Summary Objective Disruptions of extracellular matrix (ECM) homeostasis are key events in the pathogenesis of osteoarthritis (OA). MicroRNA-140 (miRNA-140) is expressed specifically in cartilage and ...regulates ECM-degrading enzymes. Our objective in this study was to determine if intra-articular injection of miRNA-140 can attenuate OA progression in rats. Design miRNA-140 levels in human normal and OA cartilage derived chondrocytes and synovial fluid were assessed by polymerase chain reaction (PCR). After primary human chondrocytes were transfected with miRNA-140 mimic or inhibitor, PCR and western blotting were performed to quantify Collagen II, MMP-13, and ADAMTS-5 expression. An OA model was induced surgically in rats, and subsequently treated with one single intra-articular injection of miRNA-140 agomir. At 4, 8, and 12 weeks after surgery, OA progression were evaluated macroscopically, histologically, and immunohistochemically in these rats. Results miRNA-140 levels were significantly reduced in human OA cartilage derived chondrocytes and synovial fluid compared with normal chondrocytes and synovial fluid. Overexpressing miRNA-140 in primary human chondrocytes promoted Collagen II expression and inhibited MMP-13 and ADAMTS-5 expression. miRNA-140 levels in rat cartilage were significantly higher in the miRNA-140 agomir group than in the control group. Moreover, behavioural scores, chondrocyte numbers, cartilage thickness and Collagen II expression levels in cartilage were significantly higher, while pathological scores and MMP-13 and ADAMTS-5 expression levels were significantly lower in the miRNA-140 agomir group than in the control group. Conclusion Intra-articular injection of miRNA-140 can alleviate OA progression by modulating ECM homeostasis in rats, and may have potential as a new therapy for OA.
The associated risk of phthalate exposure, both parent compounds in the home and their metabolites in urine, to childhood allergic and respiratory morbidity, after adjusting for exposures of indoor ...pollutants, especially bioaerosols, was comprehensively assessed. Levels of five phthalates in settled dust from the homes of 101 children (3–9 years old) were measured, along with their corresponding urinary metabolites. Other environmental risk factors, including indoor CO2, PM2.5, formaldehyde, 1,3‐β‐d‐glucan, endotoxin, allergen and fungal levels, were concomitantly examined. Subject’s health status was verified by pediatricians, and parents recorded observed daily symptoms of their children for the week that the home investigation visit took place. Significantly increased level of benzylbutyl phthalate, in settled dust, was associated with test case subjects (allergic or asthmatic children). Higher levels of dibutyl phthalate and its metabolites, mono‐n‐butyl phthalate, and mono‐2‐ethylhexyl phthalate were found to be the potential risk factors for the health outcomes of interest. Similarly, indoor fungal exposure remained a significant risk factor, especially for reported respiratory symptoms. The relative contribution from exposure to phthalates and indoor biocontaminants in childhood allergic and respiratory morbidity is, for the first time, quantitatively assessed and characterized.
Practical Implications
For asthmatic and allergic children living in subtropical and highly developed environments like homes in Taiwan, controlling environmental exposure of phthalates may be viewed as equally important as avoiding indoor microbial burdens, for the management of allergy‐related diseases. It is also recognized that multidisciplinary efforts will be critical in realizing the true underlying mechanisms associated with these observations.
Layered deformation in the Taiwan orogen Huang, T.-Y.; Gung, Y.; Kuo, B.-Y. ...
Science (American Association for the Advancement of Science),
08/2015, Letnik:
349, Številka:
6249
Journal Article
Recenzirano
The underthrusting of continental crust during mountain building is an issue of debate for orogens at convergent continental margins. We report three-dimensional seismic anisotropic tomography of ...Taiwan that shows a nearly 90° rotation of anisotropic fabrics across a 10- to 20-kilometer depth, consistent with the presence of two layers of deformation. The upper crust is dominated by collision-related compressional deformation, whereas the lower crust of Taiwan, mostly the crust of the subducted Eurasian plate, is dominated by convergence-parallel shear deformation. We interpret this lower crustal shearing as driven by the continuous sinking of the Eurasian mantle lithosphere when the surface of the subducted plate is coupled with the orogen. The two-layer deformation clearly defines the role of subduction in the formation of the Taiwan mountain belt.
Gastric cancer is one of the most aggressive cancers and is the second leading cause of cancer death worldwide. Approximately 40% of global gastric cancer cases occur in China, with peritoneal ...metastasis being the prevalent form of recurrence and metastasis in advanced disease. Currently, there are limited clinical approaches for predicting and treatment of peritoneal metastasis, resulting in a 6-month average survival time. By comprehensive genome analysis will uncover the pathogenesis of peritoneal metastasis. Here we describe a comprehensive whole-genome and transcriptome sequencing analysis of one advanced gastric cancer case, including non-cancerous mucosa, primary cancer and matched peritoneal metastatic cancer. The peripheral blood is used as normal control. We identified 27 mutated genes, of which 19 genes are reported in COSMIC database (ZNF208, CRNN, ATXN3, DCTN1, RP1L1, PRB4, PRB1, MUC4, HS6ST3, MUC17, JAM2, ITGAD, IREB2, IQUB, CORO1B, CCDC121, AKAP2, ACAN and ACADL), and eight genes have not previously been described in gastric cancer (CCDC178, ARMC4, TUBB6, PLIN4, PKLR, PDZD2, DMBT1and DAB1).Additionally,GPX4 and MPND in 19q13.3-13.4 region, is characterized as a novel fusion-gene. This study disclosed novel biological markers and tumorigenic pathways that would predict gastric cancer occurring peritoneal metastasis.
Superelastic conducting fibers with improved properties and functionalities are needed for diverse applications. Here we report the fabrication of highly stretchable (up to 1320%) sheath-core ...conducting fibers created by wrapping carbon nanotube sheets oriented in the fiber direction on stretched rubber fiber cores. The resulting structure exhibited distinct short- and long-period sheath buckling that occurred reversibly out of phase in the axial and belt directions, enabling a resistance change of less than 5% for a 1000% stretch. By including other rubber and carbon nanotube sheath layers, we demonstrated strain sensors generating an 860% capacitance change and electrically powered torsional muscles operating reversibly by a coupled tension-to-torsion actuation mechanism. Using theory, we quantitatively explain the complementary effects of an increase in muscle length and a large positive Poisson's ratio on torsional actuation and electronic properties.
Impressive performance of hybrid perovskite solar cells reported in recent years still awaits a comprehensive understanding of its microscopic origins. In this work, the intrinsic Hall mobility and ...photocarrier recombination coefficient are directly measured in these materials in steady-state transport studies. The results show that electron-hole recombination and carrier trapping rates in hybrid perovskites are very low. The bimolecular recombination coefficient (10(-11) to 10(-10) cm(3) s(-1)) is found to be on par with that in the best direct-band inorganic semiconductors, even though the intrinsic Hall mobility in hybrid perovskites is considerably lower (up to 60 cm(2) V(-1) s(-1)). Measured here, steady-state carrier lifetimes (of up to 3 ms) and diffusion lengths (as long as 650 μm) are significantly longer than those in high-purity crystalline inorganic semiconductors. We suggest that these experimental findings are consistent with the polaronic nature of charge carriers, resulting from an interaction of charges with methylammonium dipoles.
The dual role of the microRNA-29 (miR-29) family in tumor progression and metastasis in solid tumors has been reported. Evidence for the role of miR-29 in tumor malignancy and its prognostic value in ...overall survival (OS) and relapse-free survival (RFS) in non-small cell lung cancer (NSCLC) remains conflicting. Mechanistic studies presented herein demonstrated that c-Myc suppressed the expression of miR-29b, promoting soft agar growth and invasion capability in lung cancer cells. Interestingly, the decrease in the expression of miR-29b by c-Myc is responsible for soft agar growth and invasiveness mediated by FHIT loss due to promoter methylation. Among patients, low expression of miR-29b and FHIT was more common in tumors with high c-Myc expression than in tumors with low c-Myc expression. Kaplan-Meier and Cox regression analysis showed that tumors with high c-Myc, low miR-29b and low FHIT expression had shorter OS and RFS periods than their counterparts. In conclusion, the decrease in the expression of miR-29b by c-Myc may be responsible for FHIT loss-mediated tumor aggressiveness and for poor outcome in NSCLC. Therefore, we suggest that restoration of the miR-29b expression using the c-Myc inhibitor might be helpful in suppressing tumor aggressiveness mediated by FHIT loss and consequently improving outcomes in NSCLC patients with tumors with low expression of FHIT.
Transforming growth factor-β (TGFβ) is enriched in the bone matrix and serves as a key factor in promoting bone metastasis in cancer. In addition, TGFβ signaling activates mammalian target of ...rapamycin (mTOR) functions, which is important for the malignant progression. Here, we demonstrate that TGFβ regulates the level of microRNA-96 (miR-96) through Smad-dependent transcription and that miR-96 promotes the bone metastasis in prostate cancer. The enhanced effects in cellular growth and invasiveness suggest that miR-96 functions as an oncomir/and metastamir. Supporting this idea, we identified a downstream target of the TGFβ-miR-96 signaling pathway to be AKT1S1 mRNA, whose translated protein is a negative regulator of mTOR kinase. Our findings provide a novel mechanism accounting for the TGFβ signaling and bone metastasis.
To understand the status of oropharyngeal yeast colonization in human immunodeficiency virus (HIV) -infected outpatients in the era of highly active antiretroviral therapy (HAART), we conducted a ...prospective, cross-sectional study from October 2009 to January 2010 at a medical centre in southern Taiwan. Fungal cultures of the oropharyngeal swabs were performed on 327 enrolled patients. At enrolment, 258 (79%) patients had been receiving HAART, and 42 (12.8%), 73 (22.3%) and 212 (64.8%) patients had CD4 cell counts ≤200, 201–350, and >350 cells/mm3, respectively. Oral yeast colonization was detected in 193 (59%) patients, among whom 157 (81.3%), 25 (13.0%), and 11 (5.7%) were colonized by a single, two and more than two species, respectively. Multivariate analysis showed that receipt of efavirenz-containing regiments and CD4 cell counts >200 cells/mm3 were associated with lower risks of oral yeast colonization, while intravenous drug users were at a higher risk. Among the 241 isolates recovered, Candida albicans accounted for 69.7%, followed by C. dubliniensis (9.5%), C. glabrata (8.3%), C. tropicalis (3.3%), C. intermedia (2.1%), C. parapsilosis (1.7%), and 11 other species (5.4%). Overall, 230 (95.4%), 236 (97.9%) and 240 (99.6%) isolates were susceptible to fluconazole, voriconazole and amphotericin B, respectively. In conclusion, colonization by C. dubliniensis has emerged in recent years. In addition to a CD4 cell count ≤200 cells/mm3, which is a known risk factor for oropharyngeal yeast colonization in HIV-infected patients that was identified in our previous studies, two risk factors, non-receipt of efavirenz-based combinations and intravenous drug use, were first identified in the present study. Fluconazole remained effective in vitro against the yeasts colonizing the oropharynx in this population.
PDF
