1.Synergistic Activation of LEPR and ADRB2 Induced by Leptin Enhances Reactive Oxygen Specie Generation in Triple-Negative Breast Cancer Cells
Chang LIU ; Jing YU ; Yongjun DU ; Yu XIE ; Xiaofei SONG ; Chang LIU ; Yan YAN ; Yue WANG ; Junfang QIN
Cancer Research and Treatment 2025;57(2):457-477
Purpose:
Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear.
Materials and Methods:
The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2.
Results:
LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects.
Conclusion
This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.
2.Synergistic Activation of LEPR and ADRB2 Induced by Leptin Enhances Reactive Oxygen Specie Generation in Triple-Negative Breast Cancer Cells
Chang LIU ; Jing YU ; Yongjun DU ; Yu XIE ; Xiaofei SONG ; Chang LIU ; Yan YAN ; Yue WANG ; Junfang QIN
Cancer Research and Treatment 2025;57(2):457-477
Purpose:
Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear.
Materials and Methods:
The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2.
Results:
LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects.
Conclusion
This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.
3.Synergistic Activation of LEPR and ADRB2 Induced by Leptin Enhances Reactive Oxygen Specie Generation in Triple-Negative Breast Cancer Cells
Chang LIU ; Jing YU ; Yongjun DU ; Yu XIE ; Xiaofei SONG ; Chang LIU ; Yan YAN ; Yue WANG ; Junfang QIN
Cancer Research and Treatment 2025;57(2):457-477
Purpose:
Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear.
Materials and Methods:
The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2.
Results:
LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects.
Conclusion
This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.
4.Prospective Study on Tooth Loss and Risk of Esophageal Cancer Among Residents of A Natural Village in Wenfeng District, Anyang City, Henan Province
Jingjing WANG ; Ruihua XU ; Yanfang ZHANG ; Xueke ZHAO ; Qiang ZHANG ; Xin SONG ; Mengxia WEI ; Junfang GUO ; Xuena HAN ; Yaru FU ; Bei LI ; Junqing LIU ; Lingling LEI ; Min LIU ; Qide BAO ; Lidong WANG
Cancer Research on Prevention and Treatment 2025;52(7):548-553
Objective To investigate the relationship between tooth loss and the occurrence of esophageal cancer in a natural village in Wenfeng District, Anyang City, Henan Province. Methods A prospective cohort study was conducted to observe the occurrence of tooth loss and esophageal cancer among the asymptomatic residents of the natural village for 16 years from January 2008 to July 2024. Data were analyzed by chi-square test, binary logistic regression, and restricted cubic spline. Results Among the total population of 711 cases, 136 cases were lost to follow-up and 575 cases were included in the final statistics, including 45 cases with esophageal cancer. Significant statistical difference was found between esophageal cancer patients with and without tooth loss (P<0.05). Logistic regression analysis showed that tooth loss was associated with the occurrence of esophageal cancer (OR=3.977, 95%CI: 1.543-10.255). After the adjustment for confounders, tooth loss
5.Prospective Study of Disease Occurrence Spectrum in Asymptomatic Residents in Areas with High Incidence of Esophageal Cancer: 16-year Observation of 711 Cases in Natural Population
Qide BAO ; Fangzhou DAI ; Xueke ZHAO ; Jingjing WANG ; Xin SONG ; Zongmin FAN ; Yanfang ZHANG ; Zhuo YANG ; Junfang GUO ; Kan ZHONG ; Qiang ZHANG ; Junqing LIU ; Min LIU ; Lidong WANG
Cancer Research on Prevention and Treatment 2025;52(8):656-660
Objective To understand the disease spectrum of a natural village in an area with high incidence of esophageal cancer to provide a reference for precise prevention and control. Methods From 2008 to 2024, 711 asymptomatic people over the age of 35 years in a natural village with high incidence of esophageal cancer in China were surveyed, and 171 of them were subjected to gastroscopy, biopsy, and pathological examination. All participants were followed up for a long time, and their disease history was recorded. Results A total of 16 years of follow-up were performed, and 703 people were effectively followed up. In 2008, 171 people underwent gastroscopy, and 160 people had biopsy and pathological results in endoscopic screening. By 2024, 76 people had been diagnosed with malignant tumors of 12 different types, and among these people, 45 had esophageal cancer. Conclusion Esophageal cancer remains a significant cause of morbidity and mortality from malignant tumors in this region. Biopsy and pathological examination should be strengthened during gastroscopy, and follow-ups and regular check-ups should be given high importance to reduce the incidence and mortality rates of esophageal cancer.
6.Analysis of the relationship between umbilical cord blood chemokines RANTES,CXCL12,CXCR4 and neonatal septicemia inflammatory response and outcome
Panqiang JIA ; Xiaohong LIU ; Junfang XU ; Limin MA ; Xin SI ; Jiaojiao FENG ; Shufen ZHAI
International Journal of Laboratory Medicine 2025;46(4):398-403
Objective To analyze the relationship between umbilical cord blood chemokines regulated upon activation normal T cell expressed and secreted(RANTES),C-X-C motif chemokine ligand 12(CXCL12),C-X-C motif chemokine receptor 4(CXCR4)and neonatal septicemia inflammatory response and outcome.Meth-ods A total of 242 children with neonatal septicemia admitted to a hospital from January 2020 to January 2024 were selected as the study subjects,and were divided into non-critical group(101 cases),critical group(79 cases)and extremely critical group(62 cases)according to neonatal critical case score.According to the prognosis,the subjects were divided into good prognosis group and bad prognosis group.The levels of RAN-TES,CXCL12,CXCR4 and inflammatory factors[C-reactive protein(CRP),interleukin-6,IL-1β]in umbilical cord blood of each group were detected.The correlation between RANTES,CXCL12,CXCR4 and inflammato-ry factors in umbilical cord blood of neonatal septicemia was analyzed by Pearson correlation,and the influen-cing factors of poor prognosis of neonatal septicemia were analyzed by multivariate Logistic regression.Re-ceiver operating characteristic(ROC)curve was drawn to analyze the value of umbilical cord blood RANTES,CXCL12 and CXCR4 in predicting the poor prognosis of neonatal septicemia.Results The levels of RAN-TES,CXCL12,CXCR4,CRP,IL-6 and IL-1β in umbilical cord blood of extremely critical group were higher than those of critical group and non-critical group,and the differences were statistically significant(P<0.05).The levels of RANTES,CXCL12 and CXCR4 in umbilical cord blood of neonatal septicemia were posi-tively correlated with CRP,IL-6 and IL-1β(P<0.05).Multivariate Logistic regression analysis showed that extremely severe,early-onset septicemia,high RANTES,high CXCL12 and high CXCR4 were risk factors for poor prognosis of neonatal septicemia(P<0.05).ROC curve analysis results showed that the area under the curve(AUC)of umbilical cord blood RANTES,CXCL12 and CXCR4 in predicting poor prognosis of neonatal septicemia were 0.810,0.814 and 0.763,respectively,and the AUC of three indicators combined prediction was 0.914,which was higher than that of single prediction.Conclusion The increased levels of RANTES,CX-CL12 and CXCR4 in umbilical cord blood of neonatal septicemia are associated with inflammation,aggravation and poor prognosis,and the combination of RANTES,CXCL12 and CXCR4 can predict the risk of poor prog-nosis of neonatal septicemia.
7.Correlation between serum CTHRC1,galectin-10 levels and disease severity in psoriasis vulgaris patients
Qin YANG ; Xiuyan LIU ; Junfang YIN
International Journal of Laboratory Medicine 2025;46(18):2196-2200,2206
Objective To investigate the correlation between serum levels of collagen triple helix repeat containing protein 1(CTHRC1)and galectin-10 and disease severity in patients with psoriasis vulgaris(PV).Methods From October 2021 to March 2023,a total of 105 confirmed PV patients treated in the hospital were regarded as the research objects.According to the disease severity,they were separated into a severe group(46 cases)and mild to moderate group(59 cases).Additionally,105 healthy individuals who came to the hospital for physical examination were selected as the control group.The levels of CTHRC1 and galectin-10 in serum were compared and analyzed.Multivariate Logistic regression analysis was conducted to identify the influen-cing factors for the development of severe PV in patients.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum CTHRC1 and galectin-10 levels for the development of severe PV in patients.Results Compared with the control group,the serum levels of CTHRC1 and galectin-10 in the severe group and mild to moderate group were significantly increased(P<0.05).Compared with the mild to moderate group,the serum levels of CTHRC1 and galectin-10 in the severe group were significantly increased(P<0.05).Compared with the mild to moderate group,the levels of inflammatory factors interleukin-26(IL-26),interleukin-22(IL-22),and interleukin-17(IL-17)were all increased in the severe group(P<0.05).Ser-um IL-26,IL-22,CTHRC1,and galectin-10 levels were all influencing factors for the development of severe PV in patients(P<0.05).The area under the curve(AUC)of serum IL-26,IL-22,CTHRC1 and galectin-10 levels for predicting the development of severe PV in patients were 0.809,0.784,0.863 and 0.874,respective-ly,the AUC predicted by the combination of the four was 0.966,and the combined prediction of the four was better than the prediction of the four separately(Z combination of the four-IL-26=3.581,Zcombination of the four-IL-22=3.285,Zcombination of the four-CTHRC1=2.671,Zcombination of the four-galectin10=2.434,P<0.05).Conclusion The increased levels of CTHRC1 and galectin-10 in the serum of PV patients are related to the severity of the disease.
8.Over-expression of miR-101 alleviates ventricular remodeling in rat models with acute myocardial infarction by inhibiting JAK2/STAT3 signaling
Bo WU ; Hao GUO ; Zhao ZHONG ; Junfang LIU ; Qi WANG ; Jibo GUO
Basic & Clinical Medicine 2025;45(3):281-289
Objective To explore the effect and underlying molecular mechanism of miR-101 on ventricular remod-eling in rats after acute myocardial infarction(AMI).Methods The AMI rat model was established using the left anterior descending coronary artery ligation method.The AMI rats were randomly divided into AMI group,agomir-NC group,miR-101 agomir group and coumermycin A1 group,another 12 rats were selected as sham group with 12 in each.The targeting relationship between miR-101 and JAK2 was analyzed by Target Scan 8.0 database and double luciferase reporter gene assay.The expression of miR-101 in rat myocardium was detected by RT-qPCR.LVESD,LVEDD,LVEF and LVFS were measured by ultrasonography.The level of IL-1β,IL-6 and TNF-α in rats serum was determined by ELISA.The myocardial tissue lesion and fibrosis were detected by HE staining and Mas-son staining.The expression of collagenⅠand TGF-β in rat myocardial tissue was detected by immunohistochemical staining.The expression of E-cadherin,N-cadherin,Vimentin,p-JAK2,JAK2,p-STAT3 and STAT3 proteins was detected by Western blot.Results Compared with AMI group and agomir-NC group,the myocardial tissue lesions and fibrotic area in miR-101 agomir group were significantly decreased(P<0.05),the level of LVESD,LVEDD,L-1β,IL-6,TNF-α,collagenⅠ,TGF-β,N-cadherin,vimentin,p-JAK2 and p-STAT3 decreased(P<0.05).The levels of miR-101,LVEF,LVFS and E-cadherin were increased(P<0.05).Compared with miR-101 agomir group,the myocardial tissue lesions and fibrotic area in coumermycin A1 group significantly increased(P<0.05),the level of LVESD,LVEDD,L-1β,IL-6,TNF-α,collagenⅠ,TGF-β,N-cadherin,vimentin,p-JAK2 and p-STAT3 was increased(P<0.05).The level of miR-101,LVEF,LVFS and E-cadherin was decreased(P<0.05).Conclusions miR-101 inhibits myocardial inflammatory lesions,myocardial fibrosis and epithelial-mesenchymal fransition(EMT)process after AMI with a mechanism targeting at JAK2/STAT3 signaling pathway,thus alleviates ventricular remodeling in rats after AMI.
9.Application of digital three-dimensional reconstruction in placenta accreta spectrum disorders
Junfang WANG ; Ying LIU ; Fanjie MENG ; Leilei ZHANG
Chinese Journal of Perinatal Medicine 2024;27(2):166-169
Placenta accreta spectrum (PAS) disorders are one of the important causes of adverse pregnancy outcomes. Some studies reported that the limitations in commonly used auxiliary examination methods led to missed or misdiagnosis, resulting in adverse pregnancy outcomes. Digital three-dimensional (3D) reconstruction is the 3D graphical visualization constructed on the original data to illustrate the spatial relationship between structures, overcoming the limitations of two-dimensional images. As a novel auxiliary diagnostic tool, digital 3D reconstruction provides promising insights into the development of personalized precision medicine. This article reviews the research and application of ultrasound and MRI 3D reconstruction in the field of PAS.
10.Analysis of the trend of radiological diagnostic examination frequency and the related influencing factors
Yongxian ZHANG ; Yantao NIU ; Tianliang KANG ; Yunfu LIU ; Liping XU ; Lin XU ; Senlin GUO ; Dandan LIU ; Binbin YU ; Junfang XIAN
Chinese Journal of Radiological Medicine and Protection 2024;44(1):29-35
Objective:To investigate the trend of radiological diagnostic examination frequency and the related influencing factors in a general hospital in recent four years.Methods:The hospital information system and the radiology information system were used to collect the information on the numbers of the outpatients, the emergency patients, and the inpatients and the radiology examination information from 2019 to 2022. The examination frequency and proportion of various imaging equipment were counted by using the perspective table of data, and the examination items and the proportion of the radiological diagnostic examinations were calculated. The positive rates of the radiological examinations were measured from 2019 to 2022. The gender and age distribution of the patients were analyzed. Spearman correlation analysis was used to analyze the relationships between the numbers of the patients undergoing radiological examinations and the numbers of the outpatients, emergency patients and the inpatients.Results:The annual frequency of radiological diagnostic examinations from 2019 to 2022 were 307 306, 245 418, 317 250 and 325 625, respectively, with a total of 1 195 599. Among them, the proportions of CT, X-rays, bedside X-rays, bone density, gastrointestinal imaging and mammography were 59.74%, 38.04%, 1.39%, 0.42%, 0.21% and 0.19%, respectively. In each year, the proportion of CT in all radiological diagnostic examinations was 49.58%, 63.40%, 60.40% and 65.20%, respectively. The frequency of emergency CT and emergency chest CT was correlated with the number of emergency patients( r =0.63, 0.61, P<0.05), and the frequency of non-emergency CT was correlated with the number of outpatients and inpatients ( r =0.61, 0.66, P<0.05). The positive rates of the CT examinations were higher than 80% except the lowest of 79.95% in 2021. Conclusions:Radiological examinations especially CT examinations have increased significantly, and played an important role in the diagnosis of diseases. However, attention should be paid to the Justification of the CT examinations. Timely statistical analysis of radiological examination information can provide data supports and references for scientific management of radiological examinations.

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