1.Ablation of macrophage transcriptional factor FoxO1 protects against ischemia-reperfusion injury-induced acute kidney injury.
Yao HE ; Xue YANG ; Chenyu ZHANG ; Min DENG ; Bin TU ; Qian LIU ; Jiaying CAI ; Ying ZHANG ; Li SU ; Zhiwen YANG ; Hongfeng XU ; Zhongyuan ZHENG ; Qun MA ; Xi WANG ; Xuejun LI ; Linlin LI ; Long ZHANG ; Yongzhuo HUANG ; Lu TIE
Acta Pharmaceutica Sinica B 2025;15(6):3107-3124
Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.
2.Perifornical UCN3 Neurons Regulate Overeating-Induced Weight Gain.
Shanshan LU ; Xinran ZHANG ; Wanqi CHEN ; Baofang ZHANG ; Haiyang JING ; Yunlong XU ; Fengling LI ; Chenyu JIANG ; Gaowei CHEN ; Xiaofei DENG ; Yingjie ZHU
Neuroscience Bulletin 2025;41(6):1103-1108
3.Mechanism study of lncRNA SNHG1/miR-340-5p/PTX3 signaling pathway in osimertinib resistance of lung cancer
Lu ZHANG ; Wenli ZHAO ; Lingwen HE ; Chenyu XU
International Journal of Laboratory Medicine 2025;46(14):1758-1763
Objective To explore the mechanism of the long non-coding RNA(lncRNA)small nucleolar RNA host gene 1(SNHG1)/microRNA(miR)-340-5p/pentraxin 3(PTX3)signaling pathway in osimertinib resistance of lung cancer.Methods The expression levels of SNHG1,miR-340-5p and PTX3 in lung cancer tissues,adjacent tissues and osimertinib-sensitive and resistant cell lines were detected by real-time fluores-cence quantitative PCR.SNHG1 was knockdown using siRNA to detect its effects on cell proliferation,apopto-sis and osimertinib sensitivity.The dual-luciferase reporter assay verified the binding relationship between SNHG1 and miR-340-5p,as well as between miR-340-5p and PTX3.Western blotting was used to analyze the expression changes of PTX3 protein.Results SNHG1 was highly expressed in lung cancer tissues and osimer-tinib-resistant cells,while the expression of miR-340-5p was downregulated.SNHG1 inhibits the function of miR-340-5p by directly binding to it and releases the negative regulation of miR-340-5p on PTX3,resulting in the high expression of PTX3 in lung cancer drug-resistant cells.Knockdown of SNHG1 can increase the apop-tosis rate of drug-resistant cells,inhibit the ability of colony formation,and enhance the sensitivity of cells to osimertinib.The miR-340-5p inhibitor upregulated the expression of PTX3 in lung cancer sensitive cells.Con-clusion SNHG1 as competitive endogenous RNA inhibition of miR-340-5p,thus raising PTX3 expression,the drug resistance of lung cancer cells,SNHG1/miR-340-5p/PTX3 shaft may provide potential targets in the treatment of lung cancer drug resistance.
4.Overexpression of the cell growth regulator 1 with EF-hand domains inhibits the malignant behavior of colorectal cancer cells by suppressing the mitogen-activated protein kinase pathway
Changhui JI ; Yayan FU ; Jun REN ; Qiannan SUN ; Chenyu LU ; Daorong WANG
International Journal of Surgery 2025;52(5):332-338
Objective:To explore the effects and potential mechanisms of cell growth regulator 1 ( CGREF1) with an EF hand domain in colorectal cancer proliferation and migration. Methods:Fifty paraffin specimens of colorectal cancer tissues and corresponding paracancerous tissues were selected from January 2023 to January 2024 from the Northern Jiangsu People's Hospital Affiliated to Yangzhou University for analysis, and TCGA, GDSC, KMPLOT and STRING databases were used to explore the expression, prognosis, immune microenvironment, drug sensitivity and related signaling pathway functions of CGREF1 in colorectal cancer. Tissue and cellular expression levels of CGREF1 were analyzed by immunohistochemistry and qRT-PCR. Lentiviral-mediated CGREF1 overexpression in SW-620 cells (OE- CGREF1 vs NC groups) was functionally characterized through CCK-8 proliferation assays, colony formation tests, and scratch wound healing migration assays, with mechanistic investigation via Western blot analysis of apoptosis markers, invasion-related proteins, and RAS/RAF/ERK pathway components. In vivo tumorigenicity was assessed by subcutaneous injection of control or CGREF1-overexpressing SW620 cells in nude mice ( n=3 per group) with tumor growth monitoring. Software of GraphPad Prism 9 was used for statistical analysis of experimental data. Results:CGREF1CGREF1RASERK Studies based on databases, clinical samples and colorectal cancer cell line analyses demonstrated that CGREF1 is downregulated in colorectal cancer, where low CGREF1 expression showed positive correlation with tumor diameter and invasion depth. CGREF1 is closely related to tumor immune infiltration microenvironment and sensitivity to multiple anti-tumor drugs. Overexpression of CGREF1 promoted cell apoptosis while inhibiting cell proliferation, invasion and migration. Overexpression of CGREF1 downregulated the expression levels of RAS, ERK and P-P38/MAPK pathway proteins. CGREF1 inhibited tumor growth in vivo. Conclusion:CGREF1 can inhibit the proliferation, colony formation, and migration of CRC cells through the RAS/ERK/MAPK pathway.
5.Monitoring and analysis of iodine nutrition status among children aged 8 - 10 years in Shenzhen
Chenyu Zhou ; Yang Chen ; Lu Zhu ; Lingquan Kong ; Lan Zhuo ; Zhou Wang ; Xianru Luo ; Jiayi Song ; Jianqing Zhang
Acta Universitatis Medicinalis Anhui 2025;60(12):2333-2337,2345
Objective:
To investigate the iodine nutrition status of children aged 8-10 in Guangming, Longhua and Yantian District of Shenzhen in 2023, and to explore the influencing factors of thyroid volume. To evaluate prevention strategies and to provide a scientific basis for the elimination of iodine deficiency disorders.
Methods:
Urine and household salt samples were randomly collected from 580 non-boarding students aged 8-10 years foriodine content detection. Thyroid volume was measured using a fully digital ultrasound imaging system, and goiter prevalence was calculated.
Results:
A total of 580 samples was tested. The median salt iodine concentration was 23.86 mg/kg, with 93.62% qualified iodized salt and 94.48% coverage rate. The median of urinary iodine was 265.00 μg/L, mainly distributed between 200 - < 300 μg/L and ≥300 μg/L. The proportion of children with ap⁃ propriate iodine was 20. 86% , and the proportion of children with insufficient or excessive urinary iodine levels was 10. 86% and 68. 28% of the total surveyed population , respectively. The median thyroid volume was 3. 27 mL , and the goiter rate was 1. 72% . Multiple linear regression analysis showed that age was the risk factor for thyroid volume (8=0 328, P<0.05). while urinary iodine was the protective factor for thyroid volume(B=-4.134x10-4,P<0.05).
Conclusion
The qualified iodized salt rate, median of urinary iodine,and goiter prevalence of 580 children aged 8 - 10 meet the elimination criteria for iodine deficiency disorders. Age and urinary iodine are closely related to thyroid volume change. The urinary iodine level of children is generally high and requires serious attention.
6.Disease burden and three-grade prevention of cancer in China
Chenyu LUO ; Yueyang ZHOU ; Na LI ; Jiahui LUO ; Yuhan ZHANG ; Bin LU ; Hongda CHEN ; Min DAI
Chinese Journal of Epidemiology 2024;45(5):621-625
Cancer is one of the leading causes of morbidity and mortality worldwide. Due to population aging, lifestyle variation and other factors, the morbidity and mortality of cancer continue to rise in China, resulting in a serious public health problem threating people's health. In response to this increasingly serious problem, tremendous efforts have been made in China, including the development of a series of policies and measures for specific needs of cancer prevention and treatment. Currently, China's strategy to reduce the disease burden of cancer mainly focuses on primary and secondary prevention. This paper summarizes the current status of disease burden of cancer and the performance of three-grade cancer prevention in China.
7.Research progress on dietary patterns and cancer etiology
Jiahui LUO ; Chenyu LUO ; Yuhan ZHANG ; Bin LU ; Na LI ; Yueyang ZHOU ; Kai SONG ; Dong WU ; Min DAI ; Hongda CHEN
Chinese Journal of Preventive Medicine 2024;58(3):370-380
In recent years, the incidence of cancer in China has been increasing steadily. Advancing primary prevention measures for cancers could be an effective strategy to curb this trend. Diet has been considered a modifiable and shared risk factor for various cancers. Studying dietary patterns, with consideration of the interactions between foods and nutrients, has a practical implication for cancer prevention. This study provided an overview of dietary pattern extraction methods, summarized the research findings on the association between dietary patterns and cancers in the digestive system, respiratory system, and genitourinary system, and elucidated the potential mechanisms underlying these associations, in order to provide scientific references for future research in this field.
8.Research progress on dietary patterns and cancer etiology
Jiahui LUO ; Chenyu LUO ; Yuhan ZHANG ; Bin LU ; Na LI ; Yueyang ZHOU ; Kai SONG ; Dong WU ; Min DAI ; Hongda CHEN
Chinese Journal of Preventive Medicine 2024;58(3):370-380
In recent years, the incidence of cancer in China has been increasing steadily. Advancing primary prevention measures for cancers could be an effective strategy to curb this trend. Diet has been considered a modifiable and shared risk factor for various cancers. Studying dietary patterns, with consideration of the interactions between foods and nutrients, has a practical implication for cancer prevention. This study provided an overview of dietary pattern extraction methods, summarized the research findings on the association between dietary patterns and cancers in the digestive system, respiratory system, and genitourinary system, and elucidated the potential mechanisms underlying these associations, in order to provide scientific references for future research in this field.
9.Compositional Analysis and Antitumor Activity of Aqueous Extracts of Polygonatum Cyrtonema Hua
Lu SONG ; Chunye GENG ; Chenyu XING ; Qian WANG ; Yaoyao GUO ; Yanjun CHEN ; Fang WANG ; Guosi LI ; Wei WANG ; Leilei GAO ; Dong LIU ; Bangxing HAN
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(7):952-962
Objective To analyze the composition of the aqueous extract of Polygonatum Cyrtonema Hua(PCHE)and evaluate its antitumor activity in vitro and in vivo.Our aim is to provide a theoretical basis for the further development and utilization of Polygonatum Cyrtonema Hua.Methods(1)PCHE was prepared by aqueous extraction,and the chemical composition of PCHE was analyzed by UPLC-Q-TOF/MS and phenol-sulfuric acid method.The inhibitory activity on tumor cells proliferation of PCHE was detected by CCK-8 assay.Cell cycle and apoptosis were detected by flow cytometry,and the expression of apoptosis-related proteins Bcl-2 and Bax was detected by Western Blot.The inhibitory activity of PCHE-containing serum on cell proliferation was detected.(2)A B16 tumor-bearing mice model was constructed and model mice were randomly divided into the model group(saline),the positive drug group(CTX:50 mg·kg-1),and PCHE low-,medium-,and high-dose groups(55.9,111.8,223.6 mg·kg-1),and treated by gavage for 7 days.Changes in body weight and tumor volume of mice were observed during the treatment period.The mice were executed after the treatment,and the histopathological changes of heart,liver,spleen,lung,kidney and tumor were observed by hematoxylin-eosin(HE)staining.The protein expression of Bcl-2 and Bax in tumor tissues was detected by immunohistochemistry(IHC).Results The polysaccharide content of PCHE reached(10.07±1.3)%,and the flavonoid content was(0.044±0.004)%,and thirty-nine components were detected by UPLC-Q-TOF/MS,which contained antitumor components such as flavonoids(baicalein,quercetin,luteolin and rutin),organic acids(ferulic acid)and polyphenols(gallic acid),etc.PCHE exhibited the inhibitory effects on Hela,A549,4T1,B16,MFC and HepG2 cells,among which the inhibitory effect on B16 cells was the most significant(P<0.001),and PCHE induced cell cycle arrest at G0/G1 phase in B16 cells(P<0.001).The results of double-staining flow cytometry and Western Blot showed that PCHE significantly promoted apoptosis of B16 cells,decreased the expression of Bcl-2,and promoted the expression of Bax(P<0.01,P<0.001).and PCHE constituents absorbed into blood also had an inhibitory effect on B16 cells(P<0.001).In addition,the results of in vivo activity assay showed that different doses of PCHE could inhibit tumor growth,induce tumor cell necrosis,reduce Bcl-2 expression,and increase Bax expression compared with the model group.Conclusion The ingredients in PCHE are abundant.It contains a variety of antitumor active ingredients,which can inhibit tumor growth,induce tumor cell apoptosis,show strong anti-tumor effects and be worthy of in-depth study.
10.Changes of choroidal biomarkers in patients with central serous chorioretinopathy
Pei LIU ; Guangqi AN ; Chenyu LU ; Shu LI ; Liping DU ; Xuemin JIN
Chinese Journal of Ocular Fundus Diseases 2023;39(4):290-296
Objective:To quantitatively evaluate the changes of choroidal biomarkers in patients with central serous chorioretinopathy (CSC) and preliminarily explore its pathogenesis.Methods:Clinical cross-sectional study. From July 2021 to December 2022, 74 eyes of 65 patients with CSC (CSC group) confirmed by ophthalmic examination at the First Affiliated Hospital of Zhengzhou University were included in the study. Among them, 46 patients (51 eyes) were male, 19 patients (23 eyes) were female. The duration from the onset of symptoms to the time of treatment was less than or equal to 3 months. A control group consisted of 40 healthy volunteers (74 eyes) matched in age and gender. Among them, 26 patients (50 eyes) were male, and 14 patients (24 eyes) were female. Using VG200D from Microimaging (Henan) Technology Co., Ltd., macular scanning source light coherence tomography angiography was performed, with scanning range 6 mm × 6 mm. According to the division of the diabetes retinopathy treatment research group, the choroid within 6 mm of the macular fovea was divided into three concentric circles centered on the macular fovea, namely, the central area with a diameter of 1 mm, the macular area with a diameter of 1-3 mm, and the surrounding area of the fovea with a diameter of 3-6 mm. The device comes with software to record the three-dimensional choroidal vascular index (CVI), choroidal vascular volume (CVV), perfusion area of the choroidal capillary layer (CFA), choroidal thickness (CT), and three-dimensional CVI, CVV, and CT in the upper, temporal, lower, and subnasal quadrants within 6 mm of the fovea. Quantitative data between the two groups were compared using an independent sample t-test. Qualitative data comparison line χ2 inspection. The value of receiver operating curve (ROC) analysis in predicting the occurrence of CSC, including CVI, CVV, CFA, and CT. Results:Compared with the control group, the CVI ( t=3.133, 4.814), CVV ( t=7.504, 9.248), and CT ( t=10.557, 10.760) in the central and macular regions of the affected eyes in the CSC group significantly increased, while the CFA ( t=-8.206, -5.065) significantly decreased, with statistically significant differences ( P<0.05); CVI ( t=7.129), CVV ( t=10.020), and CT ( t=10.488) significantly increased within 6 mm of the central fovea, while CFA ( t=-2.548) significantly decreased, with statistically significant differences ( P<0.05). The CVI ( t=4.980, 4.201, 4.716, 8.491), CVV ( t=9.014, 7.156, 7.719, 10.730), and CT ( t=10.077, 8.700, 8.960, 11.704) in the upper, temporal, lower, and lower nasal quadrants within 6 mm of the central fovea were significantly increased, with statistically significant differences ( P<0.05). In the CSC group, the maximum CVI and CVV were (0.39±0.10)% and (1.09±0.42) mm 3, respectively, on the nasal side of the affected eye. Upper CT was (476.02±100.89) μm. The nasal side CVI, CVV, and CT have the largest changes. The ROC curve analysis results showed that the area under the curve of CT, CVV, and CVI within 6 mm of the central region, macular region, and fovea was over than 0.5. Subcentral CT was the most specific for the diagnosis of CSC. Conclusion:Choroidal biomarkers CVI, CVV, and CT in CSC patients increase, while CFA decreases. Central CT is the most specific for the diagnosis of CSC.


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