1.SOCS3 ameliorates Parkinson's disease neuropathology by suppressing NF-κB signaling-mediated microglial inflammation
Fangya ZUO ; Dan FENG ; Yun LIU ; Fenfen LIU ; Xiuhong GUO ; Yuqi LIU ; Lanlan CHEN ; Yujie WANG ; Jinyong TIAN
Journal of Army Medical University 2025;47(21):2611-2620
Objective To investigate the mechanism by which suppressor of cytokine signaling 3(SOCS3)regulates microglial inflammation through nuclear factor-kappaB(NF-κB),providing novel mechanistic insights into microglial involvement in Parkinson's disease(PD)pathogenesis.Methods ① Ten male C57BL/6 mice(12 weeks old,weighing 20~25 g)were subjected to intraperitoneal injection of 15 mg/kg MPTP to establish a PD model.Rotarod test was used to assess motor function.Western blotting was employed to detect the protein expression of tyrosine hydroxylase(TH)and ionized calcium-binding adapter molecule 1(IBA-1)in the substantia nigra.RT-qPCR was utilized to measure the mRNA level of SOCS3 in the substantia nigra.Immunohistochemistry was performed to assess NF-κB p65 subunit expression.The expression of SOCS3,NF-κB and p-NF-κB was measured with Western blotting.② Microglial cell line BV2 was stimulated with 1 000 ng/mL lipopolysaccharide(LPS)for 6 h to establish an inflammatory model.Subsequently,SOCS3 was knocked down.NF-κB inhibitor BAY 11-7082 was used to treat the cells.RT-qPCR and Western blotting were used to measure the expression of SOCS3 at mRNA and protein levels.Western blotting was also applied to detect the expression of NF-κB and p-NF-κB,and ELISA was conducted to measure TNF-α and IL-1β levels in the culture supernatant.Immunofluorescence assay was carried out to localize NF-κB(nuclear vs cytoplasmic).③ A co-culture system of BV2 microglia and N2a neuroblastoma cells was established to investigate the regulatory effects of microglia on neuronal cells.MTT assay and TUNEL staining were used respectively to determine cell viability and apoptosis of N2a cells.Results ① Compared to the control mice,the PD mouse model exhibited reduced rotarod fall latency,down-regulation in TH and SOCS3(P<0.01),up-regulation in IBA-1 and increased p-NF-κB/NF-κB ratio(P<0.01).② In BV2 cells,LPS stimulation increased TNF-α,IL-1β,and p-NF-κB/NF-κB ratio(P<0.01),while down-regulated SOCS3 expression(P<0.01).SOCS3 knockdown in LPS-stimulated BV2 cells further increased the p-NF-κB/NF-κB ratio(P<0.01),increased nuclear localization of NF-κB,and elevated TNF-α and IL-1β levels(P<0.01).BAY 11-7082 treatment in these SOCS3-knockdown,LPS-stimulated cells resulted in reduced p-NF-κB/NF-κB ratio,TNF-α,and IL-1β(P<0.01),and decreased NF-κB nuclear distribution.③ LPS-stimulated BV2 cells reduced cell viability and increased cell apoptosis in N2a cells(P<0.01).SOCS3 knockdown in BV2 cells exacerbated the reduction in N2a cell viability(P<0.01)and the increase in cell apoptosis in N2a cells(P<0.01).BAY 11-7082 treatment of these SOCS3-knockdown BV2 microglia attenuated the reduction in N2a cell viability and decreased apoptosis in N2a cells(P<0.01).Conclusion SOCS3 inhibits microglia inflammatory response through down-regulation of NF-kB activity,and in turn attenuates neuronal cell death and ameliorates PD nerve injury.
2.Neferine attenuates parkinson's disease via modulating microglial pyroptosis mediated by ROS/NLRP3/Caspase-1 signaling pathway
Fenfen LIU ; Dan FENG ; Yun LIU ; Fangya ZUO ; Xiuhong GUO ; Yuqi LIU ; Lanlan CHEN ; Yujie WANG ; Jinyong TIAN
Journal of Army Medical University 2025;47(23):2933-2942
Objective To demonstrate that neferine(Nef)alleviates Parkinson's disease(PD)by inhibiting microglial pyroptosis mediated through the reactive oxygen species(ROS)/NOD-like receptor protein 3(NLRP3)/Caspase-1 pathway.Methods BV2 microglial cells were divided into:control group,lipopolysaccharides(LPS)-adenosine triphosphate(ATP)group,and LPS-ATP+Nef group.Pyroptosis was induced by 1 μg/mL LPS+5 mmol/L ATP,with 2 mmol/L Nef pretreatment.Eighteen 10-12-week-old male C57BL/6 mice(22~25 g)were randomly assigned to:control(n=6),1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)(n=6),and MPTP+Nef(n=6)groups.Detection methods included:flow cytometry for pyroptosis,Cell Counting Kit-8(CCK-8)for viability,2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)for ROS,commercial kits for malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH),ELISA/Western blot for interleukin-1β(IL-1β)/IL-18,immunofluorescence/immunohistochemistry for NLRP3/Caspase-1,tyrosine hydroxylase(TH)immunohistochemistry,hematoxylin-eosin staining for neuropathology,and modified neurological severity score(mNSS).Results Versus control,LPS-ATP group showed decreased viability(P=0.002),increased pyroptosis(P<0.001),elevated ROS(P<0.001)/MDA(P<0.001)/IL-1β(P<0.001)/IL-18(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001),and reduced GSH(P<0.001)/SOD(P<0.001).Nef treatment reversed these effects(all P<0.05).According to the results of murine studies,compared with the control group,the MPTP group had increased mNSS(P<0.001)/tissue ROS(P<0.001),downregulated TH(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001).Nef treatment significantly attenuated the MPTP-induced deleterious effects(P<0.05).Histopathological analysis revealed that control group exhibited uniformly distributed hippocampal neurons with distinct nuclear morphology;MPTP group showed neuronal swelling,interstitial edema,and nuclear atrophy;MPTP+Nef group demonstrated ameliorated neuronal damage.Conclusion Nef inhibits microglial pyroptosis via ROS/NLRP3/Caspase-1 axis,ameliorating PD neuroinflammation and pathology.
3.Effect of AngioJet thrombectomy on proximal iliofemoral vein thrombosis after trauma
Xuan TIAN ; Jianlong LIU ; Wei JIA ; Peng JIANG ; Zhiyuan CHENG ; Yunxin ZHANG ; Jinyong LI ; Chenyang TIAN
Chinese Journal of General Surgery 2020;35(9):698-702
Objective:To investigate the effect of AngioJet thrombectomy on proximal iliofemoral vein thrombosis after trauma.Methods:The clinical data of patients with proximal iliofemoral vein thrombosis treated with AngioJet thrombectomy were retrospectively analyzed at Vascular Surgery Department of our hospital in 2019.Results:A total of 76 patients were enrolled. After PMT 20 patients had grade Ⅲ thrombolysis clearance(26.3%), 41 patients (53.9%) had grade Ⅱ clearance, and 15 cases (19.7%) had grade Ⅰ clearance. Thirty four cases (44.7%) of grade Ⅲ were cleared after catheter aspiration or catheter thrombolysis, 35 cases (46.1%) of grade Ⅱ, 7 cases (9.2%) of grade Ⅰ were cleared, thrombus clearance rate increased significantly ( P<0.05). Cerebral hemorrhage occurred in 1 case (1.3%), and thrombosis recurred in 2 cases (2.6%). The patency rate was 91.8% at 3 months follow-up. Conclusions:AngioJet thrombectomy is a safe and effective method for treating post-traumatic proximal iliac femoral vein thrombosis. Intraoperative application of urokinase thrombolysis, catheter aspiration and catheter-directed thrombolysis can increase thrombus clearance effect.
4. Analysis of occupational and mental health status in high-speed railway locomotive drivers
Lubing ZHANG ; Yue TIAN ; Shaoshou CHEN ; Jinyong XIONG ; Yongquan LIU
China Occupational Medicine 2019;46(04):434-437
OBJECTIVE: To understand the exposure of occupational hazards, occupational and mental health status of high-speed railway locomotive drivers. METHODS: A total of 150 male high-speed railway locomotive drivers from Nanchang Railway administration were selected as experimental group, and 80 male ordinary train drivers were selected as control group by using a judgment sampling method. The occupational disease hazard testing and occupational health examinations were conducted in drivers of these two groups. The mental health status survey was conducted using the Symptom Checklist 90(SCL-90). RESULTS: The noise, power frequency electric field, formaldehyde, benzene, toluene, xylene and carbon dioxide in all the work place of these two groups were in line with the national occupational health standards. The exposure noise intensity of the experimental group was lower than that of the control group [(70.5±3.7) vs(77.4±4.1) dB(A), P<0.05]. The detection rates of hypertension and chronic gastritis were higher in the experimental group(18.7% vs 34.7%, 26.2% vs 42.0%, P<0.05). The detection rate of high frequency hearing loss decreased in the experimental group compared with the control group(22.5% vs 10.7%, P<0.05). The total score of SCL-90 in the experimental group was higher than that in the control group [(169.5±6.1) vs(148.0±6.0) score, P<0.01]. The positive rate of psychological symptoms was higher in the experimental group than that of the control group(41.3% vs 23.8%, P<0.01). CONCLUSION: The concentration/intensity of occupational disease hazards in the workplace of high-speed railway locomotives drivers is within normal limit. The occupational health status of high-speed railway locomotive drivers is generally good, but attention should be paid to their occupational mental health hazards.
5.monitoring of the structural change of microemulsions in simulated gastrointestinal conditions by SAXS and FRET.
Xia LV ; Shuguang ZHANG ; Huipeng MA ; Peipei DONG ; Xiaodong MA ; Ming XU ; Yan TIAN ; Zeyao TANG ; Jinyong PENG ; Haibo CHEN ; Jianbin ZHANG
Acta Pharmaceutica Sinica B 2018;8(4):655-665
Microemulsions are promising drug delivery systems for the oral administration of poorly water-soluble drugs. However, the evolution of microemulsions in the gastrointestinal tract is still poorly characterized, especially the structural change of microemulsions under the effect of lipase and mucus. To better understand the fate of microemulsions in the gastrointestinal tract, we applied small-angle X-ray scattering (SAXS) and fluorescence resonance energy transfer (FRET) to monitor the structural change of microemulsions under the effect of lipolysis and mucus. First, the effect of lipolysis on microemulsions was studied by SAXS, which found the generation of liquid crystalline phases. Meanwhile, FRET spectra indicated micelles with smaller particle sizes were generated during lipolysis, which could be affected by CaCl, bile salts and lecithin. Then, the effect of mucus on the structural change of lipolysed microemulsions was studied. The results of SAXS and FRET indicated that the liquid crystalline phases disappeared, and more micelles were generated. In summary, we studied the structural change of microemulsions in simulated gastrointestinal conditions by SAXS and FRET, and successfully monitored the appearance and disappearance of the liquid crystalline phases and micelles.
6. Simultaneous determination of 9 kinds of anion in workplace air by Ion chromatography
Jinyong XIONG ; Yue TIAN ; Li JIN ; Wenjuan CHENG ; Yongquan LIU
China Occupational Medicine 2018;45(06):748-752
OBJECTIVE: To establish a simultaneously detecting method for 9 kinds of anion in workplace air by ion chromatography. METHODS: Nine kinds of anions in workplace air include fluoride ion,chloride ion,nitrite ion,bromide ion,nitrate ion,sulfate ion,phosphate ion,oxalate denominationbl and iodide ion were sampled with sodium carbonatesodium bicarbonate( concentration 3. 2,1. 1 mmol/L respectively),separated by the anion column,detected by the conductivity detector and quantified by external standard method. RESULTS: The linearity of the 9 anions in the corresponding mass concentration range was good( correlation coefficient > 0. 999). The detection limit was 0. 02-0. 18mg/L and the marking recovery was 96. 0%-100. 5%. The within-run relative standard deviation( RSD) was 0. 3%-2. 5%,and the between-run RSD was 0. 4%-3. 1%. All the sampling efficiencies were > 96. 8%,and the samples could be stored at room temperature for 5 days. CONCLUSION: The method has good accuracy,high sensitivity,with simple and rapid operation,and can simultaneously measure various anions in the air of workplace.
7.Study of the relationship between anti-cardiolipin antibody and cerebral infarction
Jinyong TIAN ; Xiangxiang GUI ; Mingxiang ZHAO
Journal of Clinical Neurology 1997;0(06):-
Objective To study the relationship between anticardiolipin antibody(ACA) and cerebral infarction(CI).Methods The positive rate of serum ACA were determined by enzyme linked immunosorbent assay(ELISA) in 137 patients with CI at first day,first,second,third and fourth week after the onset of the disease.The results were compared with transient ischemia attach(TIA) group,intracerebral hemorrhage(ICH) group and normal control group.Results The positive rate of ACA in CI group(64.9%) was significantly higher than TIA group(24.6%),ICH group(33.6%) and normal control group(17.6%)(all(P

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