{"title":"Maternal Electronic Cigarette Exposure Induces Dysregulation of Autophagy via Oxidative Stress/DNA Methylation in Pulmonary Hypertension Offspring.","authors":"Ze-Wen Chen, Yi-Fan Li, Hai-Long Qiu, Wen Xie, Tian-Yu Chen, Yong Zhang, Ji-Mei Chen, Jian Zhuang, Shu-Sheng Wen","doi":"10.1007/s11596-025-00074-8","DOIUrl":"https://doi.org/10.1007/s11596-025-00074-8","url":null,"abstract":"<p><strong>Objective: </strong>Electronic cigarettes (ECs) differ from traditional tobacco smoke but may contribute to cardiopulmonary remodeling. Pulmonary hypertension (PH), characterized by pulmonary artery and right ventricle remodeling, poses a significant risk of mortality in infants, children, and adolescents. However, the impact of maternal EC exposure on PH development in offspring remains unclear. To address this, we established a PH rat model with maternal EC exposure.</p><p><strong>Methods: </strong>Maternal EC exposure was initiated on gestation day 12 via electronic nicotine delivery systems. Offspring were administered monocrotaline (MCT) at 6 weeks of age (6-wo) to induce PH. Mechanistic experiments were conducted at 10-week-old (10-wo). Protein expression of NADPH oxidases, DNA methyltransferases, and autophagy-related markers was analyzed by Western blot. Morphological changes and the severity of PH were evaluated via hematoxylin and eosin (HE) staining and echocardiography, respectively. Furthermore, the involvement of the oxidative stress/DNA methylation/autophagy axis in response to maternal EC exposure was confirmed through a combination of ELISA, Western blot, HE staining, and echocardiography. Additionally, ATG5 mRNA expression was measured by qRT-PCR.</p><p><strong>Results: </strong>Compared with control conditions, maternal EC exposure significantly worsened MCT-induced PH in male offspring. This was associated with increased oxidative stress, DNA hypomethylation, and anomalous autophagy in the offspring. In vivo treatment with chloroquine inhibited autophagy and ameliorated PH development in offspring exposed to maternal EC. Furthermore, N-acetylcysteine (NAC), an antioxidant, attenuated maternal EC exposure-induced oxidative stress, DNA hypomethylation, and excessive autophagy, thereby improving PH. DNA hypermethylation also reversed PH development, accompanied by reduced oxidative stress and suppressed autophagy. ATG5, a key regulator of autophagy, was identified as a potential therapeutic target, as its repression mitigated PH in maternal EC-exposed offspring.</p><p><strong>Conclusion: </strong>Maternal EC exposure induces oxidative stress and DNA hypomethylation in offspring, leading to anomalous autophagy and exacerbation of PH development. Targeting ATG5-mediated autophagy may represent a novel therapeutic approach for improving PH outcomes in offspring exposed to maternal EC.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474182","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}
Dan Lv, Shi-Yao Chen, Xu-Fang Li, Praseth Leakana, Jia-Qi Han, Jun-Rong Xian, Fan-Fan Li, Meng-Zhou He, Yao Fan, He-Ze Xu, Li Liu, Wei Li, Xing-Guang Lin, Fang Ye, Dong-Rui Deng
{"title":"Long Sleep Duration Is Associated with Fetal Brain Parameter Extreme Values: A Prospective Cohort Study.","authors":"Dan Lv, Shi-Yao Chen, Xu-Fang Li, Praseth Leakana, Jia-Qi Han, Jun-Rong Xian, Fan-Fan Li, Meng-Zhou He, Yao Fan, He-Ze Xu, Li Liu, Wei Li, Xing-Guang Lin, Fang Ye, Dong-Rui Deng","doi":"10.1007/s11596-025-00073-9","DOIUrl":"https://doi.org/10.1007/s11596-025-00073-9","url":null,"abstract":"<p><strong>Objective: </strong>Sleep is fundamental to the physical and mental health of both the general population and pregnant women. Most studies have focused on the impact of certain trimester sleep behaviors on gestational complications and birth outcomes. This study aimed to explore the association between maternal sleep duration and fetal growth development from as early as 23 gestational weeks to birth.</p><p><strong>Methods: </strong>A total of 803 pregnant women were prospectively enrolled. The self-reported maternal nocturnal sleep duration during all 3 trimesters was recorded. The outcome measures were reference-population-based Z-scores of fetal biometric measurements obtained through routine ultrasonographic examination.</p><p><strong>Results: </strong>Using multiple linear regression, a marginally significant negative association was observed between second-trimester sleep duration and second-trimester fetal head circumference (HC) and third-trimester fetal biparietal diameter (BPD). Then the associations of long sleep duration in each trimester with fetal biometry extreme values were evaluated. A significant impact of second-trimester long sleep duration on the second-trimester BPD below the 10th percentile of the reference population was observed. Longitudinal analysis reported similar results for BPD and HC.</p><p><strong>Conclusions: </strong>Overall, a negative association between sleep duration and fetal biometric measurements was observed. Long sleep durations in the second trimester might negatively impact fetal growth, particularly brain parameters, including BPD and HC.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474181","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":"Genotype Identification of Complete Hydatidiform Moles without a Maternal Component: Attempts at a Novel 26-plex STR System.","authors":"Yi-Na Jiang, Lu-Yao Li, Peng-Fei Nan, Fu-Quan Jia, Li-Qin Chen","doi":"10.1007/s11596-025-00071-x","DOIUrl":"https://doi.org/10.1007/s11596-025-00071-x","url":null,"abstract":"<p><strong>Objective: </strong>Current autosomal short tandem repeat (STR) assays can analyze the zygotic composition by comparing the allelic genes at each locus of complete hydatidiform moles (CHM), with a maternal genotype serving as an essential reference for comparative analysis. However, their application in pathology represents a challenge because of deficiency or contamination of maternal-origin tissues. This study aimed to develop a novel STR genotyping method for identifying CHM genotypes without a maternal component.</p><p><strong>Methods: </strong>Samples with the pathologic description of molar pregnancy were collected. Routine hematoxylin-eosin (HE) staining and p57 immunohistochemistry staining were conducted in accordance with standard guidelines. A novel 26-plex system was explored to classify CHM and diploid pregnancies. The system combined 22 STRs on chromosomes 21/18/13/X, 3 sex loci, and 1 quality control marker (TAF9L), enabling molecular diagnosis in the absence of maternal tissue. At last, traditional DNA typing based on villi and decidua (maternal component) of each case was used for result consistency analysis.</p><p><strong>Results: </strong>CHM and nonmolar abortus could not be distinguished by the basic HE staining with no fetal evidence or other prominent features. DNA typing was successfully processed for all cases according to the novel 26-plex and traditional system. CHM (46XX) diagnosis required single A-STR/X-STR peaks and absent Y-chromosome markers, excluding chromosomal abnormalities via TAF9L analysis. When the villous tissue analysis revealed single peaks at X-STR/SRY loci, a 1:1 amelogenin ratio, and a 2:1 TAF9L peak ratio, these results overlapped with those of 46XY hydropic abortus or CHM. Notably, p57 immunohistochemical staining resolved the ambiguity. Consistency with traditional DNA genotyping confirmed system accuracy. This multiplex assay enhanced reliability in mole diagnosis, supporting clinical differentiation and genetic counseling.</p><p><strong>Conclusion: </strong>This study presents a rapid and cost-effective assay for the genotypic identification of CHM without the need for a maternal component. The method combined the characteristics of STR loci distributed across different chromosomes and developed the clinic application of forensic biomarkers.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474180","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}
Chun Hoe Tan, Haresh Sivakumar, Da-Gui Luo, Yu-Xin Cen
{"title":"Integrative Network Pharmacology and Molecular Docking Analyses on the Mechanisms of San-Zhong-Kui-Jian-Tang in Treating Oral Squamous Cell Carcinoma.","authors":"Chun Hoe Tan, Haresh Sivakumar, Da-Gui Luo, Yu-Xin Cen","doi":"10.1007/s11596-025-00067-7","DOIUrl":"https://doi.org/10.1007/s11596-025-00067-7","url":null,"abstract":"<p><strong>Objective: </strong>Oral squamous cell carcinoma (OSCC) is an aggressive cancer with a high mortality rate. San-Zhong-Kui-Jian-Tang (SZKJT), a Chinese herbal formula, has long been used as an adjuvant therapy in cancer clinical practice. Although its therapeutic effects and molecular mechanisms in OSCC have been previously elucidated, the potential interactions and mechanisms between the active phytochemicals and their therapeutic targets are still lacking.</p><p><strong>Methods: </strong>The present study employed network pharmacology and topology approaches to establish a \"herbal ingredients-active phytochemicals-target interaction\" network to explore the potential therapeutic targets of SZKJT-active phytochemicals in the treatment of OSCC. The role of the target proteins in oncogenesis was assessed via GO and KEGG enrichment analyses, and their interactions with the active phytochemicals of SZKJT were calculated via molecular docking and dynamic simulations. The pharmacokinetic properties and toxicity of the active phytochemicals were also predicted. RESULTS: A total of 171 active phytochemicals of SZKJT fulfilled the bioavailability and drug-likeness screening criteria, with the flavonoids quercetin, kaempferol, and naringenin having the greatest potential. The 4 crucial targets of these active phytochemicals are PTGS2, TNF, BCL2, and CASP3, which encode cyclooxygenase-2, tumor necrosis factor (TNF), BCL-2 apoptosis regulator, and caspase-3, respectively. The interactions between phytochemicals and target proteins were predicted to be thermodynamically feasible and stable via molecular docking and dynamics simulations. Finally, the results revealed that the IL-6/JAK/STAT3 pathway and TNF signaling via NF-κB are the two prominent pathways targeted by SZKJT.</p><p><strong>Conclusion: </strong>In summary, this study provides computational data for in-depth exploration of the mechanism by which SZKJT activates phytochemicals to treat OSCC.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316066","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}
Miao Li, Wei Chen, Yao-Bing Chen, Lei Wang, Liu Huang
{"title":"Effects of Thymidine Phosphorylase and Sine Oculis Homeobox Homologue 1 on the Prognosis and Immune Microenvironment of Gastric Cancer.","authors":"Miao Li, Wei Chen, Yao-Bing Chen, Lei Wang, Liu Huang","doi":"10.1007/s11596-025-00065-9","DOIUrl":"https://doi.org/10.1007/s11596-025-00065-9","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the combined effects of thymidine phosphorylase (TYMP) and sine oculis homeobox homologue 1 (Six1) on the tumor microenvironment and their role in promoting metastasis in gastric cancer (GC).</p><p><strong>Methods: </strong>A total of 674 GC patients who underwent surgical resection were enrolled. Correlations between TYMP/Six1 expression and the clinicopathological characteristics and overall survival of patients were analysed. The expression of TYMP, Six1 and vascular endothelial growth factor C (VEGFc) was quantified via immunohistochemistry and quantitative real-time polymerase chain reaction. Cell transfection, wound-healing assays and bioinformatics analyses were used to explore the potential underlying mechanisms involved.</p><p><strong>Results: </strong>Compared with the other groups, the Six1+ /TYMP+ patients exhibited poor differentiation, advanced tumor stage, a higher rate of lymphatic vessel invasion and shorter survival. Additionally, the protein expression of TYMP and Six1 was positively correlated with the VEGFc level. A significant increase in VEGFc expression was observed in cells transfected with TYMP, Six1, and TYMP/Six1 vectors. The results of the wound-healing assay indicated that the synergistic effect of TYMP and Six1 enhanced the migratory ability of GC cells. Furthermore, bioinformatics analysis revealed that TYMP and Six1 were positively correlated with immunosuppressive immune cell subsets and elevated the expression of inhibitory immune checkpoints in GC.</p><p><strong>Conclusions: </strong>The combination of TYMP and Six1 is a good predictive and prognostic biomarker for GC. This combination enhances the expression of VEGFc, facilitates the invasion of GC cells, and may be linked to inhibitory immune cells and the tumor immune microenvironment.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301310","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":"Radiomic Analysis of Molecular Magnetic Resonance Imaging of Aortic Atherosclerosis in Rabbits.","authors":"Hwunjae Lee","doi":"10.1007/s11596-025-00069-5","DOIUrl":"https://doi.org/10.1007/s11596-025-00069-5","url":null,"abstract":"<p><strong>Objective: </strong>Atherosclerosis involves not only the narrowing of blood vessels and plaque accumulation but also changes in plaque composition and stability, all of which are critical for disease progression. Conventional imaging techniques such as magnetic resonance angiography (MRA) and digital subtraction angiography (DSA) primarily assess luminal narrowing and plaque size, but have limited capability in identifying plaque instability and inflammation within the vascular muscle wall. This study aimed to develop and evaluate a novel imaging approach using ligand-modified nanomagnetic contrast (lmNMC) nanoprobes in combination with molecular magnetic resonance imaging (mMRI) to visualize and quantify vascular inflammation and plaque characteristics in a rabbit model of atherosclerosis.</p><p><strong>Methods: </strong>A rabbit model of atherosclerosis was established and underwent mMRI before and after administration of lmNMC nanoprobes. Radiomic features were extracted from segmented images using discrete wavelet transform (DWT) to assess spatial frequency changes and gray-level co-occurrence matrix (GLCM) analysis to evaluate textural properties. Further radiomic analysis was performed using neural network-based regression and clustering, including the application of self-organizing maps (SOMs) to validate the consistency of radiomic pattern between training and testing data.</p><p><strong>Results: </strong>Radiomic analysis revealed significant changes in spatial frequency between pre- and post-contrast images in both the horizontal and vertical directions. GLCM analysis showed an increase in contrast from 0.08463 to 0.1021 and a slight decrease in homogeneity from 0.9593 to 0.9540. Energy values declined from 0.2256 to 0.2019, while correlation increased marginally from 0.9659 to 0.9708. Neural network regression demonstrated strong convergence between target and output coordinates. Additionally, SOM clustering revealed consistent weight locations and neighbor distances across datasets, supporting the reliability of the radiomic validation.</p><p><strong>Conclusion: </strong>The integration of lmNMC nanoprobes with mMRI enables detailed visualization of atherosclerotic plaques and surrounding vascular inflammation in a preclinical model. This method shows promise for enhancing the characterization of unstable plaques and may facilitate early detection of high-risk atherosclerotic lesions, potentially improving diagnostic and therapeutic strategies.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282795","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":"Rifaximin Inhibits Small Bowel Angiodysplasia-Associated Angiogenesis by Attenuating LncRNA-HIF1A-AS2/miR-153-3p/HIF-1 α/Ang-2 Axis.","authors":"Shuai Peng, An-Ning Yin, Fei Liao, Liang Zhao","doi":"10.1007/s11596-025-00061-z","DOIUrl":"https://doi.org/10.1007/s11596-025-00061-z","url":null,"abstract":"<p><strong>Backgrounds and objective: </strong>Angiopoietin-2 (Ang-2) is a promising biomarker and therapeutic target for gastrointestinal angiodysplasia (GIAD). We hypothesized that the lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 axis plays a critical role in small bowel angiodysplasia (SBAD)-associated angiogenesis, which can be blocked by rifaximin. The purpose of this study was to investigate the expression and pro-angiogenic effects of the lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 in SBAD and to evaluate the therapeutic potential of rifaximin on SBAD by targeting this axis.</p><p><strong>Methods: </strong>The expression and pro-angiogenic effects of lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 were analysed in SBAD tissues and human umbilical vein endothelial cells (HUVECs). The anti-angiogenic effect of rifaximin and its impact on the lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 axis were evaluated in HUVECs.</p><p><strong>Results: </strong>Increased expression of lncRNA-HIF1A-AS2 and decreased expression of miR-153-3p were detected in SBAD tissues. LncRNA-HIF1A-AS2/miR-153-3p /HIF-1α were upstream regulators of Ang-2, and this axis was involved in angiogenesis in HUVECs. Rifaximin exerted antiangiogenic effects on HUVECs by blocking this axis.</p><p><strong>Conclusions: </strong>The lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 axis is critically involved in SBAD-associated angiogenesis. Rifaximin is a potential therapeutic option for SBAD via blockade of this axis.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282796","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}
Kan-Paatib Barnabo Nampoukime, Adeoumi Esperance Monteiro Igwenandji, You-Min Pan, Lud Merveil Norbely Nouani, Djessica Fortes Gomes, Mustafa Abbas Farhood Sultani, Hai-Hao Wang
{"title":"Malperfusion in Acute Type A Aortic Dissection: Development of a Predictive Diagnostic Model.","authors":"Kan-Paatib Barnabo Nampoukime, Adeoumi Esperance Monteiro Igwenandji, You-Min Pan, Lud Merveil Norbely Nouani, Djessica Fortes Gomes, Mustafa Abbas Farhood Sultani, Hai-Hao Wang","doi":"10.1007/s11596-025-00070-y","DOIUrl":"https://doi.org/10.1007/s11596-025-00070-y","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the clinical predictors of malperfusion in patients with acute type A aortic dissection (ATAAD) and to construct a diagnostic model to identify high-risk individuals.</p><p><strong>Methods: </strong>A retrospective analysis of 553 ATAAD patients from Tongji Hospital divided into malperfusion and non-malperfusion groups was conducted. Logistic regression was used to identify independent predictors of the outcome. Model performance via the Hosmer-Lemeshow test, decision curve analysis (DCA), the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and predictive values.</p><p><strong>Results: </strong>Malperfusion was observed in 28.4% of ATAAD patients. Significant predictors included elevated lactate dehydrogenase (LDH) (OR: 1.0019, 95% CI: 1.0002-1.0036, P = 0.027), alanine aminotransferase (ALT) (OR: 0.9936, 95% CI: 0.987-1.000, P = 0.046) and estimated glomerular filtration rate (eGFR) (OR: 0.9877, 95% CI: 0.977-0.998, P = 0.021), suggesting roles for tissue ischemia and impaired renal or hepatic function. Other variables, such as D-dimer, uric acid, creatinine, and NT-proBNP, showed trends toward significance but did not reach the 0.05 threshold. The model demonstrated good calibration (Hosmer-Lemeshow P = 0.318), moderate discriminatory power (AUC = 0.725), high specificity (93.62%), and low sensitivity (26.75%).</p><p><strong>Conclusion: </strong>The model based on routine biochemical markers provides a practical approach for the early identification of malperfusion in ATAAD patients. It shows strong specificity and clinical utility, although its limited sensitivity highlights the need for further refinement. Future improvements should focus on incorporating additional clinical or imaging data to increase diagnostic accuracy.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282794","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}
Luan Chen, Jie Zhang, Jing-Yi Peng, Yuan Yuan, Yang Ding, Yi Wang, Xing-Xing He
{"title":"Global and Country-Level Analysis of Liver Cancer: Disease Burden and Recent Trends.","authors":"Luan Chen, Jie Zhang, Jing-Yi Peng, Yuan Yuan, Yang Ding, Yi Wang, Xing-Xing He","doi":"10.1007/s11596-025-00064-w","DOIUrl":"https://doi.org/10.1007/s11596-025-00064-w","url":null,"abstract":"<p><strong>Background: </strong>Liver cancer is the sixth most prevalent cancer globally and the third leading cause of cancer-related mortality, with more than three-quarters of a million deaths. This has presented a significant challenge and imposed considerable strain on global public health systems. Therefore, evaluating the updated global burden of liver cancer and its recent trends in incidence and mortality is highly important, as it provides valuable insights for shaping public health policies and improving clinical practices.</p><p><strong>Methods: </strong>The data in our article were obtained from the Global Burden of Disease Study 2021 (GBD 2021), which is available at https://vizhub.healthdata.org/gbd-results/ . In this study, liver cancer mortality and incidence were estimated via the cause of death ensemble (CODEm) model for every combination of sex, age, location, and year. The incidence was modelled with DisMod-MR 2.1, a Bayesian meta-regression tool. A linear regression model was employed to explore the temporal trend of these rates, formulated as y = α + βx + ε, where x represents the calendar year and y signifies the natural logarithm of the rate. For both incidence and mortality, the estimated annual percentage change (EAPC) was computed via the formula 100 × (e<sup>β</sup> - 1), accompanied by a 95% confidence interval (CI).</p><p><strong>Results: </strong>First, 529,000 cases were newly diagnosed, with an age-standardized incidence rate (ASIR) of 6.15 per 100,000 people. In terms of etiology, the incidence of liver cancer caused by metabolic factors has tended to increase. Additionally, the incidence of liver cancer was greater in males and older populations. Several specific regions presented liver cancer burdens that overwhelmingly surpassed the expected age-standardized rates (ASRs) each year from 1990 to 2021, regardless of their respective sociodemographic index (SDI) scores.</p><p><strong>Conclusion: </strong>Our findings reveal that liver cancer continues to pose a significant public health challenge. These findings suggest that targeted interventions are needed to address both the infectious and non-infectious drivers of liver cancer in different socioeconomic settings. Hence, continued efforts in prevention through vaccination, antiviral therapies, and strategies to combat metabolic diseases are crucial for reducing the global burden of liver cancer in the coming decades.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282793","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}
Ye-Na Zhou, Ji-Kai Xia, Chun-Ru Shi, Yan He, Shun-Lai Shang
{"title":"Crosstalk Between Th17 Cells and Renal Tubular Epithelial Cells Promotes Fibrotic Progression in IgA Nephropathy.","authors":"Ye-Na Zhou, Ji-Kai Xia, Chun-Ru Shi, Yan He, Shun-Lai Shang","doi":"10.1007/s11596-025-00068-6","DOIUrl":"https://doi.org/10.1007/s11596-025-00068-6","url":null,"abstract":"<p><strong>Objective: </strong>Th17 cell-mediated immune injury is a crucial factor contributing to tubulointerstitial fibrosis in patients with IgA nephropathy (IgAN). However, the exact mechanisms by which Th17 cells induce tubulointerstitial fibrosis remain to be fully elucidated.</p><p><strong>Methods: </strong>An IgAN mouse model was established and validated. Transcriptome sequencing, combined with bioinformatics analysis, was carried out to explore the immune injury pathways in renal tissues and the activation pathways in Th17 cells that were co-cultured with tubular epithelial cells. In subsequent experiments, small interfering RNA (siRNA) and overexpression plasmids were used to manipulate cellular targets. Validation was conducted through quantitative real-time polymerase chain reaction (qPCR), Western blotting, and immunofluorescence assays.</p><p><strong>Results: </strong>Compared with the control mice, IgAN mice exhibited elevated serum creatinine levels and increased urine protein-to-creatinine ratios. Renal pathological examination revealed the characteristic features of IgAN. Transcriptomic analysis of the kidney tissues from the model mice showed the activation of Th17 differentiation pathways, which was further confirmed by immunofluorescence analysis showing increased expression of interleukin-17A (IL-17A). These findings indicate an increased abundance of Th17 cells with potential pathogenic significance. When Th17 cells were co-cultured with tubular epithelial cells, the level of interleukin-9 (IL-9) in the system increased. This increase in IL-9 activated the Janus kinase 1-signal transducer and activator of transcription 3 (JAK1-STAT3) pathway through the IL-9 receptor (IL-9R) and upregulated the signature transcription factor retinoic acid-related orphan receptor gamma (ROR-γ), thus promoting Th17 cell differentiation. When IL-9R was silenced using siRNA or when the activity of STAT3 was inhibited, both the levels of phosphorylated STAT3 (p-STAT3) and ROR-γ decreased. Moreover, IL-17A secreted by Th17 cells promoted the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in tubular epithelial cells by activating the IL-17 receptor A (IL-17RA)-adaptor protein Act1-tumor necrosis factor receptor-associated factor 6 (TRAF6) complex. This process regulated the production of inflammatory cytokines and drove the initiation and progression of fibrosis. Treatment with a STAT3 inhibitor in IgAN mice led to a reduction in the number of renal Th17 cells and alleviated the fibrotic phenotype.</p><p><strong>Conclusion: </strong>This study demonstrated that the interaction between Th17 cells and tubular epithelial cells triggers excessive extracellular matrix deposition in the tubulointerstitium, thereby exacerbating the fibrotic phenotype and accelerating the progression of IgAN.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265451","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}