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21.
Osric A. Forrest Daniel M. Chopyk Yael Gernez Milton R. Brown Carol K. Conrad Richard B. Moss Vin Tangpricha Limin Peng Rabindra Tirouvanziam 《Journal of cystic fibrosis》2019,18(1):64-70
Background
Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.Methods
Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function.Results
Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype).Conclusions
Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF. 相似文献22.
23.
《Revista espa?ola de anestesiología y reanimación》2020,67(5):245-252
Pneumonia caused by coronavirus, which originated in Wuhan, China, in late 2019, has been spread around the world already becoming a pandemic. Unfortunately, there is not yet a specific vaccine or effective antiviral drug for treating COVID-19. Many of these patients deteriorate rapidly and require intubation and are mechanically ventilated, which is causing the collapse of the health system in many countries due to lack of ventilators and intensive care beds.In this document we review two simple adjuvant therapies to administer, without side effects, and low cost that could be useful for the treatment of acute severe coronavirus infection associated with acute respiratory syndrome (SARS-CoV-2). Vitamin C, a potent antioxidant, has emerged as a relevant therapy due to its potential benefits when administered intravenous. The potential effect of vitamin C in reducing inflammation in the lungs could play a key role in lung injury caused by coronavirus infection. Another potential effective therapy is ozone: it has been extensively studied and used for many years and its effectiveness has been demonstrated so far in multiples studies. Nevertheless, our goal is not to make an exhaustive review of these therapies but spread the beneficial effects themselves.Obviously clinical trials are necessaries, but due to the potential benefit of these two therapies we highly recommended to add to the therapeutic arsenal. 相似文献
24.
Simeprevir added to peginterferon and ribavirin lessens time with fatigue,depressive symptoms and functional limitations in patients with chronic hepatitis C compared with peginterferon and ribavirin: results from 1161 patients in the QUEST‐1, QUEST‐2 and PROMISE studies 下载免费PDF全文
J. Scott L. Gilles M. Fu E. Brohan C. Panter R. Arbuckle W. Jessner M. Beumont 《Journal of viral hepatitis》2015,22(8):639-650
The value of adding simeprevir (SMV) vs placebo (PBO) to peginterferon and ribavirin (PR) for treatment of chronic hepatitis C virus infection was examined using patient‐reported outcomes (PROs); further, concordance of PROs with virology endpoints and adverse events (AEs) was explored. Patients (n = 768 SMV/PR, n = 393 PBO/PR) rated fatigue (FSS), depressive symptoms (CES‐D) and functional impairment (WPAI: Hepatitis C Productivity, Daily Activity and Absenteeism) at baseline and throughout treatment in three randomised, double‐blind trials comparing the addition of SMV or PBO during initial 12 weeks of PR. PR was administered for 48 weeks (PBO group) and 24/48 weeks (SMV group) using a response‐guided therapy (RGT) approach. Mean PRO scores (except Absenteeism) worsened from baseline to Week 4 to the same extent in both groups but reverted after Week 24 for SMV/PR and only after Week 48 for PBO/PR. Accordingly, there was a significantly lower area under the curve (baseline–Week 60, AUC60) and fewer weeks with clinically important worsening of scores in the SMV/PR group at any time point. Incidences of patients with fatigue and anaemia AEs were similar in both groups, but FSS scores showed that clinically important increases in fatigue lasted a mean of 6.9 weeks longer with PBO/PR (P < 0.001). PRO score subgroup analysis indicated better outcomes for patients who met the criteria for RGT or achieved sustained virological response 12 weeks post‐treatment (SVR12); differences in mean PRO scores associated with fibrosis level were only observed with PBO/PR. Greater efficacy of SMV/PR enabled reduced treatment duration and reduced time with PR‐related AEs without adding to AE severity. 相似文献
25.
目的评估血肌酐和尿常规的常规检测基础上联合血清胱抑素C和尿微量白蛋白检测在人类免疫缺陷病毒(HIV)感染者肾功能损伤检测中的应用价值。
方法以2019年2~5月于首都医科大学附属北京地坛医院感染一科住院的169例HIV感染者为研究对象,完善其尿常规、尿微量白蛋白、血肌酐、血清胱抑素C检测;分析尿蛋白及尿微量白蛋白的阳性检出率及其差异,血肌酐升高及血清胱抑素C升高的比例及其差异。计算应用替诺福韦酯(TDF)及合并丙型肝炎、高血压、糖尿病、肿瘤的肾功能损伤的相对危险度。
结果169例HIV感染者中尿常规示尿蛋白阳性者5例(3.0%),尿微量白蛋白升高者17例(10.1%),两者阳性检出率差异具有统计学意义(χ2 = 5.9、P = 0.007)。血肌酐升高者10例(5.9%),血清胱抑素C升高者20例(11.8%),两者阳性检出率差异具有统计学意义(χ2 = 3.0、P = 0.042)。在尿常规和血肌酐检测的基础上联合检测尿微量白蛋白和血清胱抑素C的总体阳性检出率为49例(30.0%)。CD4+ T淋巴细胞计数< 200个/μl与≥ 200个/μl组患者血清胱抑素C水平分别为0.94(0.83,1.05)mg/L、0.85(0.77,0.95)mg/L,差异具有统计学意义(Z =-3.02、P = 0.003)。应用TDF及合并丙型肝炎、高血压、糖尿病、肿瘤的肾功能损伤的相对危险度分别为1.1、1.5、1.9、2.2和1.4。
结论HIV感染者中,单纯以尿常规为依据评估有无蛋白尿,以血肌酐水平为依据评估肾小球滤过功能会低估肾功能损伤的患病率。在常规检测血肌酐和尿常规的基础上联合检测血清胱抑素C和尿微量白蛋白在提高HIV感染者肾功能损伤检出率方面具有重要的应用价值。低CD4+ T淋巴细胞计数、应用TDF及合并丙型肝炎、高血压、糖尿病、肿瘤均为肾功能损伤的危险因素。 相似文献
26.
Primary cutaneous anaplastic large cell lymphomas with 6p25.3 rearrangement exhibit particular histological features 下载免费PDF全文
27.
JeongYun Choi Haeseung Lee EunJi Kwon HyeonJoon Kong OkSeon Kwon HyukJin Cha 《Molecular oncology》2021,15(2):679
The acquisition of chemoresistance remains a major cause of cancer mortality due to the limited accessibility of targeted or immune therapies. However, given that severe alterations of molecular features during epithelial‐to‐mesenchymal transition (EMT) lead to acquired chemoresistance, emerging studies have focused on identifying targetable drivers associated with acquired chemoresistance. Particularly, AXL, a key receptor tyrosine kinase that confers resistance against targets and chemotherapeutics, is highly expressed in mesenchymal cancer cells. However, the underlying mechanism of AXL induction in mesenchymal cancer cells is poorly understood. Our study revealed that the YAP signature, which was highly enriched in mesenchymal‐type lung cancer, was closely correlated to AXL expression in 181 lung cancer cell lines. Moreover, using isogenic lung cancer cell pairs, we also found that doxorubicin treatment induced YAP nuclear translocation in mesenchymal‐type lung cancer cells to induce AXL expression. Additionally, the concurrent activation of TGFβ signaling coordinated YAP‐dependent AXL expression through SMAD4. These data suggest that crosstalk between YAP and the TGFβ/SMAD axis upon treatment with chemotherapeutics might be a promising target to improve chemosensitivity in mesenchymal‐type lung cancer.
Abbreviations
- AUC
- area under the curve
- AXL
- AXL receptor tyrosine kinase
- BCL2
- B‐cell lymphoma 2
- CTD2
- cancer target discovery and development
- CTGF
- connective tissue growth factor
- DEG
- differentially expressed genes
- DOXO
- doxorubicin
- EMT
- epithelial–mesenchymal transition
- Eto
- etoposide
- FDA
- Food and Drug Administration
- ITGB3
- integrin beta‐3
- MAPK
- mitogen‐activated protein kinase
- MMP2
- matrix metalloproteinase‐2
- MMP9
- matrix metalloproteinase‐9
- mRNA
- messenger RNA
- NF‐κB
- nuclear factor kappa‐light‐chain‐enhancer of activated B cells
- SBE
- SMAD binding element
- SERPINE1
- serpin family E member 1
- siRNA
- small interfering RNA
- ssGSEA
- single‐sample gene set enrichment analysis
- TCGA
- The Cancer Genome Atlas
- TGFβ
- transforming growth factor beta
- YAP
- Yes‐associated protein
- YAP8SA
- mutants of inhibitory phosphorylation site at eight serine to Alanine of YAP
- ZEB1
- zinc finger E‐box binding homeobox 1
- ZEB2
- zinc finger E‐box‐binding homeobox 2
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