1.Therapeutic effect of fibroblast growth factor 21 on NAFLD in MSG-iR mice and its mechanism.
Shenglong ZHU ; Zhenyu ZHANG ; Guiping REN ; Xianlong YE ; Lei MA ; Dan YU ; Miaomiao HAN ; Jingzhuang ZHAO ; Tianyuan ZHANG ; Deshan LI
Acta Pharmaceutica Sinica 2013;48(12):1778-84
This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on NAFLD in MSG-IR mice and to provide mechanism insights into its therapeutic effect. The MSG-IR mice with insulin resistance were treated with high dose (0.1 micromol.kg-1d-1) and low dose (0.025 micromol.kg-1d-1) of FGF21 once a day for 5 weeks. Body weight was measured weekly. At the end of the experiment, serum lipids, insulin and aminotransferases were measured. Hepatic steatosis was observed. The expression of key genes regulating energy metabolism were detected by real-time PCR. The results showed that after 5 weeks treatment, both doses of FGF21 reduced body weight (P<0.01), corrected dyslipidemia (P<0.01), reversed steatosis and restored the liver morphology in the MSG model mice and significantly ameliorated insulin resistance. Additionally, real-time PCR showed that FGF21 significantly reduced transcription levels of fat synthetic genes, decreased fat synthesis and promoted lipolysis and energy metabolism by up-regulating key genes of lipolysis, thereby liver fat accumulation was reduced and liver function was restored to normal levels. In conclusion, FGF21 significantly reduces body weight of the MSG-IR mice, ameliorates insulin resistance, reverses hepatic steatosis. These findings provide a theoretical support for clinical application of FGF21 as a novel therapeutics for treatment of NAFLD.
2.Recent advance in pathogenesis of oligodendrocyte progenitor cells in neurodegenerative diseases
Xiuzhao YANG ; Tianyuan YE ; Dongmei QI ; Xiaorui CHENG
Chinese Journal of Neuromedicine 2022;21(7):727-734
Oligodendrocyte progenitor cells are distributed throughout the central nervous system and can proliferate, migrate and differentiate into oligodendrocytes. The core function of oligodendrocytes is to produce myelin, form a myelin sheath, wrap the axons, and increase the conduction rate of neurons. Recent studies have shown that large numbers of oligodendrocyte progenitor cells exist in the lesions of neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease, and these cells play an important role in the repair of neurological damage. The physiological functions of oligodendrocyte progenitor cells and their roles in neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease are reviewed in order to provide a new idea and direction for the research and treatment of neurodegenerative diseases.
3.Advances in the application of 5×FAD transgenic mice in Alzheimer's disease research
Yiduan LIU ; Yixiao LIU ; Xinyuan HAN ; Yitong XIAO ; Tianyuan YE
Acta Laboratorium Animalis Scientia Sinica 2024;32(2):260-274
Transgenic 5 × FAD mice are APP/PS1 transgenic mice carrying five familial Alzheimer's disease(AD)gene mutations.Beta-amyloid precursor protein(amyloid precursor protein,APP)expression is related to the K670N/M671L(Swedish),1716V(Florida),and V7171(London)mutations,and presenilin 1(PSI)is affected by the M146L and L286V mutations.5 × FAD mice express high levels of β-amyloid in the brain at 1.5 months old,and neuritic plaques began to appear at 2 months old.The pathological phenotypes of 5 × FAD mice include amyloid plaque aggregation,neuronal loss,gliosis,and memory dysfunction,while their biological characteristics include changes in the formation of brain β-amyloid plaques,hyperphosphorylation of Tau protein,synaptic dysfunction,neuroinflammatory response,mitochondrial dysfunction,blood-brain barrier injury,neuronal injury,endoplasmic reticulum stress,and eye lesions.As a classic animal model of AD,5 × FAD transgenic mice can simulate the neuropathological process and behavioral manifestations of late-stage AD in humans,and these mice are thus widely used in research into the pathogenesis of AD and the development of new drugs.In this review,we summarize the model construction,biological background,and biological characteristics of 5 x FAD transgenic mice,and the development and application of drugs for the prevention and treatment of AD,to provide references for the application of 5 x FAD transgenic transgenic mice in AD research.
4.Effect of lipiodol on recovery of goiter in children aged 8 to 10 years
Yanpeng GAO ; Rongchang MA ; Tianyuan JIANG ; Weiqi DING ; Yaoyi ZHANG ; Zhiqiong TANG ; Ye RUAN
Chinese Journal of Endemiology 2022;41(5):384-388
Objective:To analyze the changes of thyroid volume before and after supplementation with lipiodol pills in children with goiter, and to evaluate the recovery effect of lipiodol pills supplementation on children with goiter in the short term.Methods:In October 2018, 4 townships and towns in Linxia Hui Autonomous Prefecture with relatively serious historical conditions and high goiter rate of children aged 8 to 10 were selected for thyroid examination in 19 primary schools within the jurisdiction. Sixty children with goiter were selected as research subjects; at the same time, 138 children of the same age with normal thyroid B-ultrasound examination results were selected as control in the same period. Under the condition of normal diet, children with goiter were intervened by taking 200 mg lipiodol pills at one time. After 6 months, the thyroid volume of children with goiter and control children was measured by B-ultrasound.Results:Fifty-three children with goiter were finally included, with a sex ratio of 1.00 ∶ 1.04 (26 ∶ 27). There were 138 control children in the same period, with a sex ratio of 1.00 ∶ 1.30 (60 ∶ 78). Six months after taking lipiodol pills, the median thyroid volume of children with goiter was 3.7 ml, which was significantly different from that before supplementing with lipidol pills (5.8 ml, Z = - 7.95, P < 0.001), and not significantly different from that of control children (4.1 ml) in the same period ( Z = - 0.91, P = 0.365). Among them, 90.6% (48/53) of children with goiter recovered to the normal range, and 100.0% (15/15), 81.8% (18/22) and 93.8% (15/16) children's thyroid recovered returned to the normal range in the 8-, 9-, and 10-year-old age groups, respectively, and the highest proportion was in the 8-year-old age group. Stratified by age and gender, the thyroid volume of children with goiter in all age groups and gender after supplementation with lipiodol pills was lower than that before supplementation with lipiodol pills ( P < 0.001), but there was no difference compared with the control children in the same period ( P > 0.05). After supplementing with lipiodol pills, the diameters of thyroid in children with goiter were significantly lower than those before supplementing with lipiodol pills ( P < 0.001). Compared with the control children in the same period, there were significant differences in the right width, left length and right long diameter of the thyroid ( P < 0.05). Conclusion:Supplementing lipiodol pills can restore the thyroid volume of 8 - 10 year old children with goiter to normal range in a short term, and can effectively treat simple goiter.
5.The role of signaling crosstalk of microglia in hippocampus on progression of ageing and Alzheimer's disease
He LI ; Tianyuan YE ; Xingyang LIU ; Rui GUO ; Xiuzhao YANG ; Yangyi LI ; Dongmei QI ; Yihua WEI ; Yifan ZHU ; Lei WEN ; Xiaorui CHENG
Journal of Pharmaceutical Analysis 2023;13(7):788-805
Based on single-cell sequencing of the hippocampi of 5x familiar Alzheimer's disease(5x FAD)and wild type mice at 2-,12-,and 24-month of age,we found an increased percentage of microglia in aging and Alzheimer's disease(AD)mice.Blood brain barrier injury may also have contributed to this increase.Immune regulation by microglia plays a major role in the progression of aging and AD,according to the functions of 41 intersecting differentially expressed genes in microglia.Signaling crosstalk between C-C motif chemokine ligand(CCL)and major histocompatibility complex-1 bridges intercellular communi-cation in the hippocampus during aging and AD.The amyloid precursor protein(APP)and colony stimulating factor(CSF)signals drive 5x FAD to deviate from aging track to AD occurrence among intercellular communication in hippocampus.Microglia are involved in the progression of aging and AD can be divided into 10 functional types.The strength of the interaction among microglial subtypes weakened with aging,and the CCL and CSF signaling pathways were the fundamental bridge of communication among microglial subtypes.