Enalaprilat (Ena.), an angiotensin II (Ang II) converting enzyme inhibitor (ACEI), can produce some therapeutic effects on hypertension, ventricular hypertrophy and myocardial remodeling in clinic, but its precise mechanism, especially its signaling pathways remain elusive. In this study, cardiac fibroblasts (CFb) was isolated by the trypsin digestion method; a BrdU proliferation assay was adopted to determine cell proliferation; an immunofluorescence assay was used to measure intracellular reactive oxygen species (ROS); immunocytochemistry staining and Western blotting assay were used to detect phosphorylated p38 mitogen activated protein kinase (p-p38MAPK) and transforming growth factor-β 1 (TGF-β 1 ) protein expression, respectively. The results showed that Ang II (10 -7 M) stimulated the cardiac fibroblast proliferation which was inhibited by NAC (an antioxidant), SB203580 (a p38MAPK inhibitor) or enalaprilat; Ang II caused an burst of intracellular ROS level within thirty minutes, an increase in p-p38MAPK (3.6-fold of that in the control group), as well as an elevation of TGF-β 1 meantime; NAC, an antioxidant, and enalaprilat treatment attenuated cardiac fibroblast proliferation induced by Ang II and decreased ROS and p-p38MAPK protein levels in rat cardiac fibroblast; SB203580 lowered TGF-β 1 protein expression in rats' CFb in a dose-dependent manner. It could be concluded that enalaprilat can inhibit the cardiac fibroblast proliferation induced by Ang II via blocking ROS/P38MAPK/TGF-β 1 signaling pathways and the study provides a theoretical proof for the application of ACEIs in treating OPEN ACCESSMolecules 2012, 17 2739 myocardial fibrosis and discovering the primary mechanism through which ACEIs inhibit CFb proliferation.
Background and ObjectivesLocal recurrence of cancer after surgery has long been a tough problem. In the present study, thermosensitive gel‐based chemophotothermal therapy was applied to prevent the recurrence of liver cancer after surgery.Study Design/Materials and MethodsMesoporous silica nanoparticles (MSNs) were used as first‐level carrier to co‐load doxorubicin (DOX) and ICG. Then, the drug‐loaded MSNs (D‐I@MSN) were incorporated into poloxamer gel. A mimic model of liver cancer recurrence after surgery was prepared by subcutaneously injecting H22 cells into the armpit of mice. Then the two‐level composite gel (D‐I@MSN/gel) was also subcutaneously injected at the same site before the formation of tumor, followed by 808 nm laser irradiation.ResultsThe loading efficiency and entrapment efficiency of DOX were as high as 8.85% and 96.9%, and that of ICG were 9.24% and 99.3%, respectively. The results of in vitro cytotoxicity showed that cell viability in D‐I@MSN+Laser group was only 5.8% after being irradiated by 808 nm laser for 5 minutes (0.5 W/cm2). In animal studies, tumor formation (tumor recurrence) was greatly inhibited in D‐I@MSN+Laser group.ConclusionsThe thermosensitive gel‐based chemophotothermal therapy showed excellent safety and efficacy when applied in the prevention of mimic local tumor replase after surgery in mice, presenting its great potential clinically. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Background: Tuberculous pleurisy is inflammation caused by direct infection of Mycobacterium tuberculosis (MTB) and/or delayed allergic reaction of the pleura to MTB thallus components. The diagnosis of tuberculous pleurisy is mainly confirmed by bacterial culture, smear staining or histopathology, but has some clinical limitations. Next-generation sequencing (NGS), as a new diagnostic technology, has good application prospects in the diagnosis of tuberculous pleurisy. Case Presentation: A patient admitted with right pleural effusion and pneumonia was actively treated with anti-infection, anti-inflammatory and symptomatic support while various etiological tests of right pleural effusion were improved. However, all the etiological tests for MTB infection were negative. At this time, the patient's condition worsened and pleural effusion also appeared on the left side. In order to clarify the cause of the disease as soon as possible and prevent the disease from worsening again, the left and right pleural effusions of the patient were sent for NGS testing. The test results suggested MTB infection, which finally clarified the diagnosis of tuberculous pleurisy, and the next treatment plan of the patient was timely adjusted. Conclusion: NGS is instructive in the diagnosis of tuberculous pleurisy when various conventional tests and imaging methods fail.
The present meta-analysis is consistent with the hypothesis that increased expression of OPN protein may be significantly associated with poor prognosis in patients with NSCLC.
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