DJ-1,also known as Parkinson’s disease protein 7(PARK7),is a multifunctional protein that plays an important role in oxidative stress regulation and neuroprotection.Previous studies have shown that DJ-1 affects early...DJ-1,also known as Parkinson’s disease protein 7(PARK7),is a multifunctional protein that plays an important role in oxidative stress regulation and neuroprotection.Previous studies have shown that DJ-1 affects early-onset Parkinson’s disease by regulating neuroinflammation,but its specific mechanism remains unclear.The study investigated the role of DJ-1 in mediating microglia-neuron communication to identify potential therapeutic targets for neuroinflammation in Parkinson’s disease.In this study,we observed a significant decrease in the levels of C-X3-C motif chemokine ligand 1(CX3CL1)in Park7 knockout mice and SH-SY5Y cells with Park7 knockdown.Protein microarray analysis and validation using GEO datasets confirmed that knockout of the Park7 gene led to downregulation of CX3CL1 and two other chemokines,namely monocyte chemoattractant protein-1 and interleukin-8.Further investigation revealed that Park7 deficiency reduced the processing of a disintegrin and metalloproteinase domain-containing protein 10(ADAM10)in the neuronal endoplasmic reticulum of both mice and SH-SY5Y cells,thereby decreasing CX3CL1 secretion.This subsequently led to abnormal microglial activation,with a shift toward the proinflammatory M1 phenotype,exacerbating neuroinflammatory responses.These effects were mitigated by exogenous CX3CL1 administration.Concurrently,exogenous CX3CL1 improved motor function in Parkinson’s disease model mice with the Park7 knockout,promoting survival of tyrosine hydroxylase-positive neurons in the substantia nigra and reducing Iba-1-positive microglial activation.These findings demonstrate that DJ-1 exerts neuroprotective effects on dopaminergic neurons by suppressing microglial activation through CX3CL1 regulation,suggesting that targeting the DJ-1/CX3CL1 axis may represent a novel therapeutic strategy for modulating neuroinflammation and protecting dopaminergic neurons.展开更多
以骨形态发生蛋白9(bone morphogenetic protein 9,BMP9)作为诱导小鼠间充质干细胞C3H10T1/2定向成骨分化的细胞因子,观察过表达S100A6对成骨分化的影响。用重组腺病毒AdBMP9与AdS100A6共感染C3H10T1/2细胞,随后检测成骨分化标志物,包括...以骨形态发生蛋白9(bone morphogenetic protein 9,BMP9)作为诱导小鼠间充质干细胞C3H10T1/2定向成骨分化的细胞因子,观察过表达S100A6对成骨分化的影响。用重组腺病毒AdBMP9与AdS100A6共感染C3H10T1/2细胞,随后检测成骨分化标志物,包括Runx2、碱性磷酸酶(alkaline phosphatase,ALP)、骨桥素(osteopontin,OPN)和钙盐沉积;检测方法包括免疫细胞化学、ALP染色、活性分析以及茜素红S染色;同时,用Western blot检测β-catenin的表达。过表达S100A6对所诱导的间充质干细胞C3H10T1/2成骨分化的早期指标Runx2的蛋白水平无明显影响(P>0.05;ICC法),对第7天的ALP和第18天钙盐的沉积也无明显影响(P>0.05);但是,能够引起第12天的OPN升高(P<0.05);同时,S100A6对BMP9诱导的C3H10T1/2细胞中的β-catenin水平的影响在第3、7天不明显(P>0.05),但在第12天时可致β-catenin水平下调(P<0.05)。过表达S100A6可促进BMP9诱导的C3H10T1/2细胞中OPN的表达,但对最终的成骨分化无明显影响。展开更多
A new 10-hydroxyl anthrone glycoside, 1, 8, 10 - trihydroxyl-1ObDglucopyrano- syl-3-methyl-10- C (S) b D- glucopyranosyl-anthrone-9 1 was isolated from the stem of Cassia siamea Lam. The structure was elucidated by...A new 10-hydroxyl anthrone glycoside, 1, 8, 10 - trihydroxyl-1ObDglucopyrano- syl-3-methyl-10- C (S) b D- glucopyranosyl-anthrone-9 1 was isolated from the stem of Cassia siamea Lam. The structure was elucidated by spectral evidences, especially by 2 D techniques.展开更多
Sjögren’s syndrome(SS)is an autoimmune disease characterized primarily by oral and periocular dryness.Astragalus-Salvia(AS)and Ophiopogon-Dendrobium(OD)represent two frequently utilized herb pairs in SS treatmen...Sjögren’s syndrome(SS)is an autoimmune disease characterized primarily by oral and periocular dryness.Astragalus-Salvia(AS)and Ophiopogon-Dendrobium(OD)represent two frequently utilized herb pairs in SS treatment.While the combination of AS-OD herb pairs demonstrates clinical efficacy in alleviating SS symptoms,its underlying mechanism remains unclear.This investigation sought to assess the therapeutic effects and elucidate the potential mechanisms of AS-OD in non-obese diabetic(NOD)/Ltj mice with SS.The study utilized NOD/Ltj mice as SS models,administering AS-OD treatment for 10 weeks at doses of 113.1,226.2,and 339.3 mg·d−1·20 g−1.Results demonstrated that AS-OD improved SS symptoms,evidenced by enhanced salivary flow rate,decreased anti-SSA/Ro and anti-SSB/La antibody levels,increased swimming duration,and reduced lactate(LA)and blood urea nitrogen(BUN)levels in NOD/Ltj mice.AS-OD reduced lymphocyte infiltration,enhanced Aquaporin-5(AQP5)expression in the submandibular gland,decreased inflammatory cytokine levels in the submandibular gland,and reduced the T helper type 17/regulatory T lymphocyte(Th17/Treg)cell ratio in the spleen.Transcriptomic and proteomic analyses indicated AS-OD’s involvement in regulating phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)and Janus kinase 3/signal transducer and activator of transcription 3(JAK1/STAT3)pathways,with inhibitory effects validated in both NOD/Ltj mice submandibular gland and A-253 cells.Furthermore,AS-OD enhanced cell viability and reduced A-253 cell apoptosis through the PI3K/AKT pathway.In A-253 cells,AS-OD reduced inflammatory cytokine levels,CXC chemokine ligand 9/10(CXCL9/10),and T-cell chemotaxis by inhibiting the JAK1/STAT3 pathway.AS-OD mitigates SS by suppressing inflammation and immune responses through the PI3K/AKT and JAK1/STAT3 pathways.展开更多
The stable structures and stabilities of AgnH2S（n = 1-10） clusters have been calculated using the B3P86-DFT method. The results predicate that the stable geometries of AgnH2 S clusters can be got by directly adding ...The stable structures and stabilities of AgnH2S（n = 1-10） clusters have been calculated using the B3P86-DFT method. The results predicate that the stable geometries of AgnH2 S clusters can be got by directly adding the H2 S molecule on different sites of Agn clusters. Agn clusters would like to bond with sulfur atom and the H2 S molecules are partial to adsorb at the top site in the clusters. After adsorption, the structures of Agn clusters and H2 S molecule keep the original structures except Ag9. The binding energy of AgnH2 S is distinctly larger than that of pure Agn clusters. The second difference in energy and the HOMO and LUMO gaps of Agn and AgnH2 S exhibit an obvious odd-even oscillation, which demonstrate that the stabilities of even-numbered silver clusters are relatively more stable than the neighboring odd-numbered silver clusters. Mulliken population analysis shows that charges always transfer from the H2 S molecule to Agn clusters in all clusters.展开更多
基金National Natural Science Foundation of China,Nos.82471264(to YL),82201392(to AZ),82071415(to JL)Shanghai Rising Stars of Medical Talents Youth Development Program,No.2023-62(to YL)+2 种基金the Shanghai Municipal Health Commission Clinical Research Special Fund for the Health Industry,No.20234Y0026(to YL)the Shanghai Sailing Program,No.22YF1425100(to AZ)Chinese Postdoctoral Science Foundation,No.2021M702169(to YJ).
文摘DJ-1,also known as Parkinson’s disease protein 7(PARK7),is a multifunctional protein that plays an important role in oxidative stress regulation and neuroprotection.Previous studies have shown that DJ-1 affects early-onset Parkinson’s disease by regulating neuroinflammation,but its specific mechanism remains unclear.The study investigated the role of DJ-1 in mediating microglia-neuron communication to identify potential therapeutic targets for neuroinflammation in Parkinson’s disease.In this study,we observed a significant decrease in the levels of C-X3-C motif chemokine ligand 1(CX3CL1)in Park7 knockout mice and SH-SY5Y cells with Park7 knockdown.Protein microarray analysis and validation using GEO datasets confirmed that knockout of the Park7 gene led to downregulation of CX3CL1 and two other chemokines,namely monocyte chemoattractant protein-1 and interleukin-8.Further investigation revealed that Park7 deficiency reduced the processing of a disintegrin and metalloproteinase domain-containing protein 10(ADAM10)in the neuronal endoplasmic reticulum of both mice and SH-SY5Y cells,thereby decreasing CX3CL1 secretion.This subsequently led to abnormal microglial activation,with a shift toward the proinflammatory M1 phenotype,exacerbating neuroinflammatory responses.These effects were mitigated by exogenous CX3CL1 administration.Concurrently,exogenous CX3CL1 improved motor function in Parkinson’s disease model mice with the Park7 knockout,promoting survival of tyrosine hydroxylase-positive neurons in the substantia nigra and reducing Iba-1-positive microglial activation.These findings demonstrate that DJ-1 exerts neuroprotective effects on dopaminergic neurons by suppressing microglial activation through CX3CL1 regulation,suggesting that targeting the DJ-1/CX3CL1 axis may represent a novel therapeutic strategy for modulating neuroinflammation and protecting dopaminergic neurons.
文摘A new 10-hydroxyl anthrone glycoside, 1, 8, 10 - trihydroxyl-1ObDglucopyrano- syl-3-methyl-10- C (S) b D- glucopyranosyl-anthrone-9 1 was isolated from the stem of Cassia siamea Lam. The structure was elucidated by spectral evidences, especially by 2 D techniques.
基金the National Natural Science Foundation of China(No.82074341).
文摘Sjögren’s syndrome(SS)is an autoimmune disease characterized primarily by oral and periocular dryness.Astragalus-Salvia(AS)and Ophiopogon-Dendrobium(OD)represent two frequently utilized herb pairs in SS treatment.While the combination of AS-OD herb pairs demonstrates clinical efficacy in alleviating SS symptoms,its underlying mechanism remains unclear.This investigation sought to assess the therapeutic effects and elucidate the potential mechanisms of AS-OD in non-obese diabetic(NOD)/Ltj mice with SS.The study utilized NOD/Ltj mice as SS models,administering AS-OD treatment for 10 weeks at doses of 113.1,226.2,and 339.3 mg·d−1·20 g−1.Results demonstrated that AS-OD improved SS symptoms,evidenced by enhanced salivary flow rate,decreased anti-SSA/Ro and anti-SSB/La antibody levels,increased swimming duration,and reduced lactate(LA)and blood urea nitrogen(BUN)levels in NOD/Ltj mice.AS-OD reduced lymphocyte infiltration,enhanced Aquaporin-5(AQP5)expression in the submandibular gland,decreased inflammatory cytokine levels in the submandibular gland,and reduced the T helper type 17/regulatory T lymphocyte(Th17/Treg)cell ratio in the spleen.Transcriptomic and proteomic analyses indicated AS-OD’s involvement in regulating phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)and Janus kinase 3/signal transducer and activator of transcription 3(JAK1/STAT3)pathways,with inhibitory effects validated in both NOD/Ltj mice submandibular gland and A-253 cells.Furthermore,AS-OD enhanced cell viability and reduced A-253 cell apoptosis through the PI3K/AKT pathway.In A-253 cells,AS-OD reduced inflammatory cytokine levels,CXC chemokine ligand 9/10(CXCL9/10),and T-cell chemotaxis by inhibiting the JAK1/STAT3 pathway.AS-OD mitigates SS by suppressing inflammation and immune responses through the PI3K/AKT and JAK1/STAT3 pathways.
基金supported by the National Natural Science Foundation of China(11247229,11304246)the Scientific Research Program Fund by Shaanxi Provincial Education Department(2013JK0629)+1 种基金the Natural Science Basic Research Plan in Shaanxi Province of China(2014JQ6206)the Innovation and Entrepreneurship Training Project of Provincial College Students
文摘The stable structures and stabilities of AgnH2S（n = 1-10） clusters have been calculated using the B3P86-DFT method. The results predicate that the stable geometries of AgnH2 S clusters can be got by directly adding the H2 S molecule on different sites of Agn clusters. Agn clusters would like to bond with sulfur atom and the H2 S molecules are partial to adsorb at the top site in the clusters. After adsorption, the structures of Agn clusters and H2 S molecule keep the original structures except Ag9. The binding energy of AgnH2 S is distinctly larger than that of pure Agn clusters. The second difference in energy and the HOMO and LUMO gaps of Agn and AgnH2 S exhibit an obvious odd-even oscillation, which demonstrate that the stabilities of even-numbered silver clusters are relatively more stable than the neighboring odd-numbered silver clusters. Mulliken population analysis shows that charges always transfer from the H2 S molecule to Agn clusters in all clusters.
