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1.
Clin Exp Immunol ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32365221

RESUMO

Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease-2019 (COVID-19) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COVID-19 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C-reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL-2R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL-2R to lymphocytes was found to be remarkably increased in severe and critical patients. IL-2R/lymphocytes were superior compared with other markers for the identification of COVID-19 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL-2R/lymphocytes were significantly decreased in recovered patients, but further increased in disease-deteriorated patients, which might be correlated with the outcome of COVID-19. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL-2R/lymphocyte was a prominent biomarker for early identification of severe COVID-19 and predicting the clinical progression of the disease.

2.
Zhonghua Nei Ke Za Zhi ; 59(5): 347-352, 2020 May 01.
Artigo em Chinês | MEDLINE | ID: mdl-32370462

RESUMO

Objective: To investigate the efficacy and safety of daratumumab in relapsed and refractory multiple myeloma (RRMM). Methods: The efficacy and adverse events (AEs) of daratumumab based regimens were retrospectively analyzed in 37 patients with RRMM from Peking University People's Hospital, Beijing Hospital and Fu Xing Hospital affiliated to Capital Medical University in China. The deadline for inclusion was December, 2019. Results: Among the 37 patients, 35 patients were available for response evaluation. The overall response rate (ORR) was 68.6%, which was better in patients receiving 16 mg/kg daratumumab than in those with fixed doses of 800 mg daratumumab [ORR: 78.3%(18/23) vs. 40.0%(4/10)]. The percentage of infusion related reactions of daratumumab was 27.0%(10/37). The most common hematological AEs were lymphocytopenia and thrombocytopenia, with the incidences of grade 3 or more severe 59.5%(22/37) and 43.2%(16/37) respectively. Pulmonary infections(37.8%, 14/37) were the most common non-hematological AEs. One patient with positive hepatitis B surface antigen (HBsAg) and two patients dependent on dialysis were safely treated with daratumumab. Conclusion: Daratumumab is highly effective in relapsed and refractory multiple myeloma. Adverse reactions are mild and well tolerable.

3.
Eur J Neurol ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32374076

RESUMO

BACKGROUND AND PURPOSE: Stroke-associated pneumonia is a common, severe but preventable complication after acute ischemic stroke (AIS). Early identification of patients at high risk of stroke-associated pneumonia is especially necessary. However, the previous prediction models were not widely used in clinical practice. Thus, we aimed to develop a model to predict stroke-associated pneumonia in Chinese AIS patients using machine learning methods. METHODS: AIS patients were prospectively collected at the National Advanced Stroke Center of Nanjing First Hospital (China) between September 2016 and November 2019, and the data was randomly subdivided into a training set and a testing set. With the training set, five machine learning models (logistic regression with regulation, support vector machine, random forest classifier, extreme gradient boosting and fully-connected deep neural network) were developed. These models were assessed by the area under curve of receiver operating characteristic on the testing set. Our models were also compared with ISAN score and PNA score. RESULTS: 3160 AIS patients were eventually included into this retrospective study. Among the five machine learning models, extreme gradient boosting model performed best. The area under curve of the extreme gradient boosting model on the testing set was 0.841 (sensitivity: 81.0%; specificity: 73.3%). It also achieved significantly better performance than ISAN score and PNA score. CONCLUSIONS: Our study firstly demonstrated that the extreme gradient boosting model with six common variables can predict stroke-associated pneumonia in Chinese AIS patients more optimally than ISAN score and PNA score.

4.
Eur Rev Med Pharmacol Sci ; 24(9): 4687-4696, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32432732

RESUMO

OBJECTIVE: In cervical carcinoma (CC), microRNAs (miRNAs) were reported to be involved in its development. In this study, we explored how miR-377-3p regulates cell metastasis and epithelial-mesenchymal transition (EMT) in CC. PATIENTS AND METHODS: Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), Dual-Luciferase Assay, transwell assays, and Western blot analysis were performed to explore the dysregulation of miR-377-3p. RESULTS: MiR-377-3p expression was decreased in CC, and the downregulation of miR-377-3p could predict poor prognosis in CC patients. Moreover, miR-377-3p overexpression repressed cell invasion and migration in CC. Similarly, miR-377-3p overexpression also inhibited EMT in CC cells. Furthermore, miR-377-3p directly targeted SGK3 in CC cells. SGK3 silence had the same function as miR-377-3p overexpression in CC. Especially, the upregulation of SGK3 abolished the inhibitory action of miR-377-3p in CC. CONCLUSIONS: Taken together, miR-377-3p inhibited cell metastasis and EMT by suppressing SGK3 expression. Moreover, the high miR-377-3p expression could predict good prognosis of CC patients.

6.
Eur Rev Med Pharmacol Sci ; 24(7): 3898-3906, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32329865

RESUMO

OBJECTIVE: To compare volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) for the treatment of Graves' ophthalmopathy (GO) based on the dosimetric data. PATIENTS AND METHODS: 19 patients diagnosed with GO were recruited in this study. For each patient, a dual-partial-arc VMAT plans and a 7-fixed-field IMRT plans were replanned. Dosimetric parameters of the targets and organs at risk (OARs) originated from the two kinds of plans were compared and analyzed. RESULTS: Homogeneity index (HI) was superior in IMRT plans compared with VMAT (p=0.0014) but there was no significant statistical difference in conformity index (CI) between them (p=0.0673). IMRT plans revealed advantage in the OARs protection especially for the left and right lenses, optic nerves and eyeballs (p<0.05). CONCLUSIONS: VMAT and IMRT are both feasible techniques in radiotherapy in GO from the perspective of dosimetric parameters. Homogeneity and OAR protection were slightly superior in IMRT plans compared with VMAT plans.

7.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(4): 277-281, 2020 Apr 12.
Artigo em Chinês | MEDLINE | ID: mdl-32294811

RESUMO

The treatment of critically ill patients with coronavirus disease 2019(COVID-19) faces compelling challenges. In this issue, we'd like to share our first-line treatment experience in treating COVID-19. Hemodynamics need be closely monitored and different types of shock should be distinguished. Vasoconstrictor drugs should be used rationally and alerting of complications is of the same importance. The risk of venous thromboembolism (VTE) needs to be assessed, and effective prevention should be carried out for high-risk patients. It is necessary to consider the possibility of pulmonary thromboembolism (PTE) in patients with sudden onset of oxygenation deterioration, respiratory distress, reduced blood pressure. However, comprehensive analysis of disease state should be taken into the interpretation of abnormally elevated D-Dimer. Nutritional support is the basis of treatment. It's important to establish individual therapy regimens and to evaluate, monitor and adjust dynamically. Under the current epidemic situation, convalescent plasma can only be used empirically, indications need to be strictly screened, the blood transfusion process should be closely monitored and the curative effect should be dynamically evaluated.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Betacoronavirus , Transfusão de Sangue , Infecções por Coronavirus/tratamento farmacológico , Estado Terminal , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hemodinâmica , Humanos , Apoio Nutricional , Pandemias , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/prevenção & controle , Choque/diagnóstico , Choque/terapia , Vasoconstritores/uso terapêutico , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/prevenção & controle
8.
J Dent Res ; : 22034520916400, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32339468

RESUMO

Hyperlipidemia adversely affects bone metabolism, often resulting in compromised osseointegration and implant loss. In addition, genetic networks associated with osseointegration have been proposed. Serologically defined colon cancer antigen 3 (Sdccag3) is a novel endosomal protein that functions in actin cytoskeleton remodeling, protein trafficking and secretion, cytokinesis, and apoptosis, but its roles in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and in implant osseointegration under hyperlipidemic conditions have not been uncovered. Here, we performed microarray and RNA sequencing analysis to determine the differential expression of the Sdccag3 gene and related noncoding RNAs (ncRNAs) and to assess the long noncoding RNA (lncRNA) MSTRG.97162.4-miR-193a-3p-Sdccag3 coexpression network in bone tissues within the region 0.5 mm around implants in hyperlipidemic rats. In this experiment, we found that Sdccag3 and the previously uncharacterized lncRNA-MSTRG.97162.4 were downregulated during hyperlipidemia, while miR-193a-3p was upregulated. Sdccag3 overexpression increased new trabecular formation, the bone volume/total volume (BV/TV) (1.24-fold), and bone-implant combination ratio (BIC%) (1.26-fold). An RNA pulldown experiment revealed that Sdccag3 protein targeted lncRNA-MSTRG.97162.4 nucleotides 361 to 389. In addition, lncRNA-MSTRG.97162.4 overexpression significantly enhanced Sdccag3 (2.78-fold) expression and increased BV/TV (1.45-fold) and BIC% (1.07-fold) at the bone-implant interface. Taken together, these findings indicate that Sdccag3 overexpression enhances implant osseointegration under hyperlipidemic conditions by binding to lncRNA-MSTRG.97162.4. Furthermore, miR-193a-3p overexpression inhibited lncRNA-MSTRG.97162.4 (0.63-fold) and Sdccag3 (0.88-fold) expression and induced poor implant osseointegration (BV/TV, 0.86-fold; BIC%, 0.82-fold), while miR-193a-3p downregulation produced the opposite results (lncRNA-MSTRG.97162.4, 10.69-fold; Sdccag3, 6.96-fold; BV/TV, 1.20-fold; BIC%, 1.26-fold). Therefore, our findings show that Sdccag3 promotes implant osseointegration, and its related lncRNA-MSTRG.97162.4 and miR-193a-3p play an important role in osseointegration during hyperlipidemia, which might be a promising therapeutic target for improving dental implantation success rates.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32251842

RESUMO

OBJECTIVES: To describe the clinical characteristics of patients in a Fangcang Hospital. METHODS: Non-critically ill individuals with positive SARS-CoV-2 RT-PCR tests admitted between 7 February and 12 February 2020 to Dongxihu Fangcang Hospital, which was promptly constructed because of the rapid, exponential increase in COVID-19 patients in Wuhan, China, were included; clinical course through to 22 February was recorded. RESULTS: A total of 1012 non-critically ill individuals with positive SARS-CoV-2 RT-PCR tests were included in the study. Thirty (of 1012, 3.0%) individuals were asymptomatic on admission. During hospitalization, 16 of 30 (53.3%) asymptomatic individuals developed different symptoms. Fourteen of 1012 patients (1.4%) remained asymptomatic from exposure to the end of follow up, with a median duration of 24 days (interquartile range 22-27). Fever (761 of 1012, 75.2%) and cough (531 of 1012, 52.4%) were the most common symptoms. Small patchy opacities (355 of 917, 38.7%) and ground-glass opacities (508 of 917, 55.4%) were common imaging manifestations in chest CT scans. One hundred patients (9.9%) were transferred to designated hospitals due to aggravation of illness. Diarrhoea emerged in 152 of 1012 patients (15.0%). Male, older age, diabetes, cardiovascular diseases, chills, dyspnoea, So2 value of ≤93%, white blood cell counts of >10 × 109/L and large consolidated opacities on CT images were all risk factors for aggravation of illness. CONCLUSIONS: Non-critically ill individuals had different clinical characteristics from critically ill individuals. Asymptomatic infections only accounted for a small proportion of COVID-19. Although with a low incidence, diarrhoea was observed in patients with COVID-19, indicating the possibility of faecal-oral transmission.

11.
Hum Exp Toxicol ; : 960327120918291, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32329368

RESUMO

BACKGROUND: Quercetin exerts anti-inflammatory effects, but whether it can benefit patients with the chronic inflammatory disease of oral lichen planus (OLP), which is a common chronic mucocutaneous disorder with an immune-mediated pathogenesis, is unclear. The present research examined the impacts of quercetin in a cell-based OLP model in which human oral keratinocytes (HOKs) were treated with lipopolysaccharide (LPS). METHODS: Effects of quercetin on viability, proliferation, and apoptosis of HOKs were assessed using the Cell Counting Kit-8 assay, Western blotting, and flow cytometry, respectively. Effects of treatment on levels of microRNA-22 (miR-22) were measured using stem-loop reverse transcription polymerase chain reaction, while levels of proteins and phosphorylation in the PI3K/AKT and JAK1/STAT3 cascades were analyzed by Western blot. RESULTS: Quercetin mitigated LPS-induced reduction in HOK viability and elevation of apoptosis. It also weakened LPS-induced upregulation of miR-22. Quercetin treatment led to significantly higher levels of p-PI3K, p-AKT, p-JAK1, and p-STAT3. These effects of quercetin were enhanced when miR-22 was knocked down and partly reversed when miR-22 was overexpressed. CONCLUSION: Quercetin can mitigate LPS-induced injury in HOKs by downregulating miR-22, thereby activating PI3K/AKT and JAK1/STAT3 cascades.

12.
Zhonghua Yi Xue Za Zhi ; 100(14): 1081-1083, 2020 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-32294871

RESUMO

Objective: Investigating the diagnostic value of MRI for cervical cancer, including preoperative staging, vagina involvement and lymph node metastasis is the aim of this pape. Methods: Select 116 patients with UCC of the second hospital of JiLin University from October 2016 to April 2019. All patients accept MRI examination. Ultimately, all patients accept surgical treatment. Use SPSS19.0 software to analyze MRI results of all the patients.Using the postoperative pathological results as the golden standard in the diagnosis of cervicalcancer diagnosis. The dates from the MRI preoperative staging, preoperative clinical staging and the postoperative pathologic staging were compared through chi-square test. And the dates of preoperative MRI in cervical cancer vagina involvement and lymph node metastasis diagnosis and postoperative pathological results were compared through Mcnemar chi-square test. The difference was statistically significant(P<0.05). Results: 1, The differences between MRI staging and the postoperative pathologic staging have no statistical significance (P>0.05), whilethe difference between MRI staging and preoperative clinical staging during was statistically significant (P<0.05). Using the postoperative pathological staging as the examination standards, the accuracy of preoperative clinical staging is only 67.5%, and cervical cancer overall preoperative MRI staging accuracy was 95%; 2, Preoperative MRI diagnosis and postoperative pathologic results in cervical vaginal involvement and lymph node metastasis has highsensitivity and specificity, were 97.0%, 96.2%, 93.2%, 97.8%. Checked by Mcnemar chi-square test, the differences between themhave no statisticalsignificance (P>0.05), namely the preoperative MRI diagnosis and postoperative pathological results have consistency in clinical. Conclusion: The combination of MRI and FIGO clinical stage can impro the accuracy of clinical staging of cervical cancer. MRI can be used as the important tool to assess cervical cancer preoperative staging, and to choose and formulate reasonable cervical cancer treatment plan.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Linfonodos , Metástase Linfática , Imagem por Ressonância Magnética , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/diagnóstico por imagem
13.
Zhonghua Yi Xue Za Zhi ; 100(12): 899-903, 2020 Mar 31.
Artigo em Chinês | MEDLINE | ID: mdl-32234163

RESUMO

Objective: To investigate the effect of long non-coding RNA-AC013472.3 on lipopolysaccharide (LPS)-stimulated secretion of tumor necrosis factor (TNF)-α in NR8383 rat alveolar macrophages. Methods: Silencing and overexpression models of lncRNA-AC013472.3 were established with NR8383 rat alveolar macrophages as the experimental subjects. The silencing models were divided into three groups: random nonsense negative small interfering RNA sequence (si-con) group (si-con group, si-con transfected NR8383 cells), LPS+si-con group (10 µg/L LPS was used to treat si-con transfected NR8383 cells for 24 h), and siRNA group (siRNA transfected NR8383 cells), and LPS+siRNA group (10 µg/L LPS was used to treat siRNA transfected NR8383 cells for 24 h). The overexpression models were divided into the empty plasmid (p-con) group (p-con transfected NR8383 cells), LPS+p-con group (10 µg/L LPS was used to treat p-con transfected NR8383 cells for 24 h), lncRNA overexpression plasmid (plncRNA) group (plncRNA transfected NR8383 cells), and the LPS+plncRNA group (10 µg/L LPS was used to treat plncRNA transfected NR8383 cells for 24 h). The mRNA levels of TNF-α in each group were examined by quantitative real-time PCR (qPCR). The protein levels of tumor necrosis factor receptor-related factor-6 (TRAF-6) and phosphorylated nuclear factor-κB (NF-κB) p65 were examined by Western blot. Results: In the silencing model, the mRNA levels of TNF-α, the protein levels of TRAF-6 and NF-κB p65 in the LPS+si-con group were significantly higher than those in the si-con group (2.040±0.195 vs 1.048±0.207, 0.473±0.022 vs 0.293±0.076 and 0.469±0.062 vs 0.252±0.038)(all P<0.05). The mRNA levels of TNF-α, the protein levels of TRAF-6 and NF-κB p65 in the LPS+siRNA group were significantly higher than those in the siRNA group (4.158±0.119 vs 1.028±0.019, 0.700±0.104 vs 0.231±0.023 and 0.771±0.095 vs 0.258±0.050)(all P<0.05). The relative expression levels of all indexes in the LPS+siRNA group were significantly higher than those in the LPS+si-con group (all P<0.05). In the overexpression model, the mRNA levels of TNF-α, the protein levels of TRAF-6 and NF-κB p65 in the LPS+p-con group were significantly higher than those in the p-con group (1.961±0.169 vs 0.999±0.143, 0.533±0.047 vs 0.247±0.020 and 0.565±0.108 vs 0.276±0.048) (all P<0.05). The mRNA levels of TNF-α, the protein levels of TRAF-6 and NF-κB p65 in the LPS+plncRNA group were significantly higher than those in the plncRNA group (1.322±0.110 vs 1.043±0.093, 0.347±0.035 vs 0.232±0.023 and 0.405±0.072 vs 0.268±0.031) (all P<0.05). The relative expression of all indexes in the LPS+plncRNA group were significantly lower than that in the LPS+p-con group (all P<0.05). Conclusion: LncRNA-AC013472.3 may inhibit the activation of NF-κB signaling pathway, thereby inhibiting the LPS-stimulated secretion of TNF-α in NR8383 rat alveolar macrophages.


Assuntos
Macrófagos Alveolares , Animais , Lipopolissacarídeos , NF-kappa B , RNA Longo não Codificante , Ratos , Fator de Necrose Tumoral alfa
14.
Zhonghua Fu Chan Ke Za Zhi ; 55(3): 177-182, 2020 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-32268715

RESUMO

Objective: To detect karyotype homology of vaginal isolates from patients with recurrent vulvovaginal candidiasis (RVVC) in recurrent episodes, and to discuss changes of susceptibility of Candida strains to antifungal drugs with clinical progress. Method: s Ten patients were recruited from Beijing Obstetrics and Gynecology Hospital, Capital Medical University from September 2018 to June 2019, who were firstly diagnosed with RVVC. Vaginal discharges were collected before first treatment and after first relapse. Vaginal strains were isolated, purificated and identificated. Then karyotype of 20 strains isolated from 10 patients were detected by restriction endonuclease analysis of genomic DNA (REAG) using enzyme BssHⅡand pulsed field gel electrophoresis (PFGE) methods, and sensitivity of clinical isolates to 5 antifungal drugs (clostridium, fluconazole, miconazole, itraconazole and nystatin) was also detected using disk diffusion method. Result: s (1) All 20 strains of 10 patients with RVVC were Candida albicans, and their chromosomes were extremely similar after BssHⅡ enzyme digestion. The gene bands of isolated strains from the same patient were completely identical. (2) After clinical medication, the sensitivity of vaginal isolates to azoles was generally decreased, but remained highly sensitive to nystatin, nystatin (first and second clinical isolates: 100% sensitivity and 100% sensitivity)>clotrimazole (100% sensitivity and 90% sensitivity)>fluconazole (80% sensitivity and 70% sensitivity)>itraconazole (60% sensitivity and 50% sensitivity)>miconazole (30% sensitivity and 20% sensitivity). Conclusions: (1) The latency of the same colonized strain in the vagina may be the cause of repeated RVVC episodes. (2) Antifungal agents could selectively induce drug resistance to Candidas, and Candidas show cross-resistance to antifungal agents. Repeated fungal culture and drug sensitivity test in patients with RVVC are very necessary for correct selection of antifungals.


Assuntos
Candidíase Vulvovaginal , Antifúngicos , Candida albicans , Farmacorresistência Fúngica , Feminino , Fluconazol , Humanos , Testes de Sensibilidade Microbiana
15.
Eur Rev Med Pharmacol Sci ; 24(6): 3293-3301, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32271447

RESUMO

OBJECTIVE: Dysfunction of vascular endothelial cells was associated with diverse human diseases, including cardiovascular disease. Long noncoding RNAs (LncRNAs) were involved in the regulation of cell injury. We aimed to investigate the role of lncRNA testis-specific transcript, Y-linked 15 (TTTY15) in hypoxia-induced cell injury in human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: Cell counting kit-8 (CCK8) assay was used to check cell viability. Lactate dehydrogenase (LDH) assay kit and flow cytometry were utilized to evaluate the leakage rate of LDH and cell apoptosis, respectively. The protein levels of Cyclin D1 and B-cell lymphoma-2-Associated X (Bax) in hypoxia-induced HUVECs were measured by Western blot. Quantitative Real-time polymerase chain reaction (qRT-PCR) was conducted to detect the expression levels of TTTY15 and miR-186-5p in hypoxia-induced HUVECs. The starBase was utilized to predict the binding sites between TTTY15 and miR-186-5p and the dual-luciferase reporter assay was performed to verify the interaction. RESULTS: Hypoxia inhibited cell viability and promoted the release of LDH and cell apoptosis in HUVECs. Besides, hypoxia significantly decreased the protein level of Cyclin D1 and increased the protein level of Bax in HUVECs. In addition, the expression level of TTTY15 was obviously upregulated in hypoxia-induced HUVECs, opposite to the level of miR-186-5p. Meanwhile, knockdown of TTTY15 or upregulation of miR-186-5p mitigated hypoxia-induced cell injury in HUVECs. Further studies suggested that TTTY15 targeted miR-186-5p and regulated hypoxia-induced cell injury via interacting with miR-186-5p in HUVECs. CONCLUSIONS: Downregulation of TTTY15 ameliorated hypoxia-induced cell injury by targeting miR-186-5p in HUVECs.

17.
18.
Pol J Vet Sci ; 23(1): 119-126, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32233299

RESUMO

To explore the role of Toll-like receptors (TLRs) and interferon (IFN) in the innate immunity against porcine epidemic diarrhea virus (PEDV), we detected the expression of TLR genes in PEDV-infected IPEC-J2 cells by real-time PCR. We also detected the level of interferon α (IFN-α) and interferon γ (IFN-γ) by enzyme-linked immunosorbent assay (ELISA). Results showed that IPEC-J2 cells exhibited a clear pathological change after PEDV infection at 24 h. In addition, TLR7, TLR9 and TLR10 expressions were significantly upregulated in PEDV-infected IPEC-J2 cells at 24 h. Interestingly, the expression patterns of TLR2 and TLR4 were consistent at different stages of PEDV infection. The expression level of TLR3 decreased significantly with the increase of infection time, but the expression levels of TLR5 and TLR8 genes at 6 h and 12 h were significantly lower than those in the control group (p⟨0.01). There were significant correlations among the expression levels of TLR genes (p⟨0.05). Cytokine detection showed that the secretion level of IFN-α in the PEDV-infected group was significantly higher than that in the control group (p⟨0.01), and IFN-γ at 6 h and 12 h after PEDV infection was significantly higher than that in control group (p⟨0.01). Therefore, our results suggest that PEDV infection can induce innate immune responses in intestinal porcine jejunum epithelial cells, leading to changes in the expression of Toll-like receptors, and can regulate the resistance to virus infection by affecting the release levels of downstream cytokines.

20.
Artigo em Chinês | MEDLINE | ID: mdl-32306687

RESUMO

Objective: To explore the possible role of C5a in the pathogenesis of renal injury in TCE- sensitized mice, to analyze the impact of expression of neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemotactic protein-1 (MCP-1) in the presence or absence of C5a receptor antagonist (C5aRA) pretreatment. Methods: A total of 50 female specific pathogens free(SPF) BALB/c mice were randomly divided into blank control group (n=5) , solvent control group (n=5) , TCE group (n=20) , and TCE+C5aRA group (n= 20) . After one week for adaptive feeding, a mouse model of TCE-induced skin sensitization was established by treating with 50% TCE and 30% TCE in turn. The mice in solvent control group accept same reagents without TCE and the mice in blank control group underwent nothing. In TCE +C5aRA group, except for the TCE solution treatment, mice were intraperitoneally injected with 0.5 mg/kg C5aRA solution at the time of challenge. And the skin erythema and edema reaction were scored 24 h after the last challenge. The mice were divided into sensitization positive group and sensitization negative group according to the scoring result. The mice were aseptically sacrificed 72 h after the last challenge to obtain the kidneys. The structural damage of kidney was observed after histopathological staining. The levels of NGAL and MCP-1 mRNA and proteins were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) , respectively. Results: The sensitization rate of mice in TCE group and TCE+C5aRA group was 45.0% (9/20) and 40.0% (8/20) , respectively. No skin lesions was found in the mice of blank control group and solvent control group. The results of histopathological staining showed that the TCE sensitization positive mice showed renal tubular dilatation, vacuolar degeneration of renal tubular epithelial cells, and infiltration of interstitial cells. The pathological damage of the kidney in TCE sensitization positive group was mild, and no inflammatory cell infiltration was seen. The data of qRT-PCR showed that the expression levels of NGAL and MCP-1 mRNA in the TCE sensitization positive group were significantly increased than in solvent control group and TCE sensitization negative group (P<0.05) , while the levels of NGAL and MCP-1 mRNA in TCE+C5aRA sensitization positive group were decreased than TCE sensitization positive group (P <0.05) . The results of IHC showed that the expression levels of NGAL and MCP-1 in TCE protein sensitization positive group were significantly higher than those in solvent control group and TCE sensitization negative group (P<0.05) . After C5aRA pretreatment, the expression levels of NGAL and MCP-1 protein were decreased than the mice in TCE sensitization positive group (P<0.05) . Conclusion: The regulation of C5a on the expression of MCP-1 and NGAL may participate in TCE- induced mice kidney damage, and pharmacological inhibition of C5a seems to be an effective way to protect the kidney injury in TCE-sensitized mice.

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