1.STAT3: A key molecule in the progression of liver cancer mediated by chronic inflammation
Jinping YIN ; Zichen YUE ; Shaoyuan ZHUO
Journal of Clinical Hepatology 2020;36(4):948-952
STAT3, a member of the signal transducer and activator of transcription family, is abnormally activated in chronic inflammation-related tumors including liver cancer. As a key signal molecule in the microenvironment of liver cancer and inflammation, STAT3 not only participates in the inflammation-cancer transformation during the development of liver cancer, but also promotes the proliferation, invasion, and metastasis of hepatoma cells through many ways, and therefore, it may be a potential target for the treatment of liver cancer. This article reviews the recent advances in the association between STAT3 and liver cancer.
2.The relationship between fluoride exposure, basal metabolic rate, body fat percentage, and grip strength among adults in rural areas with fluorosis of China
Xuanyin ZHANG ; Meng GUO ; Ruiqin CHEN ; Zichen FENG ; Meng YANG ; Xiaoxue LIU ; Fangfang YU ; Zhiyuan LI ; Yue BA ; Guoyu ZHOU
Chinese Journal of Endemiology 2024;43(1):29-34
Objective:To study the relationship between adult fluoride exposure and grip strength in rural areas of China with fluorosis, as well as the roles of basal metabolic rate (BMR) and body fat percentage (BFP) in the association between fluoride exposure and grip strength.Methods:From April to May 2017, a cluster sampling method was used to conduct a questionnaire survey, physical examination, and biological sample collection on residents aged 18 - 60 in Tongxu County, Kaifeng City, Henan Province (epidemic areas of drinking-water-borne fluorosis). A total of 1 168 subjects were included in the study, including 427 males and 741 females. The fluoride ion selective electrode method and the picric acid method were used to determine the concentrations of urine fluoride and urine creatinine, and the adjusted urine fluoride concentration (CUF) was calculated. BMR and BFP were measured by a bioelectrical impendence method, and the grip strength was measured by a Jamar grip dynamometer. The relationship between CUF, BMR, BFP and grip strength were analyzed using a generalized linear model regression. The mediation effect model was used to assess the mediating effect of BMR and BFP on the association between CUF and grip strength.Results:Female grip strength decreased by 0.28 kg ( P = 0.043) for every 1.00 mg/L increment in CUF. No similar association was found between the two in males ( P = 0.744). Regardless of gender stratification, BMR was positively correlated with grip strength ( P < 0.001). For every 1.00% increase in BFP, female grip strength decreased by 0.18 kg ( P = 0.043). The mediation effect model analysis results showed that the mediation effect ratios of BMR and BFP in the association between CUF and grip strength in female were 65.1% ( P < 0.001) and 8.4% ( P = 0.111), respectively. Conclusion:Fluoride exposure is associated with changes in female grip strength, and BMR changes play a partial mediating role in the association between fluoride exposure and female grip strength.
3.Study on Therapeutic Effects and Its Mechanism of Jianpi Yiqi Decoction on Liver Cancer Model Rats
Chao WANG ; Zichen YUE ; Jinping YIN ; Xiao JIANG ; Shaoyuan ZHUO
China Pharmacy 2021;32(19):2342-2346
OBJECTIVE:To explore the therap eutic effects and its mech anism of Jianpi yiqi decoction on diethylnitrosamine (DEN)induced liver cancer model rats. METHODS :Totally 80 male SD rats were divided into normal group ,model group , Nod-like receptor family 3(NLRP3)inhibition group (MCC950,4.5 mg/kg),caspase-1 inhibitory group (VX-765,4.5 mg/kg), Jianpi yiqi decoction low-dose ,medium-dose and high-dose groups (5.25,10.5,21 g/kg),with 10 rats in each group except for 20 rats in model group (10 of them were only used to judge whether modeling was successful ). Rats in each group were intraperitoneally injected with DEN (70 mg/kg)to induce liver cancer model ,except for the rats in normal group which were replaced by normal saline. After modeling ,normal group and model group were given normal saline intragastrically ;inhibitor groups were given relevant medicine intraperitoneally ;Jianpi yiqi decoction groups were given relevant medicine intragastrically , once a day ,for consecutive 4 weeks. After last administration ,histopathological morphology of liver tissue was observed. The contents of serum inflammatory factors TNF-α and IL-1β were detected. The expression of NLRP3 and programmed cell necrosis associated protein (ASC,pro-caspase-1,RIP1,RIP3 and MLKL )in liver tissue were detected. RESULTS :Compared with the normal group ,the hepatocytes of model group showed varying, degrees of steatosis ,enlarged nuclei ,lumpy,bleeding and necrosis,accompanied by proliferative foci and nodules. Liver 198086, tissue injury index ,serum content of TNF-α and IL-1β as well as the protein expression of NLRP 3,ASC,pro-caspase-1,RIP1,RIP3 and MLKL in liver tissue were significantly increased (P<0.05 or P<0.01). Compared with model 防治。E-mail:sherwin_zhuo@126.com group,there were still a large number of inflammatory cell infiltration in the liver tissue of rats in Jianpi yiqi decoction low-dose and medium dose groups ,while the inflammatory cell infiltration of rats in high-dose group and inhibitor groups decreased significantly ;the liver tissue injury index and above indexes levels in serum and liver tissue were decreased significantly (P<0.05 or P<0.01). CONCLUSIONS :Jianpi yiqi decoction shows therapeutic effect on liver cancer model rats ,the mechanism of which may be associated with down-regulating the expression of NLRP3 inflammasome and inhibiting programmed cell necrosis.
4.Do methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 polymorphisms modify changes in intelligence of school-age children in areas of endemic fluorosis?
Zichen FENG ; Ning AN ; Fangfang YU ; Jun MA ; Na LI ; Yuhui DU ; Meng GUO ; Kaihong XU ; Xiangbo HOU ; Zhiyuan LI ; Guoyu ZHOU ; Yue BA
Chinese Medical Journal 2022;135(15):1846-1854
BACKGROUND:
Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 ( MTHFD1 ) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with children's intelligence changes in endemic fluorosis areas has been rarely explored.
METHODS:
A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April to May in 2017. A total of 694 children aged 8 to 12 years were included in the study with the recruitment by the cluster sampling method. Urinary fluoride (UF) and urinary creatinine were separately determined using the fluoride ion-selective electrode and creatinine assay kit. Children were classified as the high fluoride group and control group according to the median of urinary creatinine-adjusted urinary fluoride (UF Cr ) level. Four loci of MTHFD1 were genotyped, and the Combined Raven's Test was used to evaluate children's intelligence quotient (IQ). Generalized linear model and multinomial logistic regression model were performed to analyze the associations between children's UF Cr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence.
RESULTS:
In the high fluoride group, children's IQ scores decreased by 2.502 when the UF Cr level increased by 1.0 mg/L (β = -2.502, 95% confidence interval [CI]:-4.411, -0.593), and the possibility for having "excellent" intelligence decreased by 46.3% (odds ratio = 0.537, 95% CI: 0.290, 0.994). Children with the GG genotype showed increased IQ scores than those with the AA genotype of rs11627387 locus in the high fluoride group ( P < 0.05). Interactions between fluoride exposure and MTHFD1 polymorphisms on intelligence were observed (Pinteraction < 0.05).
CONCLUSION
Our findings suggest that excessive fluoride exposure may have adverse effects on children's intelligence, and changes in children's intelligence may be associated with the interaction between fluoride and MTHFD1 polymorphisms.
Child
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Creatinine
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Cross-Sectional Studies
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Fluorides/urine*
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Formate-Tetrahydrofolate Ligase
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Humans
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Intelligence/genetics*
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Methylenetetrahydrofolate Dehydrogenase (NADP)
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Methylenetetrahydrofolate Reductase (NADPH2)