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The key for better antitumor efficacy is to improve the specificity of antitumor drugs for tumor cells and diminish their cytotoxicity to normal tissues. Targeted nanoparticles as antitumor drug delivery system can resolve this problem. In this study, we prepared folate and TAT (arginine-rich cell-penetrating peptide) modified N-PEG-N'-octyl-chitosan to form the folate/TAT-PEG-OC micelles. Then, the molecular structure, morphology, size distribution and bio-safety of the micelles were characterized. In order to investigate the drug-loading capacity of folate/TAT-PEG-OC micelles, doxorubicin (DOX) was used as model drug to prepare DOX-loaded chitosan micelles. Here, the confocal microscopy was used to evaluate the cellular uptake of DOX/folate/TAT-PEG-OC micelles, while the self-built NIR imaging system was used to evaluate the dynamic behavior of ICG-Der-01/folate/TAT-PEG-OC micelles in vivo. Our results demonstrate that the dual-modified PEG-OC micelles not only have good morphology, uniform size distribution and excellent drug loading capacity, but also show a strong capability for the efficient intracellular uptake and enhanced targeting behaviors in a folate receptor positive tumor model (Bel-7402 human hepatocellular cells). All these results suggest the potential application of folate/TAT-PEG-OC micelles in the targeted diagnosis and therapy to different kinds of folate receptor positive tumors.

Thyroid hormone (TH) is critical for the maintenance of cellular homeostasis during stress responses, but its role in lung fibrosis is unknown. Here we found that the activity and expression of iodothyronine deiodinase 2 (DIO2), an enzyme that activates TH, were higher in lungs from patients with idiopathic pulmonary fibrosis than in control individuals and were correlated with disease severity. We also found that Dio2-knockout mice exhibited enhanced bleomycin-induced lung fibrosis. Aerosolized TH delivery increased survival and resolved fibrosis in two models of pulmonary fibrosis in mice (intratracheal bleomycin and inducible TGF-β1). Sobetirome, a TH mimetic, also blunted bleomycin-induced lung fibrosis. After bleomycin-induced injury, TH promoted mitochondrial biogenesis, improved mitochondrial bioenergetics and attenuated mitochondria-regulated apoptosis in alveolar epithelial cells both in vivo and in vitro. TH did not blunt fibrosis in Ppargc1a- or Pink1-knockout mice, suggesting dependence on these pathways. We conclude that the antifibrotic properties of TH are associated with protection of alveolar epithelial cells and restoration of mitochondrial function and that TH may thus represent a potential therapy for pulmonary fibrosis.

Background COPD is a leading cause of mortality worldwide, and cigarette smoke is a pivotal risk factor. Adenovirus is a common cause of acute exacerbations of COPD and expedites COPD progression. Lung stem/progenitor cells play an important role in the development of COPD, while the relevant mechanism remains elusive. Here, we investigated the number of lung CD31-CD45-Sca-1+ cells and sonic hedgehog (Shh) signaling pathway expression levels in cigarette smoke extract (CSE)-induced emphysema mice, as well as the relevant effects of acute adenovirus infection (AAI). Materials and methods BALB/c mice were treated with CSE by intraperitoneal injection and/or adenovirus endotracheal instillation at different time points for 28 days. Lung function, lung histomorphology, CD31-CD45-Sca-1+ cell count, and expression levels of major components in the Shh signaling pathway in the lungs were measured. Results CSE intraperitoneal injection and adenovirus endotracheal instillation successfully induced emphysema and AAI in mice, respectively. In the lungs of emphysema mice, both the number of CD31-CD45-Sca-1+ cells and expression levels of Shh signaling pathway molecules were reduced. However, AAI increased the number of inhibited CD31-CD45-Sca-1+ cells and activated the suppression of the Shh signaling pathway. Conclusion Both CD31-CD45-Sca-1+ cell numbers and Shh signaling pathway expression levels were downregulated in the lungs of emphysema mice induced by CSE intraperitoneal injection, which likely contributes to the pathogenesis of emphysema. Additionally, these inhibited lung CD31-CD45-Sca-1+ cells and Shh signaling pathway molecules were upregulated during AAI, indicating that they play a protective role in the epithelial repair process after AAI injury.

The method of wavelet compression and reconstruction is studied. The wind turbine vibration signal is compressed and reconstructed by wavelet transformation. The compression and reconstruction of wind turbine vibration signal are achieved with different wavelet base. The compression ratio and the compression reconstruction accuracy are analyzed. The method and the result facilitate the choice of wavelet base for transmission of wind turbine vibration signal.

The characteristics of three-order elliptical gear is analyzed. The parameters of three-order elliptical gear are chosen and calculated. The three-dimensional solid modeling of three-order elliptical gear is achieved. The dynamic model of three-order elliptical gear is established by FEM and modal analysis of three-order elliptical gear is investigated. The natural frequency and major modes of the first six orders are clarified. The method and the result facilitate the dynamic design and dynamic response analysis of high-order elliptical gear.

Cigarette smoking has long been tied to a multitude of poor health outcomes; however, in reproductive biology, smoking has shown several unintuitive findings. Smoking is associated with significantly decreased rates of endometriosis and endometrial cancer. Here, we show that treatment with cigarette smoke extract leads to increased mRNA and protein expression of homeobox A10 (HOXA10) and progesterone receptor (PGR) as well as more rapid decidualization of endometrial stromal cells in vitro. In vivo, mice exposed to cigarette smoke similarly showed increased expression of HOXA10 and PGR in the endometrium. Both HOXA10 and PGR drive endometrial differentiation and are suppressed in endometrial tumors and in endometriosis. The increased expression found upon exposure to cigarette smoke may provide a protective effect, mediating the decreased incidence of endometrial disease among smokers. This mechanism contrasts with the accepted paradigm that the effects of smoking on the uterus are secondary to ovarian alterations rather than direct effects on endometrium as demonstrated here.

Ye Gan1,2, Erica L Herzog2, Richard H Gomer31Department of Medicine, Central South University, Changsha, Hunan, China; 2Department of Medicine, Yale University School of Medicine, New Haven, CT, USA; 3Department of Biology, Texas A&M University, College Station, TX, USAAbstract: Idiopathic pulmonary fibrosis (IPF) is a discrete clinicopathologic entity defined by the presence of usual interstitial pneumonia on high-resolution CT scan and/or open lung biopsy and the absence of an alternate diagnosis or exposure explaining these findings. There are currently no FDA-approved therapies available to treat this disease, and the 5-year mortality is ~80%. The pyridone derivative pirfenidone has been studied extensively as a possible therapeutic agent for use in this deadly disease. This review will present the unique clinical features and management issues encountered by physicians caring for IPF patients, including the poor response to conventional therapy. The biochemistry and preclinical efficacy of pirfenidone will be discussed along with a comprehensive review of the clinical efficacy, safety, and side effects and patient-centered foci such as quality of life and tolerability. It is hoped that this information will lend insight into the complex issues surrounding the use of pirfenidone in IPF and lead to further investigation of this agent as a possible therapy in this devastating disease.Keywords: pirfenidone, fibrosis, clinical trials&nbsp

Statins are the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that function as potent inhibitors of cholesterol biosynthesis and have been used for many years for the treatment of hypercholesterolemia. However, accumulating experimental and clinical studies have revealed that the health benefits associated with statins treatment, particularly those conferred on the cardiovascular system, were the cholesterol-independent. Because statins inhibit an early step in the cholesterol biosynthetic pathway, they also inhibit the synthesis of isoprenoids such as farnesylpyrophosphate and geranylgeranylpyrophosphate, which are important postranslational lipid attachments for intracellular signaling molecules such as the Rho GTPases. The isoprenylation of Rho is a prerequisite for Rho activation, facilitating its interaction with the plasma membrane, undergoing GDP-GTP exchange and be activated. Inhibition of RhoA geranylgeranylation by statins decreases membrane GTP-bound active RhoA and subsequent Rho-kinase activity. Activated RhoA via its downstream effector Rho-kinase is involved in a wide range of cellular functions, such as cell migration, proliferation and apoptosis. Recently, rising evidences suggested that RhoA/Rho-kinase pathway was essentially involved in various models of pulmonary hypertension and statins effectively ameliorated pulmonary hypertension. Based on this findings, we hypothesis that statins attenuate pulmonary hypertension via RhoA/Rho-kinase signaling pathway in vivo.

Epithelial injury, alternative macrophage accumulation, and fibroproliferation coexist in the lungs of patients with idiopathic pulmonary fibrosis (IPF). Chitinase 3-like 1 (CHI3L1) is a prototypic chitinase-like protein that has been retained over species and evolutionary time. However, the regulation of CHI3L1 in IPF and its ability to regulate injury and/or fibroproliferative repair have not been fully defined. We demonstrated that CHI3L1 levels were elevated in patients with IPF. High levels of CHI3L1 are associated with progression--as defined by lung transplantation or death--and with scavenger receptor-expressing circulating monocytes in an ambulatory IPF population. In preterminal acute exacerbations of IPF, CHI3L1 levels were reduced and associated with increased levels of apoptosis. We also demonstrated that in bleomycin-treated mice, CHI3L1 expression was acutely and transiently decreased during the injury phase and returned toward and eventually exceeded baseline levels during the fibrotic phase. In this model, CHI3L1 played a protective role in injury by ameliorating inflammation and cell death, and a profibrotic role in the repair phase by augmenting alternative macrophage activation, fibroblast proliferation, and matrix deposition. Using three-dimensional culture system of a human fibroblast cell line, we found that CHI3L1 is sufficient to induce low grade myofibroblast transformation. In combination, these studies demonstrate that CHI3L1 is stimulated in IPF, where it represents an attempt to diminish injury and induce repair. They also demonstrate that high levels of CHI3L1 are associated with disease progression in ambulatory patients and that a failure of the CHI3L1 antiapoptotic response might contribute to preterminal disease exacerbations.

Immunoassay devices including microarray and microfluidic systems were fabricated with an UV-curable resin by a new economic approach, which can not only simply produce a 3-dimensional (3D) patterned structure, but also simultaneously introduce functional epoxide groups for efficient protein immobilization. The performance of the epoxy resin-based microarray was improved by optimization of printing buffer, probe concentration, and immobilization time, showing a detection dynamic range of 5 orders of magnitude and a limit of detection (LOD) of 10 pg mL(-1) for immunoglobulin G (IgG). The developed microfluidic immunoassay device demonstrates a LOD of 100 pg mL(-1) for IL-5 detection. The device can also be used to colorimetrically detect proteins via naked human eyes for immunoassays. This work provides a simple and inexpensive method to fabricate a sensitive immunoassay device, especially a 3D microfluidic system, which has great potential to develop a portable immunoassay device via human eye detection for point-of-care service and/or high throughput screening of infectious diseases.

Patients who need both capsule endoscopy (CE) and colonoscopy often undergo both examinations on the same day to avoid repeated bowel preparation and fasting. Sedation can relieve pain and is commonly used for colonoscopies but may influence the CE completion rate. To determine whether sedation with propofol influences the completion rate and small-bowel transit time (SBTT) of CE. From July 2014 to December 2014, patients (18–65 years old) who needed both CE and colonoscopy were assessed consecutively for enrollment in our study. Colonoscopies were performed with or without sedation based on patient preferences on the day of capsule ingestion. The completion rate, SBTT, and diagnostic yield of CEs were recorded. Patients’ satisfaction and pain scores were also recorded. Sedation with propofol had no significant effect on CE completion rates (83.3% sedation group vs 81.8% nonsedation group, P = 0.86) but was associated with increased SBTT (403.6 ± 160.3 sedation group vs 334.5 ± 134.4 nonsedation group, P = 0.006). The diagnostic yields in the sedation and nonsedation groups were 69.4% and 65.9%, respectively (P = 0.74). The median satisfaction scores were 8.6 in the sedation group and 3.5 in the nonsedation group (P

The above sketches give only a glimpse of some of the things going on in China. There are plenty of problems waiting for us to be solved in the future.