Journal of Translational Internal Medicine最新文献

{"title":"Role of viral hepatitis in pregnancy and its triggering mechanism.","authors":"Jian Wu, Huiqing Wang, Ze Xiang, Chun Jiang, Yunyang Xu, Guanghua Zhai, Zongxin Ling","doi":"10.2478/jtim-2024-0015","DOIUrl":"10.2478/jtim-2024-0015","url":null,"abstract":"<p><p>Hepatitis viral infection can cause severe complications, even mortality in pregnant women and their offspring. Multiple studies have shown that vertical transmission can cause viral hepatitis infections in newborns, especially in hepatitis B, C, and E. Screening for hepatitis viral infection in pregnant women is essential. Once infected, pregnant women should be given timely antiviral treatments, which could effectively alleviate the disease progression and reduce adverse outcomes. Besides, the mechanism of viral hepatitis mediating adverse pregnancy outcomes has been a hot topic. Hepatitis B virus has been found to mediate both mother- to-child and parent-child transmission. Liver injury in hepatitis C virus infection is associated with immune-mediated mechanisms, which can be regulated by hormonal factors as well. The mediating mechanism of adverse maternal and infant outcomes caused by hepatitis E virus infection is mainly related to viral replication in the placenta and changes in cytokine and estrogen. Nevertheless, the specific mechanisms related to hepatitis A virus and hepatitis D virus remain unclear, and more research is needed. This review shows that the existence of viral hepatitis during pregnancy can pose certain risks for pregnant women and infants, and different interventions have been used to treat pregnant women infected with viral hepatitis. It may provide deep insight into adverse pregnancy outcomes caused by viral hepatitis and give guidance on treatment.</p>","PeriodicalId":51339,"journal":{"name":"Journal of Translational Internal Medicine","volume":"12 4","pages":"344-354"},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRP improves the outcomes of autologous skin graft transplantation on the esophagus by promoting angiogenesis and inhibiting fibrosis and inflammation.","authors":"Ning Xu, Longsong Li, Jiale Zou, Wenyi Yue, Pengju Wang, Mi Chai, Li Li, Lihua Zhang, Xiao Li, Yaxuan Cheng, Zixin Wang, Xueting Wang, Runzi Wang, Jingyuan Xiang, Enqiang Linghu, Ningli Chai","doi":"10.2478/jtim-2023-0126","DOIUrl":"10.2478/jtim-2023-0126","url":null,"abstract":"<p><strong>Background and objectives: </strong>Autologous skin graft (ASG) transplantation is a challenging approach but a promising option for patients to prevent postoperative esophageal stricture. Nonetheless, the current strategies require improvement. We aimed to investigate the effectiveness of the injection of platelet-rich plasma (PRP) before skin graft transplantation for extensive esophageal defects after endoscopic resection.</p><p><strong>Methods: </strong>Standardized complete circular endoscopic resection (5 cm in length) was performed in 27 pigs allocated into 3 groups. The artificial ulcers were treated with a fully covered esophageal stent (control group), ASG (ASG group), and submucosal injection of PRP with ASG (PRP-ASG group). Macroscopic evaluation and histological analysis of the remolded esophagus were performed 7, 14, and 28 days after surgery.</p><p><strong>Results: </strong>The macroscopic evaluation indicated that submucosal injection of PRP before transplantation effectively promoted the survival rate of skin grafts and decreased the rate of mucosal contraction compared with those treated with ASG or stent alone. Histological analysis of submucosal tissue showed that this modified strategy significantly promoted wound healing of reconstructed tissues by enhancing angiogenesis, facilitating collagen deposition, and decreasing inflammation and fibrogenesis.</p><p><strong>Conclusions: </strong>These findings suggested that PRP might be used as a biological supplement to increase the esophageal skin graft survival rate and improve submucosal tissue remolding in a clinically relevant porcine model. With extremely low mucosal contraction, this novel combination strategy showed the potential to effectively prevent stenosis in extensive esophageal ulcers.</p>","PeriodicalId":51339,"journal":{"name":"Journal of Translational Internal Medicine","volume":"12 4","pages":"384-394"},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chinese expert consensus on blood lipid management in patients with diabetes (2024 edition).","authors":"Yang Xiao, Bilian Yu, Chen Chao, Shuai Wang, Die Hu, Chao Wu, Yonghong Luo, Lingxiang Xie, Chenyu Li, Daoquan Peng, Zhiguang Zhou","doi":"10.2478/jtim-2024-0014","DOIUrl":"10.2478/jtim-2024-0014","url":null,"abstract":"<p><p>Diabetes is a significant independent risk factor for atherosclerotic cardiovascular disease (ASCVD), with dyslipidemia playing a critical role in the initiation and progression of ASCVD in diabetic patients. In China, the current prevalence of dyslipidemia in diabetes is high, but the control rate remains low. Therefore, to enhance lipid management in patients with diabetes, the Endocrinology and Metabolism Physician Branch of the Chinese Medical Doctor Association, in collaboration with the Experts' Committee of the National Society of Cardiometabolic Medicine, has convened experts to develop a consensus on the management of dyslipidemia in patients with type 1 or type 2 diabetes. The development of this consensus is informed by existing practices in lipid management among Chinese diabetic patients, incorporating contemporary evidence-based findings and guidelines from national and international sources. The consensus encompasses lipid profile characteristics, the current epidemiological status of dyslipidemia, ASCVD risk stratification, and lipid management procedures in diabetic patients. For the first time, both low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol have been recommended as primary targets for lipid intervention in diabetic patients. The consensus also includes a summary and recommendations for lipid management strategies in special diabetic populations, including children and adolescents, individuals aged 75 years and older, patients with chronic kidney disease, metabolic-associated fatty liver disease, and those who are pregnant. This comprehensive consensus aims to improve cardiovascular outcomes in diabetic patients by contributing to the dissemination of key clinical advancements and guiding clinical practice.</p>","PeriodicalId":51339,"journal":{"name":"Journal of Translational Internal Medicine","volume":"12 4","pages":"325-343"},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A bibliometric analysis of immune-related adverse events in cancer patients and a meta-analysis of immune-related adverse events in patients with hepatocellular carcinoma.","authors":"Bengang Wang, Xiangjun Hao, Jinshan Yan, Xin Li, Mingfang Zhao, Tao Han","doi":"10.2478/jtim-2024-0003","DOIUrl":"10.2478/jtim-2024-0003","url":null,"abstract":"<p><strong>Background and objectives: </strong>Immunotherapy has become the standard treatment for hepatocellular carcinoma (HCC), but it carries a risk of immune-related adverse events (irAEs) that can be life-threatening. This study employs bibliometric analysis to understand global scientific research on irAEs in cancer, focusing on characteristics and areas of interest. Additionally, a meta-analysis provides a comprehensive overview of irAEs in HCC patients receiving immune checkpoint inhibitor (ICI)-based therapies.</p><p><strong>Methods: </strong>We conducted a thorough search of Web of Science Core Collection (WoSCC) publications from 1999 to 2022. R and VOSviewer software were used for analysis. A meta-analysis was performed using data from PubMed, Embase, and the Cochrane Library databases up to March 22, 2022. Trials with HCC patients reporting irAE incidence were included. Quality assessment followed Cochrane risk of bias, Newcastle-Ottawa Scale (NOS), and Methodological Index for Non-Randomized Studies (MINORS). We used random-effects or fixed-effects models based on I2 values. Primary outcomes included any-grade irAEs and grade ≥ 3 irAEs. This review and meta-analysis are registered in PROSPERO as CRD42022318885.</p><p><strong>Results: </strong>In bibliometric analysis, we included 2946 papers, showing a consistent rise in annual publications on irAEs in cancer research. Frequent keywords were \"nivolumab\", \"immune checkpoint inhibitor\", and \"immune-related adverse event\". \"Hepatocellular carcinoma\" emerged as a prominent research focus linked to irAEs. We conducted a comprehensive meta-analysis on irAE incidence in HCC patients, including 29 studies. The overall incidence of any-grade irAEs was 61.0% (95% CI 38.5%-81.3%), and grade ≥ 3 irAEs was 13.2% (95% CI 7.9%-19.6%). Treatment-related mortality occurred in 3.1% (95% CI 0.8%-6.3%), with treatment discontinuation at 10.7% (95% CI 6.3%-16.0%). Reactive cutaneous capillary endothelial proliferation (RCCEP) was the most common any-grade irAE, while elevated aspartate aminotransferase (AST) was the most common grade ≥ 3 irAE. Treatment strategies were independently associated with specific irAEs, as indicated by multivariable analysis.</p><p><strong>Conclusion: </strong>This study provides valuable insights into the current research landscape of irAEs in cancer and ofers a comprehensive overview of irAEs in HCC patients undergoing ICI-based therapy. The relatively high incidence of irAEs and their association with treatment strategies emphasize the need for careful management by clinicians when treating HCC patients. These findings offer significant guidance for optimizing care and treatment for HCC patients.</p>","PeriodicalId":51339,"journal":{"name":"Journal of Translational Internal Medicine","volume":"12 3","pages":"225-243"},"PeriodicalIF":4.7,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution of the causes of fever of unknown origin in China, 2013-2022.","authors":"Sihan Kang, Rui Zheng","doi":"10.2478/jtim-2024-0008","DOIUrl":"10.2478/jtim-2024-0008","url":null,"abstract":"<p><strong>Background and objectives: </strong>Fever of unknown origin (FUO) has long been a cause for concern among clinicians, and its spectrum has evolved with progress in medicine. This study aimed to investigate the distribution of causes of FUO in China between 2013 and 2022 to facilitate the clinical understanding of the etiology of FUO.</p><p><strong>Materials and methods: </strong>Case series of FUO in China published between 2013 and 2022 were retrieved from PubMed, Wanfang Data, and CNKI databases and retrospectively analyzed. The rates of different causes of FUO were calculated, and these data were compared with previously published distributions of causes of FUO in China.</p><p><strong>Results: </strong>The causes of FUO with the highest rates from the 51 identified case series (<i>n</i> = 19,874) were infectious, autoimmune, and neoplastic diseases (59.6%, 14.3%, and 7.9%, respectively). A comparison of a subset (43 case series subdivided by disease category, <i>n</i> = 16,278) with previously reported data revealed an increased rate of FUO attributed to infectious diseases in the past decade, with a significantly higher rate attributed to bloodstream infections (10.0% <i>vs</i>. 4.8%) and a significantly lower rate attributed to tuberculosis (9.3% <i>vs</i>. 28.4%), compared with the rates from the previous period. In contrast, the rates of FUO attributed to both autoimmune and neoplastic diseases decreased, with significantly decreased rates attributed to adult-onset Still's disease among autoimmune diseases (4.6% <i>vs</i>. 8.5%) and lung cancer among neoplastic diseases (0.6% <i>vs</i>. 1.6%).</p><p><strong>Conclusion: </strong>Despite an overall increase in the rate attributed to infectious diseases, that attributed to tuberculosis has decreased. The rates attributed to both autoimmune and neoplastic diseases have also decreased.</p>","PeriodicalId":51339,"journal":{"name":"Journal of Translational Internal Medicine","volume":"12 3","pages":"299-307"},"PeriodicalIF":4.7,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis and prediction of research hotspots and trends in heart failure research.","authors":"Zeye Liu, Yuan Huang, Yang Yang, Wenchao Li, Wenhao Ju, Fengwen Zhang, Wenbin Ouyang, Shouzheng Wang, Cheng Wang, Xuanqi An, Ruibing Xia, Yakun Li, Xiangbin Pan","doi":"10.2478/jtim-2023-0117","DOIUrl":"10.2478/jtim-2023-0117","url":null,"abstract":"<p><strong>Background and objectives: </strong>Comprehensive data analyses in heart failure research can provide academics with information and help policymakers formulate relevant policies. We collected data from reports published between 1945 and 2021 to identify research topics, trends, and cross-domains in the heart failure disease literature.</p><p><strong>Methods: </strong>Text fragments were extracted and clustered from the titles and abstracts in 270617 publications using artificial intelligence techniques. Two algorithms were used to corroborate the results and ensure that they were reliable. Experts named themes and document clusters based on the results of these semiautomated methods. Using consistent methods, we identified and flagged 107 heart failure topics and 16 large document clusters (divided into two groups by time). The annual vocabularies of research hotspots were calculated to draw attention to niche research fields.</p><p><strong>Results: </strong>Clinical research is an expanding field, followed by basic research and population research. The most frequently raised issues were intensive care treatment for heart failure, applications of artificial intelligence technologies, cardiac assist devices, stem cells, genetics, and regional distribution and use of heart failure-related health care. Risk scoring and classification, care for patients, readmission, health economics of treatment and care, and cell regeneration and signaling pathways were among the fastest-growing themes. Drugs, signaling pathways, and biomarkers were all crucial issues for clinical and basic research in the entire population. Studies on intelligent medicine and telemedicine, interventional therapy for valvular disease, and novel coronavirus have emerged recently.</p><p><strong>Conclusion: </strong>Clinical and population research is increasingly focusing on the customization of intelligent treatments, improving the quality of patients' life, and developing novel treatments. Basic research is increasingly focusing on regenerative medicine, translational medicine, and signaling pathways. Additionally, each research field exhibits mutual fusion characteristics. Medical demands, new technologies, and social support are all potential drivers for these changes.</p>","PeriodicalId":51339,"journal":{"name":"Journal of Translational Internal Medicine","volume":"12 3","pages":"263-273"},"PeriodicalIF":4.7,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of body area network wearable smart bracelet in epidemic isolation scenario.","authors":"Wei Han, Hongbin Cai, Jiafa Lu, Le Yang, Yu Pang, Jiaqin Fang, Haojun Fan, Shike Hou","doi":"10.2478/jtim-2024-0010","DOIUrl":"10.2478/jtim-2024-0010","url":null,"abstract":"","PeriodicalId":51339,"journal":{"name":"Journal of Translational Internal Medicine","volume":"12 3","pages":"321-324"},"PeriodicalIF":4.7,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of metaraminol and norepinephrine on hemodynamics and kidney function in a miniature pig model of septic shock.","authors":"Xiaodan Li, Yi Bai, Ci Tian, Fan Yang, Wenyang Fan, Kuo Zhang, Qingbian Ma","doi":"10.2478/jtim-2023-0131","DOIUrl":"10.2478/jtim-2023-0131","url":null,"abstract":"<p><strong>Objective: </strong>To compare the effects of metaraminol and norepinephrine on hemodynamics and kidney injury in the treatment of septic shock, and calculate the conversion dose ratio between the two vasopressors.</p><p><strong>Methods: </strong>This randomized controlled study was performed on 15 Guizhou miniature pigs. Septic shock was induced by fecal peritonitis in 10 animals, and 5 were used as a sham-operated group (shams). Fluid resuscitation and vasopressors were initiated 30 min after the onset of septic shock. The septic shock pigs were randomly assigned to receive one of the two drugs to restore and maintain mean arterial pressure (MAP) ≥ 65 mmHg for 3 h. Hemodynamics and heart rate were continuously monitored.</p><p><strong>Results: </strong>There was no significant difference in MAP, heart rate, cardiac output (CO) and central venous pressure (CVP) between the two groups after treatment. No arrhythmias such as atrial fibrillation and ventricular fibrillation presented during continuous monitoring. After septic shock, the animals showed obvious kidney injury. In addition, compared with norepinephrine, the creatinine at 3 h was significantly lower with metaraminol. According to propensity score matching, the ratio of 6: 1 was considered appropriate for the dose equivalence calculation of metaraminol (μg·kg-1·min-1): norepinephrine (μg·kg-1·min-1).</p><p><strong>Conclusion: </strong>Metaraminol has a similar pressor effect to norepinephrine in septic shock; it does not increase heart rate and aggravate kidney injury after shock compared with norepinephrine. And our research may provide some laboratory evidence for the clinical usage of metaraminol.</p>","PeriodicalId":51339,"journal":{"name":"Journal of Translational Internal Medicine","volume":"12 3","pages":"253-262"},"PeriodicalIF":4.7,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nomogram for predicting risk of mild renal dysfunction among general residents from rural Northeast China.","authors":"Shasha Yu, Hongmei Yang, Bo Wang, Xiaofan Guo, Guangxiao Li, Yingxian Sun","doi":"10.2478/jtim-2023-0003","DOIUrl":"10.2478/jtim-2023-0003","url":null,"abstract":"<p><strong>Background and objectives: </strong>Cumulative evidence confirms that mild renal dysfunction (MRD) is correlated with many cardiovascular risk factors and increases cardiovascular morbidity and mortality. The purpose of this study was to establish an effective nomogram for predicting the risk of MRD in the rural population of Northeast China.</p><p><strong>Methods: </strong>We analyzed the reports of 4944 subjects from the Northeast China Rural Cardiovascular Health Study (NCRCHS). All the participants completed the questionnaires, anthropometric measurements, and blood tests during the baseline study (2012-2013) and the follow-up study during 2015-2017 (an average of 4.6 years). The Chronic Kidney Disease Epidemiology (CKD-EPI) equation was used to calculate the estimated glomerular filtration rate (eGFR), and eGFR in the range of 60-90 mL/min/1.73m2 was defined as MRD.</p><p><strong>Results: </strong>The study revealed that a total of 889 subjects (18.0%) had MRD. Multivariate logistic analysis showed that annual income, abdominal obesity, hypertension, hyperglycemia, and frequent tea consumption were the independent risk factors (<i>P</i> < 0.05) for MRD. Thereafter, a nomogram with an area under the receiver operating characteristic curve (AUC) of 0.705 was constructed to accurately predict MRD. The calibration plot also showed an excellent consistency between the probability of prediction and observation.</p><p><strong>Conclusion: </strong>We constructed a nomogram based on epidemiological data, which could provide an individual prediction of MRD with good accuracy.</p>","PeriodicalId":51339,"journal":{"name":"Journal of Translational Internal Medicine","volume":"12 3","pages":"244-252"},"PeriodicalIF":4.7,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RN486, a Bruton's Tyrosine Kinase inhibitor, antagonizes multidrug resistance in ABCG2-overexpressing cancer cells.","authors":"Xing-Duo Dong, Qisi Lu, Yi-Dong Li, Chao-Yun Cai, Qiu-Xu Teng, Zi-Ning Lei, Zeng-Hui Wei, Fan Yin, Leli Zeng, Zhe-Sheng Chen","doi":"10.2478/jtim-2024-0011","DOIUrl":"10.2478/jtim-2024-0011","url":null,"abstract":"<p><strong>Background and objectives: </strong>Overcoming ATP-binding cassette subfamily G member 2 (ABCG2)-mediated multidrug resistance (MDR) has attracted the attention of scientists because one of the critical factors resulting in MDR in cancer is the overexpression of ABCG2. RN486, a Bruton's Tyrosine Kinase (BTK) inhibitor, was discovered to potentially reverse ABCB1-mediated MDR. However, there is still uncertainty about whether RN486 has a reversal off-target impact on ABCG2-mediated MDR.</p><p><strong>Methods: </strong>MTT assay was used to detect the reversal effect of RN486 on ABCG2-overexpressing cancer cells. The ABCG2 expression level and subcellular localization were examined by Western blotting and immunofluorescence. Drug accumulation and eflux assay and ATPase assay were performed to analyze the ABCG2 transporter function and ATPase activity. Molecular modeling predicted the binding between RN486 and ABCG2 protein.</p><p><strong>Results: </strong>Non-toxic concentrations of RN486 remarkably increased the sensitivity of ABCG2-overexpressing cancer cells to conventional anticancer drugs mitoxantrone and topotecan. The reversal mechanistic studies showed that RN486 elevated the drug accumulation because of reducing the eflux of ABCG2 substrate drug in ABCG2-overexpressing cancer cells. In addition, the inhibitory efect of RN486 on ABCG2-associated ATPase activity was also verified. Molecular docking study implied a strong binding afinity between RN486 and ABCG2 transporter. Meanwhile, the ABCG2 subcellular localization was not altered by the treatment of RN486, but the expression level of ABCG2 was down-regulated.</p><p><strong>Conclusions: </strong>Our studies propose that RN486 can antagonize ABCG2-mediated MDR in cancer cells via down-regulating the expression level of ABCG2 protein, reducing ATPase activity of ABCG2 transporter, and inhibiting the transporting function. RN486 could be potentially used in conjunction with chemotherapy to alleviate MDR mediated by ABCG2 in cancer.</p>","PeriodicalId":51339,"journal":{"name":"Journal of Translational Internal Medicine","volume":"12 3","pages":"288-298"},"PeriodicalIF":4.7,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}