The nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome is a critical modulator in inflammatory disease.Activation and mutation of NLRP3 can cause severe inflammation...The nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome is a critical modulator in inflammatory disease.Activation and mutation of NLRP3 can cause severe inflammation in diseases such as chronic infantile neurologic cutaneous and articular syndrome,Muckle-Wells syndrome,and familial cold autoinflammatory syndrome 1.To date,a great effort has been made to decode the underlying mechanisms of NLRP3 activation.The priming and activation of NLRP3 drive the maturation and release of active interleukin(IL)-18 and IL-1βto cause inflammation and pyroptosis,which can significantly trigger many diseases including inflammatory diseases,immune disorders,metabolic diseases,and neurodegenerative diseases.The investigation of NLRP3 as a therapeutic target for disease treatment is a hot topic in both preclinical studies and clinical trials.Developing potent NLRP3 inhibitors and downstream IL-1 inhibitors attracts wide-spectrum attention in both research and pharmaceutical fields.In this minireview,we first updated the molecular mechanisms involved in NLRP3 inflammasome activation and the associated downstream signaling pathways.We then reviewed the molecular and cellular pathways of NLRP3 in many diseases,including obesity,diabetes,and other metabolic diseases.In addition,we briefly reviewed the roles of NLRP3 in cancer growth and relative immune checkpoint therapy.Finally,clinical trials with treatments targeting NLRP3 and its downstream signaling pathways were summarized.展开更多
Liver fibrosis is a vital cause of morbidity in patients with liver diseases and developing novel anti-fibrotic drugs is imperative.Isovalerylspiramycin I(ISP I)as a major component of carrimycin applied to upper resp...Liver fibrosis is a vital cause of morbidity in patients with liver diseases and developing novel anti-fibrotic drugs is imperative.Isovalerylspiramycin I(ISP I)as a major component of carrimycin applied to upper respiratory infections,was first found to possess anti-fibrotic potential.The present study aims to evaluate the functions and mechanisms of ISP I in protecting against liver fibrosis.According to our results,ISP I not only reduced the expressions of fibrogenic markers in LX-2 cells but also appeared great protective effects on liver injury and liver fibrosis in bile duct ligation(BDL)rats and carbon tetrachloride(CCl4)mice.We proved that nucleotide-binding protein 2(NUBP2)was the direct target of ISP I.ISP I through targeting NUBP2,increased the amount of vascular non-inflammatory molecule-1(VNN1)on the cell membrane,which will inhibit oxidative stress and fibrosis.Simultaneously,the original carrimycin's protective effect on liver damage and fibrosis was verified.Therefore,our study provides potential agents for patients with liver fibrosis-related diseases,and the clear mechanism supports wide application in the clinic.展开更多
Adenine is an essential building block of genetic material and a range of coenzymes.Chemical probes containing an adenine moiety have been used in kinase profiling studies in cell lysates.Here we report that adenine-d...Adenine is an essential building block of genetic material and a range of coenzymes.Chemical probes containing an adenine moiety have been used in kinase profiling studies in cell lysates.Here we report that adenine-derived small-molecule probes with an activated ester reactive group can covalently modify a conserved lysine residue of protein kinases and capture a number of nucleotide-binding proteins within living cells.展开更多
BACKGROUND Gastric intestinal metaplasia(IM)is a precancerous lesion that is associated with an elevated risk of gastric carcinogenesis.Weiwei Decoction(WWD)is a promising traditional Chinese herbal formula widely emp...BACKGROUND Gastric intestinal metaplasia(IM)is a precancerous lesion that is associated with an elevated risk of gastric carcinogenesis.Weiwei Decoction(WWD)is a promising traditional Chinese herbal formula widely employed in clinical for treating IM.Previous studies suggested the potential involvement of the olfactomedin 4(OLFM4)/nucleotide-binding oligomerization domain 1(NOD1)/caudal-type homeobox gene 2(CDX2)signaling pathway in IM regulation.AIM To verify the regulation of the OLFM4/NOD1/CDX2 pathway in IM,specifically investigating WWD’s effectiveness on IM through this pathway.METHODS Immunohistochemistry for OLFM4,NOD1,and CDX2 was conducted on tissue microarray.GES-1 cells treated with chenodeoxycholic acid were utilized as IM cell models.OLFM4 short hairpin RNA(shRNA),NOD1 shRNA,and OLFM4 pcDNA were transfected to clarify the pathway regulatory relationships.Protein interactions were validated by coimmunoprecipitation.To explore WWD’s pharmacological actions,IM rat models were induced using N-methyl-N’-nitro-N-nitrosoguanidine followed by WWD gavage.Gastric cells were treated with WWD-medicated serum.Cytokines and chemokines content were assessed by enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction.RESULTS The OLFM4/NOD1/CDX2 axis was a characteristic of IM.OLFM4 exhibited direct binding and subsequent downregulation of NOD1,thereby sustaining the activation of CDX2 and promoting the progression of IM.WWD improved gastric mucosal histological lesions while suppressing intestinal markers KLF transcription factor 4,villin 1,and MUCIN 2 expression in IM rats.Regarding pharmacological actions,WWD suppressed OLFM4 and restored NOD1 expression,consequently reducing CDX2 at the mRNA and protein levels in IM rats.Parallel regulatory mechanisms were observed at the protein level in IM cells treated with WWD-medicated serum.Furthermore,WWD-medicated serum treatment strengthened OLFM4 and NOD1 interaction.In case of antiinflammatory,WWD restrained interleukin(IL)-6,interferon-gamma,IL-17,macrophage chemoattractant protein-1,macrophage inflammatory protein 1 alpha content in IM rat serum.WWD-medicated serum inhibited tumor necrosis factor alpha,IL-6,IL-8 transcriptions in IM cells.CONCLUSION The OLFM4/NOD1/CDX2 pathway is involved in the regulation of IM.WWD exerts its therapeutic efficacy on IM through the pathway,additionally attenuating the inflammatory response.展开更多
Nucleotide-binding oligomerization domain 1(NOD1) is an intracellular innate immune sensor for small molecules derived from bacterial cell components. NOD1 activation by its ligands leads to robust production of pro-i...Nucleotide-binding oligomerization domain 1(NOD1) is an intracellular innate immune sensor for small molecules derived from bacterial cell components. NOD1 activation by its ligands leads to robust production of pro-inflammatory cytokines and chemokines by innate immune cells, thereby mediating mucosal host defense systems against microbes. Chronic gastric infection due to Helicobacter pylori(H. pylori) causes various upper gastrointestinal diseases, including atrophic gastritis, peptic ulcers, and gastric cancer. It is now generally accepted that detection of H. pylori by NOD1 expressed in gastric epithelial cells plays an indispensable role in mucosal host defense systems against this organism. Recent studies have revealed the molecular mechanism by which NOD1 activation caused by H. pylori infection is involved in the development of chronic gastritis and gastric cancer. In this review, we have discussed and summarized how sensing of H. pylori by NOD1 mediates the prevention of chronic gastritis and gastric cancer.展开更多
Objective To investigate the effects of stimulant for nucleotide-binding oligomerization domain 1 （NOD1） on secretion of proinflammatory chemokine/cytokines and insulin-dependent glucose uptake in human differentiat...Objective To investigate the effects of stimulant for nucleotide-binding oligomerization domain 1 （NOD1） on secretion of proinflammatory chemokine/cytokines and insulin-dependent glucose uptake in human differentiated adipocytes. Methods Adipose tissues were obtained from patients undergoing liposuction. Stromal vascular cells were extracted and differentiated into adipocytes. A specific ligand for NOD1, was administered to human adipocytes in culture. Nuclear factor-κB transcriptional activity and proinflammatory chemokine/cytokines production were determined by reporter plasmid assay and enzyme-linked immunosorbent assay, respectively. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[ 3 H] glucose uptake assay. Furthermore, chemokine/cytokine secretion and glucose uptake in adipocytes transfected with small interfering RNA （siRNA） targeting NOD1 upon stimulation of NOD1 ligand were analyzed. Results Nuclear factor-κB transcriptional activity and monocyte chemoattractant protein-1 （MCP-1）, interleukin （IL）-6, and IL-8 secretion in human adipocytes were markedly increased stimulated with NOD1 ligand （all P〈0.01）. Insulin-induced glucose uptake was decreased upon the activation of NOD1 （P〈0.05）. NOD1 gene silencing by siRNA reduced NOD1 ligand-induced MCP-1, IL-6, and IL-8 release and increased insulin-induced glucose uptake （all P〈0.05）. Conclusion NOD1 activation in adipocytes might be implicated in the onset of insulin resistance.展开更多
Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 （NOD1）, a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes. Methods Adipo...Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 （NOD1）, a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes. Methods Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments. The effect of oleate/palmitate mixture on nuclear factor-κB （NF-κB） activation was analyzed by reporter plasmid assay. The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[SH] glucose uptake assay. Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA （siRNA） targeting NOD 1 upon fatty acids treatment were analyzed. Results Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6, tumor necrosis factor-R, and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4, and these effects were blocked by siRNA targeting NOD1. Furthermore, saturated fatty acids decreased the ability of insulin-stimulated glucose uptake. Importantly, siRNA targeting NOD 1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake. Conclusion NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes, suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.展开更多
Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecul...Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.展开更多
Host-pathogen co-evolution shapes resistance(R)proteins and their recognition of pathogen avirulence factors.However,little attention has been paid to naturally occurring genetic diversity in R genes.In this study,12 ...Host-pathogen co-evolution shapes resistance(R)proteins and their recognition of pathogen avirulence factors.However,little attention has been paid to naturally occurring genetic diversity in R genes.In this study,12 Solanum bulbocastanum accessions from the Commonwealth Potato Collection were screened for resistance to Phytophthora infestans,identifying 11 resistant and one susceptible accession.Targeted enrichment sequencing of nucleotide-binding leucine-rich repeat(NLR)genes using RenSeq,followed by diagnostic RenSeq(dRenSeq)analysis,revealed that all accessions except 7650 contained Rpi-blb1/RB variants.Variants in accessions 7641 and 7648 were non-functional,while three novel functional variants were identified.Cloning and functional analysis of Rpi-blb1/RB variants assessed their recognition of the avirulence factor IPI-O1.Three variants were functional,conferring resistance to P.infestans.Variants in accessions 7644 and 7647 also recognized IPI-O4,confirmed in transgenic potatoes.Analysis of a non-functional variant in S.bulbocastanum accession 7648 identified amino acid Ser347 in the nucleotide-binding(NB-ARC)domain as critical for cell-death initiation following IPI-O1 recognition.Predictions from the FunFOLD2 protein-ligand interaction model suggested that Ser347 is essential for ATP binding,suggesting potential inhibition on pentameric resistosome assembly.Western blot analysis revealed that the mutation of Ser347 to Asn markedly compromises the Rpi-blb1/RB protein stability,and co-immunoprecipitation assay further confirmed that this mutation severely disrupts the self-association of CCNB,thereby preventing Rpi-blb1/RB activation.Consistently,substituting Asn347 with serine restored function,underscoring its key role in Rpi-blb1/RB activity.Cell biology experiments demonstrated that Rpi-blb1/RB relocalize to the plasma membrane in response to IPI-O1.This relocalization depends on Ser347,further supporting the idea that its mutation affects resistosome formation,impairing resistance.This study provides an in-depth functional analysis of natural Rpi-blb1/RB diversity,offering insights into NLR protein evolution and resistance mechanisms in potatoes.展开更多
Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the...Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R).This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation ofNLRP3 inflammasome.Methods:A mouse model of ORG was established by high-fat diet feeding.The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079).The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3,ASC,and caspase-1,as well as the podocyte-associated molecules including nephrin,podocin,and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Westem blot analysis,respectively.Results:The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo,which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules.Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression ofpodocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro,and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079.Conclusions:P2X7R could trigger the activation ofNLRP3 inflammasome,and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.展开更多
Bacterial wilt disease caused by several Ralstonia species is one of the most destructive diseases in Solanaceae crops.Only a few functional resistance genes against bacterial wilt have been cloned to date.Here,we sho...Bacterial wilt disease caused by several Ralstonia species is one of the most destructive diseases in Solanaceae crops.Only a few functional resistance genes against bacterial wilt have been cloned to date.Here,we showthat the broadly conserved typeⅢsecreted effector RipY is recognized by the Nicotiana benthamiana immune system,leading to cell death induction,induction of defense-related gene expression,and restriction of bacterial pathogen growth.Using a multiplexed virus-induced gene-silencing-based N.benthamiana nucleotide-binding and leucine-rich repeat receptor(NbNLR)library,we identified a coiled-coil(CC)nucleotide-binding and leucine-rich repeat receptor(CNL)required for recognition of RipY,which we named RESISTANCE TO RALSTONIA SOLANACEARUM RIPY(RRS-Y).Genetic complementation assays in RRS-Y-silenced plants and stable rrs-y knockout mutants demonstrated that RRS-Y is sufficient to activate RipY-induced cell death andRipY-induced immunity to Ralstonia pseudosolanacearum.RRS-Y function is dependent on the phosphate-binding loop motif of the nucleotide-binding domain but independent of the characterized signaling components ENHANCED DISEASE SUSCEPTIBILITY 1,ACTIVATED DISEASE RESISTANCE 1,and N REQUIREMENT GENE 1 and the NLR helpers NB-LRR REQUIRED FOR HR-ASSOCIATED CELL DEATH-2,-3,and-4 in N.benthamiana.We further show that RRS-Y localization at the plasma membrane is mediated by two cysteine residues in the CC domain and is required for RipY recognition.RRSY also broadly recognizes RipY homologs across Ralstonia species.Lastly,we show that the C-terminal region of RipY is indispensable for RRS-Y activation.Together,our findings provide an additional effector/receptor pair system to deepen our understanding of CNL activation in plants.展开更多
This editorial discusses Pellegrino and Gravina's essay.Crohn’s disease(CD)is a complex and multifactorial disease that is influenced by a combination of genetic and environmental factors.While genetic factors pl...This editorial discusses Pellegrino and Gravina's essay.Crohn’s disease(CD)is a complex and multifactorial disease that is influenced by a combination of genetic and environmental factors.While genetic factors play a key role in the deve-lopment of the disease,environmental factors also play a significant role in influencing the risk of developing CD.By looking at present understanding of CD pathogenesis,we emphasize the important factors involved in the development of this illness,such as nucleotide-binding oligomerization domain-2,smoking,and vitamin D.Understanding the interplay between genetic and environmental factors is crucial for developing effective strategies for preventing and treating this chronic inflammatory bowel disease.展开更多
Inflammatory bowel disease(IBD),including ulcerative colitis and Crohn’s disease,is a chronic intestinal inflammation with complex pathogenesis.Pyroptosis a pro-inflammatory programmed cell death mediated by gasdermi...Inflammatory bowel disease(IBD),including ulcerative colitis and Crohn’s disease,is a chronic intestinal inflammation with complex pathogenesis.Pyroptosis a pro-inflammatory programmed cell death mediated by gasdermin D(GSDMD)cleavage plays a pivotal role in disease progression through nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP-3)/caspase-1 classical and caspase-4/5/11 non-classical pathways.Targeting pyroptosis has emerged as a promising therapeutic strategy,with recent advances highlighting the potential of pyroptosis inhibitors such as small-molecule compounds,biologics,and repurposed drugs that specifically target NLRP3,caspases,or GSDMD to suppress inflammasome activation,block pore formation,and mitigate downstream inflammation.This review systematically summarizes the mechanisms and therapeutic effects of these inhibitors,while addressing critical challenges including drug specificity,delivery efficiency,and long-term safety,and explores their potential in combination therapies with existing IBD treatments to enhance clinical efficacy.By integrating preclinical and clinical evidence,we provide valuable insights into the translational prospects of pyroptosis-targeted therapies for precision management of IBD.展开更多
Background:Noninfectious uveitis,a chronic ocular inflammatory disease,is char-acterized by the activation of immune cells in the eye,with most studies focusing on the role of the adaptive immune system in the disease...Background:Noninfectious uveitis,a chronic ocular inflammatory disease,is char-acterized by the activation of immune cells in the eye,with most studies focusing on the role of the adaptive immune system in the disease.However,limited data exist on the potential contribution of the innate immune system,specifically the nucleotide-binding oligomerization domain and leucine-rich repeat receptor-3(NLRP3)inflamma-some pathway.This pathway has previously been identified as a driver of inflammation in several low-grade,progressive inflammatory eye diseases such as diabetic retin-opathy.The aim of this study was to determine whether the NLRP3 inflammasome pathway plays a role in the pathogenesis and chronicity of experimental autoimmune uveitis(EAU).Methods:EAU was induced in C57BL/6J mice via intraperitoneal pertussis toxin and subcutaneous interphotoreceptor retinoid-binding protein injections.After 12 weeks,eyes were enucleated,and whole eye sections were assessed for inflammasome,macrophage,and microglial markers in the retina,ciliary body,and cornea using immunohistochemistry.Results:Our study confirmed higher NLRP3 inflammasome activation(increased ex-pression of NLRP3 and cleaved caspase 1 labeling)in EAU mouse retinas compared to controls.This correlated with increased astrogliosis and microglial activation through-out the eye.Migratory innate and adaptive peripheral immune cells(macrophages and leukocytes)were also found within the retina and ciliary body of EAU mice.Connexin43 proteins,which form hexameric hemichannels that can release adeno-sine triphosphate(ATP),an upstream inflammasome priming signal,were also found upregulated in the retina and cornea of EAU mice.Conclusion:Overall,our findings support the idea that in the EAU model there is active inflammation,even 12 weeks post induction,and that it can be correlated to inflammasome activation.This contributes to the pathogenesis and chronicity of non-infectious uveitis,and our results emphasize that targeting the inflammasome path-way could be efficacious for noninfectious uveitis treatment.展开更多
This article provides commentary on the article by Zhang et al.In this original research,Zhang et al investigated the therapeutic potential of teneligliptin for diabetic cardiomyopathy(DCM),which was mediated by targe...This article provides commentary on the article by Zhang et al.In this original research,Zhang et al investigated the therapeutic potential of teneligliptin for diabetic cardiomyopathy(DCM),which was mediated by targeting the NOD-like receptor protein 3(NLRP3)inflammasome.Through the use of both in vivo and in vitro models,the study demonstrated that teneligliptin alleviates cardiac hyper-trophy,reduces myocardial injury,and mitigates the inflammatory responses as-sociated with DCM.These findings suggest that teneligliptin’s cardioprotective effects are mediated through the inhibition of NLRP3 inflammasome activation,positioning it as a promising therapeutic option for managing DCM in diabetic patients.展开更多
Two pairs of degenerate primers were designed based on nucleotide-binding site (NBS) and serine/threonine kinase domain. PCR was performed with the primers and cDNA from the Triticum aestivum-Haynaldia villosa translo...Two pairs of degenerate primers were designed based on nucleotide-binding site (NBS) and serine/threonine kinase domain. PCR was performed with the primers and cDNA from the Triticum aestivum-Haynaldia villosa translocation line 6VS/6AL. Amplified products were cloned and sequenced. Nine clones with NBS and one with serine/threonine kinase domain were obtained. The NBS clones were classified to six groups according to their nucleotide sequence identities (90% or higher). These resistance gene analogs (RGAs) all have open reading frames (ORF), and their amino acid sequences show high similarity to Yr10 in wheat, Mla1 and Mla6 in barley, RPS2 in Arabidopsis and other resistance (R) genes with conserved motifs. They were preliminarily mapped on the chromosomes of homoeologous groups 1, 2 and 5 of common wheat by nulli-tetrasomic analysis. The 5'-end sequence of an RGA N5 was obtained by 5'-RACE PCR. It encodes six leucine zipper (LZ) and has high sequence similarity to RPS2.展开更多
Spontaneous bacterial peritonitis(SBP) is a frequent, life-threatening bacterial infection in patients with liver cirrhosis and ascites. Portal hypertension leads to increased bacterial translocation from the intestin...Spontaneous bacterial peritonitis(SBP) is a frequent, life-threatening bacterial infection in patients with liver cirrhosis and ascites. Portal hypertension leads to increased bacterial translocation from the intestine. Failure to eliminate invading pathogens due to immune defects associated with advanced liver disease on the background of genetic predisposition may result in SBP. The efficacy of antibiotic treatment and prophylaxis has declined due to the spread of multi-resistant bacteria. Patients with nosocomial SBP and with prior antibiotictreatment are at a particularly high risk for infection with resistant bacteria. Therefore, it is important to adapt empirical treatment to these risk factors and to the local resistance profile. Rifaximin, an oral, nonabsorbable antibiotic, has been proposed to prevent SBP, but may be useful only in a subset of patients. Since novel antibiotic classes are lacking, we have to develop prophylactic strategies which do not induce bacterial resistance. Farnesoid X receptor agonists may be a candidate, but so far, clinical studies are not available. New diagnostic tests which can be carried out quickly at the patient's site and provide additional prognostic information would be helpful. Furthermore, we need tools to predict antibiotic resistance in order to tailor first-line antibiotic treatment of spontaneous bacterial peritonitis to the individual patient and to reduce mortality.展开更多
AIM: To investigate if the presence of relevant genetic polymorphisms has effect on the effectual clearance of bacteria by monocytes and granulocytes in patients with Crohn’s disease (CD).
Two sets of degenerate oligonucleotide primers were designed according to amino acid conserved regions of reported plant disease resistance genes which encode proteins that contain nucleotide-binding site and leucine-...Two sets of degenerate oligonucleotide primers were designed according to amino acid conserved regions of reported plant disease resistance genes which encode proteins that contain nucleotide-binding site and leucine-rich repeats(NBS-LRR), and the plant disease resistance genes which encode serine/threonine protein kinase(STK). By polymerase chain reaction(PCR), disease resistance gene analogues have been amplified from three wild rice species in Yunnan Province, China. The DIN A fragments from amplification have been cloned into the pGEM-T vector respectively. Sequencing of the DNA fragments indicated that 7 classes, 2 classes and 6 classes NBS-LRR disease resistance gene analogues from Oryza rufipogon Griff. , Oryza officinalis Wall. , and Oryza meyeriana Baill. were obtained respectively. The two representative fragments of TO12 from Oryza officinalis Wall, and TR19 from Oryza rufipogon Griff, belong to the same class and homology of their sequences are 100%. The result shows that the sequences of the same class disease resistance gene analogues have no difference among different species of wild rice. 5 classes STK disease resistance gene analogues were also obtained among which 4 classes from Oryza rufipogon Griff. , 1 class from Oryza officinalis Wall. By comparison analysis of amino acid sequences. we found that the obtained disease resistance gene analogues have very low identity(low to 25%) with the reported disease resistance gene L6, N, Bs2, Prf, Pto, Lr10 and Xa21 etc. The finding suggests that the obtained disease resistance gene analogues are analogues of putative disease resistance genes that have not been isolated so far.展开更多
文摘The nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome is a critical modulator in inflammatory disease.Activation and mutation of NLRP3 can cause severe inflammation in diseases such as chronic infantile neurologic cutaneous and articular syndrome,Muckle-Wells syndrome,and familial cold autoinflammatory syndrome 1.To date,a great effort has been made to decode the underlying mechanisms of NLRP3 activation.The priming and activation of NLRP3 drive the maturation and release of active interleukin(IL)-18 and IL-1βto cause inflammation and pyroptosis,which can significantly trigger many diseases including inflammatory diseases,immune disorders,metabolic diseases,and neurodegenerative diseases.The investigation of NLRP3 as a therapeutic target for disease treatment is a hot topic in both preclinical studies and clinical trials.Developing potent NLRP3 inhibitors and downstream IL-1 inhibitors attracts wide-spectrum attention in both research and pharmaceutical fields.In this minireview,we first updated the molecular mechanisms involved in NLRP3 inflammasome activation and the associated downstream signaling pathways.We then reviewed the molecular and cellular pathways of NLRP3 in many diseases,including obesity,diabetes,and other metabolic diseases.In addition,we briefly reviewed the roles of NLRP3 in cancer growth and relative immune checkpoint therapy.Finally,clinical trials with treatments targeting NLRP3 and its downstream signaling pathways were summarized.
基金supported by the Beijing Natural Science Foundation,China(Grant No.:7222118)the National Natural Science Foundation of China(Grant No.:82073900)the CAMS Innovation Fund for Medical Sciences,China(CIFMS,Grant Nos.:2021-I2M-1-030,and 2021-I2M-1-028).
文摘Liver fibrosis is a vital cause of morbidity in patients with liver diseases and developing novel anti-fibrotic drugs is imperative.Isovalerylspiramycin I(ISP I)as a major component of carrimycin applied to upper respiratory infections,was first found to possess anti-fibrotic potential.The present study aims to evaluate the functions and mechanisms of ISP I in protecting against liver fibrosis.According to our results,ISP I not only reduced the expressions of fibrogenic markers in LX-2 cells but also appeared great protective effects on liver injury and liver fibrosis in bile duct ligation(BDL)rats and carbon tetrachloride(CCl4)mice.We proved that nucleotide-binding protein 2(NUBP2)was the direct target of ISP I.ISP I through targeting NUBP2,increased the amount of vascular non-inflammatory molecule-1(VNN1)on the cell membrane,which will inhibit oxidative stress and fibrosis.Simultaneously,the original carrimycin's protective effect on liver damage and fibrosis was verified.Therefore,our study provides potential agents for patients with liver fibrosis-related diseases,and the clear mechanism supports wide application in the clinic.
基金funding support from the National Natural Science Foundation of China(No.81872749)Shenzhen Science and Technology Innovation Commission(Nos.20200815000631001 and JCYJ20200109120414564)Peking University。
文摘Adenine is an essential building block of genetic material and a range of coenzymes.Chemical probes containing an adenine moiety have been used in kinase profiling studies in cell lysates.Here we report that adenine-derived small-molecule probes with an activated ester reactive group can covalently modify a conserved lysine residue of protein kinases and capture a number of nucleotide-binding proteins within living cells.
基金Supported by National Natural Science Foundation of China,No.82104747 and No.82305133Basic and Applied Basic Research Foundation of Guangdong Province,China,No.2020A1515110947+1 种基金General Project of Shenzhen Science and Technology Innovation Commission,No.JCYJ20230807094659030,No.JCYJ20230807094805012,No.JCYJ20210324111602007,and No.JCYJ20220531091815034the Scientific Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine,No.20221349.
文摘BACKGROUND Gastric intestinal metaplasia(IM)is a precancerous lesion that is associated with an elevated risk of gastric carcinogenesis.Weiwei Decoction(WWD)is a promising traditional Chinese herbal formula widely employed in clinical for treating IM.Previous studies suggested the potential involvement of the olfactomedin 4(OLFM4)/nucleotide-binding oligomerization domain 1(NOD1)/caudal-type homeobox gene 2(CDX2)signaling pathway in IM regulation.AIM To verify the regulation of the OLFM4/NOD1/CDX2 pathway in IM,specifically investigating WWD’s effectiveness on IM through this pathway.METHODS Immunohistochemistry for OLFM4,NOD1,and CDX2 was conducted on tissue microarray.GES-1 cells treated with chenodeoxycholic acid were utilized as IM cell models.OLFM4 short hairpin RNA(shRNA),NOD1 shRNA,and OLFM4 pcDNA were transfected to clarify the pathway regulatory relationships.Protein interactions were validated by coimmunoprecipitation.To explore WWD’s pharmacological actions,IM rat models were induced using N-methyl-N’-nitro-N-nitrosoguanidine followed by WWD gavage.Gastric cells were treated with WWD-medicated serum.Cytokines and chemokines content were assessed by enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction.RESULTS The OLFM4/NOD1/CDX2 axis was a characteristic of IM.OLFM4 exhibited direct binding and subsequent downregulation of NOD1,thereby sustaining the activation of CDX2 and promoting the progression of IM.WWD improved gastric mucosal histological lesions while suppressing intestinal markers KLF transcription factor 4,villin 1,and MUCIN 2 expression in IM rats.Regarding pharmacological actions,WWD suppressed OLFM4 and restored NOD1 expression,consequently reducing CDX2 at the mRNA and protein levels in IM rats.Parallel regulatory mechanisms were observed at the protein level in IM cells treated with WWD-medicated serum.Furthermore,WWD-medicated serum treatment strengthened OLFM4 and NOD1 interaction.In case of antiinflammatory,WWD restrained interleukin(IL)-6,interferon-gamma,IL-17,macrophage chemoattractant protein-1,macrophage inflammatory protein 1 alpha content in IM rat serum.WWD-medicated serum inhibited tumor necrosis factor alpha,IL-6,IL-8 transcriptions in IM cells.CONCLUSION The OLFM4/NOD1/CDX2 pathway is involved in the regulation of IM.WWD exerts its therapeutic efficacy on IM through the pathway,additionally attenuating the inflammatory response.
文摘Nucleotide-binding oligomerization domain 1(NOD1) is an intracellular innate immune sensor for small molecules derived from bacterial cell components. NOD1 activation by its ligands leads to robust production of pro-inflammatory cytokines and chemokines by innate immune cells, thereby mediating mucosal host defense systems against microbes. Chronic gastric infection due to Helicobacter pylori(H. pylori) causes various upper gastrointestinal diseases, including atrophic gastritis, peptic ulcers, and gastric cancer. It is now generally accepted that detection of H. pylori by NOD1 expressed in gastric epithelial cells plays an indispensable role in mucosal host defense systems against this organism. Recent studies have revealed the molecular mechanism by which NOD1 activation caused by H. pylori infection is involved in the development of chronic gastritis and gastric cancer. In this review, we have discussed and summarized how sensing of H. pylori by NOD1 mediates the prevention of chronic gastritis and gastric cancer.
基金Supported by Grant from Department of Education of Liaoning Province(2008810)
文摘Objective To investigate the effects of stimulant for nucleotide-binding oligomerization domain 1 （NOD1） on secretion of proinflammatory chemokine/cytokines and insulin-dependent glucose uptake in human differentiated adipocytes. Methods Adipose tissues were obtained from patients undergoing liposuction. Stromal vascular cells were extracted and differentiated into adipocytes. A specific ligand for NOD1, was administered to human adipocytes in culture. Nuclear factor-κB transcriptional activity and proinflammatory chemokine/cytokines production were determined by reporter plasmid assay and enzyme-linked immunosorbent assay, respectively. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[ 3 H] glucose uptake assay. Furthermore, chemokine/cytokine secretion and glucose uptake in adipocytes transfected with small interfering RNA （siRNA） targeting NOD1 upon stimulation of NOD1 ligand were analyzed. Results Nuclear factor-κB transcriptional activity and monocyte chemoattractant protein-1 （MCP-1）, interleukin （IL）-6, and IL-8 secretion in human adipocytes were markedly increased stimulated with NOD1 ligand （all P〈0.01）. Insulin-induced glucose uptake was decreased upon the activation of NOD1 （P〈0.05）. NOD1 gene silencing by siRNA reduced NOD1 ligand-induced MCP-1, IL-6, and IL-8 release and increased insulin-induced glucose uptake （all P〈0.05）. Conclusion NOD1 activation in adipocytes might be implicated in the onset of insulin resistance.
基金Supported by the Grant from the Educational Department of Liaoning Province(2008810)
文摘Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 （NOD1）, a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes. Methods Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments. The effect of oleate/palmitate mixture on nuclear factor-κB （NF-κB） activation was analyzed by reporter plasmid assay. The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[SH] glucose uptake assay. Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA （siRNA） targeting NOD 1 upon fatty acids treatment were analyzed. Results Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6, tumor necrosis factor-R, and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4, and these effects were blocked by siRNA targeting NOD1. Furthermore, saturated fatty acids decreased the ability of insulin-stimulated glucose uptake. Importantly, siRNA targeting NOD 1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake. Conclusion NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes, suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.
基金supported by grants from the National Natural Science Foundation of China(Nos.81870067 and 82170664).
文摘Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.
基金supported by the National Natural Science Foundation of China(32372558)National Natural Science Foundation of China-The Royal Society(32061130211)the Rural and Environment Science and Analytical Services Division of the Scottish Government through project JHI-B1-1,the Biotechnology and Biological Sciences Research Council(BBSRC)through award BB/SO15663/1,the Royal Society through award NAF/R1/201061.
文摘Host-pathogen co-evolution shapes resistance(R)proteins and their recognition of pathogen avirulence factors.However,little attention has been paid to naturally occurring genetic diversity in R genes.In this study,12 Solanum bulbocastanum accessions from the Commonwealth Potato Collection were screened for resistance to Phytophthora infestans,identifying 11 resistant and one susceptible accession.Targeted enrichment sequencing of nucleotide-binding leucine-rich repeat(NLR)genes using RenSeq,followed by diagnostic RenSeq(dRenSeq)analysis,revealed that all accessions except 7650 contained Rpi-blb1/RB variants.Variants in accessions 7641 and 7648 were non-functional,while three novel functional variants were identified.Cloning and functional analysis of Rpi-blb1/RB variants assessed their recognition of the avirulence factor IPI-O1.Three variants were functional,conferring resistance to P.infestans.Variants in accessions 7644 and 7647 also recognized IPI-O4,confirmed in transgenic potatoes.Analysis of a non-functional variant in S.bulbocastanum accession 7648 identified amino acid Ser347 in the nucleotide-binding(NB-ARC)domain as critical for cell-death initiation following IPI-O1 recognition.Predictions from the FunFOLD2 protein-ligand interaction model suggested that Ser347 is essential for ATP binding,suggesting potential inhibition on pentameric resistosome assembly.Western blot analysis revealed that the mutation of Ser347 to Asn markedly compromises the Rpi-blb1/RB protein stability,and co-immunoprecipitation assay further confirmed that this mutation severely disrupts the self-association of CCNB,thereby preventing Rpi-blb1/RB activation.Consistently,substituting Asn347 with serine restored function,underscoring its key role in Rpi-blb1/RB activity.Cell biology experiments demonstrated that Rpi-blb1/RB relocalize to the plasma membrane in response to IPI-O1.This relocalization depends on Ser347,further supporting the idea that its mutation affects resistosome formation,impairing resistance.This study provides an in-depth functional analysis of natural Rpi-blb1/RB diversity,offering insights into NLR protein evolution and resistance mechanisms in potatoes.
基金grants from the National Natural Science Foundation of China (No.81573745and No.8160140274)Beijing Municipal Natural Science Foundation (No.7172066) Beijing Development Foundation of Traditional Chinese Medicine (QN2016-23).
文摘Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R).This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation ofNLRP3 inflammasome.Methods:A mouse model of ORG was established by high-fat diet feeding.The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079).The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3,ASC,and caspase-1,as well as the podocyte-associated molecules including nephrin,podocin,and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Westem blot analysis,respectively.Results:The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo,which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules.Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression ofpodocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro,and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079.Conclusions:P2X7R could trigger the activation ofNLRP3 inflammasome,and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.
基金supported by the National Research Foundation of Korea(NRF)funded by the Korean Ministry of Education(Global PhD Fellowship Program Project 500–20190213)by the Ministry of Sciences and ICT(Projects 2018R1A5A1023599,2020R1A2C1101419).
文摘Bacterial wilt disease caused by several Ralstonia species is one of the most destructive diseases in Solanaceae crops.Only a few functional resistance genes against bacterial wilt have been cloned to date.Here,we showthat the broadly conserved typeⅢsecreted effector RipY is recognized by the Nicotiana benthamiana immune system,leading to cell death induction,induction of defense-related gene expression,and restriction of bacterial pathogen growth.Using a multiplexed virus-induced gene-silencing-based N.benthamiana nucleotide-binding and leucine-rich repeat receptor(NbNLR)library,we identified a coiled-coil(CC)nucleotide-binding and leucine-rich repeat receptor(CNL)required for recognition of RipY,which we named RESISTANCE TO RALSTONIA SOLANACEARUM RIPY(RRS-Y).Genetic complementation assays in RRS-Y-silenced plants and stable rrs-y knockout mutants demonstrated that RRS-Y is sufficient to activate RipY-induced cell death andRipY-induced immunity to Ralstonia pseudosolanacearum.RRS-Y function is dependent on the phosphate-binding loop motif of the nucleotide-binding domain but independent of the characterized signaling components ENHANCED DISEASE SUSCEPTIBILITY 1,ACTIVATED DISEASE RESISTANCE 1,and N REQUIREMENT GENE 1 and the NLR helpers NB-LRR REQUIRED FOR HR-ASSOCIATED CELL DEATH-2,-3,and-4 in N.benthamiana.We further show that RRS-Y localization at the plasma membrane is mediated by two cysteine residues in the CC domain and is required for RipY recognition.RRSY also broadly recognizes RipY homologs across Ralstonia species.Lastly,we show that the C-terminal region of RipY is indispensable for RRS-Y activation.Together,our findings provide an additional effector/receptor pair system to deepen our understanding of CNL activation in plants.
文摘This editorial discusses Pellegrino and Gravina's essay.Crohn’s disease(CD)is a complex and multifactorial disease that is influenced by a combination of genetic and environmental factors.While genetic factors play a key role in the deve-lopment of the disease,environmental factors also play a significant role in influencing the risk of developing CD.By looking at present understanding of CD pathogenesis,we emphasize the important factors involved in the development of this illness,such as nucleotide-binding oligomerization domain-2,smoking,and vitamin D.Understanding the interplay between genetic and environmental factors is crucial for developing effective strategies for preventing and treating this chronic inflammatory bowel disease.
基金Supported by the Science and Technology Program of Gansu Province,No.23JRRA1015.
文摘Inflammatory bowel disease(IBD),including ulcerative colitis and Crohn’s disease,is a chronic intestinal inflammation with complex pathogenesis.Pyroptosis a pro-inflammatory programmed cell death mediated by gasdermin D(GSDMD)cleavage plays a pivotal role in disease progression through nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP-3)/caspase-1 classical and caspase-4/5/11 non-classical pathways.Targeting pyroptosis has emerged as a promising therapeutic strategy,with recent advances highlighting the potential of pyroptosis inhibitors such as small-molecule compounds,biologics,and repurposed drugs that specifically target NLRP3,caspases,or GSDMD to suppress inflammasome activation,block pore formation,and mitigate downstream inflammation.This review systematically summarizes the mechanisms and therapeutic effects of these inhibitors,while addressing critical challenges including drug specificity,delivery efficiency,and long-term safety,and explores their potential in combination therapies with existing IBD treatments to enhance clinical efficacy.By integrating preclinical and clinical evidence,we provide valuable insights into the translational prospects of pyroptosis-targeted therapies for precision management of IBD.
基金funded by a Maurice and Phyllis Paykel Trust Grant(203134)supported by a Buchanan Ocular Therapeutics Unit Doctoral Scholarship.Odunayo O.Mugisho is supported by a Neurological Foundation First Postdoctoral Research Fellowship(2001 FFE)+2 种基金an Auckland Medical Research Foundation Grant(1121013)an Auckland Medical Research Foundation Postdoctoral Fellowship(1323001)supported by the Buchanan Charitable Foundation,with part of her salary also supported by the Health Research Council of New Zealand(20/317).
文摘Background:Noninfectious uveitis,a chronic ocular inflammatory disease,is char-acterized by the activation of immune cells in the eye,with most studies focusing on the role of the adaptive immune system in the disease.However,limited data exist on the potential contribution of the innate immune system,specifically the nucleotide-binding oligomerization domain and leucine-rich repeat receptor-3(NLRP3)inflamma-some pathway.This pathway has previously been identified as a driver of inflammation in several low-grade,progressive inflammatory eye diseases such as diabetic retin-opathy.The aim of this study was to determine whether the NLRP3 inflammasome pathway plays a role in the pathogenesis and chronicity of experimental autoimmune uveitis(EAU).Methods:EAU was induced in C57BL/6J mice via intraperitoneal pertussis toxin and subcutaneous interphotoreceptor retinoid-binding protein injections.After 12 weeks,eyes were enucleated,and whole eye sections were assessed for inflammasome,macrophage,and microglial markers in the retina,ciliary body,and cornea using immunohistochemistry.Results:Our study confirmed higher NLRP3 inflammasome activation(increased ex-pression of NLRP3 and cleaved caspase 1 labeling)in EAU mouse retinas compared to controls.This correlated with increased astrogliosis and microglial activation through-out the eye.Migratory innate and adaptive peripheral immune cells(macrophages and leukocytes)were also found within the retina and ciliary body of EAU mice.Connexin43 proteins,which form hexameric hemichannels that can release adeno-sine triphosphate(ATP),an upstream inflammasome priming signal,were also found upregulated in the retina and cornea of EAU mice.Conclusion:Overall,our findings support the idea that in the EAU model there is active inflammation,even 12 weeks post induction,and that it can be correlated to inflammasome activation.This contributes to the pathogenesis and chronicity of non-infectious uveitis,and our results emphasize that targeting the inflammasome path-way could be efficacious for noninfectious uveitis treatment.
文摘This article provides commentary on the article by Zhang et al.In this original research,Zhang et al investigated the therapeutic potential of teneligliptin for diabetic cardiomyopathy(DCM),which was mediated by targeting the NOD-like receptor protein 3(NLRP3)inflammasome.Through the use of both in vivo and in vitro models,the study demonstrated that teneligliptin alleviates cardiac hyper-trophy,reduces myocardial injury,and mitigates the inflammatory responses as-sociated with DCM.These findings suggest that teneligliptin’s cardioprotective effects are mediated through the inhibition of NLRP3 inflammasome activation,positioning it as a promising therapeutic option for managing DCM in diabetic patients.
文摘Two pairs of degenerate primers were designed based on nucleotide-binding site (NBS) and serine/threonine kinase domain. PCR was performed with the primers and cDNA from the Triticum aestivum-Haynaldia villosa translocation line 6VS/6AL. Amplified products were cloned and sequenced. Nine clones with NBS and one with serine/threonine kinase domain were obtained. The NBS clones were classified to six groups according to their nucleotide sequence identities (90% or higher). These resistance gene analogs (RGAs) all have open reading frames (ORF), and their amino acid sequences show high similarity to Yr10 in wheat, Mla1 and Mla6 in barley, RPS2 in Arabidopsis and other resistance (R) genes with conserved motifs. They were preliminarily mapped on the chromosomes of homoeologous groups 1, 2 and 5 of common wheat by nulli-tetrasomic analysis. The 5'-end sequence of an RGA N5 was obtained by 5'-RACE PCR. It encodes six leucine zipper (LZ) and has high sequence similarity to RPS2.
文摘Spontaneous bacterial peritonitis(SBP) is a frequent, life-threatening bacterial infection in patients with liver cirrhosis and ascites. Portal hypertension leads to increased bacterial translocation from the intestine. Failure to eliminate invading pathogens due to immune defects associated with advanced liver disease on the background of genetic predisposition may result in SBP. The efficacy of antibiotic treatment and prophylaxis has declined due to the spread of multi-resistant bacteria. Patients with nosocomial SBP and with prior antibiotictreatment are at a particularly high risk for infection with resistant bacteria. Therefore, it is important to adapt empirical treatment to these risk factors and to the local resistance profile. Rifaximin, an oral, nonabsorbable antibiotic, has been proposed to prevent SBP, but may be useful only in a subset of patients. Since novel antibiotic classes are lacking, we have to develop prophylactic strategies which do not induce bacterial resistance. Farnesoid X receptor agonists may be a candidate, but so far, clinical studies are not available. New diagnostic tests which can be carried out quickly at the patient's site and provide additional prognostic information would be helpful. Furthermore, we need tools to predict antibiotic resistance in order to tailor first-line antibiotic treatment of spontaneous bacterial peritonitis to the individual patient and to reduce mortality.
文摘AIM: To investigate if the presence of relevant genetic polymorphisms has effect on the effectual clearance of bacteria by monocytes and granulocytes in patients with Crohn’s disease (CD).
文摘Two sets of degenerate oligonucleotide primers were designed according to amino acid conserved regions of reported plant disease resistance genes which encode proteins that contain nucleotide-binding site and leucine-rich repeats(NBS-LRR), and the plant disease resistance genes which encode serine/threonine protein kinase(STK). By polymerase chain reaction(PCR), disease resistance gene analogues have been amplified from three wild rice species in Yunnan Province, China. The DIN A fragments from amplification have been cloned into the pGEM-T vector respectively. Sequencing of the DNA fragments indicated that 7 classes, 2 classes and 6 classes NBS-LRR disease resistance gene analogues from Oryza rufipogon Griff. , Oryza officinalis Wall. , and Oryza meyeriana Baill. were obtained respectively. The two representative fragments of TO12 from Oryza officinalis Wall, and TR19 from Oryza rufipogon Griff, belong to the same class and homology of their sequences are 100%. The result shows that the sequences of the same class disease resistance gene analogues have no difference among different species of wild rice. 5 classes STK disease resistance gene analogues were also obtained among which 4 classes from Oryza rufipogon Griff. , 1 class from Oryza officinalis Wall. By comparison analysis of amino acid sequences. we found that the obtained disease resistance gene analogues have very low identity(low to 25%) with the reported disease resistance gene L6, N, Bs2, Prf, Pto, Lr10 and Xa21 etc. The finding suggests that the obtained disease resistance gene analogues are analogues of putative disease resistance genes that have not been isolated so far.
