages":"e71167"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}