1.Curcumin inhibits lipid metabolism in non-small cell lung cancer by downregulating the HIF-1α pathway.
Dandan LI ; Jiaxin CHU ; Yan YAN ; Wenjun XU ; Xingchun ZHU ; Yun SUN ; Haofeng DING ; Li REN ; Bo ZHU
Journal of Southern Medical University 2025;45(5):1039-1046
OBJECTIVES:
To investigate the effect of curcumin on lipid metabolism in non-small cell lung cancer (NSCLC) and its molecular mechanism.
METHODS:
The inhibitory effect of curcumin (0-70 μmol/L) on proliferation of A549 and H1299 cells was assessed using MTT assay, and 20 and 40 μmol/L curcumin was used in the subsequent experiments. The effect of curcumin on lipid metabolism was evaluated using cellular uptake assay, wound healing assay, triglyceride (TG)/free fatty acid (NEFA) measurements, and Oil Red O staining. Western blotting was performed to detect the expressions of PGC-1α, PPAR-α, and HIF-1α in curcumin-treated cells. Network pharmacology was used to predict the metabolic pathways, and the results were validated by Western blotting. In a nude mouse model bearing A549 cell xenograft, the effects of curcumin (20 mg/kg) on tumor growth and lipid metabolism were assessed by measuring tumor weight and observing the changes in intracellular lipid droplets.
RESULTS:
Curcumin concentration-dependently inhibited the proliferation of A549 and H1299 cells and significantly reduced TG and NEFA levels and intracellular lipid droplets. Western blotting revealed that curcumin significantly upregulated PGC-1α and PPAR‑α expressions in the cells. KEGG pathway enrichment analysis predicted significant involvement of the HIF-1 signaling pathway in curcumin-treated NSCLC, suggesting a potential interaction between HIF-1α and PPAR‑α. Western blotting confirmed that curcumin downregulated the expression of HIF-1α. In the tumor-bearing mice, curcumin treatment caused significant reduction of the tumor weight and the number of lipid droplets in the tumor cells.
CONCLUSIONS
Curcumin inhibits NSCLC cell proliferation and lipid metabolism by downregulating the HIF-1α pathway.
Curcumin/pharmacology*
;
Humans
;
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
;
Animals
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Lipid Metabolism/drug effects*
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Carcinoma, Non-Small-Cell Lung/pathology*
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Lung Neoplasms/pathology*
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Mice, Nude
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Down-Regulation
;
Mice
;
Cell Proliferation/drug effects*
;
Cell Line, Tumor
;
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
;
PPAR alpha/metabolism*
;
Signal Transduction/drug effects*
;
A549 Cells
2.Association of gene polymorphisms in microRNA with blood pressure responses to salt and potassium intake
Lan WANG ; Ying CUI ; Yanjie GUO ; Yanni YAO ; Beibei YANG ; Nairong LIU ; Jiaxin WANG ; Panpan LIU ; Mingfei DU ; Guilin HU ; Zejiaxin NIU ; Xi ZHANG ; Dan WANG ; Chao CHU ; Hao JIA ; Yue SUN ; Weihua GAO ; Jianjun MU ; Yang WANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(3):435-442
Objective To investigate the relationship of miRNA gene polymorphisms with blood pressure(BP)responses to the sodium and potassium diet intervention.Methods In 2004,we recruited 514 participants from 124 families in seven villages of Baoji,Shaanxi Province,China.All subjects were given a three-day normal diet,followed by a seven-day low-salt diet,a seven-day high-salt diet,and finally a seven-day high-salt and potassium supplementation.A total of 19 miRNA single nucleotide polymorphisms(SNPs)were selected for analysis.Results Throughout the sodium-potassium dietary intervention,the BP of the subjects fluctuated across all phases,showing a decrease during the low-salt period and an increase during the high-salt period,followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet.MiR-210-3p SNP rs 12364149 was significantly associated with systolic BP(SBP),diastolic BP(DBP)and mean arterial pressure(MAP)responses to low-salt diet.MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention.In addition,miR-26b-3p SNP rs115254818 was significantly correlated with SBP,DBP and MAP responses to high-salt intervention.MiR-1307-5p SNPs rs1 1191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet.MiR-4638-3p SNP rs6601178,miR-210-3p SNP rs12364149,miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet.In addition,miR-26b-3p SNP rs115254818 was significantly associated with SBP,DBP and MAP responses to potassium supplementation.MiR-1307-5p SNPs rs11191676,rs2292807,and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation.Conclusion miRNA gene polymorphisms are associated with BP response to sodium and potassium,suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity.
3.Palliative care quality assessment tools based on the cancer patient experience:a systematic review
Yunyi CHU ; Zifang JIANG ; Zefan HE ; Jiaxin ZHANG ; Yanfei CHEN
Chinese Journal of Nursing 2024;59(13):1657-1665
Objective To systematically evaluate the measurement properties and methodological quality of the palliative quality assessment tools based on the cancer patient experiences,and to provide an evidence-based basis for the selection of a high-quality assessment tool for healthcare professionals.Methods Systematic search of PubMed,Embase,Web of Science,CINAHL,CNKI,Wanfang database,VIP database,and China Biomedical Literature database for studies related to the evaluation of the measurement properties of the self-report palliative care quality assessment tools for cancer patients.The search period from the date of creation to December 10,2023.There are 2 researchers who independently conducted literature screening and data extraction according to the COSMIN selection criteria,and used the COSMIN Risk of Bias Inventory and Quality Criteria Scale to measure the academic characteristics and form the final recommendations.Results A total of 19 studies involving 8 assessment tools for cancer patients were included.The final 6 assessment tools were recommended at level B.2 assessment tools are recommended at level A.Conclusion The SF-QCQ-PC and the Self-Report Palliative Care Quality Assessment Tool for Terminal Cancer Patients can be provisionally recommended.However,further validation of its measurement properties is still needed.
4.Associations of genetic polymorphisms in Corin with blood pressure responses to salt and potassium intake
Lan WANG ; Zejiaxin NIU ; Yanjie GUO ; Nairong LIU ; Yanni YAO ; Beibei YANG ; Jiaxin WANG ; Chuang LI ; Panpan LIU ; Chang’e YANG ; Mingfei DU ; Guilin HU ; Xi ZHANG ; Dan WANG ; Xiaoyu ZHANG ; Chao CHU ; Yueyuan LIAO ; Qiong MA ; Keke WANG ; Hao JIA ; Yue SUN ; Tongshuai GUO ; Weihua GAO ; Jianjun MU ; Yang WANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(1):22-29
【Objective】 Corin, a transmembrane serine protease that can cleave atrial natriuretic peptide precursor (pro-ANP) into atrial natriuretic peptide with smaller bioactive molecules, participates in the pathophysiological process of hypertension and cardiac hypertrophy. The purpose of this study was to explore the relationship of Corin gene variation with blood pressure responses to sodium and potassium dietary interventions. 【Methods】 In 2004, we recruited 514 participants from 124 families in 7 villages of Baoji, Shaanxi Province, China. All the subjects received a 3-day normal diet, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Fifteen single nucleotide polymorphisms (SNPs) of Corin gene were selected for final analysis. 【Results】 SNPs rs12509275 were significantly associated with diastolic blood pressure (DBP) response to low-salt diet, while rs3749584 was associated with pulse pressure (PP) response to low-salt diet.SNP rs3749584 and rs10517195 were significantly associated with PP response to high-salt diet. In addition,rs17654278 were significantly associated with systolic blood pressure (SBP) response to high-salt and potassium supplementation, rs2271037 was significantly correlated with DBP responses to high-salt and potassium supplementation, and rs4695253, rs12509275, rs2351783, rs36090894 were significantly associated with PP response to high-salt and potassium supplementation. 【Conclusion】 Corin gene polymorphisms were associated with blood pressure response to sodium and potassium, suggesting that Corin gene may be involved in pathophysiological process of salt sensitivity and potassium sensitivity.
5.Preliminary experience in guiding individualized targeted therapy of advanced metastatic renal cell carcinoma with gene detection technology
Da XU ; Xiuwu PAN ; Jiaxin CHEN ; Jianqing YE ; Chuanmin CHU ; Yijun TIAN ; Xi LIU ; Jianmin LYU ; Xingang CUI
Chinese Journal of Urology 2019;40(5):365-369
Objective To explore the efficacy and tolerance of adverse reactions of gene detection technique in guiding individualized targeted therapy for advanced metastatic renal cell carcinoma.Methods Retrospective analysis was performed on the clinical data of 62 patients with advanced metastatic renal cell carcinoma before and after receiving targeted drug treatment in our department from October 2015 to October 2017.Among the 62 patients,there were 36 males and 26 females,with an average age of (54 ± 13) years old.16 patients were treated with sunitinib,20 patients were treated with sorafenib and 26 patients were treated with pazopanib.A total of 28 patients (individualized group) were selected to receive targeted drug according to the results of gene detection,and 34 patients were treated with targeted drug empirically (empirical group).In individualized group,there were 17 males and 11 females with the average age of (51.3 ± 15.6) years old.20 patients accepted the operation.The distant metastasis included bone metastasis in 21 cases,lung metastasis in 7 cases,liver metastasis in 16 cases,epidermal metastasis in 4 cases and lymphatic metastasis in 14 cases.According to risk of MSKCC,the case number of low risk,moderate risk and high risk were 15,7,6,respectively.7 patients were treated with sunitinib,8 patients were treated with sorafenib and 13 patients were treated with pazopanib.In empirical group,there were 19 males and 15 females with the average age of (56.3 ± 10.1) years old.22 patients accepted the operation.The distant metastasis included bone metastasis in 20 cases,lung metastasis in 5 cases,liver metastasis in 13 cases,epidermal metastasis in 3 cases and lymphatic metastasis in 15 cases.According to risk of MSKCC,the case number of low risk,moderate risk and high risk were 20,g,6,respectively.9 patients were treated with sunitinib,12 patients were treated with sorafenib and 13 patients were treated with pazopanib.The baseline characteristics of the two groups of patients,including gender,age,whether operation was performed,site of metastasis,and risk of MSKCC,didn't show significant difference.Patients in both groups received the standard treatment regimen and the follow-up duration was 4-26 months to observe the efficacy,progression-free survival and tolerance to adverse reactions of the targeted therapy.Results After 12 months of treatment,15 patients in the individualized group was recorded objective remission.7 patients in the empirical group was recorded objective remission,as well.The tumor control efficacy of the individualized group was significantly better than that of the empirical group (46.4% vs.20.6%,P =0.03).Meanwhile,the median progression-free survival time (15.2 months,3.7-24.2 months) in the individualized group was significantly longer than that in the empirical group (12.1 months,2.8-22.1 months) (P =0.009).Compared with the empirical group,the higher incidence of targeted treatment-related adverse reactions occurred in the individualized group,including thrombocytopenia (46.4% vs.17.6% P =0.014),leukopenia (46.4% vs.17.6% P =0.005),hypertension (71.4% vs.44.1%,P =0.031) and hypothyroidism(60.7% vs.29.4%,P=0.013).Conclusions Compared with the patients with empirical drugs,the application of gene detection technique to select individualized targeted drugs for the treatment of advanced metastatic renal cancer is obvious curatively effective,and to a certain extent extends the progression-free survival time of patients.
6.Surgical Resection and Prognosis of Bronchopulmonary Carcinoid.
Shaowei ZHANG ; Zhiqiang XUE ; Jiaxin WEN ; Bo WANG ; Xiangyang CHU
Chinese Journal of Lung Cancer 2019;22(8):494-499
BACKGROUND:
Bronchopulmonary carcinoid (BPC) is a rare neuroendocrine tumor, the clinical studies on treatment and prognostic factors of BPC are somewhat controversial. Our purpose was to evaluate the clinical efficacy of surgery on BPC, and to analyze the prognostic factors affecting the survival of BPC.
METHODS:
We retrospectively collected the clinical data of patients with BPC admitted to the Chinese PLA General Hospital between January 2000 and December 2017. The Kaplan-Meier method was used to calculate the survival rate of patients and to map the survival curve. Then the effects of different factors like pathological classification, gender, age, on prognosis were compared by univariate analysis and multivariate analysis was made by Cox proportional hazard model.
RESULTS:
A total of 98 patients had a diagnosis of BPC were included in the study. There were 41 patients with typical carcinoid (TC) and 57 patients with atypical carcinoid (AC). The 1-yr, 5-yr, and 10-yr overall survival rates of BPC were 96.9%, 80.0% and 73.6%, respectively. Univariate analysis showed age (P=0.000,1), smoking history (P=0.005), pathological subtype (P<0.000,1), T stage (P=0.000,2), TNM stage (P<0.000,1) were the prognostic factors. Multivariate analysis showed that age (P=0.005) and tumor stage (P=0.017) were independent prognostic factors.
CONCLUSIONS
BPC occurred more in middle-aged men. Surgery is the main treatment for lung cancer, and the overall prognosis is good. Age and TNM stage were independent risk factors for long-term survival after lung cancer surgery.
7.The study of clinical outcomes of extended thymectomy by robotic and video assisted thoracoscopic surgey for thymoma with myasthenia gravis
Zhiqiang XUE ; Xiangyang CHU ; Lianbin ZHANG ; Bo YANG ; Jiaxin WEN ; Tong LI ; Yang LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2017;33(3):141-143
Objective To study the clinical outcomes of robotic extended thymectomy and thoracoscopic extended thymectomy for thymoma patients with myasthenia gravis compared with conventional median sternotomy extended thymectomy.Methods The clinical data of thymoma patients with myasthenia gravis treated by extended thymectomy between June 2013 and June 2016 were retrospectively reviewed.The clinical outcome parameters were compared according to surgical approach.Results 41 thymoma patients with myasthenia gravis,8 cases underwent robotic extended thymecotmy,11 cases underwent thoracoscopic extended thymectomy and 20 underwent median sternotomy extended thymectomy.The resected extension included tumor,thymus tissue and adipose tissue in anterior mediastinum.There were no significant differences between robotic group and thoracoscopic group regarding operative time,blood loss,chest tube duration,hospital stay,postoperative complications and postoperative myasthenic crisis (P > 0.05).The blood loss of robotic group and thoracoscopic group was significantly lower than that in median sternotomy group(P < 0.05).The chest tube duration of thoracoscopic group was significantly shorter than that in median sternotomy group(P <0.05).The effective rates of MG after extended thymectomy in robotic group,thoracoscopic group and sternotomy group was 65.0% 、69.2% 、62.5% respectively and there was no significant difference (P < 0.05).Conclusion Robotic thymectomy and thoracoscopic thymecotomy are both minimal invasive surgery approach with less bleeding for thymoma patients with myasthenia gravis.The clinical outcomes of robotic thymectomy and thoracoscopic thymecotomy are similar.
8.Clinical Study of Intra-operative Computed Tomography Guided Localization with A Hook-wire System for Small Ground Glass Opacities in Minimally Invasive Resection
CHU XIANGYANG ; HOU XIAOBIN ; ZHANG LIANBIN ; XUE ZHIQIANG ; REN ZHIPENG ; WEN JIAXIN ; LIU YI ; MA KEFENG ; SUN YU’E
Chinese Journal of Lung Cancer 2014;(12):845-849
Background and objective Localization of pulmonary ground glass small nodule is the technical dif-ficulty of minimally invasive operation resection. The aim of this study is to evaluate the value of intraoperative computed tomography (CT)-guided localization using a hook-wire system for small ground glass opacity (GGO) in minimally invasive resection, as well as to discuss the necessity and feasibility of surgical resection of small GGOs (<10 mm) through a minimally invasive approach.MethodshTe records of 32 patients with 41 small GGOs who underwent intraoperative CT-guided double-thorn hook wire localization prior to video-assisted thoracoscopic wedge resection from October 2009 to October 2013 were retrospectively reviewed. All patients received video-assisted thoracoscopic surgery (VATS) within 10 min atfer wire localiza-tion. hTe effcacy of intraoperative localization was evaluated in terms of procedure time, VATS success rate, and associated complications of localization.Results A total of 32 patients (15 males and 17 females) underwent 41 VATS resections, with 2 simultaneous nodule resections performed in 3 patients, 3 lesion resections in 1 patient, and 5 lesions in a patient. Nodule di-ameters ranged from 2 mm-10 mm (mean: 5 mm). hTe distance of lung lesions from the nearest pleural surfaces ranged within 5 mm-24 mm (mean: 12.5 mm). All resections of lesions guided by the inserted hook wires were successfully performed by VATS (100% success rate). hTe mean procedure time for the CT-guided hook wire localization was 8.4 min (range: 4 min-18 min). hTe mean procedure time for VATS was 32 min (range: 14 min-98 min). hTe median hospital time was 8 d (range: 5 d-14 d). Results of pathological examination revealed 28 primary lung cancers, 9 atypical adenomatous hyperplasia, and 4 nonspe-ciifc chronic inlfammations. No major complication related to the intraoperative hook wire localization and VATS was noted. Conclusion Intraoperative CT-guided hook wire localization is useful, particularly in small GGO localization in VATS wedge resection and has a signiifcantly low rate of minor complications. Lung GGOs carry a 90% risk of malignancy. Aggressive surgi-cal resection of these GGOs is necessary and feasible through the guidance of intraoperative CT localization technique.

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