Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 802
Filtrar
1.
Pest Manag Sci ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32149457

RESUMO

BACKGROUND: The gradually elevated outbreak of plant bacterial diseases severely limits agricultural products and small amounts of pesticides can manage them. Our group has previously synthesized and screened the antimicrobial activity of diverse 1,3,4-oxadiazole thioether/sulfone compounds bridged by a sulfur atom at the 2-position of 1,3,4-oxadiazole. However, few studies evaluated the effect of eliminating the sulfur atom on bioactivity. Herein, a novel type of N-containing heterocyclic pendants-tagged 1,3,4-oxadiazoles bridged by alkyl chains only was systematically synthesized and evaluated for their antimicrobial activities. RESULTS: Bioassay results revealed that antibacterial efficacy increased by 551- and 314-folds against the corresponding phytopathogens Xanthomonas oryzae pv. oryzae and X. axonopodis pv. citri comparing to those of commercial agents. In vivo trials showed that C1 exerted remarkable curative activity against rice bacterial blight with the control effectiveness of 52.9% at 200 µg/mL. Antibacterial mechanism research found that C1 could reduce the hypersensitive response behavior and pathogenicity of Xoo through targeting the type III secretion systems (T3SS) at a lower drug dose. This outcome was verified by those observed significantly down-regulated proteins and representative genes from the related quantitative proteomics and qRT-PCR assays. CONCLUSION: This study can inspire the design of innovative molecular frameworks targeting T3SS of phytopathogens for controlling bacterial infections. This article is protected by copyright. All rights reserved.

2.
Inflamm Res ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193584

RESUMO

BACKGROUND: Fibrosis in multiple organs increases with age. Circulating fibrocytes are bone-marrow-derived mesenchymal progenitors that contribute to heart, lung, and kidney fibrosis under the diseased conditions. Whether circulating fibrocytes contribute to aging-related fibrosis is very limited. METHODS AND RESULTS: We measured the proportion and differentiation of circulating fibrocytes (CD45+/CD34+/collagen I+) from elders (n = 12) and adults (n = 12) using flow cytometry. Differentiated fibrocytes in the culture dishes were isolated and microarray was performed. The percentage of circulating fibrocytes in elders (1.95 ± 0.43%) was comparable to that in the adults (1.71 ± 0.38%). Cultured fibrocytes displayed enhanced potential of differentiation in the elder group (67.91 ± 5.88%) vs the adult group (44.03 ± 7.98%). In addition, expression of fibroblast activation markers and cell migratory ability were also increased in differentiated fibrocytes from elders. Microarray analysis revealed that differentiated fibrocytes from elders expressed high level of interleukin-18 (IL-18) receptor 1 (IL-18R1). Furthermore, we found IL-18 was elevated in the plasma of elders and IL-18/IL-18R1 was shown to promote fibrocyte differentiation. CONCLUSION: Circulating fibrocytes from elders had an enhanced capacity to differentiate into myofibroblasts, and might contribute to age-dependent fibrosis. Age-dependent increment of differentiation at least in part arose from their enhanced expression of IL-18R1. Inhibiting fibrocyte differentiation might be useful as an adjuvant treatment to delay the fibrosis process in aging population.

3.
Curr Med Sci ; 40(1): 48-54, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32166664

RESUMO

C1q/TNF-related protein 1 (CTRP1), a conserved protein of the C1q family, plays a key role in cardiovascular and metabolic diseases. However, the role of CTRP1 in renal injury is unclear. The purpose of this study is to explore the role of CTRP1 in unilateral ureteral obstruction (UUO)-induced renal fibrosis and to elucidate the underlying mechanism. Using gene delivery system, CTRP1 was overexpressed in the kidney, then the mice were operated to induce UUO model after adenovirus transfection. It was found that the expression of CTRP1 in the renal tissue was decreased in mice after UUO. CTRP1 overexpression decreased the kidney function and kidney weight index. Moreover, CTRP1 reduced oxidative stress and renal collagen deposition in vivo. As expected, we found that CTRP1 activated AMP-activated kinase (AMPK) and decreased NOX4 expression, while silencing AMPKα1 abolished the protective effects of CTRP1 overexpression in mice after UUO. In conclusion, CTRP1 may protect against UUO-induced renal injury via AMPK/NOX4 signaling. Our results indicate that CTRP1 exhibits potential effects to treat renal fibrosis caused by UUO.

4.
J Dent ; : 103318, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32169479

RESUMO

OBJECTIVES: To evaluate the short-term effects of stain-causing beverages on the effectiveness of in-office tooth bleaching. METHODS: Participants were recruited and randomly divided into 3 groups based on beverages used for rinsing during and after the bleaching procedure: group N (tap water, control group), group C (coffee), and group T (tea). Participants were instructed to rinse with the respective solutions for 30 s, 4 times daily for 4 weeks. All participants received two in-office bleaching treatment sessions with 40 % hydrogen peroxide (Opalescence BOOST PF 40 %, Ultradent); the sessions were separated by a 1-week interval. Tooth colour was assessed using a spectrophotometer (Easyshade, Vita ZahnFabrik) before the bleaching procedure (T0), immediately after the first session of bleaching (T1), immediately after the second session of bleaching (T2), as well as one week (T3) and three weeks after (T4) the end of bleaching. Tooth sensitivity (TS) was ranked using a numerical rating scale (NRS) and a visual analogue scale (VAS) at different time points. RESULTS: No significant difference in the whiteness index (W), △E, △a* and △b* values among the 3 groups was observed at any time interval (P for all > 0.05). At T4, the △L* value in group C was significantly lower than that in groups T and N (P = 0.022 and P = 0.001, respectively), though no significant difference in △L* values was observed among the 3 groups at T1 (P = 0.402), T2 (P = 0.643) and T3 (P = 0.177). Additionally, no significant difference was found in the TS values among the 3 groups at any of the evaluation time points (P for all > 0.05). CONCLUSIONS: Exposure to coffee or tea during the bleaching treatment period did not affect the effectiveness of the treatment. However, exposure to coffee after the bleaching treatment did affect the effectiveness of the treatment. Exposure to stain-causing beverages did not affect the bleaching-induced TS (ClinicalTrials.gov Identifier: NCT03933527). CLINICAL SIGNIFICANCE: The consumption of coffee or tea during tooth bleaching may not interfere with the colour change produced by the treatment. However, clinicians should advise their patients to refrain from, at least to some extent, consuming coffee after the bleaching procedure to maintain the effectiveness of the treatment.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32215707

RESUMO

The methylotrophic bacterium Methylorubrum extorquens AM1 holds a great potential of a microbial cell factory in producing high value chemicals with methanol as the sole carbon and energy source. However, many gene functions remain unknown, hampering further rewiring of metabolic networks. Clustered regularly interspaced short palindromic repeat interference (CRISPRi) has been demonstrated to be a robust tool for gene knockdown in diverse organisms. In this study, we developed an efficient CRISPRi system through optimizing the promoter strength of Streptococcus pyogenes-derived deactivated cas9 (dcas9). When the dcas9 and sgRNA were respectively controlled by medium PR/tetO and strong PmxaF-g promoters, dynamic repression efficacy of cell growth through disturbing a central metabolism gene glyA was achieved from 41.9 to 96.6% dependent on the sgRNA targeting sites. Furthermore, the optimized CRISPRi system was shown to effectively decrease the abundance of exogenous fluorescent protein gene mCherry over 50% and to reduce the expression of phytoene desaturase gene crtI by 97.7%. We then used CRISPRi technology combined with 26 sgRNAs pool to rapidly discover a new phytoene desaturase gene META1_3670 from 2470 recombinant mutants. The gene function was further verified through gene deletion and complementation as well as phylogenetic tree analysis. In addition, we applied CRISPRi to repress the transcriptional level of squalene-hopene cyclase gene shc involved in hopanoid biosynthesis by 64.9%, which resulted in enhancing 1.9-fold higher of carotenoid production without defective cell growth. Thus, the CRISPRi system developed here provides a useful tool in mining functional gene of M. extorquens as well as in biotechnology for producing high-valued chemicals from methanol. KEY POINTS: Developing an efficient CRISPRi to knockdown gene expression in C1-utilizing bacteria CRISPRi combined with sgRNAs pool to rapidly discover a new phytoene desaturase gene Improvement of carotenoid production by repressing a competitive pathway.

6.
Pest Manag Sci ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32187443

RESUMO

BACKGROUND: Induced apoptosis mechanism is an intriguing and effective manner that can reprogram cellular physiological and pathological processes to eradicate the undesired cells by their innate systems. Inspired by this opinion, numerous apoptosis inducers have been developed to treat animal diseases, especially in anticancer field. However, few studies reported to develop that kind of inductive agents for attacking plant pathogens by activation of apoptosis. With the aim of exploring and discovering abovementioned apoptosis inducers targeting phytopathogens, herein, a cluster of piperazine-tailored ursolic acid (UA) hybrids was systematically fabricated. RESULTS: In vitro testing announced that title molecules could inhibit the growth of two intractable bacterial strains, defined as Xanthomonas oryzae pv. oryzae and X. axonopodis pv. citri. The corresponding lowest EC50 values were 0.37 and 1.08 µg/mL, which exceeded those of UA (> 400 µg/mL) and positive controls. Moreover, compounds 5u and 5v could manage bacterial blight in vivo using pot experiments. Flow cytometer analysis indicted that title compounds could induce distinct apoptotic behaviors on tested bacteria. In-depth study revealed that the introduction of designed compounds could reduce the enzyme activities of catalase and superoxide dismutase, and subsequently leading to the accumulation of reactive oxygen species. CONCLUSION: This study can promote the development of apoptosis initiators for managing bacterial infections in agriculture by an innovative mode of action. This article is protected by copyright. All rights reserved.

7.
World Neurosurg ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32200014

RESUMO

This study aimed to investigate OIP5-AS1 effects on microangiopathy in diabetic mouse. Our results indicated that diabetic mice exhibited much lower OIP5-AS1 expression in the hippocampus than normal mice. Diabetic mice of OIP5-AS1 KO group showed remarkably lower OIP5-AS1 expression in the hippocampus, longer escape latency and lower percentage of CD31+ cells in the hippocampusthan those of WT group. OIP5-AS1 knockdown directly up-regulated miR-200b expression and ACE2 was directly inhibited by miR-200b. Relative to normal mice, diabetic mice had markedly higher miR-200b expression and lower ACE2 expression in the hippocampus. Diabetic mice of OIP5-AS1 KO group were with obviously higher miR-200b expression and lower ACE2 expression in the hippocampus than those of WT group. Compared with diabetic mice of OIP5-AS1 KO group, those of WT group, OIP5-AS1 KO + miR-200b inhibitor group and OIP5-AS1 KO + ACE2 group had obviously shorter escape latency and higher percentage of CD31+ cells and more caspase-3 protein expression in the hippocampus. In conclusion, OIP5-AS1 attenuated microangiopathy in diabetic mouse by regulating miR-200b/ACE2.

10.
Korean Circ J ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32212425

RESUMO

BACKGROUND AND OBJECTIVES: Little is known about the outcomes of outpatient clinic-based elective external cardioversion (OPC-ECV) for persistent atrial fibrillation (PeAF). We investigated the acute, short-term, and long-term elective external cardioversion (ECV) outcomes. METHODS: We included 1,718 patients who underwent OPC-ECV (74% male, 61.1±11.0 years old, 90.9% long-standing PeAF, 9.1% after atrial fibrillation [AF] ablation) after excluding patients with atrial tachycardia or inappropriate antiarrhythmic drug medication, and in-patient ECV. Biphasic shocks were delivered sequentially until successful cardioversion was achieved (70-100-150-200-250 J). If ECV failed at 150 J, we administered intravenous amiodarone 150 mg and delivered 200 J. RESULTS: ECV failed in 11.4%, and the complication rate was 0.47%. Within 3 months, AF recurred in 55.5% (44.7% as sustaining AF, 10.8% as paroxysmal AF), and the AF duration was independently associated (odds ratio [OR], 1.01 [1.00-1.02]; p=0.006), but amiodarone was independently protective (OR, 0.46 [0.27-0.76]; p=0.002, Log rank p<0.001) against an early recurrence. Regarding the long-term recurrence, pre-ECV heart failure was protective against an AF recurrence (hazard ratio, 0.63 [0.41-0.96], p=0.033) over 32 (9-66) months of follow-up. ECV energy (p<0.001) and early recurrence rate within 3 months (p=0.007, Log rank p=0.006) were significantly lower in post-ablation patients than in those with long-standing persistent AF. CONCLUSIONS: The success rate of OPC-ECV was 88.6%, and the complication rate was low. However, AF recurred in 55.5% within 3 months. Amiodarone was protective against short-term AF recurrences, and long-term AF recurrences were less in patients with baseline heart failure.

11.
Atherosclerosis ; 296: 59-65, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32065979

RESUMO

BACKGROUND AND AIMS: The insulin-like growth factor (IGF)-1 signalling pathway has been implicated in the pathogenesis of atherosclerosis; however, the mechanism underlying its role in stroke remains unexplained. Herein, we aimed to explore the effects of genetic polymorphisms in the IGF1 pathway on stroke in the Chinese Han population. METHODS: Twenty-six single-nucleotide polymorphisms (SNPs) in IGF1 pathway genes were genotyped in a case-control study consisting of 2070 stroke cases and 2243 controls. Main genetic effects and gene-gene interactive effects of the IGF1 pathway were evaluated. Weighted genetic risk scores (wGRS) were computed, and the associations between wGRS and gene expression were analysed. RESULTS: The variants at GHRH rs6032470 were significantly associated with high risk of hemorrhagic stroke (HS), and the adjusted OR (95%CI) was 1.368 (1.136-1.647). Significant additive interaction between rs6032470 and gender was detected for HS and ischemic stroke (IS). The association of rs6032470 and stroke was stronger in males than in females. Additionally, a significant gene-gene interaction of rs6032470-rs1874479 (IGFBP1) in relation to HS risk was identified (p < 0.05). IGF1 mRNA expression was significantly upregulated in IS, while it was linearly downregulated across rs6214 genotypes. In addition, IGFBP3 transcript variant 2 mRNA level was negatively correlated with wGRS (r = -0.285, p = 0.005). CONCLUSIONS: Our findings indicated that the IGF1 signalling pathway genes potentiated the risk of stroke through both main effects and gene-gene interactions. The genetic effect of GHRH rs6032470 on stroke was gender dependent. The wGRS of IGF1 pathway genes may be an independent predictor of stroke risk.

13.
J Agric Food Chem ; 68(8): 2340-2346, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32017553

RESUMO

Ralstonia solanacearum is an extremely destructive and rebellious phytopathogen that can cause bacterial wilt diseases in more than 200 plant species. To explore and discover the potential targets in R. solanacearum for the purpose of developing new agrochemicals targeting this infection, here, we exploited a typical activity-based protein profiling technique for target discovery in R. solanacearum based on an activity-based probe 1 derived from bioactive oxadiazole sulfones. A total of 65 specific targets were identified with high confidence through a quantitative chemical proteomic approach. Three representative proteins (glycine cleavage system H protein, thiol peroxidase, and dihydrolipoamide S-succinyltransferase) were validated as the targets by using the immunoblotting analysis with their respective antibodies. Additionally, the in vitro interaction between the recombinant thiol peroxidase and probe 1 further confirmed that this protein was a target of oxadiazole sulfones. We anticipated that these discovered protein targets in R. solanacearum can stimulate the discovery and development of novel agrochemicals targeting bacterial infections caused by R. solanacearum.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Oxidiazóis/farmacologia , Doenças das Plantas/microbiologia , Ralstonia solanacearum/efeitos dos fármacos , Sulfonas/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteômica , Ralstonia solanacearum/genética , Ralstonia solanacearum/metabolismo
14.
Int J Mol Sci ; 21(4)2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32085660

RESUMO

Verticillium dahliae (V. dahliae) infects roots and colonizes the vascular vessels of host plants, significantly reducing the economic yield of cotton and other crops. In this study, the protein VdTHI20, which is involved in the thiamine biosynthesis pathway, was characterized by knocking out the corresponding VdTHI20 gene in V. dahliae via Agrobacterium tumefaciens-mediated transformation (ATMT). The deletion of VdTHI20 resulted in several phenotypic defects in vegetative growth and conidiation and in impaired virulence in tobacco seedlings. We show that VdTHI20 increases the tolerance of V. dahliae to UV damage. The impaired vegetative growth of ΔVdTHI20 mutant strains was restored by complementation with a functional copy of the VdTHI20 gene or by supplementation with additional thiamine. Furthermore, the root infection and colonization of the ΔVdTHI20 mutant strains were suppressed, as indicated by green fluorescent protein (GFP)-labelling under microscope observation. When the RNAi constructs of VdTHI20 were used to transform Nicotiana benthamiana, the transgenic lines expressing dsVdTHI20 showed elevated resistance to V. dahliae. Together, these results suggest that VdTHI20 plays a significant role in the pathogenicity of V. dahliae. In addition, the pathogenesis-related gene VdTHI20 exhibits potential for controlling V. dahliae in important crops.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32070936

RESUMO

Leiocassis longirostris is a common fish variety that is widely cultivated in China, during the breeding process however, it is highly susceptible to bacterial haemorrhagic septicemia, which can cause great economic loss for farmers. To understand the immune responses of L. longirostris to Aeromonas hydrophila infection, Illumina sequencing was employed to identify changes in the mRNA and miRNA in spleen tissue. In this study, a total of 92.16 and 95.61 million (M) high-quality transcriptome reads were generated from the control group (CG) and experimental group (EG) spleen samples, respectively, and 207 up-regulated and 185 down-regulated genes were identified. These genes were enriched in 29 GO terms and 30 KEGG pathways (P ≤ 0.05), including cytokine-cytokine receptor interaction and complement and coagulation cascades, with 17 up-regulated genes and 12 down-regulated genes related to immune responses in the EG relative to the CG. Based on the zebrafish genome, miRNA-seq identified a total of 343 miRNAs, of which 15 were up-regulated and 10 were down-regulated (fold-change ≥2 or ≤0.5 and P ≤ 0.05). Target gene prediction and KEGG enrichment analysis revealed that all of the target genes were concentrated in 13 pathways associated with immune response, including the mTOR signaling pathway and the TGF-beta signaling pathway. The expression patterns of 8 differentially expressed genes and 4 miRNAs involved in immune response were validated by quantitative real-time RT-PCR. These results have provided valuable insights into the molecular mechanisms underlying the immune response of L. longirostris to bacterial haemorrhagic septicemia.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32011975

RESUMO

During a phylogenetic analysis of Sphingorhabdus and its closely related genera in the family Sphingomonadaceae, we found that the genus Sphingorhabdus and the species Sphingopyxis baekryungensis might not be properly assigned in the taxonomy. Phylogenetic, phenotypic and chemotaxonomic characterizations clearly showed that the genus Sphingorhabdus should be reclassified into two genera (Clade I and Clade II), for which the original genus name, Sphingorhabdus, is proposed to be retained only for Clade I, and a new genus named as Parasphingorhabdus gen. nov. is proposed for Clade II with four new combinations: Parasphingorhabdus marina comb. nov., Parasphingorhabdus litoris comb. nov., Parasphingorhabdus flavimaris comb. nov. and Parasphingorhabdus pacifica comb. nov. Moreover, Sphingopyxis baekryungensis should represent a novel genus in the family Sphingomonadaceae, for which the name Novosphingopyxis gen. nov. is proposed, with a combination of Novosphingopyxis baekryungensis comb. nov. The study provides a new insight into the taxonomy of closely related genera in the family Sphingomonadaceae.

17.
Ther Innov Regul Sci ; 54(1): 21-31, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32008228

RESUMO

Inconsistent results across regions have been reported in a number of recent large trials. In this research, by reviewing results from studies that showed inconsistent treatment effects, and summarizing lessons learned, we provide some recommendations for minimizing the chance of inconsistency and allowing more accurate interpretation when such signs of heterogeneity arise, for example: keep the number of regions for consistency evaluation at a minimum to avoid observing false inconsistency signals; proactively address in the protocol the differences in culture, medical practices, and other factors that are potentially different across regions; closely monitor the blinded data from early-enrolled patients to more effectively identify and address issues such as imbalance of baseline covariates or inconsistency of primary outcome rates across regions. For treatments of life-threatening conditions, the stakes for accurate interpretation of MRCT results are high; the criteria for decisions warrant careful consideration.

18.
J Am Chem Soc ; 142(2): 792-800, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31909617

RESUMO

The Pictet-Spengler reaction is a valuable route to 1,2,3,4-tetrahydro-ß-carboline (THBC) and isoquinoline scaffolds found in many important pharmaceuticals. Strictosidine synthase (STR) catalyzes the Pictet-Spengler condensation of tryptamine and the aldehyde secologanin to give (S)-strictosidine as a key intermediate in indole alkaloid biosynthesis. STRs also accept short-chain aliphatic aldehydes to give enantioenriched alkaloid products with up to 99% ee STRs are thus valuable asymmetric organocatalysts for applications in organic synthesis. The STR catalysis of reactions of small aldehydes gives an unexpected switch in stereopreference, leading to formation of the (R)-products. Here we report a rationale for the formation of the (R)-configured products by the STR enzyme from Ophiorrhiza pumila (OpSTR) using a combination of X-ray crystallography, mutational, and molecular dynamics (MD) studies. We discovered that short-chain aldehydes bind in an inverted fashion compared to secologanin leading to the inverted stereopreference for the observed (R)-product in those cases. The study demonstrates that the same catalyst can have two different productive binding modes for one substrate but give different absolute configuration of the products by binding the aldehyde substrate differently. These results will guide future engineering of STRs and related enzymes for biocatalytic applications.

19.
Aging (Albany NY) ; 12(1): 416-435, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899686

RESUMO

DIAPH1 is a formin protein involved in actin polymerization with important roles in vascular remodeling and thrombosis. To investigate potential associations of DIAPH1 single-nucleotide polymorphisms (SNPs) with hypertension and stroke, 2,012 patients with hypertension and 2,210 controls, 2,966 stroke cases [2,212 ischemic stroke (IS), 754 hemorrhagic stroke (HS)] and 2,590 controls were enrolled respectively in the case-control study. A total of 4,098 individual were included in the cohort study. DIAPH1 mRNA expression was compared between 66 IS [43 small artery occlusion (SAO) and 23 large-artery atherosclerosis (LAA)] and 58 controls. Odds ratio (OR), hazard ratio (HR) and 95% confidence interval (CI) were calculated by logistic and cox regression analysis. Rs7703688 T>C variation was significantly associated with an increased risk of IS [OR (95% CI) was 1.721 (1.486-1.993), P=4.139×10-12]. Association of rs7703688 with stroke risk was further validated in the cohort study [adjusted HRs (95% CIs) for additive and recessive models were 1.385 (1.001-1.918), P=0.049, and 2.882 (1.038-8.004), P=0.042, respectively)]. DIAPH1 mRNA expression was significantly downregulated in IS. In SAO stroke subtype, DIAPH1 expression has an increased trend among rs251019 genotypes (Ptrend=0.048). These novel findings suggest that DIAPH1 variation contributes to genetic susceptibility to stroke risk, especially the SAO subtype of IS.

20.
Inflammation ; 43(1): 326-335, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31701354

RESUMO

Many studies have demonstrated an association between cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). Moreover, CMV infection is more common in patients with severe or steroid-refractory IBD. However, it is not clarified whether CMV worsens IBD or if it is merely a surrogate marker for IBD. Here, we used the dextran sodium sulfate (DSS)-induced colitis model to investigate if CMV infection exacerbates colitis. The mice were injected intraperitoneally with 10 MOI of murine CMV (MCMV) and thereafter, chronic colitis was induced by one cycle of DSS exposure. Anti-IL-23R mAb at 20 µg/mice and pyrrolidine dithiocarbamate (PDTC), an effective NF-κB inhibitor, at 50 mg/kg were administrated to the mice. The MCMV-infected mice had a shorter colon length and a higher histopathology score than the mock inoculum-treated mice, while anti-IL-23R mAb administration ameliorated the pathological changes. Expression of IL-23, phospho-NF-κB p65, and phospho-IκBα was upregulated in colon tissues of the MCMV-infected mice compared to mock inoculum-treated mice, while treatment with PDTC attenuated colonic IL-23 production. These data demonstrated that CMV infection could accelerate IBD development. This effect may be due to its activation on NF-κB signaling pathway and subsequently IL-23 production.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA