Experimental and therapeutic medicine最新文献

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A laboratory micro-CT technique is useful to visualize and characterize dermal skin components in a 3D manner. 实验室微ct技术是有用的可视化和表征真皮成分的三维方式。
IF 2.3
Experimental and therapeutic medicine Pub Date : 2026-02-27 eCollection Date: 2026-05-01 DOI: 10.3892/etm.2026.13116
Katarina Lundqvist, Hanna Tufvesson, Lars B Dahlin, Marius Reichardt, Bodil Ohlsson
{"title":"A laboratory micro-CT technique is useful to visualize and characterize dermal skin components in a 3D manner.","authors":"Katarina Lundqvist, Hanna Tufvesson, Lars B Dahlin, Marius Reichardt, Bodil Ohlsson","doi":"10.3892/etm.2026.13116","DOIUrl":"10.3892/etm.2026.13116","url":null,"abstract":"<p><p>Bowel and skin biopsies from patients with gastrointestinal disorders have revealed neuropathic changes and altered connective tissue. Patients with postural orthostatic tachycardia syndrome (POTS) often suffer from gastrointestinal symptoms and concomitant hypermobility spectrum disorders, such as hypermobile Ehlers-Danlos syndrome (hEDS). Since the skin is more accessible than the bowel, the aim of the present study was to evaluate skin biopsies in a 3D manner using micro-CT in patients with POTS and controls and relate the findings to symptoms presented. Healthy controls (n=13) and patients with POTS with (n=11) or without hEDS/EDS (n=26) were evaluated. Skin biopsies were taken proximally to the lateral malleolus using a 3 mm needle, fixed in formaldehyde and embedded in paraffin. The samples were harvested using a 1.5 mm punch (length, 2-5 mm) and scanned using a laboratory X-ray phase-contrast micro-CT. Scans were evaluated in a blinded manner and the regularity, thickness and tightness of collagen fiber bundles were assessed. All dermal structures were visible without staining. Intraepidermal nerves were not visible and a number of cell types could not be separated. The percentage of disorganized collagen bundles differed between groups, due to the majority being disorganized in hEDS/EDS (P=0.030). The proportion of any disorganized and parallel bundles throughout the biopsy differed within both patient groups (P<0.001) but not within the control group (P=0.175). There were no differences in symptoms between participants with disorganized bundles and participants without disorganized bundles. In conclusion, X-ray phase-contrast micro-CT was suitable to visualize and characterize dermal skin components in 3D. Patients with POTS and hEDS/EDS exhibited more disorganized collagen bundles; however, the technique cannot currently be used for diagnostic purposes until more patients are examined.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 5","pages":"120"},"PeriodicalIF":2.3,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12997094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147488898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RNU2-1 gene copy number variations do not affect serum levels of miR-1246 as a biomarker for lung adenocarcinoma. RNU2-1基因拷贝数的变化不影响miR-1246作为肺腺癌的生物标志物的血清水平。
IF 2.3
Experimental and therapeutic medicine Pub Date : 2026-02-27 eCollection Date: 2026-05-01 DOI: 10.3892/etm.2026.13115
Makiko Ueda, Shinya Sato, Yohei Miyagi, Toshiko Aiso
{"title":"<i>RNU2-1</i> gene copy number variations do not affect serum levels of miR-1246 as a biomarker for lung adenocarcinoma.","authors":"Makiko Ueda, Shinya Sato, Yohei Miyagi, Toshiko Aiso","doi":"10.3892/etm.2026.13115","DOIUrl":"10.3892/etm.2026.13115","url":null,"abstract":"<p><p>Circulating microRNA (miR)-1246, a fragment of U2 small nuclear RNA, represents a promising biomarker for certain cancers, including lung adenocarcinoma. The gene that encodes miR-1246, <i>RNU2-1</i>, is located on human chromosome 17q21.31 and is organized as a tandem array that exhibits copy number variations (CNVs). The range of copy numbers has been reported to be quite wide, ranging from 5 to 82 per haploid genome. The present study analyzed the correlation between <i>RNU2-1</i> copy numbers and serum miR-1246 levels in healthy controls and patients with stage IV lung adenocarcinoma. Serum miR-1246 levels were quantified using reverse transcription-quantitative polymerase chain reaction (PCR), and <i>RNU2-1</i> copy numbers per diploid genome were measured via digital PCR using blood-derived DNA. The median copy numbers were 50 and 49 in the control and lung adenocarcinoma groups, respectively, with no significant difference observed between the groups. In addition, no correlation between <i>RNU2-1</i> copy number and serum miR-1246 level was identified in either group. These results suggest that CNVs of <i>RNU2-1</i> do not affect serum levels of the lung adenocarcinoma biomarker miR-1246.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 5","pages":"121"},"PeriodicalIF":2.3,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12997089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147488965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Organelle homeostasis disruption: A driving force in the progression of cardiomyopathy (Review). 细胞器稳态破坏:心肌病进展的驱动力(综述)。
IF 2.3
Experimental and therapeutic medicine Pub Date : 2026-02-26 eCollection Date: 2026-05-01 DOI: 10.3892/etm.2026.13113
Yuxing Hou, Chao Li, Youyou Chen, Danfeng Zhong, Miaomiao Chai, Lijiao Mo, Senna Lin, Fangfang Huang, Qi Chen
{"title":"Organelle homeostasis disruption: A driving force in the progression of cardiomyopathy (Review).","authors":"Yuxing Hou, Chao Li, Youyou Chen, Danfeng Zhong, Miaomiao Chai, Lijiao Mo, Senna Lin, Fangfang Huang, Qi Chen","doi":"10.3892/etm.2026.13113","DOIUrl":"10.3892/etm.2026.13113","url":null,"abstract":"<p><p>Cardiomyopathy is a complex heart disease with structural and functional defects of the myocardium, often leading to poor clinical outcomes. While traditional research has focused on myofibrillar pathology and ion channel dysfunction, emerging evidence indicates that organelle homeostasis serves a central role in the pathogenesis of the disease. Mitochondrial dysfunction disrupts energy metabolism, calcium handling, dynamics and mitophagy. Golgi fragmentation, impaired glycosylation and abnormal vesicular trafficking jeopardize protein maturation and secretion. Endoplasmic reticulum stress causes myocardial injury via unfolded protein response, calcium dyshomeostasis and disruptions of lipid metabolism. Lysosomal degradation is disrupted by autophagic dysfunction, enzyme dysregulation and calcium signaling abnormalities. Ribosomes regulate proteostasis by defective biogenesis, quality control and translational dysregulation. Nuclear envelope instability and intercalated disc dysfunction disrupt normal mechanical and gene regulation in the development of cardiomyopathy. In combination, these findings support the concept of cardiomyopathy as a multi-organelle network disease driven by coordinated dysfunction of interconnected organelles. This review systematically summarizes current evidence on organelle-specific and inter-organelle mechanisms underlying cardiomyopathy, highlighting how disrupted organelle homeostasis collectively contributes to disease initiation and progression.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 5","pages":"118"},"PeriodicalIF":2.3,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12997092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147488989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A rare case of early-onset cerebral syphilitic gummata with severe neurological decline in early-stage syphilis: A case report. 早期梅毒伴严重神经功能减退的罕见早发性脑性牙龈病1例。
IF 2.3
Experimental and therapeutic medicine Pub Date : 2026-02-26 eCollection Date: 2026-05-01 DOI: 10.3892/etm.2026.13114
Yujie Ji, Shelin Liu, Yunwei Wang, Youcai Zhao, Zheng Cai, Bing Li
{"title":"A rare case of early-onset cerebral syphilitic gummata with severe neurological decline in early-stage syphilis: A case report.","authors":"Yujie Ji, Shelin Liu, Yunwei Wang, Youcai Zhao, Zheng Cai, Bing Li","doi":"10.3892/etm.2026.13114","DOIUrl":"10.3892/etm.2026.13114","url":null,"abstract":"<p><p>Cerebral syphilitic gummata are rare granulomatous lesions associated with tertiary syphilis, typically developing several years after the initial infection. Early-stage syphilis with cerebral gummata and accompanying severe neurological symptoms is rare. Failure to recognize the lesions or delays in diagnosis may lead to marked and potentially irreversible central nervous system injury. In the present study, the case of a 60-year-old man with a 6-month history of syphilis who presented with progressive right-sided limb weakness and dysarthria is reported. Brain magnetic resonance imaging revealed multiple ring-enhancing lesions accompanied by extensive perilesional edema. Due to the severity of the symptoms and a notable mass effect, surgical intervention was performed to remove the gummatous lesion, followed by histopathological confirmation of syphilitic granuloma. The patient was subsequently treated with high-dose intravenous penicillin, which led to notable improvement in neurological function and resolution of the symptoms; follow-up imaging demonstrated no recurrence of intracranial lesions. In conclusion, the present case illustrates the importance of early recognition and a multidisciplinary approach in the management of neurosyphilis with cerebral gummata. Increased awareness of this rare presentation may facilitate a timely diagnosis and appropriate treatment in similar clinical scenarios.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 5","pages":"119"},"PeriodicalIF":2.3,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12997095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147488953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DKK1/SMDT1 participate in Ang II-induced mitochondrial injury of human smooth muscle cells in an abdominal aortic aneurysm cell model. DKK1/SMDT1参与Angⅱ诱导的人腹主动脉瘤细胞模型平滑肌细胞线粒体损伤。
IF 2.3
Experimental and therapeutic medicine Pub Date : 2026-02-25 eCollection Date: 2026-04-01 DOI: 10.3892/etm.2026.13112
Xiaoxia Chang, Baohong Yao, Zheng Liu, Zijie Guo, Pengyue Qiao, Xiaokun Li, Lin Wang, Aiqun Li
{"title":"DKK1/SMDT1 participate in Ang II-induced mitochondrial injury of human smooth muscle cells in an abdominal aortic aneurysm cell model.","authors":"Xiaoxia Chang, Baohong Yao, Zheng Liu, Zijie Guo, Pengyue Qiao, Xiaokun Li, Lin Wang, Aiqun Li","doi":"10.3892/etm.2026.13112","DOIUrl":"10.3892/etm.2026.13112","url":null,"abstract":"<p><p>Abdominal aortic aneurysm (AAA) is a lethal vascular disease, in which apoptosis and inflammation participate. However, the regulatory factors associated with aortic status remain unclear; therefore, a deeper understanding of the cell types and signaling pathways involved in the pathological process of AAAs is key to the development of medical treatments. The aim of the present study was to explore the role of dickkopf-1 (DKK1) in angiotensin (Ang) II-stimulated human smooth muscle cells (HSMCs), and to clarify the potential downstream targets and related pathological mechanisms of DKK1. HSMCs were stimulated with Ang II (1 µM) for 24 h; consequently, DKK1 protein expression was upregulated by 4.26-fold and increased mRNA expression levels of IL-1β, GRP-94 and GRP-78 were also observed, indicating mitochondrial and endoplasmic reticulum stress. DKK1 silencing via small interfering RNA reduced its expression, which was validated by reverse transcription-quantitative PCR. RNA sequencing was performed in four groups: Negative control (NC), siDKK1, NC-Ang II and siDKK1-Ang II. Differentially expressed genes (DEGs) were identified by DESeq2, and 1,332 co-expressed DEGs were revealed by Venn analysis, enriched in pathways, including 'protein processing in the endoplasmic reticulum'. Robust rank aggregation prioritized key genes, notably single-pass membrane protein with aspartate rich tail 1 (SMDT1), a mitochondrial calcium regulator. The mRNA of SMDT1 was upregulated by Ang II stimulation by 2.78-fold, which was reversed by DKK1 silencing by 0.37-fold. Functional enrichment associated DEGs to viral response, extracellular matrix and cytokine pathways. Protein-protein interaction networks highlighted gene clusters via STRING. In conclusion, the present study investigated the role of DKK1 in Ang II-induced mitochondrial dysfunction in HSMCs. To the best of our knowledge, the present study demonstrated, for the first time, that DKK1/SMDT1 mediated Ang II-induced mitochondrial injury in HSMCs, suggesting this pathway as a potential mechanism. Therefore, the results indicated that DKK1 could serve as a therapeutic target for the prevention of AAA.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 4","pages":"117"},"PeriodicalIF":2.3,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12976854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rhabdomyolysis in a patient with lung cancer with sintilimab-induced overlap syndrome and hypothyroidism: A case report. 肺癌伴辛替利单抗重叠综合征和甲状腺功能减退的横纹肌溶解1例报告。
IF 2.3
Experimental and therapeutic medicine Pub Date : 2026-02-17 eCollection Date: 2026-04-01 DOI: 10.3892/etm.2026.13110
Bingyi Chen, Yi Liu, Qin Zeng, Shitong Yan, Xiujuan Liu, Quanlin Zhao
{"title":"Rhabdomyolysis in a patient with lung cancer with sintilimab-induced overlap syndrome and hypothyroidism: A case report.","authors":"Bingyi Chen, Yi Liu, Qin Zeng, Shitong Yan, Xiujuan Liu, Quanlin Zhao","doi":"10.3892/etm.2026.13110","DOIUrl":"10.3892/etm.2026.13110","url":null,"abstract":"<p><p>The use of immune checkpoint inhibitors (ICIs) has significantly improved outcomes in advanced malignancies, although these may induce immune-related adverse events (irAEs) involving multiple organ systems. The present case study reported on a 65-year-old man with squamous cell lung carcinoma who developed bilateral limb edema, profound fatigue and muscle weakness following chemotherapy, immunosuppressive therapy and iodine-125 brachytherapy. Laboratory tests revealed markedly elevated levels of creatine kinase and other muscle enzymes, overt hypothyroidism and positive antinuclear antibodies, consistent with overlapping immune-mediated myopathy and endocrine dysfunction. The patient was treated with diuretics, levothyroxine and tapering glucocorticoids, which led to a resolution of the symptoms, the normalization of enzyme levels and restoration of thyroid function. The excessive immune activation associated with ICI therapy, in combination with the hypometabolic state caused by hypothyroidism, may have acted as a synergistic 'double-hit' to skeletal muscle, which thereby contributed to the development of rhabdomyolysis (RM). This case highlights the need for vigilant monitoring of both musculoskeletal and endocrine systems in patients on ICIs, as the early recognition of irAEs is crucial to prevent life-threatening complications such as RM.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 4","pages":"115"},"PeriodicalIF":2.3,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12976855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Secondary pulmonary lymphoma diagnosed by minimal residual disease detected in bronchoalveolar lavage fluid: A case report. 支气管肺泡灌洗液微量残留病变诊断继发性肺淋巴瘤1例。
IF 2.3
Experimental and therapeutic medicine Pub Date : 2026-02-17 eCollection Date: 2026-04-01 DOI: 10.3892/etm.2026.13109
Yingying Hu, Zheng Lv, Lehao Ren, Xin Zhao, Hong Liu, Yin Yuan
{"title":"Secondary pulmonary lymphoma diagnosed by minimal residual disease detected in bronchoalveolar lavage fluid: A case report.","authors":"Yingying Hu, Zheng Lv, Lehao Ren, Xin Zhao, Hong Liu, Yin Yuan","doi":"10.3892/etm.2026.13109","DOIUrl":"10.3892/etm.2026.13109","url":null,"abstract":"<p><p>The present study reports 2 cases of non-Hodgkin's lymphoma (NHL) that achieved complete remission following cyclophosphamide, hydroxydaunorubicin (doxorubicin), oncovin (vincristine) and prednisone chemotherapy. Both patients subsequently developed respiratory distress and rapid progression. The initial diagnosis was pulmonary infection, based on the symptoms of cough, white sputum and fever, abnormal laboratory results of high white blood cells, C-reactive protein and procalcitonin and most notably, chest CT scans showing ground-glass opacities and patchy shadows. Following treatment with a number of antibiotics, the pulmonary symptoms of the patients and their imaging manifestations improved at first. The repeated negative results of sputum culture and next-generation sequencing of bronchoalveolar lavage fluid (BALF) confirmed that the pathogens were eliminated. However, later, the symptoms and signs of both patients continued to progress. Secondary pulmonary lymphoma was not confirmed until the discovery of lymphocytes with abnormal phenotypes following minimal residual disease (MRD) testing in BALF. Both patients ultimately succumbed to respiratory failure. The present report outlines the first 2 reported cases of NHL diagnosed through MRD detection in BALF alongside a review of the relevant literature.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 4","pages":"114"},"PeriodicalIF":2.3,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12976836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gut microbiota-metabolism axis in digestive tumors: Emerging targets for novel therapies (Review). 消化道肿瘤中的肠道微生物代谢轴:新疗法的新靶点(综述)。
IF 2.3
Experimental and therapeutic medicine Pub Date : 2026-02-17 eCollection Date: 2026-04-01 DOI: 10.3892/etm.2026.13108
Zhendong Yang, Siyu Wu, Xueying Yang, Bowen Sui
{"title":"Gut microbiota-metabolism axis in digestive tumors: Emerging targets for novel therapies (Review).","authors":"Zhendong Yang, Siyu Wu, Xueying Yang, Bowen Sui","doi":"10.3892/etm.2026.13108","DOIUrl":"10.3892/etm.2026.13108","url":null,"abstract":"<p><p>Digestive tumors, including malignancies associated with the gastrointestinal tract, represent a notable global health burden. Advances in microbiome research have highlighted that the gut microbiota-metabolism axis and its associated metabolic derivatives are key modulators of tumorigenesis, immune evasion and treatment responses. The present review aimed to comprehensively discuss how key microbial metabolites, such as polyamines, short-chain fatty acids, bile acids and other compounds reshape the tumor microenvironment, modulate cellular signaling and affect immune responses. By integrating insights from microbiology, immunology, oncology and metabolic changes in digestive tumors, evidence suggests that the microbiota contributes to cancer progression through mechanisms involving epigenetic regulation, metabolic reprogramming, genotoxicity and production of inflammatory mediators. Beneficial bacteria, such as <i>Akkermansia muciniphila</i> and <i>Faecalibacterium prausnitzii</i>, exhibit antitumor activity, whereas pathogenic species, such as <i>Helicobacter pylori</i> and <i>Fusobacterium nucleatum</i>, are associated with oncogenic properties. Based on a literature search, microbiota-targeted therapy seems to be promising for the management of pathological conditions, especially digestive diseases. Further investigations into the pharmaceutical application of microbiota through prebiotics, probiotics and metabolite-targeted interventions, along with multi-omics integration and microbiome-host interactome validation, would be promising for improving personalized medicine and precision oncology.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 4","pages":"113"},"PeriodicalIF":2.3,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12977142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Metformin triggers apoptosis via endoplasmic reticulum stress in HER2-positive breast cancer cell lines. 二甲双胍通过内质网应激触发her2阳性乳腺癌细胞系细胞凋亡。
IF 2.3
Experimental and therapeutic medicine Pub Date : 2026-02-13 eCollection Date: 2026-04-01 DOI: 10.3892/etm.2026.13106
Eser Çakmak, Birşen Bilgici
{"title":"Metformin triggers apoptosis via endoplasmic reticulum stress in HER2-positive breast cancer cell lines.","authors":"Eser Çakmak, Birşen Bilgici","doi":"10.3892/etm.2026.13106","DOIUrl":"10.3892/etm.2026.13106","url":null,"abstract":"<p><p>The antidiabetic drug metformin has potential as an anticancer agent, particularly due to its observed efficacy in breast cancer. Metformin exerts its cytotoxic effects in the induction of endoplasmic reticulum (ER) stress, which can trigger apoptotic cell death pathways. Therefore, the present study aimed to investigate the dose-dependent effects of metformin on ER stress and apoptosis in HER2-positive breast cancer SKBR3 cells. For this purpose, SKBR3 cells were treated with 5, 10 and 20 mM metformin. Cell proliferation was assessed using real-time cell analysis, while expression levels of ER stress-associated genes [glucose-regulated protein 78 kDa (GRP78), PRKR-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6) and CHOP)] were measured by revese transcription-quantitative PCR. Apoptosis was analyzed by Annexin V-FITC/PI flow cytometry in cells treated with 10 and 20 mM metformin. Findings revealed that metformin (5, 10 and 20 mM) dose-dependently inhibited cell proliferation and activated ER stress pathways. Significant increases were observed in gene expression following treatment with 5, 10 and 20 mM metformin, respectively, including GRP78 (3.70-, 5.06- and 7.33-fold; all P<0.0001) PERK (2.48-, 4.36- and 9.11-fold; all P<0.0001), IRE1 (2.15-fold, P=0.001; 2.90-fold, P<0.001; 5.55-fold, P<0.0001), ATF6 (2.43-2.44- and 3.63-fold; all P<0.0001) and particularly in pro-apoptotic CHOP (3.31-, 27.47- and 49.85-fold; all P<0.0001). Flow cytometry revealed that 10 and 20 mM metformin significantly increased early apoptosis to 6.05% (P<0.001) and 7.28% (P<0.001) and late apoptosis to 13.24% (P<0.001) and 20.59% (P<0.001), respectively, compared with controls (early apoptosis, 0.02%; late apoptosis, 0.05%). The present findings demonstrated that metformin activates ER stress response and induces apoptosis in HER2-positive breast cancer cells in a dose-dependent manner. This supports the potential of metformin as an adjuvant therapy, though further <i>in vivo</i> studies are needed to evaluate its clinical applicability.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 4","pages":"111"},"PeriodicalIF":2.3,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12977141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Drug-related problems in pediatric patients with chronic kidney disease: A single-center prospective study. 儿童慢性肾病患者的药物相关问题:一项单中心前瞻性研究
IF 2.3
Experimental and therapeutic medicine Pub Date : 2026-02-12 eCollection Date: 2026-04-01 DOI: 10.3892/etm.2026.13102
Xingxing Liu, Yue Li, Zhen Mao, Xin Wang, Shan Zhao, Qiu Han, Jia Liu, Yan Zhou, Shi Li, Bing Chen, Yongfu Hang, Wan Yan, Xiaoye Jin
{"title":"Drug-related problems in pediatric patients with chronic kidney disease: A single-center prospective study.","authors":"Xingxing Liu, Yue Li, Zhen Mao, Xin Wang, Shan Zhao, Qiu Han, Jia Liu, Yan Zhou, Shi Li, Bing Chen, Yongfu Hang, Wan Yan, Xiaoye Jin","doi":"10.3892/etm.2026.13102","DOIUrl":"10.3892/etm.2026.13102","url":null,"abstract":"<p><p>Currently, there is a lack of data on drug-related problems (DRPs) in pediatric patients with chronic kidney disease (CKD) in China. The aim of the present study was to determine the incidence and determinants of DRPs in pediatric patients with CKD and to inform evidence-based pharmacotherapy for this population. For this purpose, a single-center prospective study was conducted at the Guiyang Maternal and Child Health Care Hospital (Guiyang, China) between January and December 2023. The Pharmaceutical Care Network Europe (PCNE) taxonomy [version 9.1 (v9.1)] was adapted to reflect the unique characteristics of pediatric patients with CKD; all identified DRPs were classified according to the modified PCNE v9.1 and were subsequently analyzed. The results demonstrated that among the 383 hospitalized children with CKD, 136 patients (35.51%) experienced 203 DRPs; the majority of problems pertained to treatment effectiveness (190; 93.60%) and of the 223 underlying causes identified, 79 (35.43%) were related to drug selection. Clinical pharmacists initiated 254 interventions; 243 (95.67%) were fully accepted and implemented. In conclusion, the present study demonstrated that DRPs are common in pediatric patients with CKD. The implementation of a pharmacist-led medication reconciliation model, supported by an adapted PCNE tool, was associated with a high intervention acceptance rate. However, the present study was conducted in a single center and the findings obtained need to be validated in other centers, thereby providing more valuable references for the identification and management of DRPs in children with CKD.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 4","pages":"107"},"PeriodicalIF":2.3,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12977310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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