Biomedical reports最新文献

{"title":"Polychlorinated biphenyl 153 alters the intestinal epithelial cell transcriptome.","authors":"Hanna Ham, Prakrti Senthil, Stephanie C Tan, Robert M Sargis, Gail S Prins, Hua Geng","doi":"10.3892/br.2025.2100","DOIUrl":"10.3892/br.2025.2100","url":null,"abstract":"<p><p>Polychlorinated biphenyl 153 (PCB153) is one of the most persistent environmental pollutants and abundant PCB congeners detected in human tissues, primarily acquired through dietary exposure. The intestinal epithelium therefore represents a critical initial target for PCB-related toxicity. However, the molecular mechanisms by which PCB153 disrupts normal intestinal epithelial function remain incompletely understood. The present study investigated the effects of PCB153 exposure on non-transformed human intestinal epithelial cells (IECs) using transcriptomic profiling. The data revealed that PCB153 induced dose-dependent alterations in the IEC transcriptome. Key pathways affected by PCB153 included Wnt signaling, ABC transporters, cGMP-PKG signaling and metallothionein-mediated metal homeostasis. High-dose exposure further activated inflammatory and tumorigenic pathways such as TNF and NF-κB signaling, while suppressing mitochondrial metabolism, oxidative phosphorylation and cellular detoxification processes. To the best of our knowledge, this is the first report that reveals the extensive transcriptomic remodeling in normal human IECs in response to PCB153 exposure, highlighting the disrupted intestinal regeneration, immune response and metabolic regulation. These findings provide novel mechanistic insights into how PCB153 compromises intestinal epithelial health, and establishes a transcriptomic framework for identifying biomarkers and therapeutic targets related to environmental toxicant exposure.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"24 2","pages":"27"},"PeriodicalIF":1.9,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12766560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145910168","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":"Both asparagine and proline are required to decrease <i>Sestrin2</i> mRNA levels via ATF4 reduction and regulate collagen type I alpha 1 chain production and the proliferation of quiescent RI?T hepatic stellate cells.","authors":"Ran Sawa, Manami Ogawa, Hana Suzuki, Yasuhiko Okimura","doi":"10.3892/br.2025.1971","DOIUrl":"10.3892/br.2025.1971","url":null,"abstract":"<p><p>Sestrin 2 (SESN2) is a conserved protein whose expression is upregulated under various cellular stresses including hepatic injury. In the injured liver, hepatic stellate cells (HSCs) become activated and produce collagen, contributing to fibrosis; however, SESN2 overexpression has been shown to suppress collagen synthesis. Amino acids are known to influence SESN2 expression; however, their specific effects remain unclear. In the present study, it was investigated whether specific amino acids regulate SESN2 expression and the function of quiescent RI-T HSCs, which are responsible for collagen production, using reverse transcription-quantitative PCR, western blotting, and cell proliferation assay. It was found that supplementation with asparagine (Asn) and proline (Pro) (AP), both non-essential amino acids, led to a complete reduction in <i>SESN2</i> and <i>activating transcription factor 4 (ATF4)</i> mRNA levels after 5 h of incubation. Additionally, AP partially reduced <i>collagen type I α1 (COL1A1)</i> mRNA levels. However, knockdown of SESN2 or ATF4 resulted in a more substantial reduction in <i>COL1A1</i> mRNA levels than the supplementation with AP. These results suggest that SESN2, which is induced by amino acid insufficiency, contributes to the upregulation of <i>COL1A1</i> mRNA levels and that AP may increase <i>COL1A1</i> mRNA levels through pathways independent of SESN2. The COL1A1-inducing effect of SESN2 contrasted with the inhibitory effect of SESN2 on activated HSCs. In long-term cultures, AP supplementation increased <i>COL1A1</i> mRNA and protein levels, as well as RI-T cell proliferation, while <i>SESN2</i> and <i>ATF4</i> mRNA levels remained suppressed. These findings suggested that the absence of AP induces relative amino acid starvation, leading to increased ATF4/SESN2 expression. By contrast, long-term AP supplementation alleviated this stress, promoting cell proliferation and COL1A1 synthesis. The present results indicate that SESN2 function in quiescent HSCs may differ from its role in activated cells, providing new insights into its regulatory mechanisms in collagen production.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"22 6","pages":"93"},"PeriodicalIF":2.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969278","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":"Early detection of cardiac impairment and prediction of right ventricular hypertrophy in patients with connective tissue disease.","authors":"Jiayan Shen, Guangrong Xiao, Shuqing Fang, Haohao Yang, Zheren Zhao, Yun Xu, Meng Jiang, Song Zhong","doi":"10.3892/br.2025.1970","DOIUrl":"https://doi.org/10.3892/br.2025.1970","url":null,"abstract":"<p><p>Progressive right ventricle (RV) failure and death in connective tissue disease (CTD) are related to RV hypertrophy (RVH) and dilation, irrespective of pulmonary arterial hypertension (PAH). Therefore, detecting cardiac impairment before RVH and determining RVH predictors is crucial for timely intervention. The present prospective cohort study aimed to identify cardiac markers that occur before RVH and to investigate predictors of RVH. CTD was diagnosed based on clinical features, laboratory findings and imaging data. The cardiac functions of patients with CTD were evaluated using echocardiography, cardiovascular magnetic resonance (CMR) and multi-modality cardiac imaging studies, including RV wall thickness, systolic functions, late gadolinium enhancement, T1 maps and biventricular strain analysis. A total of 52 patients with CTD with non-right ventricular hypertrophy (non-RVH), 34 patients with RVH and 50 healthy individuals were prospectively included. The impaired cardiac indices in patients with RVH included RV ejection fraction, ventricular dimensions, global myocardial deformation, late gadolinium enhancement and ventricular extracellular volume (ECV). The cardiac death rate did not differ significantly between the RVH and non-RVH groups (P=0.14). Conventional parameters, including serum cardiac markers and the left ventricular ejection fraction, showed no significant changes in the non-RVH group compared with the control group. Regarding fibrosis assessment using CMR, an elevated native T1 value (1,362±72 msec in the non-RVH group vs. 1,268±42 in the control group; P<0.001) and ECV (31±4% in the non-RVH group vs. 25±3% in the control group; P<0.001) were observed. By contrast, T1 myocardium/msec 15 min post-contrast of the left ventricle in the RVH group was significantly decreased compared with that in the non-RVH group, indicating an increase in the extracellular matrix at this stage. RVH was predicted by pulmonary arterial pressure (PAP) in patients in the non-RVH group (t-statistic, 2.84; P=0.01), whereas after RVH presentation, RV end-systolic volume (RVESV) became a progression predictor of RVH (t-statistic, 7.98; P<0.0001). No other cardiac imaging or laboratory findings predicted RVH. To the best of our knowledge, the present study was the first to highlight the non-invasive detection of cardiac tissue impairment using CMR and provide support for cardiac treatment initiation before RVH detection. The predictors of RVH vary with the heart disease stage. PAP in the non-RVH stage and incompetence of RVESV in the RVH stage predicted the progression of RVH. The present study was part of a clinical trial (NCT03271385), which was registered on July 1, 2017, and started on September 1, 2017.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"22 5","pages":"92"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963944","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":"TLE1 corepressor promotes gefitinib resistance in lung cancer A549 cells via E‑cadherin silencing.","authors":"Xin Yao, Nasir Roberts, Prince Iheukwumere, Alana Carmouche, Renwei Chen, Ma Carmela Dela Cruz, Hector Biliran","doi":"10.3892/br.2024.1914","DOIUrl":"10.3892/br.2024.1914","url":null,"abstract":"<p><p>As a putative lung specific oncogene, the transducin-like enhancer of split 1 (TLE1) corepressor drives an anti-apoptotic and pro-epithelial-mesenchymal transition (EMT) gene transcriptional programs in human lung adenocarcinoma (LUAD) cells, thereby promoting anoikis resistance and tumor aggressiveness. Through its survival- and EMT-promoting gene regulatory programs, TLE1 may impact drug sensitivity and resistance in lung cancer cells. In the present study, a novel function of TLE1 was uncovered as an inhibitor of the antitumor effects of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) gefitinib in the human LUAD cell line A549, which exhibits moderate sensitivity to EGFR-TKI. While upregulation of TLE1 expression potently inhibited the proliferation inhibitory and apoptotic effects of gefitinib in A549 cells, downregulation of endogenous TLE1 in these cells enhanced their sensitivity to gefitinib. In experimentally derived gefitinib-resistant A549 cells (A549GR) that have acquired EMT, TLE1 expression is upregulated as compared with parental A549 cells, and acute ablation of TLE1 expression is sufficient to partially restore gefitinib sensitivity and attenuate EMT phenotype. Mechanistic studies showed that TLE1 confers gefitinib resistance in A549 cells in part via downregulation of E-cadherin, a known potentiator of EGFR-TKI sensitivity and apoptosis induction. Importantly, the TLE1/E-cadherin transcriptional axis is negatively regulated by gefitinib to trigger apoptosis via the Bcl-2-inhibitor of transcription 1 cell death pathway. In conclusion, these results indicate a novel role of TLE1 in modulating EGFR-TKI sensitivity in lung cancer cells via regulation of E-cadherin expression, and its upregulation may potentiate EGFR-TKI resistance in LUAD.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"22 3","pages":"36"},"PeriodicalIF":1.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943542","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":"Quantitative analysis of HSV‑1 shedding as a predictor of cerebral vasospasm severity in patients with subarachnoid hemorrhage.","authors":"Melanie Walker, Emma Federico, Joseph R Zunt, Michael R Levitt, Christine M Johnston","doi":"10.3892/br.2024.1865","DOIUrl":"10.3892/br.2024.1865","url":null,"abstract":"<p><p>Cerebral vasospasm (CV) is a critical determinant of outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). Despite advances in neurocritical care, modifiable risk factors for CV remain poorly understood, and identifying them could significantly enhance patient management and treatment strategies. The present study explored the potential link between the reactivation of herpes simplex virus type 1 (HSV-1), a common resident virus in cranial nerves, and CV severity. It was hypothesized that higher HSV-1 viral load in saliva may be associated with increased CV severity. Saliva samples were collected on days 4, 7, 10 and 14 post-aSAH, and HSV-1 DNA levels were measured using quantitative PCR. CV severity was assessed using the Lindegaard ratio (LR), with an LR >3 considered the diagnostic threshold for CV. A total of 36 patients were enrolled, and 139 saliva samples were collected. HSV-1 DNA was detected in 19.4% of samples (27/139), and 44% of patients (16/36) developed CV. HSV-1 seropositive patients made up 88.9% (32/36) of the cohort, with 50% exhibiting viral shedding during the study period. None of the HSV-1 seronegative patients (11.1%, 4/36) exhibited viral shedding or developed CV. Regression analysis showed a positive association between HSV-1 viral load and CV severity, with viral load explaining 27.8% of the variability (P=0.005). Age was also significant, with older patients experiencing less severe CV (P<0.001). Supervised machine learning identified viral load thresholds that aligned with standard LR values for moderate and severe CV. While the small sample size and observational design limit the generalizability of the results, these findings suggested that earlier detection and intervention for CV could be informed by assessing HSV-1 serostatus and monitoring viral activity through saliva samples or other non-invasive methods, highlighting the need for larger, controlled studies to validate these results.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"21 6","pages":"177"},"PeriodicalIF":1.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387621","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":"Gallein increases prostaglandin F2α‑induced osteoprotegerin and IL‑6 secretion in osteoblasts.","authors":"Gen Kuroyanagi, Tomoyuki Hioki, Rie Matsushima-Nishiwaki, Takuya Omura, Osamu Kozawa, Haruhiko Tokuda","doi":"10.3892/br.2024.1835","DOIUrl":"10.3892/br.2024.1835","url":null,"abstract":"<p><p>Gallein is a known Gβγ subunit inhibitor, but its function in bone metabolism, especially in osteoblasts, and its molecular mechanism remains to be elucidated. Osteoprotegerin (OPG), which is secreted from osteoblasts, binds to nuclear factor kB receptor activator (RANK) ligand (RANKL) as a decoy receptor, prevents RANKL-RANK binding, and inhibits bone resorption. IL-6 is not only a bone resorption factor but also as a bone metabolism regulator. Prostaglandin F2α (PGF2α) promotes p44/p42 MAPK, p38 MAPK and stress-activated protein kinase/JNK phosphorylation in osteoblast-like MC3T3-E1 cells. In MC3T3-E1 cells, activated p44/p42 and p38 MAPKs promote IL-6 secretion and activated p44/p42 and p38 MAPKs and JNK promote OPG secretion. The present study aimed to investigate the effect and mechanism of gallein on PGF2α-induced OPG and IL-6 secretion using an osteoblastic MC3T3-E1 cell line. It was found that gallein significantly increased PGF2α-induced OPG and IL-6 secretion in the MC3T3-E1 cell. By contrast, fluorescein, which is a gallein-like compound that does not bind to Gβγ, did not affect PGF2α-induced OPG and IL-6 secretion. Gallein significantly improved the PGF2α-induced OPG and IL-6 mRNA expression levels. Gallein did not affect the PGF2α-activated phosphorylation of p44/p42 and p38 MAPKs and JNK. Gallein increased PGF2α-induced OPG and IL-6 secretion in osteoblasts, indicating that gallein may regulate bone remodeling via OPG/IL-6 in bone metabolism.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"21 5","pages":"147"},"PeriodicalIF":2.3,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783970","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":"Anti‑angiogenic and cytotoxic evaluation of green‑synthesized Fe2ZnO4 nanoparticles against MCF‑7 cell line","authors":"Asma' Al‑Zabin, Tuqa Abu Thiab, M. Zihlif, A. Al-Hunaiti, Hamzeh J. Al-Ameer, W. Al-Awaida, Amer Imraish","doi":"10.3892/br.2024.1724","DOIUrl":"https://doi.org/10.3892/br.2024.1724","url":null,"abstract":"","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"5 17","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139439773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real‑world performance and safety of vaginal ovules in reducing the vaginal symptoms associated with vulvovaginal atrophy and postmenopausal sexual dysfunction","authors":"Dominic-Gabriel Iliescu, R. Petrita, Cristina Teodorescu, R. Olaru, Andreea Alexa, Izabella Petre","doi":"10.3892/br.2024.1723","DOIUrl":"https://doi.org/10.3892/br.2024.1723","url":null,"abstract":"","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"32 34","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139442763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of two retinal fractures with ultrabroad‑angle fundus photography systems","authors":"Yong Guo, Hong Yan, Chenjun Guo, Jue Wang","doi":"10.3892/br.2024.1722","DOIUrl":"https://doi.org/10.3892/br.2024.1722","url":null,"abstract":"","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"59 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139385760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanism of honeysuckle + forsythia in treatment of acute lung injury based on network pharmacology","authors":"Xin Wen, Min Cheng, Zhongxing Song, Jinhang Hu, Xuhu Liang, Wuying Lang, Mengqi Yang, Ruina Zhou, Yunjing Hao","doi":"10.3892/br.2024.1720","DOIUrl":"https://doi.org/10.3892/br.2024.1720","url":null,"abstract":"","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"52 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139451928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}