Circulating tumor cell (CTC) enumeration and analysis has emerged as an important platform for cancer diagnosis and prognosis. A great challenge, however, is to efficiently capture low abundant CTCs with high purity from blood samples in a rapid and high-throughput manner for accurate and sensitive CTC detection. Herein, a new class of DNA-templated magnetic nanoparticle-quantum dot (QD)-aptamer copolymers (MQAPs) is developed for rapid magnetic isolation of CTCs from human blood with high capture efficiency and purity approaching 80%. The phenotype of CTCs is simultaneously profiled with QD photoluminescence (PL) at single cell level. These MQAPs are constructed through hybridization chain reaction to achieve amplified magnetic response, extraordinary binding selectivity for target cells over background cells, and ultra bright ensemble QD PL for single cell detection. MQAPs are free from nonspecific binding that would otherwise compromise the capture purity of target cells. As a result, facile isolation and enumeration of rare CTCs in blood samples could be achieved in 20 min with high sensitivity and accuracy.
An emerging paradigm proposes a crucial role for lung resident mesenchymal stem cells (LR-MSCs) via a fibroblastic transdifferentiation event in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Aberrant activation of Wnt/β-catenin signaling occurs in virtually all fibrotic lung diseases and is relevant to the differentiation of mesenchymal stem cells (MSCs). In vitro, by measuring the protein levels of several key components involved in Wnt/β-catenin signaling, we confirmed that this signaling pathway was activated in the myofibroblast differentiation of LR-MSCs. Targeted inhibition of Wnt/β-catenin signaling by a small molecule, ICG-001, dose-dependently impeded the proliferation and transforming growth factor-β1 (TGF-β1)-mediated fibrogenic actions of LR-MSCs. In vivo, ICG-001 exerted its lung protective effects after bleomycin treatment through blocking mesenchymal-myofibroblast transition, repressing matrix gene expression, and reducing cell apoptosis. Moreover, delayed administration of ICG-001 attenuated bleomycin-induced lung fibrosis, which may present a promising therapeutic strategy for intervention of IPF. Interestingly, these antifibrotic actions of ICG-001 are operated by a mechanism independent of any disruption of Smad activation. In conclusion, our study demonstrated that Wnt/β-catenin signaling may be an essential mechanism underlying the regulation of myofibroblast differentiation of LR-MSCs and their further participation in the development of pulmonary fibrosis.
Background & aims
Sarcopenia is associated with poor clinical outcomes of patients who underwent esophagectomy. The current diagnostic criteria for sarcopenia are complex and laborious. We aimed to employ the simple and economic indicator sarcopenia index (SI = creatinine/cystatin C ×100) to screen for sarcopenia and to evaluate its prognostic value in patients with esophageal cancer (EC).
Methods
Older participants in the National health and nutrition examination survey (NHANES) database (1999–2002) were divided into three groups according to tertiles of the SI value to explore the feasibility of SI in the diagnosis of sarcopenia. Restricted cubic spline (RCS) was utilized to show the non-linear relationship between all-cause mortality and SI. Patients with EC admitted to Jinling Hospital were enrolled to validate the efficacy and prognostic value of SI. Cut-off values of SI were determined using receiver operating characteristic curves. Multivariable logistic analyses and Cox analyses were used to identify the independent factors of postoperative complications and long-term survival, respectively.
Results
A total of 989 participants were identified from the NHANES database. SI showed the diagnostic value of sarcopenia (tertile 1 vs. tertile 3: odds ratio [OR]=3.67, 95% confidence interval [CI]: 1.52–8.87, p=0.004; tertile 2 vs. tertile 3: OR=1.79, 95% CI: 0.75–4.28, p=0.191) adjusted for race, gender, and body mass index (BMI). Individuals with SI ≤ 68 had a poorer overall survival (OS) (hazard ratio [HR]=2.14, 95% CI: 1.71–2.68, p<0.001), and the RCS plot showed that the all-cause mortality risk gradually decreased with the increase in SI. Then, 203 patients with EC were enrolled, of which 76 patients were diagnosed with sarcopenia. There was a linear correlation between SI and skeletal muscle index and prealbumin, indicating that SI was reliable for diagnosing sarcopenia. Patients in the high sarcopenia risk group (Male: SI < 62; Female: SI < 55) showed a higher incidence of complications (OR=3.50, 95% CI: 1.85–6.61, p<0.001) and poorer long-term survival (HR=2.62, 95% CI: 1.02–6.77, p=0.046).
Conclusion
SI could be used to identify sarcopenia in patients with EC, and it is a useful prognostic factor of postoperative complications and long-term survival.
Our study clearly demonstrates that miR-194 inhibits the acquisition of the EMT phenotype in gastric cancer cells by downregulating FoxM1, thereby inhibiting cell migration and invasion during cancer progression.
MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators through targeting mRNAs for translational repression or degradation. In this study, we showed that miR-376c expression level was decreased while transforming growth factor-alpha (TGFA) mRNA expression levels were increased in osteosarcoma tissues and cell lines, and we identified TGFA as a novel direct target of miR-376c. Overexpression of miR-376c suppressed TGFA expression and the expression of its downstream signaling molecule such as epidermal growth factor receptor, and attenuated cell proliferation and invasion. Forced expression of TGFA could partly rescue the inhibitory effect of miR-376c in the cells. Taken together, these findings will shed light on the role and mechanism of miR-376c in regulating osteosarcoma cell growth via miR-376c/TGFA axis, and miR-376c may serve as a potential therapeutic target in osteosarcoma in the future.
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