1.SiO2 Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model
Wang YONGHENG ; Li NING ; Guan YI ; LI TONG ; Zhang YUXIU ; Cao HONG ; Yu ZHIHUA ; Li ZHIHENG ; Li SHUOYAN ; Hu JIAHAO ; Zhou WENXIN ; Qin SISI ; Li SHUANG ; Yao SANQIAO
Biomedical and Environmental Sciences 2024;37(6):617-627
Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed. Results SiO2 altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO2-induced mitochondrial damage and myocardial injury.SiO2 inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion Iron overload-induced ferroptosis contributes to SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.
2.Comparison of nitrification inhibitors for mitigating cadmium accumulation in pakchoi and their associated microbial mechanisms
DU WENXIN ; ZHU QINGYANG ; JING XIANGTING ; HU WEIJIE ; ZHUANG YAO ; JIANG YIJIE ; JIN CHONGWEI
Journal of Zhejiang University. Science. B 2024;25(9):773-788
The use of nitrification inhibitors has been suggested as a strategy to decrease cadmium(Cd)accumulation in crops.However,the most efficient nitrification inhibitor for mitigating crop Cd accumulation remains to be elucidated,and whether and how changes in soil microbial structure are involved in this process also remains unclear.To address these questions,this study applied three commercial nitrification inhibitors,namely,dicyandiamide(DCD),3,4-dimethylpyrazole phosphate(DMPP),and nitrapyrin(NP),to pakchoi.The results showed that both DCD and DMPP(but not NP)could efficiently decrease Cd concentrations in pakchoi in urea-and ammonium-fertilized soils.In addition,among the three tested nitrification inhibitors,DMPP was the most efficient in decreasing the Cd concentration in pakchoi.The nitrification inhibitors decreased pakchoi Cd concentrations by suppressing acidification-induced Cd availability and reshaping the soil microbial structure;the most effective nitrification inhibitor was DMPP.Ammonia oxidation generates the most protons during nitrification and is inhibited by nitrification inhibitors.Changes in environmental factors and predatory bacterial abundance caused by the nitrification inhibitors changed the soil microbial structure and increased the potential participants in plant Cd accumulation.In summary,our study identified DMPP as the most efficient nitrification inhibitor for mitigating crop Cd contamination and observed that the soil microbial structural changes caused by the nitrification inhibitors contributed to decreasing Cd concentration in pakchoi.
3.Canagliflozin Ameliorates Nonalcoholic Fatty Liver Disease by Regulating Lipid Metabolism and Inhibiting Inflammation through Induction of Autophagy
Zhipeng XU ; Wenxin HU ; Bin WANG ; Ting XU ; Jianning WANG ; Dan WEI
Yonsei Medical Journal 2022;63(7):619-631
Purpose:
Nonalcoholic fatty liver disease (NAFLD) is closely associated with metabolic diseases, including obesity and diabetes, and has gradually become the most common cause of chronic liver disease. We investigated the effects of sodium glucose cotransporter 2 (SGLT2) inhibitor canagliflozin on NAFLD in high-fat diet (HFD)-induced obese mice and possible underlying mechanisms.
Materials and Methods:
Male C57BL/6 mice were fed a normal-diet, HFD, or HFD with canagliflozin for 14 weeks. AML-12 hepatocytes were treated with canagliflozin. Expression of related pathways was assessed.
Results:
Canagliflozin administration reduced body weight and fat mass, compared with HFD alone. Canagliflozin improved glucose and lipid metabolic disorders. Compared with HFD-fed mice, liver weight, serum alanine transaminase (ALT) levels, and hepatic lipid accumulation were decreased after canagliflozin administration. Additionally, canagliflozin upregulated lipolysis markers (CPT1a, ACOX1, and ACADM), downregulated lipogenesis markers (SREBP-1c and FASN), and suppressed the production of inflammatory cytokines (TNFα, MCP1, IL-1β, and IL-6), consistent with significantly increased LC3 II/I and Atg7 levels in the liver following canagliflozin treatment. In vitro, canagliflozin increased CPT1a, ACOX1, and ACADM expression, decreased SREBP-1c and FASN protein expression, and reduced TNFα, MCP1, IL-1β, and IL-6 mRNA levels in lipid mixture (LM)-induced hepatocytes in a dose-dependent manner. These changes were reversed by 3-MA, an autophagy inhibitor.
Conclusion
Our findings suggest that canagliflozin ameliorates the pathogenesis of NAFLD by regulating lipid metabolism and inhibiting inflammation, which may be associated with its promotion of autophagy.
4.Comparison of segmentectomy versus lobectomy for ≤2 cm lung adenocarcinoma with micropapillary and solid subtype negative by intraoperative frozen sections: A multi-center randomized controlled trial
Chang CHEN ; Yuming ZHU ; Gening JIANG ; Haifeng WANG ; Dong XIE ; Hang SU ; Long XU ; Deping ZHAO ; Liang DUAN ; Boxiong XIE ; Chunyan WU ; Likun HOU ; Huikang XIE ; Junqiang FAN ; Xuedong ZHANG ; Weirong SHI ; Honggang KE ; Lei ZHANG ; Hao WANG ; Xuefei HU ; Qiankun CHEN ; Lei JIANG ; Wenxin HE ; Yiming ZHOU ; Xiong QIN ; Xiaogang ZHAO ; Hongcheng LIU ; Peng ZHANG ; Yang YANG ; Ming LIU ; Hui ZHENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(11):1292-1298
Objective To compare the clinical effects of segmentectomy and lobectomy for ≤2 cm lung adenocarcinoma with micropapillary and solid subtype negative by intraoperative frozen sections. Methods The patients with adenocarcinoma who received segmentectomy or lobectomy in multicenter from June 2020 to March 2021 were included. They were divided into two groups according to a random number table, including a segmentectomy group (n=119, 44 males and 75 females with an average age of 56.6±8.9 years) and a lobectomy group (n=115, 43 males and 72 females with an average of 56.2±9.5 years). The clinical data of the patients were analyzed. Results There was no significant difference in the baseline data between the two groups (P>0.05). No perioperative death was found. There was no statistical difference in the operation time (111.2±30.0 min vs. 107.3±34.3 min), blood loss (54.2±83.5 mL vs. 40.0±16.4 mL), drainage duration (2.8±0.6 d vs. 2.6±0.6 d), hospital stay time (3.9±2.3 d vs. 3.7±1.1 d) or pathology staging (P>0.05) between the two groups. The postoperative pulmonary function analysis revealed that the mean decreased values of forced vital capacity and forced expiratory volume in one second percent predicted in the segmentectomy group were significantly better than those in the lobectomy group (0.2±0.3 L vs. 0.4±0.3 L, P=0.005; 0.3%±8.1% vs. 2.9%±7.4%, P=0.041). Conclusion Segmentectomy is effective in protecting lungs function, which is expected to improve life quality of patients.
5.Trajectories of body mass index Z-score and risk of high blood pressure in late adolescence in Suzhou children
Wenxin GE ; Weiliang TAN ; Haoyue TENG ; Hui SHEN ; Di HAN ; Yue XIAO ; Jieyun YIN ; Jia HU
Chinese Journal of Epidemiology 2021;42(10):1809-1816
Objective:To identify age and gender standardized body mass index among children and adolescents and explore their associations with high blood pressure (HBP) in late adolescence.Methods:The current study was based on the Health Promotion Program for Children and Adolescents, school-based surveillance successively conducted from 2012 to 2019 in Suzhou, China. A total of 11 812 children and adolescents aged 16-18 years, who had ≥4 examination records during 2012-2018 and were also involved in a surveillance program in 2019, were included. Latent class growth mixture modeling was used to identify the BMI-Z trajectories in different genders, and multivariate logistic regression was used to analyze the associations between different BMI-Z trajectories and risk of HBP in late adolescence.Results:Six distinct BMI-Z trajectories were determined for both genders:thin, slightly thin,standard, declining, overweight, and obese. Compared with the regular group, the obesity group had 94.0% ( OR=1.94, 95% CI: 1.43-2.63) and 107.0% ( OR=2.07, 95% CI: 1.33-3.22) increased risk of developing HBP in late adolescence in boys and girls, respectively. However, a neutral association was found between the descending group and HBP in late adolescence. Conclusions:Persistent obesity in children may increase the risk of HBP in their late adolescence. If an obese child restores normal weight before late adolescence, the risk of HBP may reduce.
6.Preparation of anti-GPC3 single chain antibody for targeted detection of hepatocellular carcinoma.
Xinchu XIANG ; Xue LIU ; Yaokai HU ; Chengjun ZHAO ; Wenxin LUO
Chinese Journal of Biotechnology 2020;36(12):2860-2867
Glypican-3 (GPC3) is a key member of Glypican family and plays an important role in the development, angiogenesis and metastasis of hepatocellular carcinoma (HCC). Most HCC overexpresses GPC3, but GPC3 is hardly detected in normal adult liver and benign liver lesions, so it is regarded as a highly specific diagnostic marker and an ideal therapeutic target for HCC. In this study, we cloned the heavy and light chain variable region gene from the monoclonal antibody targeted to GPC3 screened in the previous stage, and linked it with a segment of flexible peptide (Linker) to obtain the single chain antibody against GPC3. The single chain antibody gene was cloned into vector for prokaryotic expression and purified to obtain high purity protein. Detection shows that the single-chain antibody produced by us has the same binding activity with the full-length antibody, and can accurately target the tumor site of Huh7 tumor-bearing model mice after coupling Cy5.5 fluorescence, suggesting that the single-chain antibody has the potential to realize multi-directional liver cancer precise surgical navigation under the guidance of a probe.
Animals
;
Antibodies, Monoclonal
;
Carcinoma, Hepatocellular/genetics*
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Glypicans/genetics*
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Liver Neoplasms/diagnosis*
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Mice
7.Analysis of blood free carnitine levels in preterm infants with respiratory distress syndrome
Wenxin WEI ; Hua MEI ; Linlin LI ; Chunli LIU ; Yanan HU ; Yaqin ZHOU ; Yanbo ZHANG
Chinese Pediatric Emergency Medicine 2020;27(10):726-729
Objective:The blood free carnitine levels of preterm infants with neonatal respiratory distress syndrome (NRDS) were detected within 7 days after birth, and the correlation between blood free carnitine levels and NRDS in preterm infants was explored.Methods:Seventy premature infants with gestational ages from 28 to 36 weeks who were admitted to the NICU of the Affiliated Hospital of Inner Mongolia Medical University from January 1, 2017 to December 31, 2019 were selected as the participants.Among them, 35 cases were in the NRDS group, while 35 cases of premature infants without NRDS were chosen as the control group.Heel blood samples were collected from all subjects within 6 hours, 3 days and 7 days after birth, and the levels of blood free carnitine were detected by tandem mass spectrometry.Results:Within 7 days after birth, the levels of free carnitine in blood of premature infants in the two groups gradually decreased with time, but the decreasing trend was not similar( F=4.096, P=0.021). Compared with 6 hours after birth, the blood free carnitine level in NRDS group decreased significantly with 3 days after birth[(35.24±9.58) μmol/L vs.(23.96±7.12) μmol/L, P<0.05]. The levels of blood free carnitine in NRDS group at 6 hours and 3 days after birth were significantly lower than those in control group[(35.24±9.58) μmol/L vs.(40.85±11.39) μmol/L; (23.96±7.12) μmol/L vs.(29.60±8.05) μmol/L, P<0.05]. There was no significant difference in blood free carnitine levels between the two groups at 7 days after birth ( P>0.05). Conclusion:The blood free carnitine levels of premature infants decreased within 7 days after birth.The decrease of carnitine level in premature infants with NRDS may be related to the occurrence and development of NRDS.
8.Integrin β1 in Adipose-Derived Stem Cells Accelerates Wound Healing via Activating PI3K/AKT Pathway
Qihong WANG ; Na ZHANG ; Lihua HU ; Yong XI ; Wenxin MI ; Yindong MA
Tissue Engineering and Regenerative Medicine 2020;17(2):183-192
Background:
This study aims to investigate the effect of integrin β1 on wound healing induced by adipose-derived stem cells (ADSCs), as well as the corresponding mechanism.
Methods:
Integrin β1 was overexpressed in ADSCs. Thereafter, flow cytometry and transwell chambers technology were used to measure the endothelial-like differentiation (CD31 as a biomarker of endothelial cell) and cell migration, respectively. Western blot was used to detect the activation of PI3K/AKT, NF-κB and ERK signaling pathways. The effects of integrin β1 overexpression on healing time, healing rate and fibroblast number were further evaluated in the rat models of chronic refractory wound.
Results:
The overexpression of integrin β1 increased CD31+ endothelial-like cells (about 3.6-fold), promoted cell migration (about 1.9-fold) and enhanced the activation of PI3K (p-PI3K; about 2.1-fold) and AKT (p-AKT; about 2.2-fold). These effects were all weakened when PI3K/AKT pathway was inhibited by LY294002 treatment. In addition, the experiments in rat wound models showed that integrin β1 overexpression obviously shortened healing time (approximately 0.41-fold), increased healing rate (about 2.7-fold, 2.8-fold and 1.6-fold at day 7, 14 and 21) and increased the number of fibroblasts (approximately 3.1-fold at day 21). All of the above differences were statistically significant (p < 0.05).
Conclusion
Integrin β1 can promote the migration and endothelial-like differentiation of ADSCs by activating PI3K/AKT pathway and then enhance the function of ADSCs in promoting wound healing.
9. Study of the subcortical cerebral blood flow metabolism in patients with Parkinson′s disease using arterial spin labeling magnetic resonance imaging
Hongying ZHANG ; Jingtao WU ; Jing YE ; Wenxin CHEN ; Yao XU ; Meng WANG ; Huixian SHI ; Yue HU ; Jun XU ; Weiqiang DOU
Chinese Journal of Neurology 2019;52(9):739-744
Objective:
To investigate alterations of blood perfusion in subcortical regions in patients with Parkinson′s disease (PD) by three dimentional arterial spin labeling (ASL) magnetic resonance imaging (MRI).
Methods:
Thirty patients with PD and 40 control subjects were recruited from the inpatient and outpatient of the Department of Neurology of Northern Jiangsu People′s Hospital during October 2014 to October 2016, and routine brain MRI and 3D pseudo-continuous pulse ASL were performed on all the subjects. The cerebral blood flow (CBF) maps derived from 3D ASL were coregistered to the Montreal Neurological Institute brain space. The stereo-templates of bilateral caudate nucleus, putamen nucleus, globus pallidum and thalamus from Anatomical Automatic Labeling were used as region of interest (ROI) to exstract absolute CBF values in these subcortical regions, respectively. The CBF ratio (rCBF) values represented by individual whole brain CBF divided by each of the regional CBF were also calculated in consideration of the difference between individual whole brain CBF. The CBF and rCBF values were compared respectively between groups by one-way analysis of variance.
Results:
The subcortical CBF values (ml·100 g-1·min-1) for each ROI in PD (caudate nucleus (left: 35.32±6.47, right: 36.17±7.07), globus pallidum (left: 40.42±5.83, right: 40.18±5.70), putamen nucleus (left: 41.97±6.12, right: 42.91±6.43) and thalamus (left: 46.58±7.71, right: 49.11±7.10)) were significantly lower than that in the control group (caudate nucleus (left: 41.38±7.05, right: 41.63±6.85), globus pallidum (left: 45.65±8.35, right: 45.53±8.94), putamen nucleus (left: 48.49±8.78, right: 48.99±8.88) and thalamus (left: 54.32±11.94, right: 56.21±11.98),
10.Evaluation of immediate effectiveness of intervention on HIV prevention and leadership of POL among young male students who have sex with men in a city
ZHANG Wenjing, GAO Disi, CHEN Tianqi, CUI Wenxin, HU Yifei, MA Yinghua
Chinese Journal of School Health 2019;40(5):687-691
Objective:
To evaluate the immediate effectiveness of intervention on HIV prevention and leadership of POL among young male students who have sex with men in a city, and to provide reference for health education of AIDS.
Methods:
A life-skills based participatory approach was adopted to intervene the AIDS prevention and leadership of 54 POL in young male students who have sex with men in a city. A unified questionnaire was adopted before and after the intervention to investigate and evaluate the effects.
Results:
After intervention, the scores of AIDS prevention information increased from (36.30±7.30) points to (42.09±3.43) points (P<0.01). In terms of motivation, the scores of experience and attitude of condom-using were increased from (5.43±1.19) points to (5.83±1.24) points (P<0.05). As for the behavioral skills, the scores of condom-use skills increased from (4.30±1.04) points to (4.85±0.53) points (P<0.01), the scores of condom self-efficacy increased from (55.85±12.40) points to (61.48±8.01) points (P<0.01), the scores of autonomic HIV testing ability increased from (4.11±1.09) points to (4.65±0.52) points (P<0.01), the ability to avoid alcohol consumption before sexual behavior increased from (3.74±1.19) points to (4.13±0.91) points(P<0.05), and the ability to correctly seek medical advice after illness increased from (9.33±1.32) points to (9.69±0.77) points(P<0.05). In the part of the leadership, the scores of peer status increased from (26.96±5.55) points to (29.81±6.68) points (P<0.01), the scores of active communication ability increased from (21.35±5.76) points to (24.43±4.17) points (P<0.01), and the scores of psychosocial ability increased from (77.96±13.42) points to (80.89±12.42) points (P<0.05).
Conclusion
Life-skill-based intervention, which is guided by Information-Motivation-Behavioral skills model, is effective in improving AIDS prevention and leadership.


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