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2.
Aging (Albany NY) ; 132021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33591942

RESUMO

The prognosis of lung cancer patients with different clinical stages is significantly different. The 5-year survival of stage IA groups can exceed 90%, while patients with stage IV can be less than 10%. Therefore, early diagnosis is extremely important for lung cancer patients. This research focused on various diagnosis methods of early lung cancer, including imaging screening, bronchoscopy, and emerging potential liquid biopsies, as well as volatile organic compounds, autoantibodies, aiming to improve the early diagnosis rate and explore feasible and effective early diagnosis strategies.

3.
Ann Hematol ; 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33389024

RESUMO

Tumour-infiltrating lymphocytes (TILs) account for a large proportion of tumour microenvironment (TME) in angioimmunoblastic T cell lymphoma (AITL), and at present the significance of TIL in TME of AITL remains unclear. Overall, 50 de novo AITL patients undergoing lymph node flow cytometry from 2014 to 2019 were retrospectively analysed to assess the relationship between TILs and AITL prognosis. We found that high TIL-Bs (≥ 42.4%, p = 0.004) and high CD4:CD8 (≥ 0.85, p = 0.024) were independent favourable prognostic factors for de novo AITL in univariate or multivariate analyses. New TIL-related risk stratification was established based on TIL-Bs and CD4:CD8 factors. Patients in the low-risk group (TIL-Bs ≥ 42.4% and CD4:CD8 ≥ 0.85) had significantly better overall survival than the high-risk (TIL-Bs < 42.4% and CD4:CD8 < 0.85) (p < 0.001) or intermediate-risk group (TIL-Bs ≥ 42.4% and CD4:CD8 < 0.85 or TIL-Bs < 42.4% and CD4:CD8 ≥ 0.85) (p = 0.011). To our knowledge, our cohort is the largest one focusing on the TILs in de novo cases of AITL by analysing lymph node samples using flow cytometry, which is the first time to comprehensively consider humoral immunity and cellular immunity influence on AITL. Our new risk stratification was valuable and useful in evaluating prognosis of AITL and guiding immunotherapy strategies.

4.
Brain Res Bull ; 169: 1-7, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33434622

RESUMO

In the past decade, there was an increasing interest in the therapeutic potential targeting ATP-sensitive potassium (KATP) channels for an effective treatment of Parkinson's disease (PD). KATP channels are widely expressed in the central nervous system and were reported to mediate the degeneration and death of nigral dopamine neurons in the pathogenesis of PD. This review aims to address the pivotal roles of KATP channels played in the mechanisms underlying PD pathogenesis, and provide possible directions for further research from different perspectives, such as the vulnerability of dopamine neurons in the substantia nigra, neurotransmitter releasing, iron metabolism in the brain, α-synuclein secretion and mitochondrial dysfunction, which are off critical importance in the investigation of KATP channels-targeted precise therapeutic interventions for PD.

5.
Ann Palliat Med ; 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33302640

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer but with a low early diagnosis rate. With immunotherapy becomes popular in lung cancer, single immunotherapy drug treatment as the first-line or second-line plays an important role. The meta-analysis compares different clinical effects of them by overall survival (OS) and progression-free survival (PFS) because it is important to detect the best time of immunotherapy for NSCLC patients. METHODS: Randomized controlled trials (RCTs) were selected by using the Cochrane Library, Embase, PubMed and Web of science. Pool the hazard ratio (HR) and use the PFS, OS as outcomes. RESULTS: Ten RCTs were included. The pooled results indicated that first-line and second-line single immunotherapy drug treatment seems to have a tiny difference in PFS, with HR 0.79, 95% confidence interval (CI): 0.51-1.21, I2 =89% in first-line single immunotherapy drug treatment and HR 0.74, 95% CI: 0.62-0.89, I2 =84% in second-line single immunotherapy drug treatment. When it comes to OS, first-line immunotherapy drug treatment still has better effects than the second-line. In first-line single immunotherapy drug treatment, HR 0.78, 95% CI: 0.55-1.11, I2 =83%, but in second-line, HR 0.70, 95% CI: 0.64-0.76, I2 =53%. CONCLUSIONS: First-line single drug immunotherapy had the tendency better than single immunotherapy drugs used in second-line treatment.

6.
Eye (Lond) ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33188291

RESUMO

BACKGROUND: To investigate trends in the prevalence of reduced visual acuity (VA), a proxy measure for myopia, in an urban district in China. METHODS: Data were extracted from the dataset of the 2002 and 2018 Annual Survey on Students' Constitution and Health from Yuhua District, Changsha City, China. Children aged 6-15 years were included in the study. VA was measured using a LogMAR tumbling E chart. The prevalence of reduced VA was calculated by age and gender. The chi-square test was used to compare the differences between groups. RESULTS: The final VA analysis included 26217 children in 2002 and 45510 children in 2018. The overall prevalence of reduced VA increased from 28.3% in 2002 to 46.5% in 2018 (P < 0.001). The prevalence of reduced VA started to increase markedly from the age of 14 years in 2002, while in 2018 it started to increase markedly from the age of 9 years. The prevalence of severely reduced VA increased in all age groups from 2002 to 2018 and increased with age (all P < 0.001). In 2002, over 50% of children in all age groups had normal VA. By 2018, the prevalence of normal VA decreased from 61.4% in those aged 6 years to 31.9% in those aged 15 years. CONCLUSIONS: The prevalence of reduced VA among children aged 6-15 years in Yuhua District has become more common with age, and there has been a marked increase in the prevalence of reduced VA from 2002 to 2018. The remarkable epidemic of reduced VA started 5 years earlier in 2018 than in 2002. Evidence from the present study suggests that interventions should be launched before the age of 9 years.

8.
J Thorac Dis ; 12(10): 6070-6089, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209440

RESUMO

Small cell lung cancer (SCLC), a particular neuroendocrine tumor, occupies 13% of lung cancers, with the highest mortality among cancers. Immune checkpoints inhibitors (ICIs) based on programmed cell death protein-1 (PD-1)/programmed cell death one ligand (PD-L1) inhibitors and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors have been one of the most favorable therapies in SCLC. Simultaneously, not all the patients respond to ICIs due to the lack of biomarkers to predict the immunotherapeutic effect. Multiple combinational approaches are under exploration, including the integrated or successive assessment of additional immunotherapeutic agents, chemotherapy, radiotherapy, and targeted therapy with ICIs. The current review offers a general view of the rationale for clinical studies exploring the experimental result of combinational immunotherapy based on ICIs, with both available results and ongoing trials. Moreover, the development of more predictive biomarkers, specific clinical trial designs, enhancement of the efficacy, and decreasing the financial toxicity will become the trend of future research and clinical applications of ICIs. Understanding the evolving immuno-oncology is increasingly relevant and crucial to solve those problems and define therapeutic strategies and potential target populations of combinational immunotherapy. Ultimately, emerging combinational immunotherapy will transform SCLC into a chronic disease to help patients survive from tumors.

9.
Poult Sci ; 99(11): 5366-5377, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33142453

RESUMO

Mycoplasma synoviae (MS) is an important avian pathogen causing considerable economic hardship in the poultry industry. A major inflammation caused by MS is synovitis that occurs in the synovial tendon sheath and joint synovium. However, the overall appearance of pathological changes in the tendon sheath and surrounding tissues caused by MS infection at the level of pathological tissue sections was poor. Studies on the role of MS and synovial sheath cells (SSCs) interaction in the development of synovitis have not been carried out. Through histopathological observation, our study found that a major MS-induced pathological change of the tendon sheath synovium was extensive scattered and focal inflammatory cell infiltration of the tendon sheath synovial layer. In vitro research experiments revealed that the CFU numbers of MS adherent and invading SSC, the levels of expression of various pattern recognition receptors, inflammatory cytokines, and chemokines coding genes, such as IL-1ß, IL-6, IL-8, CCL-20, RANTES, MIP-1ß, TLR7, and TLR15 in SSCs, and chemotaxis of macrophages were significantly increased when the multiplicity of infection (MOI) of MS to SSC were increased tenfold. The expression level of IL-12p40 in SSC was significantly higher when the MOIs of MS to SSC were increased by a factor of 100. The interaction between MS and SSC can activate macrophages, which was manifested by a significant increase in the expression of IL-1ß, IL-6, IL-8, CCL-20, RANTES, MIP-1ß, and CXCL-13. This study systematically demonstrated that the interaction of MS with chicken SSC contributes to the inflammatory response caused by the robust expression of related cytokines and macrophage chemotaxis. These findings are helpful in elucidating the molecular mechanism of MS-induced synovitis in chickens.

10.
Dermatol Ther ; : e14452, 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33099866

RESUMO

Lymphomatoid papulosis (LyP) is a rare CD30+ lymphoproliferative primary skin disease with a benign clinical course and malignant histopathology. LyP is classified into seven subtypes based on histopathology: subtypes A through F and LyP with 6p25.3 chromosome rearrangement. We present here, a case report of a 51-year-old man, afflicted with multiple papules and nodules on his left arm for over 3 months and diagnosed with LyP subtype C. The patient refused treatment, and his lesions faded with no visible rash on the left arm 14 months after diagnosis.

11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1674-1678, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067972

RESUMO

OBJECTIVE: To explore the correlation between the of regulatory T cells, Th17 cells and the prognosis of children with aplastic anemia. METHODS: The clinical data 13 children with aplastic anemia (AA) treated by antithymocyte globulin (ATG) combined with Cyclosporine in Beijing Children's Hospital, Capital Medical University from January 2017 to January 2018 were analyized retrospectively. The changes of T cell and Th17 cell expression level in peripheral blood of AA children before and after IST for 6 and 12 month were compared and analyzed. The SPSS 19.0 statistical package was used for data analysis. RESULTS: Compared with the pre-IST, the expression level of Treg cells decreased at 6 months of IST, the difference was statistically significant (P<0.05); however the expression level of Th17 cells did not show significant difference as compared with that pre-IST. The expression level of Treg and Th17 cells at 12 months of IST was lower than that pre-IST (P<0.01), compared with the level pre-IST, the ratio of Treg cells/Th17 cell at 6 months and 12 months of IST did not show a singificand difference. CONCLUSION: Treg cells and Th17 cells in peripheral blood of AA children decrease after IST, which suggests that the change of regulatory T cells and Th17 cells correlate with the clinical outcome of children with aplastic anemia.


Assuntos
Anemia Aplástica , Linfócitos T Reguladores , Criança , Humanos , Prognóstico , Estudos Retrospectivos , Células Th17
12.
Biomed Res Int ; 2020: 9259742, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029532

RESUMO

Physical activity participation in children declines with age. It is not clear yet whether the age-related trends vary by weight status. This study is aimed at investigating the association between physical activity participation and age among children with healthy weight, overweight, or obesity, using data from the 2016-2017 National Survey of Children's Health (NSCH). Physical activity participation was evaluated by days participated in physical activity for at least 60 minutes out of 7 days. Weight status was categorized from body mass index (BMI) percentiles. Data were analyzed on 33,056 US children age 10-17 years. The percentages of been active 0 day out of 7 days in BMI5th < 85th (healthy weight), 85th < 95th (overweight), and ≥95th percentile (obese) groups were 8.9%, 11.5%, and 18.2%, respectively. Among all groups, been active 0 day out of 7 days was positively associated with age, while the strongest associations were observed in the BMI85th < 95th group (age 17 years vs. age 10 years: OR = 7.48, p < 0.0001). Older age was significantly associated with been active less than 4 days out of 7 days in the BMI5th < 85th and 85th < 95th groups, but those associations were attenuated in the BMI ≥ 95th group. This study found that physical activity participation was inversely associated with age among children with healthy weight, overweight, or obese, and the association was strongest among children with overweight and weakest among children with obesity. Interventions aimed at promoting physical activity among children should take these patterns of association into account.

13.
Mod Pathol ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973328

RESUMO

We report 17 cases of sinusoidal large B-cell lymphoma (SLBCL). Clinical, morphologic, immunophenotypic, and molecular features were detected and analyzed. All cases showed an obvious sinusoidal growth pattern, usually associated with residual atrophic lymphoid tissue. All tumors contained large pleomorphic lymphoid cells and one or more prominent nucleoli, with abundant amphophilic cytoplasms; 15/17 cases showed anaplastic morphologic features. The patient age ranged from 43 to 80 years (median 57 years), and 7 males and 10 females were included. Eleven of 15 (73.3%) patients had Ann Arbor stage III or IV disease, and 10/15 (66.6%) patients had an International Prognostic Index (IPI) score ≥3. Immunophenotypically, 16/17 (94.1%) cases displayed a nongerminal center B-cell (non-GCB) immunophenotype. Furthermore, 16/17 (94.1%) cases were positive for CD30, and p53 was expressed in 10/16 (62.5%) cases. In total, 12/14 (85.7%) cases expressed BCL2 and MYC simultaneously (double expression), and 11/14 (78.6%) cases showed PD-L1 positivity (6/11 had a PD-L1 tumor proportion score ≥50%). Cytogenetically, concurrent MYC and BCL2 and/or BCL6 abnormalities (break-apart or extra copy) were detected in 10/15 cases, and 7/13 (53.8%) cases harbored a PD-L1/L2 amplification. TP53 mutation was found in 7/13 (53.8%) cases by Sanger sequencing. Whole-exome and large-panel sequencing results revealed high mutation frequencies of TP53 (4/7), MYD88 (3/7), KMT2D (3/7), CREBBP (3/7), and PIM1 (3/7). Among the 13 patients with SLBCL treated with aggressive chemotherapy regimens, the median overall survival (OS) was 18 months, and the 2-year OS rate was 34.6%. The OS of patients with SLBCL was markedly worse than that of 35 control group patients with common diffuse large B-cell lymphoma (DLBCL) without sinusoidal features (P < 0.001). SLBCL may represent a specific type of DLBCL that has characteristic pathologic features. The cancer is aggressive in most clinical cases, and outcomes are poor. SLBCL and anaplastic DLBCL (A-DLBCL) have many overlapping clinicopathological and molecular features.

14.
Transl Lung Cancer Res ; 9(4): 1053-1066, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32953484

RESUMO

Background: A strong association between M descriptors and prognosis of non-small cell lung cancer (NSCLC) has been demonstrated recently. However, its predictive and prognostic significance for advanced NSCLC patients treated with immune checkpoint inhibitors (ICIs) remain unclear. In this study, we aimed at investigating the impact of M descriptors on clinical outcomes in those patients. Methods: A retrospective analysis was conducted. Patients treated with more than two cycles of ICIs were included. Detailed characteristics and clinical response after immunotherapy were recorded. M descriptors were classified into M1a, M1b, and M1c according to the 8th TNM classification. Results: A total of 103 patients were enrolled, including 42 with M1a disease, 16 with M1b disease and 45 with M1c disease. Patients with M1a disease demonstrated significant longer median progress-free survival (PFS) (11.9 vs. 4.1 and 3.2 months, respectively, P=0.0002) and overall survival (OS) (35 vs. 22.1 and 12 months, P=0.02) than those with M1b and M1c disease. Patients with M1a disease showed higher objective response rate (ORR) (28.6% vs. 14.8%, P=0.08) and disease control rate (DCR) (81% vs. 59%, P=0.02) compared with those with M1b and M1c disease. Multivariate analysis identified M1a stage as being independently associated with prolonged PFS and had better OS than those with M1c disease (P=0.05) but not M1b disease (P=0.06). Conclusions: The current study demonstrated a clear association between M descriptors and the therapeutic response to ICIs and confirmed its prognostic role in advanced patients treated with ICIs monotherapy. M descriptors may need to be stratified in future study design.

15.
Transl Lung Cancer Res ; 9(4): 1483-1495, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32953520

RESUMO

Background: It has been proven that the treatment window of small cell lung cancer (SCLC) is short, so it is vital to find other possible therapeutic targets. CD39 inhibits natural killer (NK) cells and promotes the occurrence and metastasis of tumors. There has been little research about the role of CD39 in SCLC, so we explored the correlation between CD39 and other surface antigens, and its association with survival in SCLC. Methods: This study included 75 patients with SCLC from Shanghai Pulmonary Hospital. After paraffin embedding and sectioning, immunohistochemistry (IHC) was applied. Then we identify cutoff value for CD39 and other surface antigens based on the analysis of ROC curve in RFS by SPSS. All statistical analyses were based on SPSS and Graphpad Prism8. Chi-square test, Kendall's tau-b correlation analysis, Logistic regression analysis, Kaplan-Meier method, univariate and multivariate Cox regression analysis were conducted. In all analyses, P = 0.05 distinguished whether they had statistical significance. Results: Of the 75 SCLC patients enrolled in this study, 61.33% positively expressed CD39. A correlation between CD39 and programmed cell death-ligand 1 (PD-L1) (P=0.007), CD3 (P<0.001), CD4 (P<0.001), CD8 (P<0.001), and forkhead box P3 (FOXP3) (P<0.001) on tumor-infiltrating lymphocytes (TILs) was identified by correlation analysis and logistic regression analysis. Based on Kaplan-Meier survival analysis, we found that CD39 affected relapse-free survival (RFS) [negative vs. positive, 95% confidence interval (CI): 0.2765-0.9862, P=0.0390]. SCLC patients with high-expressed CD39 and low-expressed PD-L1 had poor prognosis (P<0.001). Positive expression of CD39 and negative expression of CD3, CD4, CD8, and FOXP3 also indicated shorter RFS (P=0.0409). Univariate and multivariate Cox regression analysis was performed to confirm the factors that influenced RFS. Conclusions: CD39, programmed cell death-1 (PD-1), and PD-L1 expressed on TILs but not on tumor cells. CD39 has a significant association with PD-L1, CD3, CD4, CD8, and FOXP3 on TILs. The positive expression of CD39 predicts poor prognosis. SCLC patients with low expression of CD39 combined with high expression of PD-L1 or CD3, CD4, CD8, and FOXP3 have a more favorable prognosis.

16.
Onco Targets Ther ; 13: 6475-6483, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753888

RESUMO

Introduction: Immune therapy has shown good results in small-cell lung cancer (SCLC), but the impact of immune microenvironment of the disease is unclear. In this work, we detected expression of programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and other immune biomarkers of cancer. We also analyzed the correlations between these markers and survival in SCLC. Patients and Methods: Protein expression of PD-1, PD-L1, PD-L2, CD3, CD4, CD8, and FOXP3 was analyzed in surgical tissues from 102 SCLC patients by immunohistochemistry. Results: Positive expression of PD-1 on tumor-infiltrating lymphocytes (TILs) was found in 40.2% of patients; 37.3% of patients showed positive expression of PD-L1 on TILs; and 3.9% showed positive expression of PD-L1 on tumor cells. PD-L2 protein was not expressed on tumor cells or TILs. Survival analysis showed that positive expression of PD-L1 on TILs was correlated with longer relapse-free survival (RFS) (p=0.004). Positive expression of PD-1 combined with a high ratio of lymphocytes (CD3, p=0.004; CD4, p=0.011; CD8, p=0.009; FOXP3, p=0.009) was associated with significantly better RFS than negative expression of PD-1 combined with a lower ratio of lymphocytes. Positive expression of PD-L1 combined with a high ratio of lymphocytes (CD3, p<0.001; CD4, p=0.001; CD8, p=0.002; FOXP3, p=0.001) was associated with significantly better RFS than negative expression of PD-L1 combined with a lower ratio of lymphocytes. All patients' stage were between I and III. Conclusion: PD-1 and PD-L1 expression might be good prognostic factors in SCLC.

17.
Int J Surg Pathol ; : 1066896920953906, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32856508

RESUMO

We describe the clinicopathologic and molecular features of 2 cases of gastric monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), which were first diagnosed from gastric biopsies, one was primary whereas the other was gastric involvement by MEITL. Both cases were older men with stomach ulcers. Case 1 was admitted for a hemorrhage in the upper digestive tract and case 2 for edema. Histology of both cases showed infiltrated monomorphic and medium-sized lymphocytes with lymphoid epithelial phenomenon. An inflammatory background and vascular hyperplasia were also observed likely due to the ulceration. Neoplastic cells expressed CD2, CD3, CD7, CD8, CD56, TIA-1, and MYC, not CD5, CD4, Granzyme B, CD20, CD30, TdT, or EBER. Both lymphomas showed TCRG gene rearrangement and c-MYC gains. Moreover, we first affirmed polysomy of chromosome 8 in case 2. For correct diagnosis of this rare tumor at the rare location, it is important that pathologists raise the possibility and exclude other differential diagnoses.

18.
Ann Transl Med ; 8(14): 889, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32793733

RESUMO

Immunotherapy has changed the pattern of treatment in cancer. The interaction between programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibits the activation of T cells, and PD-1/PD-L1 inhibitors can increase the immune response to cancer cells by inducing the immune cells, which has become an important clinical method to treat cancer. However, the alteration in the activation of T cells might lead to misidentification between the body's own cells and tumor cells and induce immune-related adverse events (IRAEs), such as pneumonitis, liver dysfunction, rash, colitis, nephritis, and endocrinopathies. And the IRAEs might lead to serious consequences. Studies have reported that PD-1/PD-L1 inhibitor-related hepatotoxicity is one of these adverse events. Most of the studies reported that hepatitis resulting from PD-1 inhibitor was manifested as elevated liver enzymes and bilirubin. Quite a few patients experienced lower degree of hepatotoxicity treated with checkpoint inhibitors, which indicated that it was necessary to focus on immunotherapy-related liver dysfunction. Here, we report a case of immunotherapy-related liver dysfunction with hypoproteinemia as the first manifestation under the treatment of PD-1 inhibitors combined with chemotherapy. This case suggests that hypoproteinemia was one of the manifestations of immunotherapy-related liver dysfunction, which helps us better understand the immunotherapy-related disease.

19.
Ann Palliat Med ; 9(5): 2760-2765, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32787355

RESUMO

BACKGROUND: This study aimed to explore the effect and safety of computed tomography (CT) guided microwave ablation for lung cancer. METHODS: We retrospectively enrolled CT guided microwave ablation of lung cancer patients in Shanghai Pulmonary Hospital from March 2016 to September 2019. All patients were pathologically confirmed by fine needle biopsy before microwave ablation. We reviewed CT imaging of 45 patients with lung cancer before and after microwave ablation and recorded the complications. Date were analyzed by paired-samples T-test and one-way analysis of variance. RESULTS: In 45 lung cancer patients received CT guided microwave ablation, the tumor diameter changed from 2.35±0.22 cm before surgery to 2.26±0.19 cm after surgery, average reduction by 0.09 cm (P=0.518). With microwave ablation treatment, the disease control rate reached 82.93%, and the incidence of pneumothorax was 13.3%, with no other related adverse. The successful rate of operation was 100%, and there was no severe or death related adverse. CONCLUSIONS: CT-guided microwave ablation is an effective method in the treatment of lung cancer, with a low incidence of complications. It is a safe and effective method for the treatment of lung cancer.

20.
J Cell Mol Med ; 24(17): 9752-9763, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32696548

RESUMO

Tubulointerstitial fibrosis plays an important role in end-stage renal failure, and there are only limited therapeutic options available to preserve organ function. In the present study, we identified that nodakenin, a coumarin isolated from the roots of Angelicae gigas, functions effectively against unilateral ureteral obstruction (UUO)-induced fibrosis via down-regulating Snail1 expression. We established UUO-induced renal fibrosis in mice and then administered with nodakenin orally ata a dose of 1 and 10 mg/kg. The in-vivo results indicated that nodakenin protected obstructive nephropathy through its anti-inflammatory and anti-fibrotic properties. Nodakenin prevented the infiltration of inflammatory cells, alleviated the levels of pro-inflammatory cytokines, reduced the polarization of macrophages and down-regulating the aberrant deposition of extracellular matrix at the site of injury. Of note, nodakenin dramatically impeded Smad3, NF-κB p65 phosphorylation and Snail1 expression. In line with in vivo studies, nodakenin suppressed the expression of Snail1, Smad3 phosphorylation and fibrogenesis in TGF-ß1-treated renal epithelial cells in-vitro. Furthermore, we found that the effect of nodaknin against fibrosis was reversed in Snail1 overexpressing cells, whereas nodakenin could not further reduce expression of fibrogenesis in Snail1 silenced cells, suggesting that nodaknein may function through a Snail1-dependent manner. Collectively, this study reveal a critical role of nodakenin in the cure of renal fibrosis.

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