1.Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A
Junmei WANG ; Shuai HUANG ; Li ZHANG ; Yixian HE ; Xian SHAO ; A-Shan-Jiang A-NI-WAN ; Yan KONG ; Xuying MENG ; Pei YU ; Saijun ZHOU
Diabetes & Metabolism Journal 2025;49(3):421-435
Background:
In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes.
Methods:
The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments.
Results:
RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice.
Conclusion
RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.
2.Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A
Junmei WANG ; Shuai HUANG ; Li ZHANG ; Yixian HE ; Xian SHAO ; A-Shan-Jiang A-NI-WAN ; Yan KONG ; Xuying MENG ; Pei YU ; Saijun ZHOU
Diabetes & Metabolism Journal 2025;49(3):421-435
Background:
In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes.
Methods:
The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments.
Results:
RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice.
Conclusion
RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.
3.Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A
Junmei WANG ; Shuai HUANG ; Li ZHANG ; Yixian HE ; Xian SHAO ; A-Shan-Jiang A-NI-WAN ; Yan KONG ; Xuying MENG ; Pei YU ; Saijun ZHOU
Diabetes & Metabolism Journal 2025;49(3):421-435
Background:
In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes.
Methods:
The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments.
Results:
RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice.
Conclusion
RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.
4.Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A
Junmei WANG ; Shuai HUANG ; Li ZHANG ; Yixian HE ; Xian SHAO ; A-Shan-Jiang A-NI-WAN ; Yan KONG ; Xuying MENG ; Pei YU ; Saijun ZHOU
Diabetes & Metabolism Journal 2025;49(3):421-435
Background:
In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes.
Methods:
The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments.
Results:
RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice.
Conclusion
RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.
5.Identification of host proteins interacting with African swine fever virus inner envelope protein p17.
Guifang ZHONG ; Tingjuan DENG ; Kang XU ; Wenbi NI ; Pei WANG ; Boli HU ; Jiyong ZHOU
Chinese Journal of Biotechnology 2022;38(8):2883-2890
African swine fever virus (ASFV) infection leads to a mortality rate of up to 100%, causing devastating disasters to the pig industry. Understanding the ASFV infection and replication is therefore of great importance. ASFV has more than 150 open reading frames, among which the inner coat protein p17 encoded by the D117L gene is involved in the formation of the icosahedral structure of the virus. However, little is known about the mechanism how p17 regulates host cell function. In this study, the potential host proteins interacting with ASFV p17 were screened by immunoprecipitation technique combined with protein profiling analysis. The interactions of p17 with mitochondrial membrane protein TOMM70 and heat shock protein HSPA8 were confirmed by co-immunoprecipitation technique and laser confocal experiments. This study provides important information for further exploring the function of p17 during ASFV infection.
African Swine Fever
;
African Swine Fever Virus/metabolism*
;
Animals
;
Open Reading Frames
;
Swine
;
Viral Proteins/metabolism*
6.Identification of the bacteria strain and its antibiotic resistance in an epidemic of cholera
Xiao-hong ZHOU ; Pei-hua XU ; Yan-jing NI ; Jian CHI ; Xiao-wei ZHU
Shanghai Journal of Preventive Medicine 2021;33(2):128-
Objective The present study was conducted to identify the
7.Clinical features of 123 patients with hyperinsulinemic hypoglycemia auxiliarily diagnosed by 18F-DOPA-PET CT scanning
Miaoying ZHANG ; Jinwen NI ; Jingjie GE ; Yihui GUAN ; Zhou PEI ; Chengjun SUN ; Jing WU ; Zhenran XU ; Lin YANG ; Feihong LUO ; Ruoqian CHENG
Chinese Journal of Pediatrics 2021;59(10):853-858
Objective:To summarize the clinical features and therapeutic outcomes of patients with hyperinsulinemic hypoglycemia (HH) auxiliarily diagnosed by 18F-DOPA positron emission tomography (PET) CT scanning. Methods:The clinical data of 123 patients who were diagnosed with hyperinsulinemic hypoglycemia by comprehensive clinical diagnostic procedures in the Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children′s Hospital of Fudan University between January 2016 and December 2020 were retrospectively analyzed. Clinical data such as gender, age of onset, province, concurrent serum insulin level measured during hypoglycemia, lesion type of pancreas by 18F-DOPA-PET CT scanning, genetic test results, and treatment were collected successively. The clinical features and therapeutic outcomes were compared between patients with focal and diffuse pancreatic lesions. T test, Rank sum test, and χ2 test were used for comparison between groups. Results:A total of 123 patients with hyperinsulinemic hypoglycemia (72 males and 51 females), whose average age of onset was 3 days (ranging from 1 day to 4 860 days), were recruited from 24 provinces. The concurrent serum insulin level was 7.1 (0.4-303.0) mU/L during hypoglycemia. 18F-DOPA-PET CT scanning identified focal lesions in 25.2% (31/123) and diffuse lesions in 74.8% (92/123) of the patients; 64.2% (79/123) of the HH cases were found to have pathogenic gene variants, in which 88.6% (70/79) were found to have K ATP channel related genes (61 in ABCC8 and 9 in KCNJ11 mutations). Thirty-seven patients (17 focal and 20 diffuse) received surgical treatment with a success rate of 67.6% (25/37). The effective rate of diazoxide for children with diffuse type was significantly higher than that of children with focal group (28.3% (26/92) vs. 9.7% (3/31), χ2=10.31, P=0.001). Conclusions:18F-DOPA-PET CT scan can improve the success rate of surgery. Comprehensive diagnosis of the etiology of hyperinsulinemic hypoglycemia by genetic analysis and 18F-DOPA-PET CT scanning can result in better treatment and prognosis.
8. Study on the health literacy and related factors of the cancer prevention consciousness among urban residents in China from 2015 to 2017
Chengcheng LIU ; Chunlei SHI ; Jufang SHI ; Ayan MAO ; Huiyao HUANG ; Pei DONG ; Fangzhou BAI ; Yunsi CHEN ; Debin WANG ; Guoxiang LIU ; Xianzhen LIAO ; Yana BAI ; Xiaojie SUN ; Jiansong REN ; Li YANG ; Donghua WEI ; Bingbing SONG ; Haike LEI ; Yuqin LIU ; Yongzhen ZHANG ; Siying REN ; Jinyi ZHOU ; Jialin WANG ; Jiyong GONG ; Lianzheng YU ; Yunyong LIU ; Lin ZHU ; Lanwei GUO ; Youging WANG ; Yutong HE ; Peian LOU ; Bo CAI ; Xiaohua SUN ; Shouling WU ; Xiao QI ; Kai ZHANG ; Ni LI ; Wanghong XU ; Wuqi QIU ; Min DAI ; Wanqing CHEN
Chinese Journal of Preventive Medicine 2020;54(1):47-53
Objective:
To understand the health literacy and relevant factors of cancer prevention consciousness in Chinese urban residents from 2015 to 2017.
Methods:
A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The self-designed questionnaire was used to collect the information of demographic characteristics and cancer prevention consciousness focusing on nine common risk factors, including smoking, alcohol, fiber food, food in hot temperature or pickled food, chewing betel nut, helicobacter pylori, moldy food, hepatitis B infection, estrogen, and exercise. The logistic regression model was adopted to identify the influencing factors.
Results:
The overall health literacy of the cancer prevention consciousness was 77.4% (24 980 participants), with 77.4% (12 018 participants), 79.9% (6 406 participants), 77.2% (1 766 participants) and 74.5% (4 709 participants) in each group (
9. Analysis on the consciousness of the cancer early detection and its influencing factors among urban residents in China from 2015 to 2017
Ayan MAO ; Jufang SHI ; Wuqi QIU ; Chengcheng LIU ; Pei DONG ; Huiyao HUANG ; Kun WANG ; Debin WANG ; Guoxiang LIU ; Xianzhen LIAO ; Yana BAI ; Xiaojie SUN ; Jiansong REN ; Li YANG ; Donghua WEI ; Bingbing SONG ; Haike LEI ; Yuqin LIU ; Yongzhen ZHANG ; Siying REN ; Jinyi ZHOU ; Jialin WANG ; Jiyong GONG ; Lianzheng YU ; Yunyong LIU ; Lin ZHU ; Lanwei GUO ; Youqing WANG ; Yutong HE ; Peian LOU ; Bo CAI ; Xiaohua SUN ; Shouling WU ; Xiao QI ; Kai ZHANG ; Ni LI ; Min DAI ; Wanqing CHEN
Chinese Journal of Preventive Medicine 2020;54(1):54-61
Objective:
To understand the consciousness of the cancer early detection among urban residents and identify the influencing factors from 2015 to 2017.
Methods:
A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. Self-designed questionnaires were used to collect population, socioeconomic indicators, self-cancer risk assessment, regular participation in physical examination and other information. The multivariate logistic regression model was used to identify the factors of people who had not regularly participated in the regular physical examination in the past five years.
Results:
The self-assessment results of 32 357 residents showed that there were 27.54% (8 882) of total study population with self-reported cancer risk, 45.48% (14 671) without cancer risk and 26.98% (8 704) with unclear judgement on their own cancer risk. Among population with cancer risk, 79.84% (7 091) considered physical examination accounted. In the past five years, there were 21 105 (65.43%) residents participated in regular physical examination and 11 148 (34.56%) participated in non-scheduled one, respectively. The multivariate logistic regression analysis showed that compared with unmarried and western region residents, divorced, middle and eastern region residents had a stronger consciousness to participate in the regular physical examination (
10. Analysis on the consciousness of the early cancer diagnosis and its related factors among urban residents in China from 2015 to 2017
Xuan CHENG ; Pei DONG ; Jufang SHI ; Wuqi QIU ; Chengcheng LIU ; Kun WANG ; Huiyao HUANG ; Yana BAI ; Xiaojie SUN ; Debin WANG ; Guoxiang LIU ; Xianzhen LIAO ; Li YANG ; Donghua WEI ; Bingbing SONG ; Haike LEI ; Yuqin LIU ; Yongzhen ZHANG ; Siying REN ; Jinyi ZHOU ; Jialin WANG ; Jiyong GONG ; Lianzheng YU ; Yunyong LIU ; Lin ZHU ; Lanwei GUO ; Youqing WANG ; Yutong HE ; Peian LOU ; Bo CAI ; Xiaohua SUN ; Shouling WU ; Xiao QI ; Kai ZHANG ; Ni LI ; Jiansong REN ; Wanqing CHEN ; Min DAI ; Ayan MAO
Chinese Journal of Preventive Medicine 2020;54(1):62-68
Objective:
To understand the consciousness of the cancer early diagnosis among urban residents and identify the related factors from 2015 to 2017.
Methods:
A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The general demographic characteristics, the consciousness of the cancer early diagnosis (whether people would have a willingness or encourage their relatives/friends to confirm the abnormal results once which were detected from the physical examination) and other information were collected by using the self-designed questionnaire. The non-conditional logistic regression model was used to identify the relateol factors related to the consciousness of the cancer early diagnosis.
Results:
As for residents with abnormal result from the physical examination, 89.29% (28 802) of residents would choose to seek medical treatment for further diagnosis. If their relatives/friends had abnormal results from the physical examination, 89.55% (28 886) of residents would encourage their relatives/friends to confirm the diagnosis in time. The non-conditional logistic regression model analysis showed that compared with the public institution staff/civil servants, annual household income less than 20 000 CNY, the western region and the cancer risk assessment/screening intervention population, the company staff, annual household income about 40 000 CNY and more, and the residents from the middle and eastern region had a stronger consciousness to seek further diagnosis; while the unemployed residents and community residents were less likely to seek further diagnosis (

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