Background:Galacto-oligosaccharides(GOS)have been shown to modulate the intestinal microbiota of suckling piglets to exert beneficial effects on intestinal function.However,the modulation of intestinal microbiota and ...Background:Galacto-oligosaccharides(GOS)have been shown to modulate the intestinal microbiota of suckling piglets to exert beneficial effects on intestinal function.However,the modulation of intestinal microbiota and intestinal function by GOS in intestinal inflammation injury models has rarely been reported.In this study,we investigated the effects of GOS on the colonic mucosal microbiota composition,barrier function and inflammatory response of lipopolysaccharides(LPS)-challenged suckling piglets.Methods:A total of 18 newborn suckling piglets were divided into three groups,the CON group,the LPS-CON group and the LPS-GOS group.Piglets in the LPS-GOS group were orally fed with 1 g/kg body weight of GOS solution every day.On the d 14,piglets in the LPS-CON and LPS-GOS group were challenged intraperitoneally with LPS solution.All piglets were slaughtered 2 h after intraperitoneal injection and sampled.Results:We found that the colonic mucosa of LPS-challenged piglets was significantly injured and shedding,while the colonic mucosa of the LPS-GOS group piglets maintained its structure.Moreover,GOS significantly reduced the concentration of malondialdehyde(MDA)and the activity of reactive oxygen species(ROS)in the LPS-challenged suckling piglets,and significantly increased the activity of total antioxidant capacity(T-AOC).GOS significantly increased the relative abundance of norank_f_Muribaculaceae and Romboutsia,and significantly decreased the relative abundance of Alloprevotella,Campylobacter and Helicobacter in the colonic mucosa of LPS-challenged suckling piglets.In addition,GOS increased the concentrations of acetate,butyrate and total short chain fatty acids(SCFAs)in the colonic digesta of LPS-challenged suckling piglets.GOS significantly reduced the concentrations of interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factor-α(TNF-α)and cluster of differentiation 14(CD14),and the relative mRNA expression of Toll-like receptor 4(TLR4)and myeloid differentiation primary response 88(MyD88)in the LPS-challenged suckling piglets.In addition,GOS significantly reduced the relative mRNA expression of mucin2(MUC2),and significantly increased the protein expression of Claudin-1 and zonula occluden-1(ZO-1)in LPS-challenged suckling piglets.Conclusions:These results suggested that GOS can modulate the colonic mucosa-associated microbiota composition and improve the intestinal function of LPS-challenged suckling piglets.展开更多
To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide （LPS） was examined. Immuno- histochemistry and reverse tra...To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide （LPS） was examined. Immuno- histochemistry and reverse transcription-polymerase chain reaction （RT-PCR） analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly increased in LPS-treated animals in comparison with the control animals. Time-course analysis showed that the first signs of blood-brain barrier disruption and the increase of brain water content in LPS-treated animals were evident 6 h after LPS injection, with maximum value appearing at 12 h, which coincided with the expression profiles of AQP9 mRNA and protein in LPS-treated animals. The further correlation analysis revealed strong positive correlations among the brain water content, the disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA and protein in LPS-treated animals. These results suggested that the regulation of AQP9 expression may play im- portant roles in water movement and in brain metabolic homeostasis associated with the pathophysi- ology of brain edema induced by LPS injection.展开更多
OBJECTIVE: To assess the effect of lipopolysaccharides (LPS) on the expression of CD14 and TLR4 in rat Kupffer cells (KCs). METHODS: In rat KCs induced by LPS, the changes of CD14 and TLR4 expression were measured by ...OBJECTIVE: To assess the effect of lipopolysaccharides (LPS) on the expression of CD14 and TLR4 in rat Kupffer cells (KCs). METHODS: In rat KCs induced by LPS, the changes of CD14 and TLR4 expression were measured by RT-PCR and immunohistochemistry, and the expressions of TNF-αmRNA, IL-6mRNA or the concentrations of TNF-α, IL-6 were estimated by in situ hybridization, radioimmunoassay, and others. RESULTS: The expressions of CD14 and TLR4 in KCs induced by LPS were markedly increased in a dose-dependent manner (10 mg/L-1μg/L) or in a time-dependent manner (0.5 h-24 h), with the peaked expression of CD14 at 3-6 hours. The expressions of CD14 and TLR4 in KCs stimulated by the active mediators from KCs which had been exposed to LPS for 1 hour were obviously increased. CONCLUSIONS: There is a close relationship between LPS or the active mediators from KCs induced by LPS and the expressions of CD14, TLR4. It is implied that the increase of TLR4, CD14 expression may be induced by LPS within 1--3 hours, and further increase of TLR4, CD14 expression may be correlated with the cytokines produced bv KCs.展开更多
Objective To investigate the effect of emodin on lipopolysaccharides （LPS）-induced corneal injury in rats. Methods Three parallel incisions on the central surface of corneal epithelium were made and LPS was applied...Objective To investigate the effect of emodin on lipopolysaccharides （LPS）-induced corneal injury in rats. Methods Three parallel incisions on the central surface of corneal epithelium were made and LPS was applied on them to induce corneal injury in Wistar rats. All rats were randomly divided into emodin group （n=40） and keratitis group （n=40）. Rats in the emodin group received subconjunctival injection of emodin and rats in the keratitis group received its vehicle 30 minutes before LPS exposure. At different time points-1 3, 6, 12, and 24 hours after LPS exposure, the symptoms of all rats were observed and the severity of their ocular inflammation was examined with a slit lamp microscope, then 8 rats in each group were killed through cervical dislocation and their eyes were enucleated and prepared to observe pathological changes of corneal tissue under a light microscope. The activation of nuclear factor-loB （NF-κB） under different condi- tions was determined by Western blot. Immunocytochemistry staining with an antibody against intercellular adhesion molecule-1 （ICAM-1） was performed to identify positive cells in corneal tissues. Results The model of acute keratitis was successfully established in Wistar rats. LPS could induce a typical corneal inflammatory response, such as hyperemia, corneal edema and opacity, which were observed in model rats. Compared with keratitis group, both ocular behaviors and damages of the corneal structure were improved in emodin group. Furthermore, the activation of NF-κB and the expression of ICAM-1 induced by LPS were markedly inhibited in emodin group. Conclusion Emodin can inhibit the activation of NF-κB and the expression of ICAM-I induced by LPS in corneas, protect against acute corneal injury, and improve symptoms in rats.展开更多
AIM To reveal the difference of Kupffer cells in the periportal and pericentral regions in the liver to uptake lipopolysaccharides (LPS) injected by the portal vein. METHODS Male Wistar rats were divided into two g...AIM To reveal the difference of Kupffer cells in the periportal and pericentral regions in the liver to uptake lipopolysaccharides (LPS) injected by the portal vein. METHODS Male Wistar rats were divided into two groups: normal control group ( n =6) and GdCl 3 treated group ( n =8). Sixteen hours before the experiment, rats of GdCl 3 treated group were injected GdCl 3 by the tail vein to eliminate the Kupffer cell function in the periportal region selectively. LPS at a dose of 20μg/100g body weight was injected to rats of both groups by the portal vein. Zero, 2, 5, 10, 30, 60 minutes after LPS injection, liver samples were obtained and distribution of LPS in Kupffer cells was observed by the immunofluorescent method using a monoclonal antibody specific to LPS with a confocal laser scanning microscope. RESULTS In normal control group, positive reactions to LPS were found in Kupffer cells in the periportal region with the peak at 2 minutes after LPS injection. Kupffer cells in the pericentral region showed the peak at 5 minutes after LPS injection, but its fluorescent intensity to LPS at the peak time in the cytoplasm was significantly lower than that of Kupffer cells in the pericentral region at the peak point. In GdCl 3 treated group, Kupffer cells in the pericentral region showed the peak at 2 minutes after LPS injection, and its fluorescent intensity to LPS showed no significant difference from that of the normal control rats at the peak point. No significant changes of fluorescent intensities to LPS were found in Kupffer cells in the periportal region at various time points after LPS injection in GdCl 3 treated rats. CONCLUSION Kupffer cells in the periportal and pericentral regions showed difference to uptake LPS in the portal vein.展开更多
Human periodontal ligament cells (hPDLCs), with the potential for multi-directional differentiation and reproduction, are the target cells of orthodontic tooth movement. The aim of this study was to examine the effect...Human periodontal ligament cells (hPDLCs), with the potential for multi-directional differentiation and reproduction, are the target cells of orthodontic tooth movement. The aim of this study was to examine the effect of mechanical tension force and lipopolysaccharides (LPS) on hPDLCs and whether they induce proliferative and differentiated characters in vitro. Tension force was applied to hPDLCs stimulated with and without LPS for 24 hrs. Real-time polymerase chain reaction (qPCR) was carried out to analyze the mRNA expression of Cyclin 2 (CCND2), WNT1 inducible signaling pathway protein 1 (WISP1), runt-related transcription factor 2 (RUNX2) and alkaline phosphatase (ALP). Analysis of variance (ANOVA) was used for statistical analysis. Significant differences were indicated by P < 0.05. The results showed that tension force promoted the mRNA expression of both the proliferation-related genes (CCND2 and WISP1) and differentiation-related genes (RUNX2 and ALP), and that both were enhanced by the simulation of LPS. In addition, the relative expression ratios CCND2/RUNX2 and CCND2/ALP both increased significantly after the application of tension, and this effect was further enhanced by LPS. All results indicated that with the assessed level of mechanical force loading, tension could promote both the proliferation and differentiation of hPDLCs, which could be enhanced by LPS, and that proliferation is promoted to a greater extent than differentiation. These findings may be valuable for understanding the importance of the application of suitable mechanical force in periodontal remodeling, especially in the process of orthodontic tooth movement with inflammation.展开更多
Lipopolysaccharides(LPS) contamination in herbal crude polysaccharides is inevitable. The present study was performed to explore the effect of polymyxin B on abolishing the influence of LPS contamination in mononuclea...Lipopolysaccharides(LPS) contamination in herbal crude polysaccharides is inevitable. The present study was performed to explore the effect of polymyxin B on abolishing the influence of LPS contamination in mononuclear cells. LPS was pretreated with polymyxin B sulfate(PB) at different concentrations for 1, 5 or 24 h, and then used to stimulate RAW264.7 and mouse peritoneal macrophages(MPMs). The nitric oxide(NO) and tumor necrosis factor-α(TNF-α) in cell culture supernatant, as the indications of cell response, were assayed. Bupleurum chinensis polysaccharides(BCPs) with trace amount contamination of LPS was treated with PB. 30 μg·mL^(–1) of PB, treating LPS(10 and 1000 ng·mL^(–1) in stimulating RAW264.7 and MPMs respectively) at 37 ℃ for 24 h, successfully abolished the stimulating effect of LPS on the cells. When the cells were stimulated with LPS, BCPs further promoted NO production. However, pretreated with PB, BCPs showed a suppression of NO production in MPMs and no change in RAW264.7. In the in vitro experiments, LPS contamination in polysaccharide might bring a great interference in assessing the activity of drug. Pretreatment with PB(30 μg·mL^(–1)) at 37 °C for 24 h was sufficient to abolish the effects of LPS contamination(10 and 1 000 ng·mL^(–1)).展开更多
Cyanobacteria are an interesting group of photosynthetic prokaryotes with a great potential in drug discovery and scientific research. Due to their high degree of diversification, they have been able to adapt to almos...Cyanobacteria are an interesting group of photosynthetic prokaryotes with a great potential in drug discovery and scientific research. Due to their high degree of diversification, they have been able to adapt to almost all ecological niches. Similarly to Gram-negative bacteria, cyanobacterial cell wall contains Lipopolysaccharides (LPSs) in the outer membrane layer. LPSs are molecules that possess the ability to elicit an innate immune response via Toll-like receptor 4 (TLR-4) activation. Cyanobacterial LPSs have been studied to a minor extent compared to Gram-negative bacterial LPSs. However, available data revealed important differences between the LPSs of these two groups of organisms, both in term of structure and biological activity. This review summarizes the current knowledge about cyanobacterial LPSs, highlighting their peculiarity and their potentiality compared to more characterized bacterial LPSs.展开更多
Atrial fibrillation(AF)is a growing global health burden,with a prevalence of over 52.55 million cases.Rising disability-adjusted life-years,increasing age,and disparities in care have contributed to the worsening sev...Atrial fibrillation(AF)is a growing global health burden,with a prevalence of over 52.55 million cases.Rising disability-adjusted life-years,increasing age,and disparities in care have contributed to the worsening severity and mortality of AF.Modifiable risk factors,such as hypertension,obesity,and diabetes mellitus,are associated with alterations in gut microbiota,making the gut-heart axis a potential therapeutic target.Gut dysbiosis influences AF pathogenesis through inflam-mation,metabolic disruption,and autonomic dysfunction.Key mechanisms include gut barrier dysfunction,short-chain fatty acid(SCFA)depletion,lipopoly-saccharides(LPS)-induced inflammation,and ferroptosis-mediated atrial remodeling.Trimethylamine N-oxide,bile acids,and tryptophan metabolites contribute to arrhythmogenic remodeling.Emerging evidence suggests that dietary interventions,including prebiotics and probiotics,as well as gut surveillance,may help mitigate AF progression.Clinical implications of gut modulation in AF include person-alized dietary strategies,microbiome assessment through metagenomic sequencing,and targeted interventions such as SCFA-based therapies and ferroptosis inhibition.Metabolite surveillance,including LPS and indoxyl sulfate monitoring,may influence the effectiveness of anticoagulant and antiarrhythmic therapy.Despite growing mechanistic evidence linking gut dysbiosis to AF,clinical applications remain unexplored.This review summarizes the current understanding of the gut microbiome's role in AF.展开更多
OBJECTIVE:To determine the effect of Traditional Chinese Medicine(TCM)Fuzheng Xuanfei Huashi prescription(扶正宣肺化湿方,FZXF)on lipopolysaccharide(LPS)-induced pneumonia in mice and identify the mechanism of FZXF in ...OBJECTIVE:To determine the effect of Traditional Chinese Medicine(TCM)Fuzheng Xuanfei Huashi prescription(扶正宣肺化湿方,FZXF)on lipopolysaccharide(LPS)-induced pneumonia in mice and identify the mechanism of FZXF in the treatment of LPS-induced lung inflammation.METHODS:The pneumonia model was established by intraperitoneal injection of 5 mg/kg LPS in mice.Cytokines were detected by enzyme-linked immuneosorbent assay(ELISA),macrophages in lung tissue were determined by immunofluorescence,and pathwayrelated data were determined by quantitative real-time polymerase chain reaction(qPCR)and Western blot.RESULTS:The liver,thymus,and spleen index values and the levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)obviously increased in LPS-treated mice.FZXF decreased the white blood cell count and reduced the increase in the lung wet weight/dry weight ratio caused by LPS.The hematoxylin-eosin staining result showed that FZXF could maintain the integrity of lung tissue structure,alleviate interstitial oedema and alveolar wall thickening,and reduce inflammatory cell infiltration.Moreover,FZXF markedly reduced the expression of proinflammatory cytokines.FZXF also significantly reduced LPS-induced malondialdehyde production and increased superoxide dismutase level in the lung.By immunofluorescence,we found that FZXF could reduce macrophage infiltration.The mRNA expression levels of cyclooxygenase-2(COX-2),prostaglandin E2(PGE2),toll-like receptor 4(TLR4)and nuclear transcription factorκB(NF-κB)in the lung tissue of mice were decreased by treatment with FZXF.In addition,FZXF inhibited the protein expression of TLR4,p-p65 and COX-2.These results indicated that FZXF could inhibit the inflammatory response of LPS induced cytokine storm in mice through TLR4/NF-κB and COX-2/PGE2 signaling pathway.CONCLUSION:These findings were suggested that FZXF prescription suppresses inflammation in LPSinduced pneumonia in mice via TLR4/NF-κB and COX-2/PGE2 pathway.展开更多
In the current era,metabolic dysfunction-associated steatotic liver disease(MASLD)has gradually developed into a major type of chronic liver disease that is widespread globally.Numerous studies have shown that the gut...In the current era,metabolic dysfunction-associated steatotic liver disease(MASLD)has gradually developed into a major type of chronic liver disease that is widespread globally.Numerous studies have shown that the gut microbiota plays a crucial and indispensable role in the progression of MASLD.Currently,the gut microbiota has become one of the important entry points for the research of this disease.Therefore,the aim of this review is to elaborate on the further associations between the gut microbiota and MASLD,including the changes and differences in the microbiota between the healthy liver and the diseased liver.Meanwhile,considering that metabolic dysfunction-associated fatty liver and metabolic dysfunction-associated steatohepatitis are abnormal pathological states in the development of the disease and that the liver exhibits different degrees of fibrosis(such as mild fibrosis and severe fibrosis)during the disease progression,we also conduct a comparison of the microbiota in these states and use them as markers of disease progression.It reveals the changes in the production and action mechanisms of short-chain fatty acids and bile acids brought about by changes in the gut microbiota,and the impact of lipopolysaccharide from Gram-negative bacteria on the disease.In addition,the regulation of the gut microbiota in disease and the production and inhibition of related disease factors by the use of probiotics(including new-generation probiotics)will be explored,which will help to monitor the disease progression of patients with different gut microbiota compositions in the future and carry out personalized targeted therapies for the gut microbiota.This will achieve important progress in preventing and combating this disease.展开更多
Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has...Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.展开更多
Background:Fever is characterized by an upregulation of the thermoregulatory set-point after the body encounters any pathological challenge.It is accompanied by uncomfortable sickness behaviors and may be harmful in p...Background:Fever is characterized by an upregulation of the thermoregulatory set-point after the body encounters any pathological challenge.It is accompanied by uncomfortable sickness behaviors and may be harmful in patients with other comor-bidities.We have explored the impact of an Ayurvedic medicine,Fevogrit,in an endo-toxin(lipopolysaccharide)-induced fever model in Wistar rats.Methods:Active phytoconstituents of Fevogrit were identified and quantified using ultra-high-performance liquid chromatography(UHPLC)platform.For the in-vivo study,fever was induced in male Wistar rats by the intraperitoneal administration of lipopolysaccharide(LPS),obtained from Escherichia coli.The animals were allocated to normal control,disease control,Paracetamol treated and Fevogrit treated groups.The rectal temperature of animals was recorded at different time points using a digital thermometer.At the 6-h time point,levels of TNF-α,IL-1βand IL-6 cytokines were analyzed in serum.Additionally,the mRNA expression of these cytokines was deter-mined in hypothalamus,24 h post-LPS administration.Results:UHPLC analysis of Fevogrit revealed the presence of picroside I,picroside II,vanillic acid,cinnamic acid,magnoflorine and cordifolioside A,as bioactive constitu-ents with known anti-inflammatory properties.Fevogrit treatment efficiently reduces the LPS-induced rise in the rectal temperature of animals.The levels and gene ex-pression of TNF-α,IL-1βand IL-6 in serum and hypothalamus,respectively,was also significantly reduced by Fevogrit treatment.Conclusion:The findings of the study demonstrated that Fevogrit can suppress LPS-induced fever by inhibiting peripheral or central inflammatory signaling pathways and could well be a viable treatment for infection-induced increase in body temperatures.展开更多
The purpose of this study was to investigate the hypoglycemic effect and mechanism of D endrobium officinale polysaccharide(DOP)on type 2 diabetes mellitus(T2DM)mice established by high-fat diet and streptozotocin.The...The purpose of this study was to investigate the hypoglycemic effect and mechanism of D endrobium officinale polysaccharide(DOP)on type 2 diabetes mellitus(T2DM)mice established by high-fat diet and streptozotocin.The results showed that DOP improved glycolipid metabolism and serum inflammation levels,and inhibited intestinal-derived lipopolysaccharide(LPS)translocation,suggesting that inhibiting LPS-mediated intestinal barrier damage may be a key target for DOP to alleviate T2DM.Interestingly,the study found that DOP reduced intestinal inflammation and oxidative stress levels,significantly up-regulated the mRNA expression of tight junction proteins Claudin-1,Occludin and zonula occluden-1(ZO-1),and ameliorated intestinal epithelial damage.In addition,DOP strongly inhibited the intestinal pathogenic bacteria and LPS-producing bacteria Helicobacter,Enterococcus and Desulfovibrio with a reduction rate of 95%,73% and 9%,respectively,and promoted the proliferation of anti-inflammatory bacteria Bifidobacterium and Lactobacillus by 139% and 8%,respectively.Taken together,the hypoglycemic effect of DOP was related to the protection of intestinal mucosal barrier,and its underlying mechanism lied in its excellent anti-inflammatory and gut microbiotamodulatory effects,providing a theoretical basis for developing DOP as a novel prebiotic in functional food for diabetes.展开更多
Background:To appraise the ameliorative potentials of Allium sativum aqueous extract in ovalbumin(OVA)-lipopolysaccharide(LPS)-induced asthma.Methods:Extraction,phytochemical analysis,determination of bioactive compou...Background:To appraise the ameliorative potentials of Allium sativum aqueous extract in ovalbumin(OVA)-lipopolysaccharide(LPS)-induced asthma.Methods:Extraction,phytochemical analysis,determination of bioactive compounds and LD50 study of aqueous extract of A.sativum were achieved using standard biochemical methods.Twenty-four(24)male Wistar rats averagely weighing between 168–255 g were grouped into four of six animals in each steel-metal cage.Groups 1 and 2 served as normal and positive groups respectively.Rats in groups 2–4 were sensitized and challenged with a combination of OVA and LPS.Groups 3 and 4 were administered 250 and 500 mg/kg b.w of aqueous extract of A.sativum respectively for two weeks.The effect of aqueous extracts of A.sativum in OVA and LPS-induced asthma on alterations in differential white blood cells,inflammatory cytokines,some serum biochemical as well as histological indicators of experimental rats were assessed.Results:The aqueous extract of 600 g of plant material yielded 74.1 g accounting for 11.9%of sample material used.The result of the Phytochemical analysis showed higher number of glycosides,flavonoids and phenols.The animals displayed zero behavioral adverse reaction when administered the aqueous extract up to the highest dose of 5,000 mg/kg b.w.Administrations of aqueous extract of A.sativum remarkably(P<0.05;95%confidence intervals CI)declined the levels of neutrophils,eosinophils and total white blood cell count as opposed to the untreated group.Levels of interleukin 4(IL-4),interleukin 5(IL-5),interleukin 13(IL-13)and immunoglobulin E(IgE)of groups 3 and 4 had a significant(P<0.05;95%CI)varying percentage reduction(IL-4=39.78%,49.51%;IL-5=34.66%,40.05%;IL-13=31.96%,30.81%;33.45%,21.38%)respectively in comparison to group 2(untreated).The result showed a significantly(P<0.05,95%CI)declined malonaldehyde(MDA)concentration and elevated catalase,decreased glutathione concentration and superoxide dismutase activity of the treatment groups compared to the untreated.Serum liver function enzymes including alkaline phosphatase,alanine transaminase,and aspartate transaminase in the groups receiving aqueous extract of A.sativum exhibited a significant(P<0.05;95%CI)reduction in levels compared to group 2(untreated).Conclusion:Findings from this study indicated that aqueous extracts of A.sativum have the potential to improve asthma symptoms by decreasing inflammatory cytokines and mitigating oxidative stress.This effect could enhance the efficacy of conventional treatments such as inhaled corticosteroids,including cortisone,hydrocortisone,dexamethasone,and prednisone,as well as bronchodilators,leukotriene modifiers,and biologic therapies.Further studies need to be carried out on human subjects and also expanded to other respiratory disorders like Chronic obstructive pulmonary disease and Coronavirus Disease 2019.展开更多
Background:Acute respiratory distress syndrome(ARDS)is the major therapeutic dilemma associated with significant inflammation and severe pulmonary dysfunction.Liriodendrin is a bioactive compound extract from traditio...Background:Acute respiratory distress syndrome(ARDS)is the major therapeutic dilemma associated with significant inflammation and severe pulmonary dysfunction.Liriodendrin is a bioactive compound extract from traditional Chinesemedicine,historically utilized formodulating inflammatory responses and alleviating symptoms in multiple diseasemodels.Methods:At present,BALB/c mice to explore the effects of liriodendrin on lipopolysaccharide(LPS)-induced ARDS.Before LPS was administered,the mice were treated with either liriodendrin or dexamethasone.Leukocyte infiltration,lung edema,and alveolar-capillary barrier integrity were evaluated in the bronchoalveolar lavage fluid(BALF)and pulmonary parenchyma.The expression of adhesion molecules and proinflammatory cytokines in BALF was evaluated by enzyme-linked immunosorbent assay.Western blotting assay facilitated the analysis of the expression or phosphorylation of inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),NOD-like receptor family pyrin domain-containing 3(NLRP3),apoptosis-associated speck-like protein containing a CARD(ASC),cleaved caspase-1(CL-csapase-1),nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB),inhibitor of kappa B(IκB),mitogen-activated protein kinase(MAPK),and protein kinase B(Akt)in the lungs.In addition,the anti-inflammatory effects of liriodendrin were evaluated in LPS-stimulated RAW264.7 macrophages.Before LPS was administered,the RAW264.7 macrophages were treated with either liriodendrin or dexamethasone.Nitric Oxide(NO)production was measured using the Griess reaction assay,while ELISA assessed IL-1β,IL-6,and TNF-αlevels.Western blot analysis evaluated NF-κB phosphorylation and the expression of NLRP3,ASC,and CLcaspase-1.Results:These outcomes revealed that liriodendrin intervention markedly ameliorated the pathological features of LPS-induced ARDS,including leukocyte infiltration,lung edema,and alveolar-capillary barrier disruption.Liriodendrin also reduced the LPS-induced secretion of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesionmolecule-1(VCAM-1),expression of iNOS and COX2,and production of proinflammatory cytokines.Finally,we further discovered that the concentration trend of liriodendron amelioration ofARDSwas similar to those ofNLRP3 formation,NF-κB pathway activation,and p38 MAPK,c-Jun N-terminal kinase(JNK),and Akt phosphorylation but not to that of extracellular signal-regulated kinase(ERK)phosphorylation.Liriodendrin inhibited LPS-induced inflammatory responses in RAW264.7 macrophages.It markedly reduced NO production,propro-inflammatorytokines,NF-κB phosphorylation,and NLRP3 formation.Conclusions:In summary,liriodendrin effectively ameliorated the pathological features of LPS-induced ARDS inmice,demonstrating significant anti-inflammatory properties attributed to NLRP3 formation through NF-κB pathway activation by p38MAPK,JNK,and Akt phosphorylation.In LPS-treated RAW264.7 macrophages,liriodendrin reduced NO production,pro-inflammatory cytokines,and NLRP3 formation,suggesting its potential as an agent for ARDS and relative inflammation.展开更多
Alcoholic liver disease(ALD)is one of the major global public health problems.Yeast extract(YE),a product prepared from yeast,has been proven to have antioxidant and anti-inflammatory properties.However,the potential ...Alcoholic liver disease(ALD)is one of the major global public health problems.Yeast extract(YE),a product prepared from yeast,has been proven to have antioxidant and anti-inflammatory properties.However,the potential role of YE in the prevention of ALD remains unclear.The present study aimed to investigate the protective effects of YE on ALD and explore the underlying mechanism based on gut microbiota.The result showed that YE supplementation significantly ameliorated chronic alcohol exposure-induced liver injury in mice.In addition,YE counteracted alcohol-induced gut dysbiosis,intestinal barrier dysfunction,lipopolysaccharide(LPS)leakage-induced inflammatory response in the liver.Moreover,microbiota depletion by a broad-spectrum antibiotic was sufficient to block the protective effect of YE on ALD,indicating the contribution of gut dysbiosis modulation to the hepatoprotective role of YE.Furthermore,we demonstrated the causal relationship between gut microbiota and hepatoprotective effects of YE with the fecal microbiota transplantation(FMT)experiment.Compared with the ALD-FMT mice,gut dysbiosis,intestinal barrier dysfunction,LPS/TLR4 signaling pathway activation,and liver inflammatory response were significantly improved in the YE-FMT mice.Together,our findings highlight that dietary YE protects against ALD through gut dysbiosis correction.展开更多
Alzheimer's disease(AD)is the most serious age-related neurodegenerative disease and causes destructive and irreversible cognitive decline.Failures in the development of therapeutics targeting amyloid-β(Aβ)and t...Alzheimer's disease(AD)is the most serious age-related neurodegenerative disease and causes destructive and irreversible cognitive decline.Failures in the development of therapeutics targeting amyloid-β(Aβ)and tau;principal proteins inducing pathology in AD,suggest a paradigm shift towards the development of new therapeutic targets.The gram-negative bacteria and lipopolysaccharides(LPS)are attractive new targets for AD treatment.Surprisingly,an altered distribution of gram-negative bacteria and their LPS has been reported in AD patients.Moreover,gram-negative bacteria and their LPS have been shown to affect a variety of AD-related pathologies,such as Aβ homeostasis,tau pathology,neuroinflammation,and neurodegeneration.Moreover,therapeutic approaches targeting gram-negative bacteria or gram-negative bacterial molecules have significantly alleviated AD-related pathology and cognitive dysfunction.Despite multiple evidence showing that the gram-negative bacteria and their LPS play a crucial role in AD pathogenesis,the pathogenic mechanisms of gram-negative bacteria and their LPS have not been clarified.Here,we summarize the roles and pathomechanisms of gram-negative bacteria and LPS in AD.Furthermore,we discuss the possibility of using gram-negative bacteria and gram-negative bacterial molecules as novel therapeutic targets and new pathological characteristics for AD.展开更多
We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation r...We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.展开更多
Hemorrhagic transformation is a major complication of large-artery atheroscle rotic stroke(a major ischemic stro ke subtype)that wo rsens outcomes and increases mortality.Disruption of the gut microbiota is an importa...Hemorrhagic transformation is a major complication of large-artery atheroscle rotic stroke(a major ischemic stro ke subtype)that wo rsens outcomes and increases mortality.Disruption of the gut microbiota is an important feature of stroke,and some specific bacteria and bacterial metabolites may contribute to hemorrhagic transformation pathogenesis.We aimed to investigate the relationship between the gut microbiota and hemorrhagic transformation in largearte ry atheroscle rotic stro ke.An observational retrospective study was conducted.From May 2020 to September 2021,blood and fecal samples were obtained upon admission from 32 patients with first-ever acute ischemic stroke and not undergoing intravenous thrombolysis or endovascular thrombectomy,as well as 16 healthy controls.Patients with stro ke who developed hemorrhagic transfo rmation(n=15)were compared to those who did not develop hemorrhagic transformation(n=17)and with healthy controls.The gut microbiota was assessed through 16S ribosomal ribonucleic acid sequencing.We also examined key components of the lipopolysaccharide pathway:lipopolysaccharide,lipopolysaccharide-binding protein,and soluble CD14.We observed that bacterial diversity was decreased in both the hemorrhagic transformation and non-hemorrhagic transfo rmation group compared with the healthy controls.The patients with ischemic stro ke who developed hemorrhagic transfo rmation exhibited altered gut micro biota composition,in particular an increase in the relative abundance and dive rsity of members belonging to the Enterobacteriaceae family.Plasma lipopolysaccharide and lipopolysaccharide-binding protein levels were higher in the hemorrhagic transformation group compared with the non-hemorrhagic transfo rmation group.lipopolysaccharide,lipopolysaccharide-binding protein,and soluble CD14 concentrations were associated with increased abundance of Enterobacte riaceae.Next,the role of the gut microbiota in hemorrhagic transformation was evaluated using an experimental stroke rat model.In this model,transplantation of the gut microbiota from hemorrhagic transformation rats into the recipient rats triggered higher plasma levels of lipopolysaccharide,lipopolysaccharide-binding protein,and soluble CD14.Ta ken togethe r,our findings demonstrate a noticeable change in the gut microbiota and lipopolysaccharide-related inflammatory response in stroke patients with hemorrhagic transformation.This suggests that maintaining a balanced gut microbiota may be an important factor in preventing hemorrhagic transfo rmation after stro ke.展开更多
基金supported by the National Key R&D Program of China 2017YFD0500505.
文摘Background:Galacto-oligosaccharides(GOS)have been shown to modulate the intestinal microbiota of suckling piglets to exert beneficial effects on intestinal function.However,the modulation of intestinal microbiota and intestinal function by GOS in intestinal inflammation injury models has rarely been reported.In this study,we investigated the effects of GOS on the colonic mucosal microbiota composition,barrier function and inflammatory response of lipopolysaccharides(LPS)-challenged suckling piglets.Methods:A total of 18 newborn suckling piglets were divided into three groups,the CON group,the LPS-CON group and the LPS-GOS group.Piglets in the LPS-GOS group were orally fed with 1 g/kg body weight of GOS solution every day.On the d 14,piglets in the LPS-CON and LPS-GOS group were challenged intraperitoneally with LPS solution.All piglets were slaughtered 2 h after intraperitoneal injection and sampled.Results:We found that the colonic mucosa of LPS-challenged piglets was significantly injured and shedding,while the colonic mucosa of the LPS-GOS group piglets maintained its structure.Moreover,GOS significantly reduced the concentration of malondialdehyde(MDA)and the activity of reactive oxygen species(ROS)in the LPS-challenged suckling piglets,and significantly increased the activity of total antioxidant capacity(T-AOC).GOS significantly increased the relative abundance of norank_f_Muribaculaceae and Romboutsia,and significantly decreased the relative abundance of Alloprevotella,Campylobacter and Helicobacter in the colonic mucosa of LPS-challenged suckling piglets.In addition,GOS increased the concentrations of acetate,butyrate and total short chain fatty acids(SCFAs)in the colonic digesta of LPS-challenged suckling piglets.GOS significantly reduced the concentrations of interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factor-α(TNF-α)and cluster of differentiation 14(CD14),and the relative mRNA expression of Toll-like receptor 4(TLR4)and myeloid differentiation primary response 88(MyD88)in the LPS-challenged suckling piglets.In addition,GOS significantly reduced the relative mRNA expression of mucin2(MUC2),and significantly increased the protein expression of Claudin-1 and zonula occluden-1(ZO-1)in LPS-challenged suckling piglets.Conclusions:These results suggested that GOS can modulate the colonic mucosa-associated microbiota composition and improve the intestinal function of LPS-challenged suckling piglets.
基金supported by a grant for Scientific Research Program from the Health Bureau of Henan Province (No.200202)
文摘To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide （LPS） was examined. Immuno- histochemistry and reverse transcription-polymerase chain reaction （RT-PCR） analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly increased in LPS-treated animals in comparison with the control animals. Time-course analysis showed that the first signs of blood-brain barrier disruption and the increase of brain water content in LPS-treated animals were evident 6 h after LPS injection, with maximum value appearing at 12 h, which coincided with the expression profiles of AQP9 mRNA and protein in LPS-treated animals. The further correlation analysis revealed strong positive correlations among the brain water content, the disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA and protein in LPS-treated animals. These results suggested that the regulation of AQP9 expression may play im- portant roles in water movement and in brain metabolic homeostasis associated with the pathophysi- ology of brain edema induced by LPS injection.
文摘OBJECTIVE: To assess the effect of lipopolysaccharides (LPS) on the expression of CD14 and TLR4 in rat Kupffer cells (KCs). METHODS: In rat KCs induced by LPS, the changes of CD14 and TLR4 expression were measured by RT-PCR and immunohistochemistry, and the expressions of TNF-αmRNA, IL-6mRNA or the concentrations of TNF-α, IL-6 were estimated by in situ hybridization, radioimmunoassay, and others. RESULTS: The expressions of CD14 and TLR4 in KCs induced by LPS were markedly increased in a dose-dependent manner (10 mg/L-1μg/L) or in a time-dependent manner (0.5 h-24 h), with the peaked expression of CD14 at 3-6 hours. The expressions of CD14 and TLR4 in KCs stimulated by the active mediators from KCs which had been exposed to LPS for 1 hour were obviously increased. CONCLUSIONS: There is a close relationship between LPS or the active mediators from KCs induced by LPS and the expressions of CD14, TLR4. It is implied that the increase of TLR4, CD14 expression may be induced by LPS within 1--3 hours, and further increase of TLR4, CD14 expression may be correlated with the cytokines produced bv KCs.
基金Supported by Technology Foundation of Shandong Education Department (J08LH59)
文摘Objective To investigate the effect of emodin on lipopolysaccharides （LPS）-induced corneal injury in rats. Methods Three parallel incisions on the central surface of corneal epithelium were made and LPS was applied on them to induce corneal injury in Wistar rats. All rats were randomly divided into emodin group （n=40） and keratitis group （n=40）. Rats in the emodin group received subconjunctival injection of emodin and rats in the keratitis group received its vehicle 30 minutes before LPS exposure. At different time points-1 3, 6, 12, and 24 hours after LPS exposure, the symptoms of all rats were observed and the severity of their ocular inflammation was examined with a slit lamp microscope, then 8 rats in each group were killed through cervical dislocation and their eyes were enucleated and prepared to observe pathological changes of corneal tissue under a light microscope. The activation of nuclear factor-loB （NF-κB） under different condi- tions was determined by Western blot. Immunocytochemistry staining with an antibody against intercellular adhesion molecule-1 （ICAM-1） was performed to identify positive cells in corneal tissues. Results The model of acute keratitis was successfully established in Wistar rats. LPS could induce a typical corneal inflammatory response, such as hyperemia, corneal edema and opacity, which were observed in model rats. Compared with keratitis group, both ocular behaviors and damages of the corneal structure were improved in emodin group. Furthermore, the activation of NF-κB and the expression of ICAM-1 induced by LPS were markedly inhibited in emodin group. Conclusion Emodin can inhibit the activation of NF-κB and the expression of ICAM-I induced by LPS in corneas, protect against acute corneal injury, and improve symptoms in rats.
文摘AIM To reveal the difference of Kupffer cells in the periportal and pericentral regions in the liver to uptake lipopolysaccharides (LPS) injected by the portal vein. METHODS Male Wistar rats were divided into two groups: normal control group ( n =6) and GdCl 3 treated group ( n =8). Sixteen hours before the experiment, rats of GdCl 3 treated group were injected GdCl 3 by the tail vein to eliminate the Kupffer cell function in the periportal region selectively. LPS at a dose of 20μg/100g body weight was injected to rats of both groups by the portal vein. Zero, 2, 5, 10, 30, 60 minutes after LPS injection, liver samples were obtained and distribution of LPS in Kupffer cells was observed by the immunofluorescent method using a monoclonal antibody specific to LPS with a confocal laser scanning microscope. RESULTS In normal control group, positive reactions to LPS were found in Kupffer cells in the periportal region with the peak at 2 minutes after LPS injection. Kupffer cells in the pericentral region showed the peak at 5 minutes after LPS injection, but its fluorescent intensity to LPS at the peak time in the cytoplasm was significantly lower than that of Kupffer cells in the pericentral region at the peak point. In GdCl 3 treated group, Kupffer cells in the pericentral region showed the peak at 2 minutes after LPS injection, and its fluorescent intensity to LPS showed no significant difference from that of the normal control rats at the peak point. No significant changes of fluorescent intensities to LPS were found in Kupffer cells in the periportal region at various time points after LPS injection in GdCl 3 treated rats. CONCLUSION Kupffer cells in the periportal and pericentral regions showed difference to uptake LPS in the portal vein.
文摘Human periodontal ligament cells (hPDLCs), with the potential for multi-directional differentiation and reproduction, are the target cells of orthodontic tooth movement. The aim of this study was to examine the effect of mechanical tension force and lipopolysaccharides (LPS) on hPDLCs and whether they induce proliferative and differentiated characters in vitro. Tension force was applied to hPDLCs stimulated with and without LPS for 24 hrs. Real-time polymerase chain reaction (qPCR) was carried out to analyze the mRNA expression of Cyclin 2 (CCND2), WNT1 inducible signaling pathway protein 1 (WISP1), runt-related transcription factor 2 (RUNX2) and alkaline phosphatase (ALP). Analysis of variance (ANOVA) was used for statistical analysis. Significant differences were indicated by P < 0.05. The results showed that tension force promoted the mRNA expression of both the proliferation-related genes (CCND2 and WISP1) and differentiation-related genes (RUNX2 and ALP), and that both were enhanced by the simulation of LPS. In addition, the relative expression ratios CCND2/RUNX2 and CCND2/ALP both increased significantly after the application of tension, and this effect was further enhanced by LPS. All results indicated that with the assessed level of mechanical force loading, tension could promote both the proliferation and differentiation of hPDLCs, which could be enhanced by LPS, and that proliferation is promoted to a greater extent than differentiation. These findings may be valuable for understanding the importance of the application of suitable mechanical force in periodontal remodeling, especially in the process of orthodontic tooth movement with inflammation.
基金supported by the National Natural Science Foundation of China(Nos.81330089,30925042,and 81274165)the State Key Program for New Drugs from the Ministry of Science and Technology,China(No.2012ZX09301001-003)the Science and Technology Commission of Shanghai Municipality(Nos.10XD1405900 and 12JC1400800)
文摘Lipopolysaccharides(LPS) contamination in herbal crude polysaccharides is inevitable. The present study was performed to explore the effect of polymyxin B on abolishing the influence of LPS contamination in mononuclear cells. LPS was pretreated with polymyxin B sulfate(PB) at different concentrations for 1, 5 or 24 h, and then used to stimulate RAW264.7 and mouse peritoneal macrophages(MPMs). The nitric oxide(NO) and tumor necrosis factor-α(TNF-α) in cell culture supernatant, as the indications of cell response, were assayed. Bupleurum chinensis polysaccharides(BCPs) with trace amount contamination of LPS was treated with PB. 30 μg·mL^(–1) of PB, treating LPS(10 and 1000 ng·mL^(–1) in stimulating RAW264.7 and MPMs respectively) at 37 ℃ for 24 h, successfully abolished the stimulating effect of LPS on the cells. When the cells were stimulated with LPS, BCPs further promoted NO production. However, pretreated with PB, BCPs showed a suppression of NO production in MPMs and no change in RAW264.7. In the in vitro experiments, LPS contamination in polysaccharide might bring a great interference in assessing the activity of drug. Pretreatment with PB(30 μg·mL^(–1)) at 37 °C for 24 h was sufficient to abolish the effects of LPS contamination(10 and 1 000 ng·mL^(–1)).
文摘Cyanobacteria are an interesting group of photosynthetic prokaryotes with a great potential in drug discovery and scientific research. Due to their high degree of diversification, they have been able to adapt to almost all ecological niches. Similarly to Gram-negative bacteria, cyanobacterial cell wall contains Lipopolysaccharides (LPSs) in the outer membrane layer. LPSs are molecules that possess the ability to elicit an innate immune response via Toll-like receptor 4 (TLR-4) activation. Cyanobacterial LPSs have been studied to a minor extent compared to Gram-negative bacterial LPSs. However, available data revealed important differences between the LPSs of these two groups of organisms, both in term of structure and biological activity. This review summarizes the current knowledge about cyanobacterial LPSs, highlighting their peculiarity and their potentiality compared to more characterized bacterial LPSs.
文摘Atrial fibrillation(AF)is a growing global health burden,with a prevalence of over 52.55 million cases.Rising disability-adjusted life-years,increasing age,and disparities in care have contributed to the worsening severity and mortality of AF.Modifiable risk factors,such as hypertension,obesity,and diabetes mellitus,are associated with alterations in gut microbiota,making the gut-heart axis a potential therapeutic target.Gut dysbiosis influences AF pathogenesis through inflam-mation,metabolic disruption,and autonomic dysfunction.Key mechanisms include gut barrier dysfunction,short-chain fatty acid(SCFA)depletion,lipopoly-saccharides(LPS)-induced inflammation,and ferroptosis-mediated atrial remodeling.Trimethylamine N-oxide,bile acids,and tryptophan metabolites contribute to arrhythmogenic remodeling.Emerging evidence suggests that dietary interventions,including prebiotics and probiotics,as well as gut surveillance,may help mitigate AF progression.Clinical implications of gut modulation in AF include person-alized dietary strategies,microbiome assessment through metagenomic sequencing,and targeted interventions such as SCFA-based therapies and ferroptosis inhibition.Metabolite surveillance,including LPS and indoxyl sulfate monitoring,may influence the effectiveness of anticoagulant and antiarrhythmic therapy.Despite growing mechanistic evidence linking gut dysbiosis to AF,clinical applications remain unexplored.This review summarizes the current understanding of the gut microbiome's role in AF.
基金Emergency Corona Virus Disease 2019(COVID-19)Response Project of Dongguan:Clinical Efficacy Observation and Mechanism Study of Fuzheng Xuanfei Huashi Formula in the Treatment of COVID-19 Based on the Lingnan Theory of Epidemic Diseases(No.202071715002124)National Natural Science Foundation of China:Study on the Mechanism of Lung Inflammatory Injury Induced by Gut-derived Lipopolysaccharide and Skatole in Spleen Deficiency Animals based on Pulmonary Alveolus Macrophage Heterogeneity(No.82274381)Guangdong Basic and Applied Basic Research Foundation:Development and Industrialization of Traditional Chinese Medicine Classic and Famous Prescription Compound Formulations(No.2021ZD006)。
文摘OBJECTIVE:To determine the effect of Traditional Chinese Medicine(TCM)Fuzheng Xuanfei Huashi prescription(扶正宣肺化湿方,FZXF)on lipopolysaccharide(LPS)-induced pneumonia in mice and identify the mechanism of FZXF in the treatment of LPS-induced lung inflammation.METHODS:The pneumonia model was established by intraperitoneal injection of 5 mg/kg LPS in mice.Cytokines were detected by enzyme-linked immuneosorbent assay(ELISA),macrophages in lung tissue were determined by immunofluorescence,and pathwayrelated data were determined by quantitative real-time polymerase chain reaction(qPCR)and Western blot.RESULTS:The liver,thymus,and spleen index values and the levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)obviously increased in LPS-treated mice.FZXF decreased the white blood cell count and reduced the increase in the lung wet weight/dry weight ratio caused by LPS.The hematoxylin-eosin staining result showed that FZXF could maintain the integrity of lung tissue structure,alleviate interstitial oedema and alveolar wall thickening,and reduce inflammatory cell infiltration.Moreover,FZXF markedly reduced the expression of proinflammatory cytokines.FZXF also significantly reduced LPS-induced malondialdehyde production and increased superoxide dismutase level in the lung.By immunofluorescence,we found that FZXF could reduce macrophage infiltration.The mRNA expression levels of cyclooxygenase-2(COX-2),prostaglandin E2(PGE2),toll-like receptor 4(TLR4)and nuclear transcription factorκB(NF-κB)in the lung tissue of mice were decreased by treatment with FZXF.In addition,FZXF inhibited the protein expression of TLR4,p-p65 and COX-2.These results indicated that FZXF could inhibit the inflammatory response of LPS induced cytokine storm in mice through TLR4/NF-κB and COX-2/PGE2 signaling pathway.CONCLUSION:These findings were suggested that FZXF prescription suppresses inflammation in LPSinduced pneumonia in mice via TLR4/NF-κB and COX-2/PGE2 pathway.
基金Supported by Natural Science Foundation of Chongqing,No.cstc2021jcyj-msxmx0848Chongqing Bishan Scientific Research Project,No.BSKJ2022006+1 种基金National Natural Science Foundation of China,No.81773954National College Students Innovation and Entrepreneurship Program,No.202310617015.
文摘In the current era,metabolic dysfunction-associated steatotic liver disease(MASLD)has gradually developed into a major type of chronic liver disease that is widespread globally.Numerous studies have shown that the gut microbiota plays a crucial and indispensable role in the progression of MASLD.Currently,the gut microbiota has become one of the important entry points for the research of this disease.Therefore,the aim of this review is to elaborate on the further associations between the gut microbiota and MASLD,including the changes and differences in the microbiota between the healthy liver and the diseased liver.Meanwhile,considering that metabolic dysfunction-associated fatty liver and metabolic dysfunction-associated steatohepatitis are abnormal pathological states in the development of the disease and that the liver exhibits different degrees of fibrosis(such as mild fibrosis and severe fibrosis)during the disease progression,we also conduct a comparison of the microbiota in these states and use them as markers of disease progression.It reveals the changes in the production and action mechanisms of short-chain fatty acids and bile acids brought about by changes in the gut microbiota,and the impact of lipopolysaccharide from Gram-negative bacteria on the disease.In addition,the regulation of the gut microbiota in disease and the production and inhibition of related disease factors by the use of probiotics(including new-generation probiotics)will be explored,which will help to monitor the disease progression of patients with different gut microbiota compositions in the future and carry out personalized targeted therapies for the gut microbiota.This will achieve important progress in preventing and combating this disease.
基金funded by FEDER/Ministerio de Ciencia,Innovación y Universidades Agencia Estatal de Investigación/Project(PID2020-119729GB-100,REF/AEI/10.13039/501100011033)(to EP)a predoctoral fellowship from the Spanish Ministry of Universities(FPU)and Amigos de la Universidad de Navarra(to NSS)“Programa MRR Investigo 2023”(to MGB and MMD)。
文摘Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.
基金This study was supported by internal funds from Patanjali Research Foundation Trust,Haridwar,India。
文摘Background:Fever is characterized by an upregulation of the thermoregulatory set-point after the body encounters any pathological challenge.It is accompanied by uncomfortable sickness behaviors and may be harmful in patients with other comor-bidities.We have explored the impact of an Ayurvedic medicine,Fevogrit,in an endo-toxin(lipopolysaccharide)-induced fever model in Wistar rats.Methods:Active phytoconstituents of Fevogrit were identified and quantified using ultra-high-performance liquid chromatography(UHPLC)platform.For the in-vivo study,fever was induced in male Wistar rats by the intraperitoneal administration of lipopolysaccharide(LPS),obtained from Escherichia coli.The animals were allocated to normal control,disease control,Paracetamol treated and Fevogrit treated groups.The rectal temperature of animals was recorded at different time points using a digital thermometer.At the 6-h time point,levels of TNF-α,IL-1βand IL-6 cytokines were analyzed in serum.Additionally,the mRNA expression of these cytokines was deter-mined in hypothalamus,24 h post-LPS administration.Results:UHPLC analysis of Fevogrit revealed the presence of picroside I,picroside II,vanillic acid,cinnamic acid,magnoflorine and cordifolioside A,as bioactive constitu-ents with known anti-inflammatory properties.Fevogrit treatment efficiently reduces the LPS-induced rise in the rectal temperature of animals.The levels and gene ex-pression of TNF-α,IL-1βand IL-6 in serum and hypothalamus,respectively,was also significantly reduced by Fevogrit treatment.Conclusion:The findings of the study demonstrated that Fevogrit can suppress LPS-induced fever by inhibiting peripheral or central inflammatory signaling pathways and could well be a viable treatment for infection-induced increase in body temperatures.
基金The Guangdong Basic and Applied Basic Research Foundation(2022A1515010730)the National Natural Science Foundation of China(32001647)+2 种基金the Science and Technology Plan Projects of Guangzhou City(202102100009)(the Guangzhou Key Laboratory for Intelligent Sensing and Quality Control of Agricultural Products)National Natural Science Foundation of China(31972022)the 111 Project(B17018)to conduct the project are gratefully acknowledged。
文摘The purpose of this study was to investigate the hypoglycemic effect and mechanism of D endrobium officinale polysaccharide(DOP)on type 2 diabetes mellitus(T2DM)mice established by high-fat diet and streptozotocin.The results showed that DOP improved glycolipid metabolism and serum inflammation levels,and inhibited intestinal-derived lipopolysaccharide(LPS)translocation,suggesting that inhibiting LPS-mediated intestinal barrier damage may be a key target for DOP to alleviate T2DM.Interestingly,the study found that DOP reduced intestinal inflammation and oxidative stress levels,significantly up-regulated the mRNA expression of tight junction proteins Claudin-1,Occludin and zonula occluden-1(ZO-1),and ameliorated intestinal epithelial damage.In addition,DOP strongly inhibited the intestinal pathogenic bacteria and LPS-producing bacteria Helicobacter,Enterococcus and Desulfovibrio with a reduction rate of 95%,73% and 9%,respectively,and promoted the proliferation of anti-inflammatory bacteria Bifidobacterium and Lactobacillus by 139% and 8%,respectively.Taken together,the hypoglycemic effect of DOP was related to the protection of intestinal mucosal barrier,and its underlying mechanism lied in its excellent anti-inflammatory and gut microbiotamodulatory effects,providing a theoretical basis for developing DOP as a novel prebiotic in functional food for diabetes.
文摘Background:To appraise the ameliorative potentials of Allium sativum aqueous extract in ovalbumin(OVA)-lipopolysaccharide(LPS)-induced asthma.Methods:Extraction,phytochemical analysis,determination of bioactive compounds and LD50 study of aqueous extract of A.sativum were achieved using standard biochemical methods.Twenty-four(24)male Wistar rats averagely weighing between 168–255 g were grouped into four of six animals in each steel-metal cage.Groups 1 and 2 served as normal and positive groups respectively.Rats in groups 2–4 were sensitized and challenged with a combination of OVA and LPS.Groups 3 and 4 were administered 250 and 500 mg/kg b.w of aqueous extract of A.sativum respectively for two weeks.The effect of aqueous extracts of A.sativum in OVA and LPS-induced asthma on alterations in differential white blood cells,inflammatory cytokines,some serum biochemical as well as histological indicators of experimental rats were assessed.Results:The aqueous extract of 600 g of plant material yielded 74.1 g accounting for 11.9%of sample material used.The result of the Phytochemical analysis showed higher number of glycosides,flavonoids and phenols.The animals displayed zero behavioral adverse reaction when administered the aqueous extract up to the highest dose of 5,000 mg/kg b.w.Administrations of aqueous extract of A.sativum remarkably(P<0.05;95%confidence intervals CI)declined the levels of neutrophils,eosinophils and total white blood cell count as opposed to the untreated group.Levels of interleukin 4(IL-4),interleukin 5(IL-5),interleukin 13(IL-13)and immunoglobulin E(IgE)of groups 3 and 4 had a significant(P<0.05;95%CI)varying percentage reduction(IL-4=39.78%,49.51%;IL-5=34.66%,40.05%;IL-13=31.96%,30.81%;33.45%,21.38%)respectively in comparison to group 2(untreated).The result showed a significantly(P<0.05,95%CI)declined malonaldehyde(MDA)concentration and elevated catalase,decreased glutathione concentration and superoxide dismutase activity of the treatment groups compared to the untreated.Serum liver function enzymes including alkaline phosphatase,alanine transaminase,and aspartate transaminase in the groups receiving aqueous extract of A.sativum exhibited a significant(P<0.05;95%CI)reduction in levels compared to group 2(untreated).Conclusion:Findings from this study indicated that aqueous extracts of A.sativum have the potential to improve asthma symptoms by decreasing inflammatory cytokines and mitigating oxidative stress.This effect could enhance the efficacy of conventional treatments such as inhaled corticosteroids,including cortisone,hydrocortisone,dexamethasone,and prednisone,as well as bronchodilators,leukotriene modifiers,and biologic therapies.Further studies need to be carried out on human subjects and also expanded to other respiratory disorders like Chronic obstructive pulmonary disease and Coronavirus Disease 2019.
基金supported by Chung Shan Medical University and Changhua Christian Hospital(CSMU-CCH-111-08)supported by research grants from the Chung Shan Medical University Hospital,Taichung,Taiwan(CSH-2023-C-023)the National Science and Technology Council,Taiwan,for financially supporting this research under Contract Nos.NSTC 112-2320-B-040-017,NSTC112-2314-B-040-009,and NSTC 112-2320-B-040-011.
文摘Background:Acute respiratory distress syndrome(ARDS)is the major therapeutic dilemma associated with significant inflammation and severe pulmonary dysfunction.Liriodendrin is a bioactive compound extract from traditional Chinesemedicine,historically utilized formodulating inflammatory responses and alleviating symptoms in multiple diseasemodels.Methods:At present,BALB/c mice to explore the effects of liriodendrin on lipopolysaccharide(LPS)-induced ARDS.Before LPS was administered,the mice were treated with either liriodendrin or dexamethasone.Leukocyte infiltration,lung edema,and alveolar-capillary barrier integrity were evaluated in the bronchoalveolar lavage fluid(BALF)and pulmonary parenchyma.The expression of adhesion molecules and proinflammatory cytokines in BALF was evaluated by enzyme-linked immunosorbent assay.Western blotting assay facilitated the analysis of the expression or phosphorylation of inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),NOD-like receptor family pyrin domain-containing 3(NLRP3),apoptosis-associated speck-like protein containing a CARD(ASC),cleaved caspase-1(CL-csapase-1),nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB),inhibitor of kappa B(IκB),mitogen-activated protein kinase(MAPK),and protein kinase B(Akt)in the lungs.In addition,the anti-inflammatory effects of liriodendrin were evaluated in LPS-stimulated RAW264.7 macrophages.Before LPS was administered,the RAW264.7 macrophages were treated with either liriodendrin or dexamethasone.Nitric Oxide(NO)production was measured using the Griess reaction assay,while ELISA assessed IL-1β,IL-6,and TNF-αlevels.Western blot analysis evaluated NF-κB phosphorylation and the expression of NLRP3,ASC,and CLcaspase-1.Results:These outcomes revealed that liriodendrin intervention markedly ameliorated the pathological features of LPS-induced ARDS,including leukocyte infiltration,lung edema,and alveolar-capillary barrier disruption.Liriodendrin also reduced the LPS-induced secretion of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesionmolecule-1(VCAM-1),expression of iNOS and COX2,and production of proinflammatory cytokines.Finally,we further discovered that the concentration trend of liriodendron amelioration ofARDSwas similar to those ofNLRP3 formation,NF-κB pathway activation,and p38 MAPK,c-Jun N-terminal kinase(JNK),and Akt phosphorylation but not to that of extracellular signal-regulated kinase(ERK)phosphorylation.Liriodendrin inhibited LPS-induced inflammatory responses in RAW264.7 macrophages.It markedly reduced NO production,propro-inflammatorytokines,NF-κB phosphorylation,and NLRP3 formation.Conclusions:In summary,liriodendrin effectively ameliorated the pathological features of LPS-induced ARDS inmice,demonstrating significant anti-inflammatory properties attributed to NLRP3 formation through NF-κB pathway activation by p38MAPK,JNK,and Akt phosphorylation.In LPS-treated RAW264.7 macrophages,liriodendrin reduced NO production,pro-inflammatory cytokines,and NLRP3 formation,suggesting its potential as an agent for ARDS and relative inflammation.
基金supported by Angel Nutritech Nutrition Fund(AF2021003)。
文摘Alcoholic liver disease(ALD)is one of the major global public health problems.Yeast extract(YE),a product prepared from yeast,has been proven to have antioxidant and anti-inflammatory properties.However,the potential role of YE in the prevention of ALD remains unclear.The present study aimed to investigate the protective effects of YE on ALD and explore the underlying mechanism based on gut microbiota.The result showed that YE supplementation significantly ameliorated chronic alcohol exposure-induced liver injury in mice.In addition,YE counteracted alcohol-induced gut dysbiosis,intestinal barrier dysfunction,lipopolysaccharide(LPS)leakage-induced inflammatory response in the liver.Moreover,microbiota depletion by a broad-spectrum antibiotic was sufficient to block the protective effect of YE on ALD,indicating the contribution of gut dysbiosis modulation to the hepatoprotective role of YE.Furthermore,we demonstrated the causal relationship between gut microbiota and hepatoprotective effects of YE with the fecal microbiota transplantation(FMT)experiment.Compared with the ALD-FMT mice,gut dysbiosis,intestinal barrier dysfunction,LPS/TLR4 signaling pathway activation,and liver inflammatory response were significantly improved in the YE-FMT mice.Together,our findings highlight that dietary YE protects against ALD through gut dysbiosis correction.
基金funded by the Basic Science Research Program of the National Research Foundation of Korea(NRF)which is funded by the Ministry of Science,ICT&Future Planning(NRF-2018R1D1A3B07041059 to M.M.and NRF-2016R1A5A2012284 to Y.-M.R)+3 种基金by the Cooperative Research Program for Agriculture Science and Technology Development(Project No.PJ01428603)Rural Development Administration,Republic of Koreaby the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(grant number:HF21C0021).
文摘Alzheimer's disease(AD)is the most serious age-related neurodegenerative disease and causes destructive and irreversible cognitive decline.Failures in the development of therapeutics targeting amyloid-β(Aβ)and tau;principal proteins inducing pathology in AD,suggest a paradigm shift towards the development of new therapeutic targets.The gram-negative bacteria and lipopolysaccharides(LPS)are attractive new targets for AD treatment.Surprisingly,an altered distribution of gram-negative bacteria and their LPS has been reported in AD patients.Moreover,gram-negative bacteria and their LPS have been shown to affect a variety of AD-related pathologies,such as Aβ homeostasis,tau pathology,neuroinflammation,and neurodegeneration.Moreover,therapeutic approaches targeting gram-negative bacteria or gram-negative bacterial molecules have significantly alleviated AD-related pathology and cognitive dysfunction.Despite multiple evidence showing that the gram-negative bacteria and their LPS play a crucial role in AD pathogenesis,the pathogenic mechanisms of gram-negative bacteria and their LPS have not been clarified.Here,we summarize the roles and pathomechanisms of gram-negative bacteria and LPS in AD.Furthermore,we discuss the possibility of using gram-negative bacteria and gram-negative bacterial molecules as novel therapeutic targets and new pathological characteristics for AD.
基金supported by the National Natural Science Foundation of China,Nos.82271327(to ZW),82072535(to ZW),81873768(to ZW),and 82001253(to TL).
文摘We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.
基金supported by the National Key Research and Development Projects,Nos.2022 YFC3602400,2022 YFC3602401(to JX)the Project Program of National Clinical Research Center for Geriatric Disorders(Xiangya Hospital),No.2020LNJJ16(to JX)the National Natural Science Foundation of China,No.82271369(to JX)。
文摘Hemorrhagic transformation is a major complication of large-artery atheroscle rotic stroke(a major ischemic stro ke subtype)that wo rsens outcomes and increases mortality.Disruption of the gut microbiota is an important feature of stroke,and some specific bacteria and bacterial metabolites may contribute to hemorrhagic transformation pathogenesis.We aimed to investigate the relationship between the gut microbiota and hemorrhagic transformation in largearte ry atheroscle rotic stro ke.An observational retrospective study was conducted.From May 2020 to September 2021,blood and fecal samples were obtained upon admission from 32 patients with first-ever acute ischemic stroke and not undergoing intravenous thrombolysis or endovascular thrombectomy,as well as 16 healthy controls.Patients with stro ke who developed hemorrhagic transfo rmation(n=15)were compared to those who did not develop hemorrhagic transformation(n=17)and with healthy controls.The gut microbiota was assessed through 16S ribosomal ribonucleic acid sequencing.We also examined key components of the lipopolysaccharide pathway:lipopolysaccharide,lipopolysaccharide-binding protein,and soluble CD14.We observed that bacterial diversity was decreased in both the hemorrhagic transformation and non-hemorrhagic transfo rmation group compared with the healthy controls.The patients with ischemic stro ke who developed hemorrhagic transfo rmation exhibited altered gut micro biota composition,in particular an increase in the relative abundance and dive rsity of members belonging to the Enterobacteriaceae family.Plasma lipopolysaccharide and lipopolysaccharide-binding protein levels were higher in the hemorrhagic transformation group compared with the non-hemorrhagic transfo rmation group.lipopolysaccharide,lipopolysaccharide-binding protein,and soluble CD14 concentrations were associated with increased abundance of Enterobacte riaceae.Next,the role of the gut microbiota in hemorrhagic transformation was evaluated using an experimental stroke rat model.In this model,transplantation of the gut microbiota from hemorrhagic transformation rats into the recipient rats triggered higher plasma levels of lipopolysaccharide,lipopolysaccharide-binding protein,and soluble CD14.Ta ken togethe r,our findings demonstrate a noticeable change in the gut microbiota and lipopolysaccharide-related inflammatory response in stroke patients with hemorrhagic transformation.This suggests that maintaining a balanced gut microbiota may be an important factor in preventing hemorrhagic transfo rmation after stro ke.
