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.Clinical features and early warning indicators of patients with acute-on-chronic liver failure and bacterial infection
Zhanhu BI ; Linxu WANG ; Haifeng HU ; Hong DU ; Yidi DING ; Xiaofei YANG ; Jiayi ZHAN ; Fei HU ; Denghui YU ; Hongkai XU ; Jianqi LIAN
Journal of Clinical Hepatology 2024;40(4):760-766
ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure (ACLF) and bacterial infection and early warning indicators associated with multidrug-resistant infections. MethodsA retrospective analysis was performed for 130 patients with ACLF and bacterial infection who attended The Second Affiliated Hospital of Air Force Medical University from January 1, 2010 to December 31, 2021, and according to the drug susceptibility results, the patients were divided into multidrug-resistant (MDR) bacterial infection group with 80 patients and non-MDR bacterial infection group with 50 patients. General information and laboratory examination results were compared between the two groups to screen for the early warning indicators associated with MDR bacterial infection. The Student’s t-test was used for comparison of normally distributed continuous data with homogeneity of variance between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or continuous data with heterogeneity of variance between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The binary logistic regression analysis and the receiver operating characteristic (ROC) curve were used to assess the predictive value of early warning indicators. ResultsAmong the 130 patients with ACLF and bacterial infection, sputum (27.7%) was the most common specimen for detection, followed by blood (24.6%), urine (18.5%), and ascites (17.7%). Bacterial infections were dominated by Gram-negative bacteria (58.5%). Of all bacteria, Escherichia coli (18.5%), Klebsiella pneumoniae (14.6%), and Enterococcus faecium (13.8%) were the most common pathogens. Gram-positive bacteria had a high resistance rate to the antibacterial drugs such as erythromycin (72.2%), penicillin (57.4%), ampicillin (55.6%), and ciprofloxacin (53.7%), while Gram-negative bacteria had a high resistance rate to the antibacterial drugs such as ampicillin (73.3%), cefazolin (50.0%), and cefepime (47.4%). The patients with ACLF and bacterial infection had a relatively high rate of MDR bacterial infection (61.5%). Comparison of clinical data between the two groups showed that compared with the patients with non-MDR bacterial infection, the patients with MDR bacterial infection had significantly higher levels of alanine aminotransferase (Z=2.089, P=0.037), aspartate aminotransferase (Z=2.063, P=0.039), white blood cell count (Z=2.207, P=0.027), and monocyte count (Z=4.413, P<0.001). The binary logistic regression analysis showed that monocyte count was an independent risk factor for MDR bacterial infection (odds ratio=7.120, 95% confidence interval [CI]: 2.478 — 20.456,P<0.001) and had an area under the ROC curve of 0.686 (95%CI: 0.597 — 0.776) in predicting ACLF with MDR bacterial infection(P<0.001), with the optimal cut-off value of 0.50×109/L, a sensitivity of 0.725, and a specificity of 0.400. ConclusionACLF combined with bacterial infections is mainly caused by Gram-negative bacteria, with the common pathogens of Escherichia coli and Klebsiella pneumoniae and a relatively high MDR rate in clinical practice. An increase in monocyte count can be used as an early warning indicator to distinguish MDR bacterial infection from non-MDR bacterial infection.
5.Participation of clinical pharmacists in QTc interval prolongation induced by gilteritinib
Xiaolin CUI ; Xiaofei FU ; Yanhong DU ; Juan LIU ; Qian ZHU ; Ziqi LIU
Journal of Pharmaceutical Practice and Service 2024;42(6):263-266
Objective To explore the role of clinical pharmacists involved in the case of a patient with acute myeloid leukemia whose QTc interval prolongation was induced by gilteritinib,and to provide reference for drug treatment and monitoring of those patients.Methods The abnormal electrocardiogram(ECG)of a patient with acute myeloid leukemia was found in time by clinical pharmacists,who participated in clinical diagnosis and treatment by analyzing the patient's underlying diseases,diagnosis and treatment process,therapeutic drugs and their potential interactions.Results Clinical pharmacists suspected that the prolonged QTc interval was likely to be an adverse reaction caused by gilteritinib,and recommended immediate discontinuation of the drug and re-examination of the electrocardiogram.The physician took the suggestion to stop the suspected drug therapy with gilteritinib promptly,and ECG was rechecked 3 d later,and the QTc value returned to the normal range.Conclusion Clinical pharmacists participating in clinical diagnosis and treatment could provide better pharmaceutical care for patients.
6.Effects of Pingan qushi prescription on traditional Chinese medicine syndrome,adverse events,and compliance in young and middle-aged patients with hypertension
Songbo CHAI ; Yakang DU ; Shujuan ZHANG ; Jiangbo WU ; Xiaofei WANG
Journal of China Medical University 2024;53(1):8-14
Objective To investigate the effects of the Pingan qushi prescription on traditional Chinese medicine syndrome,adverse events,and compliance in young and middle-aged hypertensive patients.Methods One hundred thirty-two young and middle-aged patients with hypertension were selected and randomly divided into two groups.After elimination,64 cases were included in each group.For 2 months,the control group was treated with irbesartan tablets,and the observation group underwent the Pingan qushi prescription based on the control group.The blood pressure,curative effect,traditional Chinese medicine syndrome score,safety,adverse events,and prognosis-related indicators were compared between the two groups.Results The total effective rate of the observation group(96.88%,92.19%)was higher than that of the control group(82.52%,78.13%),and the difference was statistically significant(P = 0.005,P = 0.025).After 1 and 2 months of treatment,the blood pressure,syndrome scores,ALD,PRA,AngⅡ,and ET-1 in the observation group were lower than those in the control group,and the differences were statistically significant(all P<0.05).There was no sig-nificant difference in the incidence of adverse reactions between the two groups(P>0.05).There was no statistically significant difference(P>0.05)in the incidence of adverse events during treatment between the observation group(1.56%)and control group(10.94%).Conclusion The treatment of young and middle-aged community patients with hypertension undergoing the Pingan qushi pre-scription can further improve patients'symptoms,increase blood pressure control,promote prognosis improvement.
7.Research progress on pathogenesis of diabetes accelerating the progression of tendinosis
Zhaoyuan DU ; Huajun WANG ; Xiaofei ZHENG
Modern Hospital 2024;24(6):959-964,969
Objective Search and collect the previous relevant literature on the influence of diabetes on the progress of tendinosis,summarize the relevant conclusions and discuss the pathogenesis of diabetes accelerating the progress of tendinosis,mainly including summarizing the biomechanical and histological changes of diseased tendons in diabetes patients,as well as its pathogenesis at the cellular level.Methods This paper reviewed and analyzed the domestic and foreign literature related to dia-betes tendinosis by searching some Chinese and English databases like PubMed,Springer Link,CNKI,Google Academic.Re-sults Most previous studies more support the theory of degeneration as the pathogenesis of tendinosis,but now more and more researchers find that diabetes,as a systemic metabolic disease,can induce the occurrence of tendinosis through a variety of mech-anisms,or aggravate the progress of tendinosis,such as the accumulation of advanced glycation end products(AGEs)at the le-sion site,chronic inflammatory reaction at the lesion site,increased oxidative stress level of tendon cells And changes in the ac-tivities of matrix metalloproteinases and glutamine transaminase.By summarizing and analyzing the various understandings of dia-betes on the pathogenesis of tendinosis proposed by previous researchers,the relationship between diabetes and tendinosis is grad-ually clear.Conclusion As a systemic metabolic disease,diabetes can induce the occurrence of tendinosis or aggravate the pro-gress of tendinosis through a variety of ways and mechanisms.Research and clarification of these ways can provide us with a pow-erful weapon to study and treat tendinosis.However,at present,there are many possible pathogenesis of diabetes tendinosis,which still needs to be studied step by step to further clarify its main pathogenesis.
8.Efficacy of Fuyang Tongluo therapy combined with conventional western medicine in elderly patients with coronary heart disease and heart failure
Songbo CHAI ; Yakang DU ; Shujuan ZHANG ; Jiangbo WU ; Xiaofei WANG
Journal of China Medical University 2024;53(6):531-535
Objective To explore the therapeutic efficacy of the Fuyang Tongluo therapy combined with conventional western medicine in elderly patients with heart failure due to coronary heart disease.Methods In this single-blind randomized controlled trial,96 elderly patients with coronary heart disease and heart failure were randomly divided into three groups,each consisting of 32 individuals.Control group A was treated with conventional western medicine(atorvastatin combined with metoprolol),control group B with Fuyang Tongluo therapy,and the observation group with Fuyang Tongluo therapy and conventional western medicine.The three groups were compared in terms of therapeutic efficacy and traditional Chinese medicine symptom points as well as blood interleukin(IL)-23 and IL-17 levels,left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),and left ventricular ejection fraction(LVEF)values before and after treatment.Results The total clinical efficacy rate in the observation group was 93.75%,which was significantly higher than those in control groups A(68.75%)and B(65.63%)(P<0.05).After 4 and 8 weeks of treatment,the primary and minor symptom scores,total symptom scores,LVESD,LVEDD,and IL-23 and IL-17 levels in the observation group were significantly lower than those in control groups A and B(P<0.05).Conclusion The combination of the Fuyang Tongluo therapy with conventional western medicine exhibited good therapeutic efficacy in elderly patients with coronary heart disease and heart failure.These effects were achieved by inhibiting excessive expression of the inflammatory axis factors IL-23 and IL-17 and promoting the recovery of cardiac function.
9.Clinical observation of ticagrelor combined with Compound xueshuantong capsule in the treatment of unstable angina pectoris
Songbo CHAI ; Yakang DU ; Shujuan ZHANG ; Jiangbo WU ; Weiping ZHANG ; Xiaofei WANG
China Pharmacy 2023;34(23):2901-2905
OBJECTIVE To observe the efficacy and safety of ticagrelor combined with Compound xueshuantong capsules in the treatment of unstable angina pectoris. METHODS Totally 120 patients with unstable angina pectoris with deficiency of Qi and Yin combined admitted to Sanmenxia Hospital of Traditional Chinese Medicine from January 2021 to December 2022 were randomly divided into clopidogrel group (group A), ticagrelor group (group B) and combined medication group (group C), with 40 patients in each group. In addition to conventional treatment, group A was given clopidogrel orally; group B was given ticagrelor orally; group C was given ticagrelor and Compound xueshuantong capsule orally. After 12 weeks of treatment, the clinical efficacy, frequency of angina attacks, coagulation function indicators, cardiac function indicators, traditional Chinese medicine syndrome efficacy, and the incidence of adverse cardiovascular events and bleeding incidence were evaluated in the 3 groups. RESULTS The total effective rates of group A, group B and group C were 77.5%, 85.0% and 90.0%, respectively. The incidence of adverse cardiovascular events and bleeding events were 7.5%, 7.5% and 5.0% in the respective groups, with no statistically significant difference (P>0.05). The frequency of angina attacks, duration of angina attacks and duration of dyspnea were significantly reduced or shortened in all 3 groups after treatment compared to before treatment (P<0.05). The frequency of angina attacks in group C was significantly lower than that in groups A and B after treatment (P<0.05). The levels of fibrinogen (FBG) and D-dimer in all 3 groups were significantly lower after treatment compared to before treatment (P<0.05); group A had significantly higher levels of FBG and D-dimer compared to group B and C (P<0.05). The left ventricular end-diastolic diameter and left ventricular end-systolic diameter in all three groups were significantly shorter after treatment, and the left ventricular ejection fraction was significantly higher compared to before treatment (P<0.05), but there were no statistically significant differences among those groups (P>0.05). The total effective rates of traditional Chinese medicine syndrome efficacy in groups A, B and C were 67.5%, 80.0% and 87.5%, respectively, with group C being significantly higher than group A (P<0.05). CONCLUSIONS In addition to conventional treatment, ticagrelor combined with Compound xueguantong capsules can more significantly reduce the frequency of angina attacks in patients with unstable angina pectoris, reduce the levels of FBG and D- dimer, improve traditional Chinese medicine syndrome efficacy, and do not increase the risk of bleeding.
10.Erratum: Author correction to "TMEM16A inhibits angiotensin II-induced basilar artery smooth muscle cell migration in a WNK1-dependent manner" Acta Pharm Sin B 11(12) (2021) 3994-4007.
Huaqing ZHENG ; Xiaolong LI ; Xin ZENG ; Chengcui HUANG ; Mingming MA ; Xiaofei LV ; Yajuan ZHANG ; Lu SUN ; Guanlei WANG ; Yanhua DU ; Yongyuan GUAN
Acta Pharmaceutica Sinica B 2023;13(3):1340-1343
[This corrects the article DOI: 10.1016/j.apsb.2021.04.013.].

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