Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"Gold-Containing Compound Auranofin Ameliorates 6-OHDA Induced Neurotoxicity in Rats: Via Targeting PI3K/Akt/GSK-3β Signalling","authors":"Divya Soni,&nbsp;Manjinder Singh,&nbsp;Yogesh Garg,&nbsp;Amit Bhatia,&nbsp;Puneet kumar","doi":"10.1111/1440-1681.70070","DOIUrl":"https://doi.org/10.1111/1440-1681.70070","url":null,"abstract":"<div>\u0000 \u0000 <p>The prevalence of parkinsonism is increasing worldwide, not only in age groups but now becoming a favourite of adults. As the onset is increasing in developed and underdeveloped countries, the current therapy lacks a permanent cure. Therefore, the research has used the gold-containing compound auranofin (AUF) in its neuroprotective form. The research was conducted to decipher the neuroprotective potential of AUF hybrid nanoparticles (AUFHNPs) using the in silico and in vivo 6-OHDA models. The in silico study was performed using CDOCKER software and the binding affinity of AUF with PI3K (5DXT), AKT (1UNQ), GSK-3β (1Q41), Nrf2 (2DYH), and HO-1 (1N45) were assessed. Then, intra-striatal unilateral injection of 6-OHDA (10 μg/2 μL) was given to rats with the help of stereotaxic surgery. After performing the amphetamine challenge test, rodents were treated with AUF (10 mg/kg) and AUFHNPs (5 and 10 mg/kg) for 21 days. All the behaviour parameters were performed on the last 2 days, and animals were sacrificed; brains were isolated for oxidative stress, neuroinflammatory, apoptotic, histological, and molecular marker analysis. In the docking study, AUF offered the highest binding score of −61.1231 with GSK-3β. In vivo administration of AUF and AUFHNPs significantly restored motor and behaviour alterations observed in open field tests, narrow beam walks, and grip strength meter. It also restored morphological changes and increased expression of pPI3K/pAKT, followed by inhibition of GSK-3β. Thus, the AUFHNPs were more significant than AUF alone and exerted neuroprotection via modulation of PI3K/AKT/GSK-3β signalling pathways.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: An MSC Bone-Homing Compound, Rab001, Increases Bone Mass and Reduces the Incidence of Osteonecrosis in a Glucocorticoid-Induced Osteonecrosis Mouse Model","authors":"","doi":"10.1111/1440-1681.70066","DOIUrl":"https://doi.org/10.1111/1440-1681.70066","url":null,"abstract":"<p>\u0000 <b>RETRACTION</b>: <span>M. Jiang</span>, <span>L. Liu</span>, <span>X. Xiang</span>, <span>R. Liang</span>, <span>X. Qin</span>, <span>J. Zhao</span>, and <span>Q. Wei</span>, “ <span>An MSC Bone-Homing Compound, Rab001, Increases Bone Mass and Reduces the Incidence of Osteonecrosis in a Glucocorticoid-Induced Osteonecrosis Mouse Model</span>,” <i>Clinical and Experimental Pharmacology and Physiology</i> <span>48</span>, no. <span>5</span> (<span>2020</span>): <span>770</span>–<span>781</span>, https://doi.org/10.1111/1440-1681.13441.\u0000 </p><p>The above article, published online on 15 December 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Yang Yang; and John Wiley &amp; Sons Australia Ltd. A third party reported concerns regarding the misreporting of Chi-square test results in this article, which originally lead to the conclusion that Rab001 significantly reduces ON incidence in GC-treated rats. The third party also indicated that the article includes several methodological issues that put into question the validity of the reported results. The authors responded to an inquiry by the publisher and provided further statistical analysis and explanations for the potential methodological shortcomings. The authors acknowledged that the statistical significance in the title, abstract, and results was overstated and proposed an erratum to update all statements which reference the significance of Rab001 reducing the incidence of ON. Upon review of the authors' proposed erratum, the journal found that the proposed modifications were extensive and would significantly impact the core findings of the article. The retraction has been agreed to because the misreported statistical significance of the findings constitutes a major error, which compromises the conclusions of the article. The authors agree with the retraction.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.70066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Associated Factors of Anxiety and Depression in Lung Cancer Patients","authors":"Xinran Gao,&nbsp;Maoying Guan,&nbsp;Bing Bo,&nbsp;Wencheng Zhao,&nbsp;Lihua Huang,&nbsp;Yayi He","doi":"10.1111/1440-1681.70065","DOIUrl":"https://doi.org/10.1111/1440-1681.70065","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Given the prevalence of anxiety and depression amongst lung cancer patients in China, it is critical to identify potential factors contributing to these symptoms to improve future treatment strategies. However, current research has primarily focused on clinical variables, leaving various sociodemographic factors largely underexplored. Examining these aspects is essential for enhancing clinical interventions and patient care, as sociodemographic factors can significantly influence psychological outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 486 lung cancer patients were included in the study. Data on anxiety and depression were collected using the Hospital Anxiety and Depression Scale (HADS), and sociodemographic information was gathered via a structured questionnaire. Clinical data was retrieved from the hospital's database. Univariate analysis and multivariate logistic regression were applied to identify sociodemographic and clinical factors that were significantly associated with anxiety and depression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The findings revealed prevalence rates of 24.07% for anxiety and 25.72% for depression. Local residency in Shanghai, internet use, financial strain, and advanced cancer stages (III or IV) were associated with a higher level of both anxiety and depression. Having a university/college education or higher was solely linked with increased anxiety levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Local residency, internet use, financial strain, cancer stage, and educational background are key predictors of anxiety and depression amongst lung cancer patients. It is crucial for healthcare professionals to monitor and support the mental well-being of lung cancer patients, especially those affected by these identified factors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Semisynthetic Derivative of Dehydrozingerone (DHZ-15) Modulates Lipopolysaccharide-Stimulated Macrophages by Targeting the NF-κB/p65 Pathway and In Vivo Evaluation in a Sepsis BALB/c Model","authors":"Irfan Qasam,&nbsp;Shah Nawaz,&nbsp;Chetan Kumar,&nbsp;Hema Kumari,&nbsp;Sumit Dhiman,&nbsp;Priya Wazir,&nbsp;Govind Yadav","doi":"10.1111/1440-1681.70063","DOIUrl":"https://doi.org/10.1111/1440-1681.70063","url":null,"abstract":"<div>\u0000 \u0000 <p>Natural products and their semisynthetic derivatives possess tremendous medicinal properties and have the potential to modulate the immune system, providing new therapeutic options for drug development. In this study, we evaluated Dehydrozingerone-15, a novel dehydrozingerone derivative, for its anti-inflammatory and antioxidant properties through standardised in vitro and in vivo approaches. Dehydrozingerone-15 suppressed the stimulatory effect of LPS in RAW 264.7 cells by reducing the secretion of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-2 (IL-2) and nitric oxide. Western blot analysis at the mechanistic level showed a reduced expression level of nitric oxide synthase (iNOS), IκB kinase beta (Ikk-β) and nuclear factor kappa-B (NF-κB/p65). Confocal microscopy studies further demonstrated that Dehydrozingerone-15 reduced the expression of NF-κB/p65 markedly. In the in vivo LPS-induced sepsis model, Dehydrozingerone-15 administration reduced TNF-α and IL-6 expression and protected vital organs (lungs, kidneys, and liver) from acute inflammation. The anti-inflammatory potential of Dehydrozingerone-15 was further validated in leukocyte migration induced by carrageenan and vascular permeability triggered by acetic acid assays, both of which showed significant inhibition. Pharmacokinetic analysis revealed that Dehydrozingerone-15 was rapidly absorbed in BALB/c mice, reaching a <i>C</i>_max of 10 349 ng/mL at 0.25 h. The total drug exposure (AUC_0–α) was 13 862 ng.h/mL, indicating sustained exposure, with high tissue distribution (20 L/kg) and moderate clearance. Additionally, toxicological evaluation at doses up to 2000 mg/kg body weight showed no significant alterations in haematological parameters compared with the vehicle control. Furthermore, based on a comparative evaluation of in vitro and in vivo results, Dehydrozingerone-15, relative to its parent molecule, demonstrates significant therapeutic potential with high efficacy against inflammation and oxidative stress.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kaempferol Suppresses Mesothelial–Mesenchymal Transition and Attenuates Postoperative Peritoneal Adhesions by Blocking the TNF-α/COX2 Signalling Pathway","authors":"Li Zhang,&nbsp;Gan Li,&nbsp;Yiwei Ren,&nbsp;Yanjun Sun,&nbsp;Kai Deng,&nbsp;Lindi Cai,&nbsp;Enmeng Li,&nbsp;Tianli Shen,&nbsp;Xuqi Li,&nbsp;Cancan Zhou","doi":"10.1111/1440-1681.70061","DOIUrl":"https://doi.org/10.1111/1440-1681.70061","url":null,"abstract":"<div>\u0000 \u0000 <p>Postoperative peritoneal adhesion (PA) formation is a common complication after abdominal surgery and can result in various severe outcomes. Inflammation and fibrosis are important processes in PA formation. The effectiveness of kaempferol (KF), a common component of several medications used to reduce inflammation and prevent fibrotic diseases, in preventing postoperative PA formation is unknown. This study explored the effectiveness and mechanism of KF in preventing PA formation following surgery. The animal adhesion model revealed that KF could effectively prevent adhesions formation and inhibit mesothelial–mesenchymal transition (MMT). Protein–protein interaction and pathway enrichment analyses revealed that TNF-α may be the key target through which KF prevents adhesion formation. Here, KF was found to inhibit TNF-α-induced MMT. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that common genes between KF and PA are enriched in the TNF signalling pathway. Moreover, cyclooxygenase 2 (COX2) was identified as a downstream target of TNF-α whose expression is positively correlated with adhesion formation. Most importantly, COX2 small interfering RNA (siRNA) and overexpression plasmid (OE) transfection experiments confirmed that KF inhibits MMT by blocking the TNF-α/COX2 signalling pathway. Finally, molecular docking revealed that TNF-α is a binding target of KF. In conclusion, these results suggest that KF inhibits MMT by blocking the TNF-α/COX2 signalling pathway, thus attenuating adhesion formation. These results provide new insights into the development of antiadhesion drugs.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in Targeted Protein Degradation Molecular Glues as Anticancer Drugs","authors":"Yulin Shen,&nbsp;Wen Wen,&nbsp;Luoyang Chen,&nbsp;Nan Zhang,&nbsp;Wei Cong,&nbsp;Honggang Hu","doi":"10.1111/1440-1681.70064","DOIUrl":"https://doi.org/10.1111/1440-1681.70064","url":null,"abstract":"<div>\u0000 \u0000 <p>Molecular glues have emerged as a novel class of targeted protein degraders with broad potential in cancer therapy. By inducing proximity between E3 ubiquitin ligases and oncogenic proteins, these agents activate the ubiquitin–proteasome system to drive selective protein degradation. This review systematically explores the application strategies of molecular glues in the targeted degradation of cancer-related proteins located in different subcellular compartments: nuclear cancer proteins (Ikaros, Helios, Aiolos, B-cell lymphoma 6 protein, cyclin K, RNA binding motif protein 39) and cytoplasmic cancer proteins (β-catenin, casein kinase 1α, G1 to S phase transition factor 1). Additionally, this work discusses current challenges and optimisation strategies, offering new perspectives for the development of precision anti-cancer therapeutics.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyroptosis-Mediated Antitumor Activity of Cinobufagin in Non-Small Cell Lung Cancer","authors":"Ying Chen,&nbsp;Feng Hu,&nbsp;Jiahuan Lu,&nbsp;Tengteng Zhu,&nbsp;Yajie Zheng,&nbsp;Yangyang Li,&nbsp;Jinwei Li,&nbsp;Kai Sheng,&nbsp;Feng Luo","doi":"10.1111/1440-1681.70055","DOIUrl":"https://doi.org/10.1111/1440-1681.70055","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aims to investigate the therapeutic efficacy and molecular mechanism of cinobufagin in non-small cell lung cancer (NSCLC) via pyroptosis induction. Bronchial epithelial cells and NSCLC cell lines were treated with gradient concentrations of cinobufagin. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) assay. RNA-sequencing was performed to identify differentially expressed genes. Lactate dehydrogenase (LDH) release was measured via cytotoxicity detection kit. Pyroptotic morphological changes were observed by transmission electron microscopy. Western blotting analysed expression levels of pyroptosis-related proteins. In vivo efficacy was validated in nude mouse xenograft models. Immunohistochemistry evaluated tumour pyroptosis markers, whilst flow cytometry analysed tumour-infiltrating CD8⁺ T cells and natural killer (NK) cells. Cinobufagin demonstrated selective cytotoxicity against NSCLC cells with minimal toxicity to normal bronchial epithelium. RNA-seq analysis revealed significant enrichment of pyroptosis-related pathways. Functional experiments confirmed cinobufagin-induced LDH release, characteristic pyroptotic morphological changes and upregulation of cleaved caspase-3 and Gasdermin E (GSDME)-NT in NSCLC cells. In xenograft models, cinobufagin treatment reduced tumour volume compared to controls. Mechanistically, this was associated with enhanced caspase-3 activation and GSDME-NT accumulation in tumour tissues. Notably, cinobufagin treatment significantly increased NK cell infiltration and activity. Cinobufagin exerts antitumor effects in NSCLC through caspase-3/GSDME-mediated pyroptosis induction, accompanied by immune microenvironment modulation. These findings provide preclinical evidence for cinobufagin as a potential therapeutic agent targeting pyroptosis in NSCLC.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Phytochemical Adjuvant Therapy in Melanoma Treatment: The Effects of MAZ-51 and Zingerone on Melanoma Cell Proliferation","authors":"Kganya Letsoalo,&nbsp;Charlise Basson,&nbsp;Trevor Nyakudya,&nbsp;Yvette Hlophe","doi":"10.1111/1440-1681.70059","DOIUrl":"https://doi.org/10.1111/1440-1681.70059","url":null,"abstract":"<p>Current melanoma treatment results in adverse effects, prompting the use of phytochemicals as adjuvant therapy to reduce the reliance on synthetic drugs and combat drug resistance. This study investigated the in vitro effect of (3-(4-Dimethylamino-naphthelen-1-ylmethylene)-1, 3-hydroindol-2-one) (MAZ-51) and zingerone, a ginger derivative, on melanoma cell proliferation in B16-F10 melanoma and HaCaT human keratinocyte cell lines. The cells were treated with MAZ-51 (0.002–0.005 mg/mL) and zingerone (0.5–2 mg/mL) at 24, 48 and 72 h, as well as combined treatment (at IC₅₀ at 48 and 72 h), to determine cell numbers using a crystal violet assay, which was also utilised to investigate the effects of vascular endothelial growth factor (VEGF) co-treated medium on cell numbers. Morphological changes were examined using haematoxylin and eosin (H&amp;E) staining and polarisation optical density inferential contrast (PlasDIC) and cell cycle progression using flow cytometry. The B16-F10 half maximal inhibitory concentrations (IC₅₀) were 0.05428, 0.03162 and 0.01204 mg/mL for MAZ-51 at 24, 48 and 72 h, respectively, and 27.9, 2.199 and 1.219 mg/mL for zingerone at 24, 48 and 72 h respectively. Both compounds reduced cell numbers at 48 and 72 h (<i>p</i> &lt; 0.05) and co-treatment with VEGF exhibited a decrease in cell numbers. Morphological analysis revealed characteristics of cell death, and flow cytometry analysis exhibited a mitotic block. Our findings demonstrate that individual treatment exhibited significant antiproliferative effects on melanoma cells. However, the combination treatment resulted in a combination index (CI) that is greater than one at IC₅₀ and IC₂₅, indicating antagonism. Therefore, future studies should consider the individual effects of the compounds on melanoma proliferation.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anatomical Classification and Clinical Significance of Right Middle Lobe Vein Confluence Variations in Right Upper Lobectomy: A Three-Dimensional Reconstruction Study","authors":"Tian Hao,&nbsp;Lei Xu,&nbsp;Si-Ming Jiang,&nbsp;Min Zhang,&nbsp;Ming-jian Ge","doi":"10.1111/1440-1681.70058","DOIUrl":"https://doi.org/10.1111/1440-1681.70058","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Anatomical variations of the right middle lobe (RML) veins pose significant risks during video-assisted thoracoscopic right upper lobectomy (RUL), where unrecognised veins traversing the horizontal fissure may be injured, compromising venous drainage. While 3D reconstruction aids surgical planning, a comprehensive classification system for RML venous confluences was lacking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective cohort study analysed 2007 patients undergoing lung surgery (2017–2023) using preoperative CT-based 3D-CT bronchography and angiography (3D-CTBA; Mimics 21.0). Two thoracic surgeons independently classified RML veins (V⁴a, V⁴b, V⁵a, V⁵b) by drainage location: horizontal fissure (H-type), anterior mediastinal (A-type), or oblique fissure (O-type). Disagreements were resolved by a radiologist. Descriptive statistics characterised anatomical patterns.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Analysis revealed complex venous drainage, with 31.83% (<i>n</i> = 639) demonstrating clinically critical H-type variations (confluencing into horizontal fissure). These were subclassified as HA (30.69%), HO (0.34%), and HAO (0.79%) patterns. V⁴a* traversed the fissure most frequently (29.07%), draining into upper lobe veins (V³b, V³a, V²c), while V⁴b* (2.86%) and V⁵a* (5.50%) exhibited lower traversal rates. No V⁵b* traversed the horizontal fissure. Rare drainage into the inferior pulmonary vein (IPV; V⁴a: 2.59%) or left atrium (0.20%) was observed, and the two-branch venous pattern predominated (42.87%). Previously unreported variants included downward-displaced RS³ (<i>n</i> = 10) and V⁶ → superior pulmonary vein drainage (<i>n</i> = 2). Intraoperative validation confirmed 3D-CTBA classification accuracy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This large-scale study establishes the novel HAO classification system for RML venous anatomy, revealing a high prevalence (31.83%) of H-type variations that critically impact RUL safety. Preoperative 3D-CTBA using this framework enables tailored surgical strategies to preserve RML veins traversing the horizontal fissure, reducing injury risks and postoperative complications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sinomenine Suppresses Hepatocellular Carcinoma Cell Migration and Invasion by Inhibiting O-GlcNAcylation of SP1","authors":"Lanqin Liu,&nbsp;Junwen Peng,&nbsp;Haixia Chen,&nbsp;Jie Chen,&nbsp;Wei Xu,&nbsp;Yehong Han","doi":"10.1111/1440-1681.70057","DOIUrl":"https://doi.org/10.1111/1440-1681.70057","url":null,"abstract":"<div>\u0000 \u0000 <p>Sinomenine (SIN) is an extract obtained from the plant <i>Sinomenium acutum</i>, which has been reported in hepatocellular carcinoma (HCC) and many other different types of human cancers as an anti-tumour agent. However, the molecular mechanism modulated or altered by SIN in HCC progression remains to be investigated. This study aims to uncover the molecular mechanism contributing to the tumour-suppressing effect of SIN in HCC. At first, HCC cells were treated with SIN for functional detections. Results of functional assays demonstrated that SIN was an efficient inhibitor of HCC cell viability, migration, and invasion. Next, O-GlcNAcylation and its removal OGA were found to be regulated by SIN treatment in HCC cells. According to rescue functional assays, OGA knockdown strengthened HCC cell viability, migration, and invasion suppressed by SIN. Moreover, as detected by mechanism experiments, OGA directly interacted with SP1 and blocked SP1 O-GlcNAcylation at site T407, indicating that SP1 was downregulated by OGA-mediated deglycosylation. Additionally, silencing of SP1 recovered the suppressing effects of SIN on HCC cell proliferation, migration, and invasion attenuated by OGA knockdown. Finally, SIN treatment inhibited the tumour tissue growth in vivo. In summary, this study unmasked the anti-tumour effect of SIN in HCC and SIN exerted functions by regulating OGA-mediated downregulation of SP1.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}