lipopolysaccharide

摘要： Neuroinflammation hinders repair of the central nervous system(CNS).Stem cell transplantation is a very promising approach for treatment of CNS injuries.However,it is difficult to select seed cells that can both facilitate nerve regeneration and improve the microenvironment in the CNS.In this study,we isolated multilineage-differentiating stress-enduring(Muse)cells from bone marrow mesenchymal stem cells.We explored the anti-inflammatory effect and mechanism of Muse cells in vitro by coculture of Muse cells with lipopolysaccharide-stimulated microglia.Our results showed that Muse cells effectively reduced the transcription and secretion of tumor necrosis factorαand interleukin-1βand increased the expression of transforming growth factor-βand interleukin-10 in microglia.In addition,Muse cells decreased the number of M1 microglia and increased the proportion of M2 microglia in an inflammatory environment more effectively than bone marrow mesenchymal stem cells.We also show that Muse cells inhibited the protein expression of toll-like receptor 4(TLR4)and myeloid differentiation primary response protein(MyD88)and inhibited the expression of the phosphorylated forms of transcription factor p65,nuclear factor(NF)-κB inhibitor alpha,and p38 mitogen-activated protein kinase(MAPK)in microglia.Therefore,we suggest Muse cells cause antineuroinflammatory effects by inhibition of the TLR4/MyD88/NF-κB and p38 MAPK signaling pathways in microglia.Our results shed light on the function of Muse cells in relation to CNS diseases and provide insight into the selection of seed cells.

摘要： Triggering receptor expressed on myeloid cells-like 2(TREML2)is a newly identified susceptibility gene for Alzheimer's disease(AD).It encodes a microglial inflammation-associated receptor.To date,the potential role of mic roglial TREML2 in neuroinflammation in the context of AD remains unclear.In this study,APP/PS1 mice were used to investigate the dynamic changes of TREML2 levels in brain during AD progression.In addition,lipopolysaccharide(LPS)stimulation of primary microglia as well as a lentivirus-mediated TREML2 overexpression and knockdown were employed to explore the role of TREML2 in neuroinflammation in the context of AD.Our res ults show that TREML2 levels gradually increased in the brains of AP P/PS1 mice during disease progression.LPS stimulation of primary microglia led to the release of inflammato ry cytokines including interleukin-1β,inte rleukin-6,and tumor necrosis factor-a in the culture medium.The LPS-induced mic roglial release of inflammatory cytokines was enhanced by TREML2 overexpression and was attenuated by TREML2 knoc kdown.LPS increased the levels of mic roglial M1-type polarization marker inducible nitric oxide synthase.This effect was enhanced by TREML2 overexpression and ameliorated by TREML2 knockdown.Furthermore,the levels of microglial M2-type polarization markers CD206 and ARG1 in the primary microglia were reduced by TREML2 overexpression and elevated by TREML2 knockdown.LPS stimulation increased the levels of NLRP3 in primary microglia.The LPS-induced increase in NLRP3 was further elevated by TREML2 overexpression and alleviated by TREML2 knockdown.In summary,this study provides the first evidence that TREML2 modulates inflammation by regulating microglial polarization and NLRP3 inflammasome activation.These findings reveal the mechanisms by which TREML2 regulates microglial inflammation and suggest that TREML2 inhibition may represent a novel therapeutic strategy for AD.

摘要： Elongation factor Tu GTP binding domain protein 2(Eftud2)is a spliceosomal GTPase that serves as an innate immune modulator restricting virus infection.Microglia are the resident innate immune cells and the key players of immune response in the central nervous system.However,the role of Eftud2 in microglia has not been reported.In this study,we performed immunofluorescent staining and western blot assay and found that Eftud2 was upregulated in microglia of a 5xFAD transgenic mouse model of Alzheimer’s disease.Next,we generated an inducible microglia-specific Eftud2 conditional knockout mouse line(CX3CR1-CreER;Eftud2^(f/f) cKO)via Cre/loxP recombination and found that Eftud2 deficiency resulted in abnormal proliferation and promoted anti-inflammatory phenotype activation of microglia.Furthermore,we knocked down Eftud2 in BV2 microglia with siRNA specifically targeting Eftud2 and found that Eftud2-mediated regulation of microglial proinflammatory/anti-inflammatory phenotype activation in response to inflammation might be dependent on the NF-κB signaling pathway.Our findings suggest that Eftud2 plays a key role in regulating microglial polarization and homeostasis possibly through the NF-κB signaling pathway.

摘要： Objective To examine the neuroanatomical substrates underlying the effects of minocycline in alleviating lipopolysaccharide(LPS)-induced neuroinflammation.Methods Forty C57BL/6 male mice were randomly and equally divided into eight groups.Over three conse-cutive days,saline was administered to four groups of mice and minocycline to the other four groups.Immediately after the administration of saline or minocycline on the third day,two groups of mice were additionally injected with saline and the other two groups were injected with LPS.Six or 24 hours after the last injection,mice were sacrificed and the brains were removed.Immunohistochemical staining across the whole brain was performed to detect microglia activation via Iba1 and neuronal activation via c-Fos.Morphology of microglia and the number of c-Fo-positive neurons were analyzed by Image-Pro Premier 3D.One-way ANOVA and Fisher’s least-significant differences were employed for statistical analyses.Results Minocycline alleviated LPS-induced neuroinflammation as evidenced by reduced activation of microglia in multiple brain regions,including the shell part of the nucleus accumbens(Acbs),paraventricular nucleus(PVN)of the hypothalamus,central nucleus of the amygdala(CeA),locus coeruleus(LC),and nucleus tractus solitarius(NTS).Minocycline significantly increased the number of c-Fo-positive neurons in NTS and area postrema(AP)after LPS treatment.Furthermore,in NTS-associated brain areas,including LC,lateral parabrachial nucleus(LPB),periaqueductal gray(PAG),dorsal raphe nucleus(DR),amygdala,PVN,and bed nucleus of the stria terminali(BNST),minocycline also significantly increased the number of c-Fo-positive neurons after LPS administration.Conclusion Minocycline alleviates LPS-induced neuroinflammation in multiple brain regions,possibly due to increased activation of neurons in the NTS-associated network.

摘要： Administration of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)is believed to be an effective method for treating neurodevelopmental disorde rs.In this study,we investigated the possibility of hUC-MSCs treatment of neonatal hypoxic/ischemic brain injury associated with maternal immune activation and the underlying mechanism.We established neonatal rat models of hypoxic/ischemic brain injury by exposing pregnant rats to lipopolysaccharide on day 16 or 17 of pregnancy.Rat offspring were intranasally administe red hUC-MSCs on postnatal day 14.We found that polypyrimidine tract-binding protein-1(PTBP-1)participated in the regulation of lipopolysaccharide-induced maternal immune activation,which led to neonatal hypoxic/ischemic brain injury.Intranasal delive ry of hUC-MSCs inhibited PTBP-1 expression,alleviated neonatal brain injury-related inflammation,and regulated the number and function of glial fibrillary acidic protein-positive astrocytes,there by promoting plastic regeneration of neurons and im p roving brain function.These findings suggest that hUC-MSCs can effectively promote the repair of neonatal hypoxic/ischemic brain injury related to maternal immune activation through inhibition of PTBP-1 expression and astrocyte activation.

摘要： Alzheimer’s disease has proven to be largely intractable to treatment,despite years of research,and numerous trials of therapies that target the hallmarks of the disease-amyloid plaques and neurofibrillary tangles.The etiology of Alzheimer’s disease remains elusive.There is a growing body of evidence for an infectious trigger of Alzheimer’s disease,and,in particular,the focus has been on the oral pathogen Porphyromonas gingivalis(P.gingivalis).Reports of the expression of a misfolded form of p53 in non-neuronal cells(fibroblasts,peripheral blood mononuclear cells,and B cells)and serum,which appears several years before clinical symptoms manifest,may provide further support for the role of bacteria in general,and P.gingivalis in particular,in the initiation of the disease.This review presents a model of the pathway from initial oral infection with P.gingivalis to amyloid plaque formation and neuronal degeneration,via the steps of chronic periodontitis;secretion of the inflammagens lipopolysaccharide and gingipains into the bloodstream;induction of an inflammatory response in both peripheral cells and tissues;disruption of the blood-brain barrier,and entry into the central nervous system of the inflammagens and the P.gingivalis bacteria themselves.In this model,the misfolded p53(or“unfolded p53”;up53)is induced in non-neuronal cells and upregulated in serum as a result of oxidative stress due to lipopolysaccharide from P.gingivalis.up53 is therefore a potential biomarker for early diagnosis of the presence of a causative agent of Alzheimer’s disease.Fastidious dental hygiene and aggressive antibiotic treatment may prevent the patient progressing to clinical Alzheimer’s disease if serum up53 is detected at this pre-symptomatic stage.

摘要： Objective:To explore the effect of ethyl acetate gum resin extract of Boswellia serrata on lipopolysaccharide(LPS)induced inflammation and oxidative damage in hepatic and renal tissues of rats.Methods:The rats were divided into four groups:control,LPS,LPS+Boswellia serrata extracts(100 mg/kg and 200 mg/kg).LPS(1 mg/kg)and the extract(100 and 200 mg/kg,30 min before LPS)were administered intraperitoneally for 3 weeks.The levels of liver enzymes,albumin,total protein,creatinine,blood urea nitrogen(BUN),interleukin(IL)-6,malondialdehyde(MDA),and total thiol groups and superoxide dismutase(SOD)and catalase(CAT)activities were measured.Results:The levels of liver enzymes,creatinine,and BUN,IL-6,MDA in the LPS group were markedly increased(P<0.001)while albumin,total protein,and total thiol concentration,as well as SOD and CAT activities,were decreased compared with the control group(P<0.05 or 0.01).Boswellia serrata extracts diminished the levels of liver enzymes,creatinine,BUN,IL-6,and MDA(P<0.01 and P<0.001),and elevated the concentration of total protein and total thiol and SOD and CAT activities(P<0.05 or 0.01).Conclusions:The ethyl acetate gum resin extract of Boswellia serrata reduces LPS-induced inflammatory reactions and oxidative damage,thus ameliorating hepatic and renal function.

摘要： There are about over 100 trillion microbial cells in human gut,which affect the nutritional,metabolic,physiological and immune functions of the host.This paper reviews the differences in gut microbiota between patients with diabetic nephropathy(DN)and healthy people.These differences lead to the disorder of symbiotic relationship,which may have induced the progression of DN,as well as targeted interventions to reconstruct the symbiotic relationship.Recent studies have found that endotoxin from intestinal bacteria and a large number of toxic metabolites were produced by fermentation of gut microbiota,such as trimethylamine-N-oxide,indoxyl sulfate and p-cresol sulfate,leading to the disruption of intestinal barrier function.Endotoxin and bacterial metabolites,entering the systemic circulation,were involved in DN progression by mediating inflammatory responses,renin-angiotensin-system and vascular injury.The reduction of some beneficial bacterial metabolites in DN patients,such as short-chain fatty acids,would weak body energy metabolism and destroy glucose homeostasis.In addition,gut microbiota is essential for the conversion of bile acids,and plays an important role in the development of DN by synthesizing secondary bile acids and regulating glucose and metabolic balance through foresaid X receptor(FXR)and G protein-coupled bile acid receptor(TGR5).Animal and clinical studies have revealed that probiotics,prebiotics,fecal microbiota transplantation,and Chinese medicine intervention may have potential therapeutic effects in maintaining a metabolically balanced gut microbiota to reduce the progression of DN,end-stage renal disease and cardiovascular complications.

摘要： The objective of this study was to isolate and identify the intracellular bioactive peptides from mouse lymphocytes before and after lipopolysaccharide(LPS)stimulation,to explore novel peptides and to research the bioactive function.Mouse spleen lymphocytes were isolated and cultured with LPS stimulation(experimental group)or not(control group)to collect intracellular peptides.Totally 385 peptides were analyzed by nanoliter liquid phase-Q Exactive quadrupole ultra-high resolution orbitrap mass spectrometer(Nano LC-Q Exactive Plus)and identifi ed by PEAKS X software.After compared with peptides reported,131 novel peptides were discovered,which then were predicted bioactivity by Peptide Ranker and 6 peptides with high bioactivity were predicted function by BIOPEP-UMW database.Prediction data showed that they may have dipeptidyl peptidase IV(DPP-IV)inhibitory activity.Finally,two peptides showed better potent inhibition were verifi ed with competitive and noncompetitive modes.

摘要： Background:Galacto-oligosaccharides(GOS)are non-digestible food ingredients that promote the growth of beneficial bacteria in the gut.This study investigated the protective effect of the early-life GOS supplement on the piglets’gut function against the oxidative stress induced by lipopolysaccharide(LPS)-challenge.Methods:Eighteen neonatal piglets were assigned to three groups including CON,LPS and LPS+GOS groups.The piglets in CON group and LPS group received physiological saline,while those in LPS+GOS group received GOS solution for 13 d after birth.On d 14,the piglets in LPS group and LPS+GOS group were injected with LPS solutions,while the piglets in CON group were injected with the same volume of physiological saline.Results:The results showed that the early-life GOS supplement blocked the LPS-induced reactive oxygen species(ROS)secretion,malondialdehyde(MDA)production and the increase of pro-apoptotic factor expression.Meanwhile,the early-life GOS supplement improved the activities of antioxidant enzymes,disaccharidase enzymes activities,and digestive enzymes activities,and increased the mRNA abundance of the gene related to nutrient digestion and absorption and the relative protein expression of tight junction.The study also showed that the early-life GOS supplement improved the expression of Hemeoxygenase-1(HO-1)and NAD(P)H/quinone acceptor oxidoreductase-1(NQO-1),and activated the AMP-activated protein kinase(AMPK).Conclusions:These results suggested that GOS enhanced the gut function,reduced the ROS production and proapoptotic factors gene expression,and activated the AMPK signaling pathway in LPS-challenged piglets.