Clinical and Experimental Pharmacology and Physiology最新文献

{"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}

{"title":"M2 Macrophages-Derived Exosomes Inhibited Podocyte Pyroptosis via lncRNA AFAP1-AS1/EZH2 Axis","authors":"Qing Zhan,&nbsp;Huiyun Liu,&nbsp;Minyang Zhao,&nbsp;Haihua Huang","doi":"10.1111/1440-1681.70056","DOIUrl":"https://doi.org/10.1111/1440-1681.70056","url":null,"abstract":"<div>\u0000 \u0000 <p>Macrophage infiltration was closely associated with inflammatory injury of podocytes in diabetic nephropathy (DN), while how macrophages affected podocytes remained not entirely clear. Here, we not only investigated the relationship between macrophages and high glucose (HG)-treated podocytes, but the underlying mechanisms were also explored. Transmission electron microscopy, nanoparticle tracking analysis, and western blot of CD9, CD63, CD81, and Calnexin were performed to identify exosomes; QRT-PCR was performed to detect AFAP1-AS1 expression; Western blot was performed to examine NLRP3, Cleaved caspase-1, and GSDMD-N protein levels; Immunofluorescence was performed to assess co-localisation of NLRP3 and ASC; ELISA was performed to detect IL-18 and IL-1β levels; Cytotoxicity LDH Assay Kit was performed to detect LDH level; RNA pulldown was performed to determine the interaction of AFAP1-AS1 and EZH2; ChIP was employed to determine the interaction of EZH2 and H3K27me3 in the NLRP3 promoter region. The results showed that AFAP1-AS1 expression was down-regulated in the peripheral blood of DN patients, and exosomes derived from M2 macrophages transfected with si-AFAP1-AS1 enhanced HG-induced podocyte pyroptosis via significantly elevating NLRP3, Cleaved caspase-1, and GSDMD-N protein levels, immunofluorescence intensity of NLRP3 and ASC, as well as IL-18, IL-1β, and LDH levels. Mechanistically, AFAP1-AS1 interacted with EZH2 to transcriptionally regulate H3K27me3 level in the NLRP3 promoter region, thus epigenetically repressing NLRP3 level to inhibit podocyte pyroptosis. These results may provide an important target for improving kidney injury in DN.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635533","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":"Potential Kidney Risks Associated With Clinical Doses of Omeprazole: In Vivo and In Vitro Studies","authors":"Zibo Xiong,&nbsp;Zhiwei Lai,&nbsp;Sanmu Li,&nbsp;Hua Zhang,&nbsp;Yongqiang Wang,&nbsp;Lishan Tan,&nbsp;Guang Yang,&nbsp;Zuying Xiong","doi":"10.1111/1440-1681.70050","DOIUrl":"https://doi.org/10.1111/1440-1681.70050","url":null,"abstract":"<p>Omeprazole is a widely used proton pump inhibitor and anti-<i>Helicobacter pylori</i> drug; however, its nephrotoxicity has been controversial. This study aimed to explore the effects and mechanisms of omeprazole on the kidney. In HK2, HPC, NRK and 293 T cells, omeprazole-induced alterations in cell morphology, density and viability in a concentration-dependent manner. Excessively high concentrations (&gt; 50 μM) led to a significant increase in cell death. Interestingly, NRK seemed insensitive to omeprazole. RNA sequencing revealed significant alterations in the genomic expression profile when HK2 cells were incubated at a concentration of 5 μM, including the inhibition of proliferative, metabolic and cytokine receptor gene expression. This alteration augments the environmental susceptibility of HK2 when exposed to H₂O₂. Animal studies have shown that omeprazole (10.4 mg/kg × day, 28 days) has no significant effect on body weight, kidney or heart weight or kidney or liver function, as well as plasma calcium and vitamin D. Tissue staining revealed increased expression of the macrophage marker F4/80 in response to omeprazole. In conclusion, therapeutic-dose omeprazole administration in the short term shows no clinically relevant nephrotoxicity. However, omeprazole decreases cell proliferation and viability by disrupting gene expression; thus, the long-term use of omeprazole may increase inflammation and environmental susceptibility. These findings provide valuable insights for the clinical use of omeprazole, highlighting the need for careful consideration of its effects in the kidney.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573761","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":"Decrease in Mitochondrial Oxidative Respiratory Function in Liver of Cricetulus barabensis Under Long and Short Photoperiods: The Role of Mitochondrial Fission and Apoptosis","authors":"Jin-Hui Xu,&nbsp;Lu-Fan Li,&nbsp;Yi-Man Liu,&nbsp;Xin-Yi Song,&nbsp;Le Chen,&nbsp;Ming-Di Wang,&nbsp;Li-Na Jiang,&nbsp;Zhe Wang","doi":"10.1111/1440-1681.70054","DOIUrl":"https://doi.org/10.1111/1440-1681.70054","url":null,"abstract":"<div>\u0000 \u0000 <p>The photoperiod is a crucial factor affecting the seasonal rhythms of mammals. Under the seasonal rhythms, the growth and development of the body are closely related to the oxidative respiratory function of mitochondria, but the influence of the single seasonal factor photoperiod on it remains unclear. In this study, mitochondrial dynamics and associated regulatory mechanisms were investigated in the livers of striped dwarf hamsters (<i>Cricetulus barabensis</i>) exposed to three distinct photoperiod regimes: short photoperiod (SP), moderate photoperiod (MP) and long photoperiod (LP). Results indicated that: (1) Liver mass responses to photoperiod varied with changes in body weight. (2) ATP synthase activity was significantly decreased under LP, whereas citrate synthase activity (CS) was selectively diminished under SP. (3) The Bcl2 associated X protein (bax) to b cell lymphoma 2 (bcl2) ratio increased under both SP and LP. (4) Dynamin-related protein 1 (DRP1) protein abundance increased under both LP and SP conditions, while mitochondrial fission factor (MFF) decreased under LP, signifying divergent remodelling of mitochondrial fission signalling. (5) Caspase3 activity unchanged under SP. In conclusion, under LP and SP treatment, the oxidative respiratory function of liver mitochondria in striped dwarf hamsters may be weakened, potentially due to increased mitochondrial membrane permeability, as indicated by an elevated bax/bcl2 ratio. Compared to long photoperiod treatment, the upregulation of the liver mitochondrial fission signalling and the lower level of apoptosis under short photoperiod conditions may help facilitate thermogenic adaptation to increased energetic demands in winter.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514703","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}