Experimental and therapeutic medicine最新文献

{"title":"Immune cross talk and therapeutic advances in lactate metabolism in the tumor microenvironment (Review).","authors":"Min Liu, Kui Su","doi":"10.3892/etm.2026.13135","DOIUrl":"10.3892/etm.2026.13135","url":null,"abstract":"<p><p>The excessive buildup of lactic acid within the tumor microenvironment (TME) serves as a hallmark of metabolic reprogramming in cancer. New studies have revealed that lactic acid is an energy metabolic product and a core biological signal that regulates the malignant process of tumors. It plays multiple roles in metabolic reprogramming, protein lactate modification, immune escape, drug resistance generation, epigenetic regulation and metastatic spread. It also has significant negative implications for patient survival. In this review, the advances in understanding the metabolic mechanisms of lactate in the TME and its crosstalk with various of immune cells were systematically reviewed and its therapeutic potential in the following ways was explored: Targeting lactate synthesis (e.g., lactate dehydrogenase inhibitors); interfering with lactate catabolism (e.g., monocarboxylate transporter blockers); and regulating lactate shuttling (microenvironmental cell-to-cell communication). The review aimed to identify new targets and ideas for anticancer strategies by analyzing the lactate metabolic network.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 5","pages":"139"},"PeriodicalIF":2.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610996","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}

{"title":"Immunohistochemical evaluation of gastric-type markers in primary extramammary Paget disease: Differential MUC5AC expression between <i>in situ</i> and invasive lesions.","authors":"Naoto Kohno, Mitsuaki Ishida, Shizuka Ono, Yoshinobu Hirose","doi":"10.3892/etm.2026.13133","DOIUrl":"10.3892/etm.2026.13133","url":null,"abstract":"<p><p>Primary extramammary Paget disease (EMPD) is a rare cutaneous adenocarcinoma characterised by intraepithelial proliferation of mucin-containing carcinoma cells, with invasive carcinoma occasionally present. A characteristic immunohistochemical feature of primary EMPD is expression of MUC5AC, a gastric-type mucin core protein; however, the expression of MUC5AC in invasive EMPD remains controversial. Furthermore, the expression of other gastric-type markers, including hepatocyte nuclear factor 4α (HNF4α) and claudin 18, has not been fully investigated in primary EMPD. The present study aimed to clarify the expression profiles of MUC5AC in both <i>in situ</i> and invasive EMPD lesions, as well as to evaluate HNF4α and claudin 18 expression in primary EMPD. Consecutive patients with primary EMPD who underwent surgical resection were included. Immunohistochemical staining for MUC5AC, HNF4α and claudin 18 was performed, and the results were semi-quantitatively assessed using a four-tier scoring system (0, <5%; 1, 5-25%; 2, 26-50%; 3, >50% positive neoplastic cells) in <i>in situ</i> and invasive components, when present. A total of 40 patients (9 female patients and 31 male patients) were included, comprising 25 cases <i>in situ</i> and 15 invasive cases. MUC5AC expression was observed in 24 <i>in situ</i> and 14 invasive EMPD cases. No significant difference in MUC5AC expression scores in <i>in situ</i> lesions was observed between <i>in situ</i>-only and invasive EMPD cases (P=0.35). By contrast, MUC5AC expression scores in invasive components were significantly lower than those in the corresponding <i>in situ</i> lesions of invasive EMPD (P=0.0015). Neither <i>in situ</i> nor invasive EMPD lesions showed immunoreactivity for HNF4α or claudin 18. These findings obtained from the second-largest cohort study to date suggested that MUC5AC expression was reduced in invasive lesions. Furthermore, MUC5AC expression in EMPD was not associated with the expression of HNF4α, despite its role in inducing MUC5AC expression in normal gastric tissues.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 5","pages":"138"},"PeriodicalIF":2.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147611053","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}

{"title":"Atorvastatin augments collateral formation and functional recovery after indirect revascularization in adult ischemic moyamoya disease: A randomized trial.","authors":"Dawei Wang, Jingya Dai, Shumei Li, Yaping Liu, Xiaofeng Xing, Lei Huang, Qijun Pang","doi":"10.3892/etm.2026.13137","DOIUrl":"https://doi.org/10.3892/etm.2026.13137","url":null,"abstract":"<p><p>The present study aimed to assess whether atorvastatin enhances indirect revascularization outcomes in adult ischemic moyamoya disease (MMD). In a randomized trial, 80 adults received postoperative atorvastatin (20 mg/day, n=40) or standard care (n=40); the primary outcome was good neovascularization (Matsushima grade, Good) at 6 months. The results revealed that good neovascularization was higher with atorvastatin (65.0 vs. 37.5%; risk ratio, 1.73; P=0.014). In addition, the atorvastatin group exhibited greater improvement in cerebral blood flow (mean difference, 4.3 ml/100 g/min; P<0.001) and functional outcome (72.5 vs. 50.0% with modified Rankin Scale improvement; P=0.039). Ischemic event recurrence was also lower in the atorvastatin group (2.5 vs. 12.5%; P=0.201), whereas safety profiles were similar. In conclusion, the present single-center randomized trial provides preliminary evidence that adjunctive atorvastatin may improve collateral formation, cerebral perfusion and functional status after indirect revascularization in adult ischemic MMD. Large-scale multi-center studies are warranted to validate these findings. This trial was registered in the Chinese Clinical Trial Registry as trail no. ChiCTR1800016363, on June 3, 2018.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 5","pages":"142"},"PeriodicalIF":2.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13492041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803575","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}

{"title":"Maresin 1 activates autophagy through SIRT1/PPAR-γ signaling to mitigate high glucose-induced pyroptosis in human retinal pigment epithelial cells.","authors":"Jun Zhang, Ding Zhao, Yuanqing Zhang, Haoxiang Sun, Zhipeng Yan, Haiyan Sun","doi":"10.3892/etm.2026.13134","DOIUrl":"10.3892/etm.2026.13134","url":null,"abstract":"<p><p>Accumulating evidence suggests that maresin 1 (MaR1), a docosahexaenoic acid-derived specialized pro-resolving lipid mediator, safeguards ARPE-19 cells against high glucose (HG)-induced ferroptosis, with potential relevance in preventing the onset and progression of diabetic retinopathy (DR). Building upon this observation, the present study aimed to elaborate on the functional role of MaR1 in DR and explore the underlying mechanisms mediating its protective effects. ARPE-19 cells were exposed to HG to mimic DR <i>in vitro</i> and treated with varying doses of MaR1. An MTT assay was conducted to assess cell viability, while ELISA was used to measure the levels of inflammatory factors in the cells. Monodansylcadaverine staining was used to evaluate autophagic flux. Additionally, immunofluorescence and western blot assays were used to detect the expression of proteins associated with pyroptosis, autophagy and the sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling pathway. To further investigate the mechanism underlying the actions of MaR1, ARPE-19 cells were pretreated with a SIRT1 inhibitor (EX-527) or an autophagy inhibitor (3-MA) before the aforementioned treatments were administered. The findings revealed that MaR1 rescued cell viability and attenuated the expression and secretion of pro-inflammatory cytokine levels (specifically IL-1β and IL-18) in HG-challenged ARPE-19 cells in a dose-dependent manner, while also alleviating the HG-induced reduction in autophagic flux. Pretreatment with MaR1 further reversed the HG-mediated downregulation of beclin 1, LC3-II/I, SIRT1 and PPAR-γ, alongside the HG-triggered upregulation of p62, gasdermin D N-terminal, cleaved caspase-1, NLR family pyrin domain containing 3, apoptosis-associated speck-like protein containing a CARD and IL-18, as demonstrated through immunofluorescence and western blot analyses. Notably, an autophagy inhibitor blunted the regulatory effects of MaR1 on pyroptosis, whereas a SIRT1 inhibitor abrogated the protective actions of MaR1 against inflammation and pyroptosis, as well as its modulation of autophagy, as demonstrated by measuring key molecular markers of pyroptosis, inflammation and autophagy in treated ARPE-19 cells. Overall, the results indicated that MaR1 mitigated HG-induced pyroptosis in human retinal pigment epithelial cells, potentially by upregulating the SIRT1/PPAR-γ signaling pathway to reinstate autophagy, thus ameliorating DR-associated damage.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 5","pages":"141"},"PeriodicalIF":2.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147611084","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}

{"title":"Advances in new ultrasound technologies in targeted prostate biopsy (Review).","authors":"Tingting Jin, Liying Wang, Shusen Zheng","doi":"10.3892/etm.2026.13136","DOIUrl":"https://doi.org/10.3892/etm.2026.13136","url":null,"abstract":"<p><p>Transrectal ultrasound-guided systematic biopsy is the standard method for diagnosing prostate cancer (PCa). As the inherent randomness of systematic biopsy results in a relatively high rate of missed diagnoses, targeted biopsy techniques guided by advanced ultrasound technologies, such as micro-ultrasound, contrast-enhanced ultrasound, ultrasound elastography and resonance-ultrasound fusion imaging, can markedly enhance the detection of clinically significant PCa and represent promising applications in prostate biopsy. The present review summarizes targeted prostate biopsy guided by new ultrasound technologies.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 5","pages":"140"},"PeriodicalIF":2.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13492040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803539","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}

{"title":"[Retracted] Icariin inhibits oral squamous cell carcinoma cell proliferation and induces apoptosis via inhibiting the NF-κB and PI3K/AKT pathways.","authors":"Ling Sun, Jing Zhang","doi":"10.3892/etm.2026.13131","DOIUrl":"10.3892/etm.2026.13131","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3892/etm.2021.10374.].</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 5","pages":"136"},"PeriodicalIF":2.3,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610934","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}

{"title":"Disrupted beginnings: Neurodevelopmental outcomes of COVID-19 lockdowns in early childhood (Review).","authors":"Ioanna Giannopoulou, Vasiliki Efstathiou, Maria-Ioanna Stefanou, Panagiota Korkoliakou, James N Tsoporis, Demetrios A Spandidos, Emmanouil Rizos","doi":"10.3892/etm.2026.13132","DOIUrl":"10.3892/etm.2026.13132","url":null,"abstract":"<p><p>Early childhood development depends on stable routines, social interaction and responsive caregiving. The 2019 coronavirus disease pandemic disrupted these supports through lockdowns, reduced early-education access and elevated caregiver stress. The present review synthesized empirical studies (2020-2025) of children aged 0-5 years and found consistent evidence of modest increases in emotional and behavioral difficulties, particularly where caregiver stress or socioeconomic adversity was elevated. Cognitive, language and executive-function (EF) outcomes were found to be more heterogeneous and appeared most affected in the contexts of reduced stimulation or limited access to early learning, with EF processes showing particular sensitivity to stress-related and environmental disruptions. Biological findings (cortisol, DNA methylation and infant brain measures) showed a number of converging signals, particularly in higher-risk contexts, but remained preliminary given modest sample sizes, methodological heterogeneity and limited replication. Overall, this suggested that pandemic-related disruptions disproportionately affected children in vulnerable family contexts. Therefore, the present study suggested targeted caregiver mental-health support, preservation of early-education access during emergencies and longitudinal follow-up of high-risk cohorts.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 5","pages":"137"},"PeriodicalIF":2.3,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610958","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}

{"title":"Effects of fullerenol C₆₀ on the liver, heart and brain tissues of streptozotocin-induced diabetic rats with sepsis.","authors":"Necmiye Şengel, Ömer Kubat, Laman Farajsoylu, Ahmet Çağri Büyükkasap, Muharrem Atli, Şaban Cem Sezen, Hasan Bostanci, Kürşat Dikmen, Işin Güneş, Fatma Er, Mustafa Kavutçu, Mustafa Arslan","doi":"10.3892/etm.2026.13130","DOIUrl":"10.3892/etm.2026.13130","url":null,"abstract":"<p><p>In the present study, the protective effects of fullerenol C₆₀, a nanomaterial with antioxidant properties, were investigated against sepsis-induced multiple organ failure in liver, heart and brain tissues using a sepsis model [cecal ligation and puncture (CLP)] in diabetic rats. A total of 30 Wistar albino male rats were divided into four groups: Control, diabetic control, diabetes + sepsis (DM/SEP) and diabetes + sepsis + fullerenol C₆₀ (FUL/C-60). Streptozotocin was administered intraperitoneally at a dose of 55 mg/kg to induce diabetes in the rats; those with blood sugar levels >250 mg/dl 72 h after injection were considered diabetic. After 4 weeks, only laparotomy was performed in the control and diabetic control groups. CLP was applied to the DM/SEP and FUL/C-60 groups to establish a sepsis model. After laparotomy, the abdomens of the rats were closed. In the FUL/C-60 group, 100 mg/kg fullerenol C₆₀ was administered intraperitoneally 30 min after the procedure. All rats were sacrificed 24 h later and blood and tissue samples from the brain, liver and heart were taken for histopathological and biochemical examination. The data distribution was analyzed using the Shapiro-Wilk test. Data were evaluated using the Kruskal-Wallis test followed by Dunn's post hoc test or one-way ANOVA followed by Tukey's post hoc test. Fullerenol C₆₀ markedly reduced sepsis-induced tissue damage in the liver, heart and brain. Histopathological evaluation demonstrated significantly less hepatocyte degeneration (P=0.042), necrosis (P=0.040) and sinusoidal dilatation (P=0.013) in liver tissue; reduced interstitial fibrosis (P=0.040) in heart tissue; and decreased inflammatory cellularity (P=0.034) in brain tissue in the FUL/C-60 group compared with the DM/SEP group. Biochemically, fullerenol C₆₀ significantly attenuated oxidative stress in liver and brain tissues, as indicated by lower thiobarbituric acid reactive substance levels (both, P<0.001) and higher catalase activity (P=0.034 and P=0.009, respectively) in the FUL/C-60 group. Consistent with these findings, liver function was substantially improved, as evidenced by reduced serum aspartate transaminase (P<0.001), alanine transaminase (P<0.001) and γ-glutamyl transferase (P=0.008) levels, as well as lower total (P<0.001) and direct bilirubin (P<0.001) levels. Overall, fullerenol C₆₀ effectively reduced organ damage by suppressing oxidative stress. Fullerenol C₆₀ demonstrated protective effects against multiple organ failure in a diabetic sepsis model, indicating its potential as a supportive agent in sepsis treatment.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 5","pages":"135"},"PeriodicalIF":2.3,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147611016","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}

{"title":"Long non-coding RNA KCNQ1OT1 promotes ovarian cancer cell malignant characteristics by targeting the miR-140-5p/KLK10 axis.","authors":"Renjie Duan, Zhenyu Tao, Shun Tao, Aichen Yang, Xu Yang, Changzheng Li, Xiaoxiang Zhu, Kexin Zhang, Zhuofu Li, Shanjun Tao","doi":"10.3892/etm.2026.13129","DOIUrl":"10.3892/etm.2026.13129","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) have emerged as key regulatory molecules involved in driving cancer progression. However, the specific functional roles of numerous lncRNAs in ovarian cancer (OC) remain largely underexplored. The present study aimed to elucidate the role and underlying mechanisms of potassium voltage-gated channel subfamily Q member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) in OC progression. Bioinformatics prediction using the TargetScan and starBase databases revealed that both KCNQ1OT1 and kallikrein-related peptidase 10 (KLK10) harbor complementary binding sites for microRNA (miR)-140-5p. The direct interaction between miR-140-5p and KCNQ1OT1 or KLK10 was experimentally validated using miRNA pull-down assays. Analysis of GEO datasets (GSE66957 and GSE47841), followed by RT-qPCR validation in SKOV3 and IOSE80 cells, revealed that KCNQ1OT1 and KLK10 were markedly upregulated, whereas miR-140-5p was downregulated in OC compared with that in normal ovarian controls. CCK-8 and wound-healing assays demonstrated that silencing KCNQ1OT1 markedly suppressed OC cell proliferation and migration, effects that were reversed by miR-140-5p inhibition. Conversely, inhibition of miR-140-5p enhanced OC cell proliferation and migration, which were abrogated by KLK10 knockdown. Collectively, these findings identified a previously unrecognized regulatory axis in OC, in which KCNQ1OT1 promotes tumor cell proliferation and migration by modulating the miR-140-5p/KLK10 pathway. The present study advances the mechanistic understanding of lncRNA-mediated oncogenesis and provides preliminary evidence supporting a potential role of KCNQ1OT1 in OC progression.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 5","pages":"134"},"PeriodicalIF":2.3,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147611086","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}

{"title":"[Retracted] Recent perspectives of electronic medical record systems (Review).","authors":"Xiao-Ying Zhang, Peiying Zhang","doi":"10.3892/etm.2026.13126","DOIUrl":"10.3892/etm.2026.13126","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3892/etm.2016.3233.].</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 5","pages":"131"},"PeriodicalIF":2.3,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610987","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}