The subcortical visual pathway is generally thought to be involved in dangerous information processing,such as fear processing and defensive behavior.A recent study,published in Human Brain Mapping,shows a new functio...The subcortical visual pathway is generally thought to be involved in dangerous information processing,such as fear processing and defensive behavior.A recent study,published in Human Brain Mapping,shows a new function of the subcortical pathway involved in the fast processing of non-emotional object perception.Rapid object processing is a critical function of visual system.Topological perception theory proposes that the initial perception of objects begins with the extraction of topological property(TP).However,the mechanism of rapid TP processing remains unclear.The researchers investigated the subcortical mechanism of TP processing with transcranial magnetic stimulation(TMS).They find that a subcortical magnocellular pathway is responsible for the early processing of TP,and this subcortical processing of TP accelerates object recognition.Based on their findings,we propose a novel training approach called subcortical magnocellular pathway training(SMPT),aimed at improving the efficiency of the subcortical M pathway to restore visual and attentional functions in disorders associated with subcortical pathway dysfunction.展开更多
In order to clarify the mechanism of action of licorice flavonoids in alleviating bone loss caused by osteoporosis,this study compared the effects of four glycyrrhiza flavonoids,naringenin,liquiritigenin,isoliquiritig...In order to clarify the mechanism of action of licorice flavonoids in alleviating bone loss caused by osteoporosis,this study compared the effects of four glycyrrhiza flavonoids,naringenin,liquiritigenin,isoliquiritigenin,and licochalcone A,on osteogenic differentiation and mineralization by molecular docking simulation,alkaline phosphatase(ALP)activity and osteocalcin(OCN)content assays,and Runt-related transcription factor 2(Runx2)expression,and explored their potential molecular mechanisms.The results of molecular docking showed that the docking score of liquiritigenin with the estrogen receptor(ER)was the highest.All four flavonoids up-regulated ALP activity and OCN concentration in MC3T3-E1 cells,thereby elevating the mineralization level,among which liquiritigenin was the most effective.Moreover,treatment with a phosphatidylinositol-3-kinase(PI3K)inhibitor(LY294002)inhibited liquiritigenin from inducing increased phosphorylation levels in the PI3K/protein kinase B(AKT)signaling pathway and up-regulation of Runx2 expression,suggesting that PI3K and AKT were involved in osteogenic action.Liquiritigenin reversed bone mineral density loss in a zebrafish osteoporosis model.These findings suggest that liquiritigenin has the most significant osteogenic effect among the four estrogen-like flavonoids,stimulating osteoblast differentiation and bone mineralization through the activation of Runx2 via the PI3K/AKT signaling pathways.In conclusion,this study highlights the great potential of liquiritigenin for preventing and treating osteoporosis.展开更多
The trace element selenium(Se)occurs naturally throughout the earth.Se deficiency has been linked to impaired breast health and other diseases in human and animals.Compared to severe Se deficiency,marginal dietary Se ...The trace element selenium(Se)occurs naturally throughout the earth.Se deficiency has been linked to impaired breast health and other diseases in human and animals.Compared to severe Se deficiency,marginal dietary Se deficiency accusers more frequently in low-Se regions.Therefore,to investigate the Se status and inflammatory response of the mammary gland under marginal dietary Se levels,an lipopolysaccharide(LPS)induced mouse mastitis model was established.Mice were fed with moderate Se diet(0.087 mg•kg^(-1) Se),adequate Se diet(0.15 mg•kg^(-1) Se)or excessive Se diet(1.5 mg•kg^(-1) Se)for 60 days.Se status and inflammatory factors were investigated.Results showed that the Se status of mammary gland correlated with dietary Se levels.Marginal Se deficiency exacerbated mammary tissue histopathology;increased the mRNA level of inflammatory genes tumor necrosis factor alpha(TNF-α),interleukin-1β(IL-1β)and cyclooxygenase-2(COX-2);and enhanced the phosphorylation of NF-κB p65 in mammary gland tissues.Supplementation of Se in diet higher than recommended levels reduced the inflammatory reaction of mammary glands in LPS-induced mastitis model and provided a protective effect.展开更多
Objective To investigate the effect of mucin 1(MUC1)on the proliferation and apoptosis of nasopharyngeal carcinoma(NPC)and its regulatory mechanism.Methods The 60 NPC and paired para-cancer normal tissues were collect...Objective To investigate the effect of mucin 1(MUC1)on the proliferation and apoptosis of nasopharyngeal carcinoma(NPC)and its regulatory mechanism.Methods The 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital.The expression of MUC1 was measured by real-time quantitative PCR(qPCR)in the patients with PNC.The 5-8F and HNE1 cells were transfected with siRNA control(si-control)or siRNA targeting MUC1(si-MUC1).Cell proliferation was analyzed by cell counting kit-8 and colony formation assay,and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells.The qPCR and ELISA were executed to analyze the levels of TNF-αand IL-6.Western blot was performed to measure the expression of MUC1,NFкB and apoptosis-related proteins(Bax and Bcl-2).Results The expression of MUC1 was up-regulated in the NPC tissues,and NPC patients with the high MUC1 expression were inclined to EBV infection,growth and metastasis of NPC.Loss of MUC1 restrained malignant features,including the proliferation and apoptosis,downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells.Conclusion Downregulation of MUC1 restrained biological characteristics of malignancy,including cell proliferation and apoptosis,by inactivating NF-κB signaling pathway in NPC.展开更多
Dichloromethane(DCM)dehalogenase stands as a crucial enzyme implicated in the degradation of methylene chloride across diverse environmental and biological contexts.However,the unbinding pathways of ligands from DCM d...Dichloromethane(DCM)dehalogenase stands as a crucial enzyme implicated in the degradation of methylene chloride across diverse environmental and biological contexts.However,the unbinding pathways of ligands from DCM dehalogenase remain unexplored.In order to gain a deeper understanding of the binding sites and dissociation pathways of dichloromethane(DCM)and glutathione(GSH)from the DCM dehalogenase,random accelerated molecular dynamics(RAMD)simulations were performed,in which DCM and GSH were forced to leave the active site.The protein structure was predicted using Alphafold2,and the conformations of GSH and DCM in the binding pocket were predicted by docking.A long equilibrium simulation was conducted to validate the structure of the complex.The results show that GSH is most commonly observed in three main pathways,one of which is more important than the other two.In addition,DCM was observed to escape along a unique pathway.The key residues and protein helices of each pathway were identified.The results can provide a theoretical foundation for the subsequent dissociation mechanism of DCM dehalogenase.展开更多
Objective Chronic stress can induce cognitive dysfunction,but the underlying mechanisms remain unknown.Studies have confirmed that the high mobility group box 1/Toll-like receptor 4(HMGB1/TLR4)pathway is closely assoc...Objective Chronic stress can induce cognitive dysfunction,but the underlying mechanisms remain unknown.Studies have confirmed that the high mobility group box 1/Toll-like receptor 4(HMGB1/TLR4)pathway is closely associated with cognitive impairment.Therefore,this research aimed to explore whether the HMGB1/TLR4 pathway involves in chronic stress-induced cognitive dysfunction.Methods The chronic unpredictable mild stress(CUMS)mouse model was established by randomly giving different types of stress every day for four consecutive weeks.Cognitive function was detected by novel object recognition test,Y-maze test,and Morris water maze test.The protein expressions of HMGB1,TLR4,B-cell lymphoma 2(BCL2),and BCL2 associated X(BAX)were determined by Western blot.The damage of neurons in the hippocampal CA1 region was observed by hematoxylin-eosin(HE)staining.Results The protein expressions of HMGB1 and TLR4 were significantly increased in the hippocampus of chronic stress mice.Furthermore,inhibition of the HMGB1/TLR4 pathway induced by ethyl pyruvate(EP,a specific inhibitor of HMGB1)and TAK242(a selective inhibitor of TLR4)treatment attenuated cognitive impairment in chronic stress mice,according to the novel object recognition test,Y-maze test,and Morris water maze test.In addition,administration of EP and TAK242 also mitigated the increase of apoptosis in the hippocampus of chronic stress mice.Conclusion These results indicate that the hippocampal HMGB1/TLR4 pathway contributes to chronic stress-induced apoptosis and cognitive dysfunction.展开更多
目的:探讨蜘蛛香总黄酮对肝癌H22小鼠抗肿瘤作用及对pathways in cancer的影响。方法:建立H22肝癌皮下荷瘤模型,随机分为模型对照组、阳性对照组、蜘蛛香总黄酮高、低剂量组。给药10 d后,解剖称取瘤重,计算抑瘤率,并应用小鼠全基因组基...目的:探讨蜘蛛香总黄酮对肝癌H22小鼠抗肿瘤作用及对pathways in cancer的影响。方法:建立H22肝癌皮下荷瘤模型,随机分为模型对照组、阳性对照组、蜘蛛香总黄酮高、低剂量组。给药10 d后,解剖称取瘤重,计算抑瘤率,并应用小鼠全基因组基因芯片考察蜘蛛香总黄酮对瘤组织pathways in cancer的影响。结果:与模型对照组相比,阳性对照组、蜘蛛香总黄酮高、低剂量组的平均瘤重明显下降(P<0.01,P<0.05,P<0.05),各组抑瘤率分别为45.32%、30.06%、25.97%。给药组pathways in cancer中有17个基因表达同时发生了显著性变化,其中Ccne2、Cdkn2b、Ctbp2、Mmp1a、Myc和Vegfa的表达发生了上调,而Vegfc、Csf1r、Epas1、Figf、Fzd9、Igf1、Pdgfra、Pik3r1、Prkcb、Tcf7l1和Tcf7l2的表达发生了下调,主要从细胞周期调控、PI3K-AKT途径、Wnt途径抑制肿瘤增殖、迁移,促进其凋亡。结论:蜘蛛香总黄酮具有一定的抗肝癌活性,作用机理可能与调节pathways in cancer的信号转导相关。展开更多
Polymeric perylene diimide(PDI)has been evidenced as a good candidate for photocatalytic water oxidation,yet the origin of the photocatalytic oxygen evolution activity remains unclear and needs further exploration.Her...Polymeric perylene diimide(PDI)has been evidenced as a good candidate for photocatalytic water oxidation,yet the origin of the photocatalytic oxygen evolution activity remains unclear and needs further exploration.Herein,with crystal and atomic structures of the self-assembled PDI revealed from the X-ray diffraction pattern,the electronic structure is theoretically illustrated by the first-principles density functional theory calculations,suggesting the suitable band structure and the direct electronic transition for efficient photocatalytic oxygen evolution over PDI.It is confirmed that the carbonyl O atoms on the conjugation structure serve as the active sites for oxygen evolution reaction by the crystal orbital Hamiltonian group analysis.The calculations of reaction free energy changes indicate that the oxygen evolution reaction should follow the reaction pathway of H_(2)O→^(*)OH→^(*)O→^(*)OOH→^(*)O_(2)with an overpotential of 0.81 V.Through an in-depth theoretical computational analysis in the atomic and electronic structures,the origin of photocatalytic oxygen evolution activity for PDI is well illustrated,which would help the rational design and modification of polymeric photocatalysts for efficient oxygen evolution.展开更多
Recent advancements have led to the synthesis of various new metal-containing explosives,particularly energetic metal-organic frameworks(EMOFs),which feature high-energy ligands within well-ordered crystalline structu...Recent advancements have led to the synthesis of various new metal-containing explosives,particularly energetic metal-organic frameworks(EMOFs),which feature high-energy ligands within well-ordered crystalline structures.These explosives exhibit significant advantages over traditional compounds,including higher density,greater heats of detonation,improved mechanical hardness,and excellent thermal stability.To effectively evaluate their detonation performance,it is crucial to have a reliable method for predicting detonation heat,velocity,and pressure.This study leverages experimental data and outputs from the leading commercial computer code to identify suitable decomposition pathways for different metal oxides,facilitating straightforward calculations for the detonation performance of alkali metal salts,and metal coordination compounds,along with EMOFs.The new model enhances predictive reliability for detonation velocities,aligning more closely with experimental results,as evi-denced by a root mean square error(RMSE)of 0.68 km/s compared to 1.12 km/s for existing methods.Furthermore,it accommodates a broader range of compounds,including those containing Sr,Cd,and Ag,and provides predictions for EMOFs that are more consistent with computer code outputs than previous predictive models.展开更多
Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are current...Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are currently no data on molecular markers associated with resistance. The conflicting data were reported regarding the AKT/m-TOR signaling pathway components as markers predicting resistance. The AKT/m-TOR signaling pathway is involved in the development of many human cancers; its activation is related to cell proliferation, angiogenesis, apoptosis, as well as to therapy resistance. Molecular alterations in the AKT/m-TOR signaling pathway provide a platform to identify universal markers associated with the development of resistance to cancer therapy.展开更多
G protein coupled receptors(GPCRs)are transmembrane receptor proteins,which allow signals to transfer across membrane.GPCRs include a large number of receptors,different receptors mediated different signaling pathways...G protein coupled receptors(GPCRs)are transmembrane receptor proteins,which allow signals to transfer across membrane.GPCRs include a large number of receptors,different receptors mediated different signaling pathways of GPCRs-adenylyl cyclase(AC)-cyclic adenosine 3',5'-monophosphate(c AMP),including β2 adrenergic receptors(β2-ARs)-AC-c AMP signaling pathways,E-prostanoid2/4(EP2/4)-AC-cA MP signaling pathways.Regulatory proteins,such as G protein coupled receptor kinases(GRKs)andβ-arrestins,play important modulatory roles in GPCRs signaling pathway.GPCRs signaling pathway and regulatory proteins implicate the pathogenesis process of inflammatory and immune response.Rheumatoid arthritis(RA)is an autoimmune disease characterized by synovitis and accompanied with inflammatory and abnormal immune response.This article review the advances on GPCRs signaling pathway implicating in the inflammatory and immune response of RA.展开更多
The treatment and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied,but without a systematic summary currently.This review comprehensively c...The treatment and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied,but without a systematic summary currently.This review comprehensively collected and analyzed the traditional Chinese medicine on the treatment and signaling pathway regulation of osteoporosis in recent ten years,such as Epimedium,Drynariae Rhizoma,Cnidium,Eucommia,Psoralen and Dipsacus.Based on the existing findings,we concluded the following conclusions:(1)kidney-tonifying traditional Chinese medicine treats osteoporosis mainly through BMP-Smads,Wnt/β-catenin,MAPK,PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/RANK,estrogen,CTSK signaling pathway to inhibit osteoclasts of bone resorption.(1)Epimedium,Drynariae Rhizoma,Cnidium and Psoralen up-regulate the key proteins and genes of BMP-Smads and Wnt/β-catenin signaling pathways to promote bone formation.(2)Epimedium,Drynariae Rhizoma,Cnidium,Eucommia,Psoralen,Dipsacusinhibit the bone resorption by mediating the OPG/RANKL/RANK signaling pathway.(2)Kidney-tonifying traditional Chinese medicine prevent and treat osteoporosis through a variety of ways:Icariin,Naringin,Osthol,Psoralen can regulate BMP-Smads,Wnt/β-catenin signaling pathway to promote bone formation,but also activate OPG/RANKL/RANK,CTSK and other signaling pathway to inhibit bone resorption.(3)The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification.展开更多
OBJECTIVE To investigate the effects of astragaloside IV(which can be extracted from the traditional Chinese medicine Astragalus membranaceus)on lipid and glucose metabolism in acute myocardial infarction(AMI).METHODS...OBJECTIVE To investigate the effects of astragaloside IV(which can be extracted from the traditional Chinese medicine Astragalus membranaceus)on lipid and glucose metabolism in acute myocardial infarction(AMI).METHODS Model of heart failure(HF)after AMI was established with ligation of left anterior descending artery on Sprague-Dawley(SD)rats.The rats were divided into three groups:sham,model and astragaloside IV treatment group.Twenty-eight days after treatment(astragaloside IV,20 mg·kg-1 daily),hematoxylin-eosin(HE)staining was applied to visualize cardiomyocyte morphological changes.High performance liquid chromatography(HPLC)was performed to assess the contents of adenosine phosphates in heart.Positron emission tomography and computed tomography(PET-CT)was conducted to evaluate the cardiac glucose metabolism.Expressions of key molecules such as peroxisome proliferatoractivated receptor γ(PPARγ),sterol carrier protein 2(SCP2)and long chain acyl CoA dehydrogenase(ACADL)were measured by Western blotting and immunohistochemistry.Oxygen-glucose deprivation-reperfusion(OGD/R)-induced H9C2 injury cardiomyocyte model was adopted for potential mechanism research in vitro.RESULTS Treatment with astragaloside Ⅳ rescued hearts from structural and functional damages as well as inflammatory infiltration.Levels of adenosine triphosphate(ATP)and energy charge(EC)in astragaloside IV group were also up-regulated compared to model group.Further results demonstrated that critical enzymes both in lipid metabolism and glucose metabolism compro mised in model group compared to sham group.Intriguingly,astragalosideⅣcould up-regulate critical enzymes including ACADL and SCP2 in lipid metabolism accompanying with promoting effect on molecules in glycolysis simultaneously.Results on upstreaming signaling pathway demonstrated that astragaloside Ⅳ could dramatically increase the expres sions of PPARγ.In vitro study suggested the efficacy of astragalosideⅣcould be blocked by T0070907,a selective PPARγ inhibitor.CONCLUSION Astragaloside IV has cardioprotective effect in improving cardiac function and energy metabolism through regulating lipid and glucose metabolism.The effects may be mediated by PPARγ pathway.展开更多
OBJECTIVE Oxidative sress is one of the key factor responsible for occurrence and development of hepatic fibrosis,a common consequence of chronic liver injury of multiple etiology.Nuclear factor erythroid 2-related fa...OBJECTIVE Oxidative sress is one of the key factor responsible for occurrence and development of hepatic fibrosis,a common consequence of chronic liver injury of multiple etiology.Nuclear factor erythroid 2-related factor 2(Nrf2)serves as a major regulator of a celular defense system against oxidative stress.Xiaochaihutang(XCHT),a compound of seven botanical extracts used for liver diseases traditionally in East Asia.However,few studies have investigated its anti-hepatic fibrosis effects and pathophysiological mechanism of action.The present study was designed to confirm the anti-hepatic fibrosis effects and explore its potential mechanism of action by investigating the intervention of Nrf2 pathway.METHODS Liver fibrosis was induced by repeated injection of Carbon tetrachloride(CCl4) over a period of 9 weeks.Starting from the 6 th week,the animals in treatment groups were given the appropriate dose of XCHT granules and silybin.Biochemical parameters,histological changes of the liver and alpha-smooth muscle actin(α-SMA) were determined.The expressions of Nrf2,Keap1,Nqo1,HO-1,Gclc and Gclm were assessed by RT-PCR and Western blot.RESULTS CCl4 caused a significant fibrosis damage in the rat liver and the liver functions and fibrosis degree were significantly improved by XCHT(5 g·kg^(-1) and 10 g·kg^(-1)).XCHT(5 g·kg^(-1) and 10 g·kg^(-1)) treatment significantly decreased the number of cells labeled with α-SMA antibodies.Moreover,XCHT(5 g·kg^(-1) and 10 g·kg^(-1))significantly increase Nqo1,HO-1,Gclc and Gclm expressions in the liver.CONCLUSION T hese studies establish XCHT is a potentially useful therapeutic agent for treatment of hepatic fibrosis and it might be via regulation of Nrf2 pathway in rats against oxidative stress,making further efforts to inhibiting the activated HSCs.Activation or up-regulation of Nrf2 pathway may be an alternative treatment strategy for liver fibrosis.展开更多
OBJECTIVE Compound Kushen injection(CKI)is a bis-herbal formulation extracted from Kushen(Radix Sophorae Flavescentis)and Baituling(Rhizoma Heterosmilacis Japonicae).Clinically,it is used as the adjuvant treatment of ...OBJECTIVE Compound Kushen injection(CKI)is a bis-herbal formulation extracted from Kushen(Radix Sophorae Flavescentis)and Baituling(Rhizoma Heterosmilacis Japonicae).Clinically,it is used as the adjuvant treatment of cancer.However,with the increased application,the cases of immediate hypersensitivity reactions(IHRs)also gradually rise.In this study,we investigated the underlying mechanism(s)and active constituent(s)for CKI-induced IHRs in experimental models.METHODS T helper 2(Th2)immunity-amplified mice were prepared by aluminum adjuvant.Anaphylactic shock was detected by measuring rectal thermometry in propranolol pretreated mice.For evaluating microvascular permeability,Evans blue extravasation assay was used.Platelet-activating factor(PAF),serum total IgE(tIgE)and mouse mast cell protease 1(MMCP1)were measured by ELISA.RESULTS The obtained results showed that CKI did not elevate serum tIgE and MMCP1 after consecutive immunization for five weeks,but could induce Evans blue extravasation(local)and cause obvious hypothermia(systemic)after a single injection.Further study showed that alkaloids in Kushen,especially matrine,were responsible for CKI-induced IHRs.Mechanism study showed that various PAF receptor antagonists could significantly counter CKI-induced IHRs locally or systemically.In cell system,CKI was able to promote PAF production in a non-cell-selective manner.In cell lysate,the effect of CKI on PAF production became stronger and could be abolished by blocking de novo pathway.CONCLUSION In conclusion,our study identifies,for the first time,that CKI is a PAF inducer.It causes non-immunologic IHRs,rather than IgE-dependent IHRs,by promoting PAF production through de novo pathway.Alkaloids in Kushen,especially matrine,are the prime culprits for IHRs.Our findings may provide a potential approach for preventing and treating CKI-induced IHRs.展开更多
Aim Magnesium lithospermate B （MLB） is the most abundant hydrophilic active component of Salvia rniltiorrhiza Radix, a traditional Chinese herbal medicine mainly used to treat cardiovascular diseases. Studies have s...Aim Magnesium lithospermate B （MLB） is the most abundant hydrophilic active component of Salvia rniltiorrhiza Radix, a traditional Chinese herbal medicine mainly used to treat cardiovascular diseases. Studies have shown that endothelial activation contributes to the pathophysiology of cardiovascular diseases such as atherosclero- sis, diabetic vasculopathy, heart failure and hypertension. In the present study, the effects of MLB on endothelial activation were investigated. Lipopolysaccharide （LPS） 1 mg L^-1 was employed to induce endothelial activation, which was determined by relative gene expression and endothelial adhesion assay. Results showed that pretreatment with MLB attenuated LPS-induced ICAM1, VCAM1 and TNF-α upregulation in human dermal microvascular endo- thelial cells （HMEC-1） in dose-dependent manner, which contributed to the reduction of THP-1 adhesion to HMEC-1. Furthermore, it was revealed that 100 μmol · L^-1 MLB significantly decreased the nuclear translocation of NF-KB p65, a critical transcription factor in LPS-indueed inflammatory response, through the inhibition of IKBμ degradation. Besides, the transcriptional activity of NF-KB p65 was also inhibited by the pretreatment of MLB. Mo- reover, MLB pretreatment considerably inhibited LPS-induced p38 phosphorylation, which at least partly contribu- ted to the reduction of ICAM1 expression. In conclusion, these findings suggest that MLB inhibits LPS-induced nu- clear translocation and transcripitional activity of NF-KB, thus attenuates the increased expression of adhesion mole- cules and inflammatory factors, protects endothelial cells from LPS-induced activation.展开更多
Aim Shengmai injection （SMI） , a Chinese patent medicine deprived from an ancient Chinese herbal compound Shengmai san, which is used extensively for the treatment of cardiovascular and cerebrovascular disease in cl...Aim Shengmai injection （SMI） , a Chinese patent medicine deprived from an ancient Chinese herbal compound Shengmai san, which is used extensively for the treatment of cardiovascular and cerebrovascular disease in clinic. To determine the neuroprotective effect of SMI, the effect and the relevant mechanism of SMI had been inves- tigated on cerebral ischemia-reperfusion injury in mice. Methods Right middle cerebral artery was occluded by in- serting a thread through intemal carotid artery for 1 h, and then reperfusion for 24 h in mice. Neuroprotective effect was testified using transmission electron microscopic examination, evaluation of infarct volume and neurological defi- cits. Related mechanism was evaluated by western blotting. The SMI was injected intraperitoneally after ischemia for 1 h at doses of 1.42, 2. 84 and 5.68 g · kg^-1. The control group received saline as vehicle of SMI. Results SMI （ 1.42, 2. 84 and 5. 68 g · kg^-1） could significantly reduced the infarct volume, SMI （5.68 g · kg^-1） could signifi- cantly improved the neurological deficits, as well as the neuron＇s morphology change. SMI （5.68 g · kg^-1） could significantly inhibited the autophagy-related proteins： Beclinl and LC3. SMI （5. 68 g · kg^-1） remarkably inhibited the phosphorylation of adenosine monophosphate activated protein kinase （AMPK）, and down-regulated the phospho- rylation of mammalian target of rapamycin （roTOR） and Jun N-terminal kinase （JNK） after 24 h reperfusion. Con-clusion The results indicated that SMI elicits potent protection against cerebral ischemia/reperfusion injury, which may partly be due to the inhibition in autophagy and related signal pathways.展开更多
OBJECTIVE To investigate the protective effect of icariin(ICA) on lipopolysaccharide(LPS)-induced BV2 microglia injury,and to clarify the role of nuclear factor erythroid 2-related factor 2(Nrf2) signaling pathway in ...OBJECTIVE To investigate the protective effect of icariin(ICA) on lipopolysaccharide(LPS)-induced BV2 microglia injury,and to clarify the role of nuclear factor erythroid 2-related factor 2(Nrf2) signaling pathway in BV2 microglia-mediated neuroinflammation.METHODS BV2 microglia were randomly divided into control,ICA(0.1 μmol·L^(-1)),LPS(1 mg·L^(-1)),LPS + ICA(0.01 μmol·L^(-1)),and LPS + ICA(0.1 μmol·L^(-1))groups.BV2 microglia were treated with ICA for 30 min and then treated with LPS for 24 h.MTT assay was used to determine the cells survival rate,Griess kit and ELISA kits were used to detect the contents of NO,IL-1β and IL-18 in the culture supernatant,Western blotting was used to detect the expression of Nrf2,HO-1 and NQO1.Real time RT-PCR was used to detect the expression of Nrf2,HO-1 and NQO1 after ICA addition for 2,6 and 24 h.And immunofluorescence was used to observe the activation of Nrf2.RESULTS ICA reduced LPS-induced NO,IL-1β and IL-18 production in the culture supernatant,and ICA increase LPS-induced mRNA and protein expression of Nrf2 signaling pathway.CONCLUSION ICA protects LPS induced neuroinflammation by regulating Nrf2 signaling pathway.展开更多
Aim Ginseng is the dried root of Panax ginseng C. A. Mayer. Since ancient times, ginseng has been used as one kind of treatment drug or tonic in China and even other eastern countries like Korea and Japan. Phar- macol...Aim Ginseng is the dried root of Panax ginseng C. A. Mayer. Since ancient times, ginseng has been used as one kind of treatment drug or tonic in China and even other eastern countries like Korea and Japan. Phar- macological active chemical ingredients and its extract of ginseng are a mixture of triterpenoid saponins, collectively called ginsenosides. Among them, ginsenoside Rgl is the most pharmacological active one. Based on prior experi- mental results and the understanding of alcoholic hepatitis, the major aim of this study is to investigate whether Rgl is beneficial in a rodent model mimic alcoholic hepatic injury associated with binge drinking and explore the under- lying possible mechanisms. Methods C57BL/6 mice were given oral consumption of 6 g · kg^-1 alcohol 1 h after treated with Rgl （ 10, 20 and 40 mg · kg^-1） or dexamethasone （ 1 mg · kg^-1） for 9 consecutive days. Biochemi- cal analyses were performed and liver fragments were processed for microscopy, immunohistochemistry and western blot analysis. Results According to our data, Rgl treatment significantly reversed the high mortality rate induced by alcohol consumption and also alleviated liver impairment as evidenced by the decrease of serum parameters. Meanwhile, histological and ultrastructural analysis of alcoholic groups showed hepatocellular impairment but re- stored in Rgl-treated groups. Overproductive inflammatory cytokines were also suppressed by Rgl in alcohol-intoxi- cated mouse livers. In addition, changes of GR related NF-KB pathway, including phospho-IKB-ot, were also mod- ulated to normal levels. Conclusion This study demonstrates that Rgl might promote GR mediating the repression of NF-KB and inhibit the inflammatory reactions in alcoholic hepatitis.展开更多
文摘The subcortical visual pathway is generally thought to be involved in dangerous information processing,such as fear processing and defensive behavior.A recent study,published in Human Brain Mapping,shows a new function of the subcortical pathway involved in the fast processing of non-emotional object perception.Rapid object processing is a critical function of visual system.Topological perception theory proposes that the initial perception of objects begins with the extraction of topological property(TP).However,the mechanism of rapid TP processing remains unclear.The researchers investigated the subcortical mechanism of TP processing with transcranial magnetic stimulation(TMS).They find that a subcortical magnocellular pathway is responsible for the early processing of TP,and this subcortical processing of TP accelerates object recognition.Based on their findings,we propose a novel training approach called subcortical magnocellular pathway training(SMPT),aimed at improving the efficiency of the subcortical M pathway to restore visual and attentional functions in disorders associated with subcortical pathway dysfunction.
文摘In order to clarify the mechanism of action of licorice flavonoids in alleviating bone loss caused by osteoporosis,this study compared the effects of four glycyrrhiza flavonoids,naringenin,liquiritigenin,isoliquiritigenin,and licochalcone A,on osteogenic differentiation and mineralization by molecular docking simulation,alkaline phosphatase(ALP)activity and osteocalcin(OCN)content assays,and Runt-related transcription factor 2(Runx2)expression,and explored their potential molecular mechanisms.The results of molecular docking showed that the docking score of liquiritigenin with the estrogen receptor(ER)was the highest.All four flavonoids up-regulated ALP activity and OCN concentration in MC3T3-E1 cells,thereby elevating the mineralization level,among which liquiritigenin was the most effective.Moreover,treatment with a phosphatidylinositol-3-kinase(PI3K)inhibitor(LY294002)inhibited liquiritigenin from inducing increased phosphorylation levels in the PI3K/protein kinase B(AKT)signaling pathway and up-regulation of Runx2 expression,suggesting that PI3K and AKT were involved in osteogenic action.Liquiritigenin reversed bone mineral density loss in a zebrafish osteoporosis model.These findings suggest that liquiritigenin has the most significant osteogenic effect among the four estrogen-like flavonoids,stimulating osteoblast differentiation and bone mineralization through the activation of Runx2 via the PI3K/AKT signaling pathways.In conclusion,this study highlights the great potential of liquiritigenin for preventing and treating osteoporosis.
基金Supported by the Natural Science Foundation of the Heilongjiang Province of China(C2016003)China Postdoctoral Science Foundation(2015M581415)Heilongjiang Postdoctoral Fund(LBH-Z15005)。
文摘The trace element selenium(Se)occurs naturally throughout the earth.Se deficiency has been linked to impaired breast health and other diseases in human and animals.Compared to severe Se deficiency,marginal dietary Se deficiency accusers more frequently in low-Se regions.Therefore,to investigate the Se status and inflammatory response of the mammary gland under marginal dietary Se levels,an lipopolysaccharide(LPS)induced mouse mastitis model was established.Mice were fed with moderate Se diet(0.087 mg•kg^(-1) Se),adequate Se diet(0.15 mg•kg^(-1) Se)or excessive Se diet(1.5 mg•kg^(-1) Se)for 60 days.Se status and inflammatory factors were investigated.Results showed that the Se status of mammary gland correlated with dietary Se levels.Marginal Se deficiency exacerbated mammary tissue histopathology;increased the mRNA level of inflammatory genes tumor necrosis factor alpha(TNF-α),interleukin-1β(IL-1β)and cyclooxygenase-2(COX-2);and enhanced the phosphorylation of NF-κB p65 in mammary gland tissues.Supplementation of Se in diet higher than recommended levels reduced the inflammatory reaction of mammary glands in LPS-induced mastitis model and provided a protective effect.
文摘Objective To investigate the effect of mucin 1(MUC1)on the proliferation and apoptosis of nasopharyngeal carcinoma(NPC)and its regulatory mechanism.Methods The 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital.The expression of MUC1 was measured by real-time quantitative PCR(qPCR)in the patients with PNC.The 5-8F and HNE1 cells were transfected with siRNA control(si-control)or siRNA targeting MUC1(si-MUC1).Cell proliferation was analyzed by cell counting kit-8 and colony formation assay,and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells.The qPCR and ELISA were executed to analyze the levels of TNF-αand IL-6.Western blot was performed to measure the expression of MUC1,NFкB and apoptosis-related proteins(Bax and Bcl-2).Results The expression of MUC1 was up-regulated in the NPC tissues,and NPC patients with the high MUC1 expression were inclined to EBV infection,growth and metastasis of NPC.Loss of MUC1 restrained malignant features,including the proliferation and apoptosis,downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells.Conclusion Downregulation of MUC1 restrained biological characteristics of malignancy,including cell proliferation and apoptosis,by inactivating NF-κB signaling pathway in NPC.
基金National Natural Science Foundation of China(22073030)the Oriental Scholars of Shanghai Universities。
文摘Dichloromethane(DCM)dehalogenase stands as a crucial enzyme implicated in the degradation of methylene chloride across diverse environmental and biological contexts.However,the unbinding pathways of ligands from DCM dehalogenase remain unexplored.In order to gain a deeper understanding of the binding sites and dissociation pathways of dichloromethane(DCM)and glutathione(GSH)from the DCM dehalogenase,random accelerated molecular dynamics(RAMD)simulations were performed,in which DCM and GSH were forced to leave the active site.The protein structure was predicted using Alphafold2,and the conformations of GSH and DCM in the binding pocket were predicted by docking.A long equilibrium simulation was conducted to validate the structure of the complex.The results show that GSH is most commonly observed in three main pathways,one of which is more important than the other two.In addition,DCM was observed to escape along a unique pathway.The key residues and protein helices of each pathway were identified.The results can provide a theoretical foundation for the subsequent dissociation mechanism of DCM dehalogenase.
文摘Objective Chronic stress can induce cognitive dysfunction,but the underlying mechanisms remain unknown.Studies have confirmed that the high mobility group box 1/Toll-like receptor 4(HMGB1/TLR4)pathway is closely associated with cognitive impairment.Therefore,this research aimed to explore whether the HMGB1/TLR4 pathway involves in chronic stress-induced cognitive dysfunction.Methods The chronic unpredictable mild stress(CUMS)mouse model was established by randomly giving different types of stress every day for four consecutive weeks.Cognitive function was detected by novel object recognition test,Y-maze test,and Morris water maze test.The protein expressions of HMGB1,TLR4,B-cell lymphoma 2(BCL2),and BCL2 associated X(BAX)were determined by Western blot.The damage of neurons in the hippocampal CA1 region was observed by hematoxylin-eosin(HE)staining.Results The protein expressions of HMGB1 and TLR4 were significantly increased in the hippocampus of chronic stress mice.Furthermore,inhibition of the HMGB1/TLR4 pathway induced by ethyl pyruvate(EP,a specific inhibitor of HMGB1)and TAK242(a selective inhibitor of TLR4)treatment attenuated cognitive impairment in chronic stress mice,according to the novel object recognition test,Y-maze test,and Morris water maze test.In addition,administration of EP and TAK242 also mitigated the increase of apoptosis in the hippocampus of chronic stress mice.Conclusion These results indicate that the hippocampal HMGB1/TLR4 pathway contributes to chronic stress-induced apoptosis and cognitive dysfunction.
文摘目的:探讨蜘蛛香总黄酮对肝癌H22小鼠抗肿瘤作用及对pathways in cancer的影响。方法:建立H22肝癌皮下荷瘤模型,随机分为模型对照组、阳性对照组、蜘蛛香总黄酮高、低剂量组。给药10 d后,解剖称取瘤重,计算抑瘤率,并应用小鼠全基因组基因芯片考察蜘蛛香总黄酮对瘤组织pathways in cancer的影响。结果:与模型对照组相比,阳性对照组、蜘蛛香总黄酮高、低剂量组的平均瘤重明显下降(P<0.01,P<0.05,P<0.05),各组抑瘤率分别为45.32%、30.06%、25.97%。给药组pathways in cancer中有17个基因表达同时发生了显著性变化,其中Ccne2、Cdkn2b、Ctbp2、Mmp1a、Myc和Vegfa的表达发生了上调,而Vegfc、Csf1r、Epas1、Figf、Fzd9、Igf1、Pdgfra、Pik3r1、Prkcb、Tcf7l1和Tcf7l2的表达发生了下调,主要从细胞周期调控、PI3K-AKT途径、Wnt途径抑制肿瘤增殖、迁移,促进其凋亡。结论:蜘蛛香总黄酮具有一定的抗肝癌活性,作用机理可能与调节pathways in cancer的信号转导相关。
基金supported by National Natural Science Foundation of China(No.523B2070,No.52225606).
文摘Polymeric perylene diimide(PDI)has been evidenced as a good candidate for photocatalytic water oxidation,yet the origin of the photocatalytic oxygen evolution activity remains unclear and needs further exploration.Herein,with crystal and atomic structures of the self-assembled PDI revealed from the X-ray diffraction pattern,the electronic structure is theoretically illustrated by the first-principles density functional theory calculations,suggesting the suitable band structure and the direct electronic transition for efficient photocatalytic oxygen evolution over PDI.It is confirmed that the carbonyl O atoms on the conjugation structure serve as the active sites for oxygen evolution reaction by the crystal orbital Hamiltonian group analysis.The calculations of reaction free energy changes indicate that the oxygen evolution reaction should follow the reaction pathway of H_(2)O→^(*)OH→^(*)O→^(*)OOH→^(*)O_(2)with an overpotential of 0.81 V.Through an in-depth theoretical computational analysis in the atomic and electronic structures,the origin of photocatalytic oxygen evolution activity for PDI is well illustrated,which would help the rational design and modification of polymeric photocatalysts for efficient oxygen evolution.
基金the research committee at Malek Ashtar University of Technology (MUT) for their invaluable support of this project
文摘Recent advancements have led to the synthesis of various new metal-containing explosives,particularly energetic metal-organic frameworks(EMOFs),which feature high-energy ligands within well-ordered crystalline structures.These explosives exhibit significant advantages over traditional compounds,including higher density,greater heats of detonation,improved mechanical hardness,and excellent thermal stability.To effectively evaluate their detonation performance,it is crucial to have a reliable method for predicting detonation heat,velocity,and pressure.This study leverages experimental data and outputs from the leading commercial computer code to identify suitable decomposition pathways for different metal oxides,facilitating straightforward calculations for the detonation performance of alkali metal salts,and metal coordination compounds,along with EMOFs.The new model enhances predictive reliability for detonation velocities,aligning more closely with experimental results,as evi-denced by a root mean square error(RMSE)of 0.68 km/s compared to 1.12 km/s for existing methods.Furthermore,it accommodates a broader range of compounds,including those containing Sr,Cd,and Ag,and provides predictions for EMOFs that are more consistent with computer code outputs than previous predictive models.
文摘Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are currently no data on molecular markers associated with resistance. The conflicting data were reported regarding the AKT/m-TOR signaling pathway components as markers predicting resistance. The AKT/m-TOR signaling pathway is involved in the development of many human cancers; its activation is related to cell proliferation, angiogenesis, apoptosis, as well as to therapy resistance. Molecular alterations in the AKT/m-TOR signaling pathway provide a platform to identify universal markers associated with the development of resistance to cancer therapy.
基金supported by National Natural Science Foundation of China(81330081,81473223and 81673444)Anhui Province Postdoctoral Science Foundation(2016B134)
文摘G protein coupled receptors(GPCRs)are transmembrane receptor proteins,which allow signals to transfer across membrane.GPCRs include a large number of receptors,different receptors mediated different signaling pathways of GPCRs-adenylyl cyclase(AC)-cyclic adenosine 3',5'-monophosphate(c AMP),including β2 adrenergic receptors(β2-ARs)-AC-c AMP signaling pathways,E-prostanoid2/4(EP2/4)-AC-cA MP signaling pathways.Regulatory proteins,such as G protein coupled receptor kinases(GRKs)andβ-arrestins,play important modulatory roles in GPCRs signaling pathway.GPCRs signaling pathway and regulatory proteins implicate the pathogenesis process of inflammatory and immune response.Rheumatoid arthritis(RA)is an autoimmune disease characterized by synovitis and accompanied with inflammatory and abnormal immune response.This article review the advances on GPCRs signaling pathway implicating in the inflammatory and immune response of RA.
文摘The treatment and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied,but without a systematic summary currently.This review comprehensively collected and analyzed the traditional Chinese medicine on the treatment and signaling pathway regulation of osteoporosis in recent ten years,such as Epimedium,Drynariae Rhizoma,Cnidium,Eucommia,Psoralen and Dipsacus.Based on the existing findings,we concluded the following conclusions:(1)kidney-tonifying traditional Chinese medicine treats osteoporosis mainly through BMP-Smads,Wnt/β-catenin,MAPK,PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/RANK,estrogen,CTSK signaling pathway to inhibit osteoclasts of bone resorption.(1)Epimedium,Drynariae Rhizoma,Cnidium and Psoralen up-regulate the key proteins and genes of BMP-Smads and Wnt/β-catenin signaling pathways to promote bone formation.(2)Epimedium,Drynariae Rhizoma,Cnidium,Eucommia,Psoralen,Dipsacusinhibit the bone resorption by mediating the OPG/RANKL/RANK signaling pathway.(2)Kidney-tonifying traditional Chinese medicine prevent and treat osteoporosis through a variety of ways:Icariin,Naringin,Osthol,Psoralen can regulate BMP-Smads,Wnt/β-catenin signaling pathway to promote bone formation,but also activate OPG/RANKL/RANK,CTSK and other signaling pathway to inhibit bone resorption.(3)The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification.
基金National Natural Science Foundation of China(81530100,81673802,81673712,81822049)。
文摘OBJECTIVE To investigate the effects of astragaloside IV(which can be extracted from the traditional Chinese medicine Astragalus membranaceus)on lipid and glucose metabolism in acute myocardial infarction(AMI).METHODS Model of heart failure(HF)after AMI was established with ligation of left anterior descending artery on Sprague-Dawley(SD)rats.The rats were divided into three groups:sham,model and astragaloside IV treatment group.Twenty-eight days after treatment(astragaloside IV,20 mg·kg-1 daily),hematoxylin-eosin(HE)staining was applied to visualize cardiomyocyte morphological changes.High performance liquid chromatography(HPLC)was performed to assess the contents of adenosine phosphates in heart.Positron emission tomography and computed tomography(PET-CT)was conducted to evaluate the cardiac glucose metabolism.Expressions of key molecules such as peroxisome proliferatoractivated receptor γ(PPARγ),sterol carrier protein 2(SCP2)and long chain acyl CoA dehydrogenase(ACADL)were measured by Western blotting and immunohistochemistry.Oxygen-glucose deprivation-reperfusion(OGD/R)-induced H9C2 injury cardiomyocyte model was adopted for potential mechanism research in vitro.RESULTS Treatment with astragaloside Ⅳ rescued hearts from structural and functional damages as well as inflammatory infiltration.Levels of adenosine triphosphate(ATP)and energy charge(EC)in astragaloside IV group were also up-regulated compared to model group.Further results demonstrated that critical enzymes both in lipid metabolism and glucose metabolism compro mised in model group compared to sham group.Intriguingly,astragalosideⅣcould up-regulate critical enzymes including ACADL and SCP2 in lipid metabolism accompanying with promoting effect on molecules in glycolysis simultaneously.Results on upstreaming signaling pathway demonstrated that astragaloside Ⅳ could dramatically increase the expres sions of PPARγ.In vitro study suggested the efficacy of astragalosideⅣcould be blocked by T0070907,a selective PPARγ inhibitor.CONCLUSION Astragaloside IV has cardioprotective effect in improving cardiac function and energy metabolism through regulating lipid and glucose metabolism.The effects may be mediated by PPARγ pathway.
文摘OBJECTIVE Oxidative sress is one of the key factor responsible for occurrence and development of hepatic fibrosis,a common consequence of chronic liver injury of multiple etiology.Nuclear factor erythroid 2-related factor 2(Nrf2)serves as a major regulator of a celular defense system against oxidative stress.Xiaochaihutang(XCHT),a compound of seven botanical extracts used for liver diseases traditionally in East Asia.However,few studies have investigated its anti-hepatic fibrosis effects and pathophysiological mechanism of action.The present study was designed to confirm the anti-hepatic fibrosis effects and explore its potential mechanism of action by investigating the intervention of Nrf2 pathway.METHODS Liver fibrosis was induced by repeated injection of Carbon tetrachloride(CCl4) over a period of 9 weeks.Starting from the 6 th week,the animals in treatment groups were given the appropriate dose of XCHT granules and silybin.Biochemical parameters,histological changes of the liver and alpha-smooth muscle actin(α-SMA) were determined.The expressions of Nrf2,Keap1,Nqo1,HO-1,Gclc and Gclm were assessed by RT-PCR and Western blot.RESULTS CCl4 caused a significant fibrosis damage in the rat liver and the liver functions and fibrosis degree were significantly improved by XCHT(5 g·kg^(-1) and 10 g·kg^(-1)).XCHT(5 g·kg^(-1) and 10 g·kg^(-1)) treatment significantly decreased the number of cells labeled with α-SMA antibodies.Moreover,XCHT(5 g·kg^(-1) and 10 g·kg^(-1))significantly increase Nqo1,HO-1,Gclc and Gclm expressions in the liver.CONCLUSION T hese studies establish XCHT is a potentially useful therapeutic agent for treatment of hepatic fibrosis and it might be via regulation of Nrf2 pathway in rats against oxidative stress,making further efforts to inhibiting the activated HSCs.Activation or up-regulation of Nrf2 pathway may be an alternative treatment strategy for liver fibrosis.
文摘OBJECTIVE Compound Kushen injection(CKI)is a bis-herbal formulation extracted from Kushen(Radix Sophorae Flavescentis)and Baituling(Rhizoma Heterosmilacis Japonicae).Clinically,it is used as the adjuvant treatment of cancer.However,with the increased application,the cases of immediate hypersensitivity reactions(IHRs)also gradually rise.In this study,we investigated the underlying mechanism(s)and active constituent(s)for CKI-induced IHRs in experimental models.METHODS T helper 2(Th2)immunity-amplified mice were prepared by aluminum adjuvant.Anaphylactic shock was detected by measuring rectal thermometry in propranolol pretreated mice.For evaluating microvascular permeability,Evans blue extravasation assay was used.Platelet-activating factor(PAF),serum total IgE(tIgE)and mouse mast cell protease 1(MMCP1)were measured by ELISA.RESULTS The obtained results showed that CKI did not elevate serum tIgE and MMCP1 after consecutive immunization for five weeks,but could induce Evans blue extravasation(local)and cause obvious hypothermia(systemic)after a single injection.Further study showed that alkaloids in Kushen,especially matrine,were responsible for CKI-induced IHRs.Mechanism study showed that various PAF receptor antagonists could significantly counter CKI-induced IHRs locally or systemically.In cell system,CKI was able to promote PAF production in a non-cell-selective manner.In cell lysate,the effect of CKI on PAF production became stronger and could be abolished by blocking de novo pathway.CONCLUSION In conclusion,our study identifies,for the first time,that CKI is a PAF inducer.It causes non-immunologic IHRs,rather than IgE-dependent IHRs,by promoting PAF production through de novo pathway.Alkaloids in Kushen,especially matrine,are the prime culprits for IHRs.Our findings may provide a potential approach for preventing and treating CKI-induced IHRs.
文摘Aim Magnesium lithospermate B （MLB） is the most abundant hydrophilic active component of Salvia rniltiorrhiza Radix, a traditional Chinese herbal medicine mainly used to treat cardiovascular diseases. Studies have shown that endothelial activation contributes to the pathophysiology of cardiovascular diseases such as atherosclero- sis, diabetic vasculopathy, heart failure and hypertension. In the present study, the effects of MLB on endothelial activation were investigated. Lipopolysaccharide （LPS） 1 mg L^-1 was employed to induce endothelial activation, which was determined by relative gene expression and endothelial adhesion assay. Results showed that pretreatment with MLB attenuated LPS-induced ICAM1, VCAM1 and TNF-α upregulation in human dermal microvascular endo- thelial cells （HMEC-1） in dose-dependent manner, which contributed to the reduction of THP-1 adhesion to HMEC-1. Furthermore, it was revealed that 100 μmol · L^-1 MLB significantly decreased the nuclear translocation of NF-KB p65, a critical transcription factor in LPS-indueed inflammatory response, through the inhibition of IKBμ degradation. Besides, the transcriptional activity of NF-KB p65 was also inhibited by the pretreatment of MLB. Mo- reover, MLB pretreatment considerably inhibited LPS-induced p38 phosphorylation, which at least partly contribu- ted to the reduction of ICAM1 expression. In conclusion, these findings suggest that MLB inhibits LPS-induced nu- clear translocation and transcripitional activity of NF-KB, thus attenuates the increased expression of adhesion mole- cules and inflammatory factors, protects endothelial cells from LPS-induced activation.
文摘Aim Shengmai injection （SMI） , a Chinese patent medicine deprived from an ancient Chinese herbal compound Shengmai san, which is used extensively for the treatment of cardiovascular and cerebrovascular disease in clinic. To determine the neuroprotective effect of SMI, the effect and the relevant mechanism of SMI had been inves- tigated on cerebral ischemia-reperfusion injury in mice. Methods Right middle cerebral artery was occluded by in- serting a thread through intemal carotid artery for 1 h, and then reperfusion for 24 h in mice. Neuroprotective effect was testified using transmission electron microscopic examination, evaluation of infarct volume and neurological defi- cits. Related mechanism was evaluated by western blotting. The SMI was injected intraperitoneally after ischemia for 1 h at doses of 1.42, 2. 84 and 5.68 g · kg^-1. The control group received saline as vehicle of SMI. Results SMI （ 1.42, 2. 84 and 5. 68 g · kg^-1） could significantly reduced the infarct volume, SMI （5.68 g · kg^-1） could signifi- cantly improved the neurological deficits, as well as the neuron＇s morphology change. SMI （5.68 g · kg^-1） could significantly inhibited the autophagy-related proteins： Beclinl and LC3. SMI （5. 68 g · kg^-1） remarkably inhibited the phosphorylation of adenosine monophosphate activated protein kinase （AMPK）, and down-regulated the phospho- rylation of mammalian target of rapamycin （roTOR） and Jun N-terminal kinase （JNK） after 24 h reperfusion. Con-clusion The results indicated that SMI elicits potent protection against cerebral ischemia/reperfusion injury, which may partly be due to the inhibition in autophagy and related signal pathways.
基金National Natural Science Foundation of China(81760658).
文摘OBJECTIVE To investigate the protective effect of icariin(ICA) on lipopolysaccharide(LPS)-induced BV2 microglia injury,and to clarify the role of nuclear factor erythroid 2-related factor 2(Nrf2) signaling pathway in BV2 microglia-mediated neuroinflammation.METHODS BV2 microglia were randomly divided into control,ICA(0.1 μmol·L^(-1)),LPS(1 mg·L^(-1)),LPS + ICA(0.01 μmol·L^(-1)),and LPS + ICA(0.1 μmol·L^(-1))groups.BV2 microglia were treated with ICA for 30 min and then treated with LPS for 24 h.MTT assay was used to determine the cells survival rate,Griess kit and ELISA kits were used to detect the contents of NO,IL-1β and IL-18 in the culture supernatant,Western blotting was used to detect the expression of Nrf2,HO-1 and NQO1.Real time RT-PCR was used to detect the expression of Nrf2,HO-1 and NQO1 after ICA addition for 2,6 and 24 h.And immunofluorescence was used to observe the activation of Nrf2.RESULTS ICA reduced LPS-induced NO,IL-1β and IL-18 production in the culture supernatant,and ICA increase LPS-induced mRNA and protein expression of Nrf2 signaling pathway.CONCLUSION ICA protects LPS induced neuroinflammation by regulating Nrf2 signaling pathway.
文摘Aim Ginseng is the dried root of Panax ginseng C. A. Mayer. Since ancient times, ginseng has been used as one kind of treatment drug or tonic in China and even other eastern countries like Korea and Japan. Phar- macological active chemical ingredients and its extract of ginseng are a mixture of triterpenoid saponins, collectively called ginsenosides. Among them, ginsenoside Rgl is the most pharmacological active one. Based on prior experi- mental results and the understanding of alcoholic hepatitis, the major aim of this study is to investigate whether Rgl is beneficial in a rodent model mimic alcoholic hepatic injury associated with binge drinking and explore the under- lying possible mechanisms. Methods C57BL/6 mice were given oral consumption of 6 g · kg^-1 alcohol 1 h after treated with Rgl （ 10, 20 and 40 mg · kg^-1） or dexamethasone （ 1 mg · kg^-1） for 9 consecutive days. Biochemi- cal analyses were performed and liver fragments were processed for microscopy, immunohistochemistry and western blot analysis. Results According to our data, Rgl treatment significantly reversed the high mortality rate induced by alcohol consumption and also alleviated liver impairment as evidenced by the decrease of serum parameters. Meanwhile, histological and ultrastructural analysis of alcoholic groups showed hepatocellular impairment but re- stored in Rgl-treated groups. Overproductive inflammatory cytokines were also suppressed by Rgl in alcohol-intoxi- cated mouse livers. In addition, changes of GR related NF-KB pathway, including phospho-IKB-ot, were also mod- ulated to normal levels. Conclusion This study demonstrates that Rgl might promote GR mediating the repression of NF-KB and inhibit the inflammatory reactions in alcoholic hepatitis.
