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1.
Mol Carcinog ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31478263

RESUMO

Protein arginine methyltransferase 1 (PRMT1) is identified as an oncogene implicated in various types of human cancers, while Yes-associated protein (YAP) as a key transcriptional coactivator of the Hippo signaling plays a vital role in tissue homeostasis and tumorigenesis. To date, the underlying biological functions, prognostic values, and potential mechanisms of PRMT1 and YAP in chondrosarcoma development have not been clearly elucidated. Here, we show that upregulation of PRMT1 and YAP is significantly detected in human chondrosarcoma specimens. Elevated levels of PRMT1 positively correlated with YAP nuclear accumulation are significantly associated with high-grade chondrosarcoma and poor prognosis. Moreover, YAP is recognized as an independent prognostic factor for chondrosarcoma patients. Ectopic expression of PRMT1 potentiates, but depletion of PRMT1 attenuates, chondrosarcoma cell growth in vitro and in vivo. Mechanistically, we have discovered that PRMT1 functions upstream of LATS1 and suppresses LATS1-mediated phosphorylation of YAP (Ser127), and thus promotes chondrosarcoma cell survival in a YAP-dependent manner. Collectively, our study identifies PRMT1 as a positive regulator of YAP activity in chondrosarcoma, highlighting a novel therapeutic target against chondrosarcoma and other YAP-driven cancers.

2.
Acta Pharmacol Sin ; 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31371781

RESUMO

Metastasis causes the main lethality in esophageal cancer patient. Garcinol, a natural compound extracted from Gambogic genera, is a histone acetyltransferase (HAT) inhibitor that has shown anticancer activities such as cell cycle arrest and apoptosis induction. In this study, we investigated the effects of garcinol on the metastasis of esophageal cancer in vitro and in vivo. We found that garcinol (5-15 µM) dose-dependently inhibited the migration and invasion of human esophageal cancer cell lines KYSE150 and KYSE450 in wound healing, transwell migration, and Matrigel invasion assays. Furthermore, garcinol treatment dose-dependently decreased the protein levels of p300/CBP (transcriptional cofactors and HATs) and p-Smad2/3 expression in the nucleus, thus impeding tumor cell proliferation and metastasis. Knockdown of p300 could inhibit cell metastasis, but CBP knockdown did not affect the cell mobility. It has been reported that TGF-ß1 stimulated the phosphorylation of Smad2/3, which directly interact with p300/CBP in the nucleus, and upregulating HAT activity of p300. We showed that garcinol treatment dose-dependently suppressed TGF-ß1-activated Smad and non-Smad pathway, inhibiting esophageal cancer cell metastasis. In a tail vein injection pulmonary metastasis mouse model, intraperitoneal administration of garcinol (20 mg/kg) or 5-FU (20 mg/kg) significantly decreased the number of lung tumor nodules and the expression levels of Ki-67, p300, and p-Smad2/3 in lung tissues. In conclusion, our study demonstrates that garcinol inhibits esophageal cancer metastasis in vitro and in vivo, which might be related to the suppression of p300 and TGF-ß1 signaling pathways, suggesting the therapeutic potential of Garcinol for metastatic tumors.

3.
Pharmacol Ther ; : 107395, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31374225

RESUMO

A major challenge in cancer treatment is predicting the clinical response to anti-cancer drugs on a personalized basis. The success of such a task largely depends on the ability to develop computational resources that integrate big "omic" data into effective drug-response models. Machine learning is both an expanding and an evolving computational field that holds promise to cover such needs. Here we provide a focused overview of: 1) the various supervised and unsupervised algorithms used specifically in drug response prediction applications, 2) the strategies employed to develop these algorithms into applicable models, 3) data resources that are fed into these frameworks and 4) pitfalls and challenges to maximize model performance. In this context we also describe a novel in silico screening process, based on Association Rule Mining, for identifying genes as candidate drivers of drug response and compare it with relevant data mining frameworks, for which we generated a web application freely available at: https://compbio.nyumc.org/drugs/. This pipeline explores with high efficiency large sample-spaces, while is able to detect low frequency events and evaluate statistical significance even in the multidimensional space, presenting the results in the form of easily interpretable rules. We conclude with future prospects and challenges of applying machine learning based drug response prediction in precision medicine.

4.
Clin Chim Acta ; 498: 1-5, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31398310

RESUMO

Shrunken pore syndrome (SPS) is a condition in which the estimated glomerular filtration rate (eGFR) based on serum/plasma cystatin C concentration is significantly lower than the eGFR based on creatinine. According to the literatures, the diagnosis of SPS could be defined when the eGFRcystatin C is <70% of eGFRcreatinine. Although the incidence of SPS varies in different patient populations and healthy seniors, it has been demonstrated that patients with SPS have poor prognosis. The present review has summarized its diagnosis, epidemiology, prognosis and possible pathophysiology basis. Moreover, we discuss the prevention and treatment of SPS in clinical practice as future challenges.

5.
Bioorg Med Chem Lett ; 29(18): 2575-2580, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31416665

RESUMO

PI3Kδ mediates key immune cell signaling pathways and is a target of interest for multiple indications in immunology and oncology. Here we report a structure-based scaffold-hopping strategy for the design of chemically diverse PI3Kδ inhibitors. Using this strategy, we identified several scaffolds that can be combined to generate new PI3Kδ inhibitors with high potency and isoform selectivity. In particular, an oxindole-based scaffold was found to impart exquisite selectivity when combined with several hinge binding motifs.

6.
Clin Nephrol ; 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31347497

RESUMO

Primary membranous nephropathy (PMN) is a common cause of adult nephrotic syndrome, most commonly associated with autoantibodies against M-type phospholipase A2 receptor (PLA2R). Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is a rare disorder characterized by asthma, eosinophilia, and multiorgan vasculitis. Here, we report the case of an adult who presented with typical nephrotic syndrome. Renal biopsy revealed PLA2R-positive PMN without crescents. He had a history of asthma, eczema, and eosinophilia, and testing revealed positive serological proteinase 3 (PR3) and antineutrophil cytoplasmic antibody (ANCA). Further skin and bone marrow biopsy revealed histologic eosinophilic infiltration, and a diagnosis of EGPA was made. The renal biopsy revealed a few eosinophils in glomerular capillary lumen and tubulointerstitial. Treatment with a glucocorticoid and cyclophosphamide was initiated. At 32 months after completing therapy, the patient was in complete clinical remission, and the PR3-ANCA result was negative.
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7.
Microbiome ; 7(1): 107, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315667

RESUMO

BACKGROUND: Early treatment is key for optimizing the therapeutic success of drugs, and the current initiating treatment that blocks the progression of bone destruction during the pre-arthritic stages remains unsatisfactory. The microbial disorder in rheumatoid arthritis (RA) patients is significantly reversed with effective treatment. Modulating aberrant gut microbiomes into a healthy state is a potential therapeutic approach for preventing bone damage. RESULTS: By using metagenomic shotgun sequencing and a metagenome-wide association study, we assessed the effect of Lactobacillus casei (L. casei) on the induction of arthritis as well as on the associated gut microbiota and immune disorders in adjuvant-induced arthritis (AIA) rats. Treatment of AIA rats with L. casei inhibited joint swelling, lowered arthritis scores, and prevented bone destruction. Along with the relief of arthritis symptoms, dysbiosis in the microbiome of arthritic rats was significantly reduced after L. casei intervention. The relative abundance of AIA-decreased Lactobacillus strains, including Lactobacillus hominis, Lactobacillus reuteri, and Lactobacillus vaginalis, were restored to normal and Lactobacillus acidophilus was upregulated by the administration of L. casei to the AIA rats. Moreover, L. casei downregulated the expression of pro-inflammatory cytokines, which are closely linked to the effect of the L. casei treatment-associated microbes. Functionally, the maintenance of the redox balance of oxidative stress was involved in the improvement in the L. casei-treated AIA rats. CONCLUSION: A single bacterium, L. casei (ATCC334), was able to significantly suppress the induction of AIA and protect bones from destruction in AIA rats by restoring the microbiome dysbiosis in the gut, indicating that using probiotics may be a promising strategy for treating RA, especially in the early stage of the disease.

8.
J Bone Miner Res ; 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31348548

RESUMO

Pregnancy and lactation-associated osteoporosis (PLO) is a rare, severe, early form of osteoporosis in which young women present with fractures, usually multiple vertebral fractures, during late pregnancy or lactation. In studies of idiopathic osteoporosis (IOP) in premenopausal women, we enrolled 78 women with low-trauma fractures and 40 healthy controls, all with normal menses and no secondary cause of bone loss. In 15 of the affected women, the PLO subgroup, fractures had occurred during late pregnancy or lactation. We hypothesized that clinical, bone structural, and metabolic characteristics would differ between women with PLO and those with (non-PLO) IOP and controls. All were evaluated > 12 months postpartum, when structural and remodeling characteristics would be expected to reflect baseline premenopausal status rather than transient postpartum changes. As previously reported, affected subjects (PLO and IOP) had BMD and microarchitectural deficiencies compared to controls. Women with PLO did not differ from those with IOP in terms of age, BMI, body fat, menarcheal age, parity, or age at first pregnancy. However, women with PLO had a more severe clinical presentation than those with IOP: more fractures (5.5 ± 3.3 versus 2.6 ± 2.1; p = 0.005); more vertebral fractures (80% versus 17%; p < 0.001); and higher prevalence of multiple fractures. BMD deficits were more profound and cortical width tended to be lower in PLO. PLO subjects also had significantly lower tissue-level mineral apposition rate and bone formation rates (0.005 ± 0.005 versus 0.011 ± 0.010 mm2 /mm/year; p = 0.006), as well as lower serum P1NP (33 ± 12 versus 44 ± 18 µg/L; p = 0.02) and CTX (257 ± 102 versus 355 ± 193 pg/mL; p = 0.01) than IOP. The finding that women with PLO have a low bone remodeling state assessed more than a year postpartum increases our understanding of the pathogenic mechanism of PLO. We conclude that women with PLO may have underlying osteoblast functional deficits which could affect their therapeutic response to osteoanabolic medications. © 2019 American Society for Bone and Mineral Research.

9.
Artif Cells Nanomed Biotechnol ; 47(1): 3013-3020, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31321998

RESUMO

This research planned to dig the impacts and potential principles of long noncoding RNA RP4 onH9c2 cell injury induced by hypoxia. The H9c2 cardiac muscle cells were cultured under 3% O2 concentration to induce hypoxia injury, followed by detection of RP4 expression. RP4 was then overexpressed and silenced to investigate its effects on cell injury induced by hypoxia. The potential correlation between RP4 and miR-939, between miR-939 and Bnip3, and between RP4/miR-939/Bnip3 axis and Wnt/ß-catenin pathway activation were explored. Biological processes (suppressed cell viability, migration and invasion, but enhanced cell apoptosis) were changed by hypoxia. Upregulation of RP4 enhanced hypoxia-produced damage in H9c2 cells. Additionally, miR-939 expression was opposite regulated by RP4, and miR-939 mimic abrogated the influences of pc-RP4 on enhanced hypoxia damage in H9c2 cells. Moreover, Bnip3 was targeted by miR-939 and their correlation is negative. Furthermore, upregulation of RP4 exacerbated hypoxia-produced injury in H9c2 cells by sensitizing Wnt/ß-catenin signals in H9c2 cells, which was regulated by miR-939/Bnip3 axis. Our findings reveal that RP4 is highly expressed in the hypoxia-resulted H9c2 cells. Enhanced expression of RP4 may exacerbate hypoxia injury in cardiomyocytes through regulating miR-939/Bnip3 axis-mediated briskness of Wnt/ß-catenin signals. Our study will offer a fresh theoretical basis for the treatment of ischemic myocardial injury.

10.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(6): 545-551, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31292059

RESUMO

Objective To illuminate whether IL-17 regulates receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) expression in human periodontal ligament fibroblasts (HPDLFs) via p38MAPK signaling pathway. Methods HPDLFs were incubated in the presence of 20 ng/mL IL-17 for 0, 20, 40, 60 and 80 minutes. HPDLFs were divided randomly into 6 groups: control group, dimethyl sulfoxide (DMSO) group, p38MAPK pathway inhibitor SB203580 group, IL-17 group, IL-17 combined with DMSO group and IL-17 combined with SB203580 group. SB203580 (10 µmol/L) and IL-17 (20 ng/mL) were added to the corresponding groups. Real-time quantitative PCR was used to detect the expression of RANKL and OPG mRNAs in HPDLFs. The levels of phospho-p38MAPK (p-p38MAPK) and RANKL protein were measured using Western blot analysis. The protein level of OPG was detected by ELISA. Results After IL-17 stimulation, the expression level of p-p38MAPK protein gradually increased starting from 0 minute and reached its highest level at 60 minutes. It started to decline at 80 minutes. Stimulation with IL-17 could increase the mRNA and protein expression level of RANKL but decrease the mRNA and protein expression level of OPG. Nevertheless, unlike the IL-17 group, IL-17 combined with inhibitor SB203580 decreased the expression of RANKL mRNA and protein and increased OPG mRNA. Conclusion IL-17 can enhance the expression of RANKL in human periodontal fibroblasts and inhibit the expression of OPG mRNA through the p38MAPK signal transduction pathways.

11.
Open Biol ; 9(7): 180227, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31337279

RESUMO

Non-small cell lung cancer (NSCLC) is considered to be the primary cause of cancer-related mortalities worldwide. Paclitaxel (PTX), either as a monotherapy or in combination with other drugs, is an alternative therapy for advanced NSCLC. However, cancer cell resistance against PTX represents a major clinical problem. This study aimed to investigate the role and underlying mechanism of miR-4262 in PTX-resistant NSCLC. The levels of miR-4262 were analysed by quantitative reverse transcription polymerase chain reaction. A luciferase reporter assay and bioinformatics were used to explore the potential target gene of miR-4262. Regulation of miR-4262 and PTEN expressions in NSCLC was conducted by transfection. PTX-resistant A549 and H1299 cells were established by stepwise screening through increasing the PTX concentration in the cultures. In vivo, tumorigenesis experiments were used to explore the effects of miR-4262 and PTX. Cell proliferation, apoptosis and cell migration were detected using a CCK-8 assay, flow cytometry and Transwell migration assay, respectively. PI3 K/Akt pathway-related proteins were detected by western blot. miR-4262 expression was significantly upregulated in NSCLC tissues and cell lines, and miR-4262 targeted PTEN. In addition, miR-4262 induced PTX chemoresistance by promoting survival and migration in A549/PTX and H1299/PTX cells. Moreover, miR-4262 expression and PI3 K/Akt signalling pathway-related proteins were upregulated and PTEN was downregulated in A549/PTX and H1299/PTX. Our results indicate that miR-4262 enhances PTX resistance in NSCLC cells through targeting PTEN and activating the PI3 K/Akt signalling pathway. The inhibition of miR-4262 expression might be an improved treatment to overcome PTX resistance in NSCLC.

12.
Sci Total Environ ; 692: 441-449, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31351288

RESUMO

The mechanisms underlying nutrient-induced diversity-stability relationships have been examined extensively. However, the effects of nutrient-induced shifts of dominant species on ecosystem stability have rarely been evaluated. We compiled a dataset from a long-term nitrogen (N) and phosphorus (P) enrichment experiment conducted in an alpine grassland on the Tibetan Plateau to test the effects of nutrient-induced shifts of dominant species on stability. Our results show that N enrichment increased synchrony among the dominant species, which contributed to a significant increase in synchrony of the whole community. Meanwhile, N-induced shifts in dominant species composition significantly increased population variability. Increases in species synchrony and population variability resulted in a decline in ecosystem stability. Our study has important implications for progress in understanding the role of plant functional compensation in the stability of ecosystem functions, which is critical for better understanding the mechanisms driving both community assembly and ecosystem functions.

13.
Molecules ; 24(13)2019 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-31284554

RESUMO

Nardochinoid B (NAB) is a new compound isolated from Nardostachys chinensis. Although our previous study reported that the NAB suppressed the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW264.7 cells, the specific mechanisms of anti-inflammatory action of NAB remains unknown. Thus, we examined the effects of NAB against LPS-induced inflammation. In this study, we found that NAB suppressed the LPS-induced inflammatory responses by restraining the expression of inducible nitric oxide synthase (iNOS) proteins and mRNA instead of cyclooxygenase-2 (COX-2) protein and mRNA in RAW264.7 cells, implying that NAB may have lower side effects compared with nonsteroidal anti-inflammatory drugs (NSAIDs). Besides, NAB upregulated the protein and mRNA expressions of heme oxygenase (HO)-1 when it exerted its anti-inflammatory effects. Also, NAB restrained the production of NO by increasing HO-1 expression in LPS-stimulated RAW264.7 cells. Thus, it is considered that the anti-inflammatory effect of NAB is associated with an induction of antioxidant protein HO-1, and thus NAB may be a potential HO-1 inducer for treating inflammatory diseases. Moreover, our study found that the inhibitory effect of NAB on NO is similar to that of the positive drug dexamethasone, suggesting that NAB has great potential for developing new drugs in treating inflammatory diseases.

14.
BMC Nephrol ; 20(1): 246, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277581

RESUMO

BACKGROUND: Mild cognitive impairment (MCI) occurs frequently in many end stage renal disease (ESRD) patients, may significantly worsen survival odds and prognosis. However, the exact neuropathological mechanisms of MCI combined with ESRD are not fully clear. This study examined functional connectivity (FC) alterations of the default-mode network (DMN) in individuals with ESRD and MCI. METHODS: Twenty-four individuals with ESRD identified as MCI patients were included in this study; of these, 19 and 5 underwent hemodialysis (HD) and peritoneal dialysis (PD), respectively. Another group of 25 age-, sex- and education level-matched subjects were recruited as the control group. All participants underwent resting-state functional MRI and neuropsychological tests; the ESRD group underwent additional laboratory testing. Independent component analysis (ICA) was used for DMN characterization. With functional connectivity maps of the DMN derived individually, group comparison was performed with voxel-wise independent samples t-test, and connectivity changes were correlated with neuropsychological and clinical variables. RESULTS: Compared with the control group, significantly decreased functional connectivity of the DMN was observed in the posterior cingulate cortex (PCC) and precuneus (Pcu), as well as in the medial prefrontal cortex (MPFC) in the ESRD group. Functional connectivity reductions in the MPFC and PCC/Pcu were positively correlated with hemoglobin levels. In addition, functional connectivity reduction in the MPFC showed positive correlation with Montreal Cognitive Assessment (MoCA) score. CONCLUSION: Decreased functional connectivity in the DMN may be associated with neuropathological mechanisms involved in ESRD and MCI.

15.
Sci Rep ; 9(1): 10172, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31308418

RESUMO

This work presents a systematic study of stress and strain of AlxGa1-xN/AlN with composition ranging from GaN to AlN, grown on a c-plane sapphire by metal-organic chemical vapor deposition, using synchrotron radiation high-resolution X-ray diffraction and reciprocal space mapping. The c-plane of the AlxGa1-xN epitaxial layers exhibits compressive strain, while the a-plane exhibits tensile strain. The biaxial stress and strain are found to increase with increasing Al composition, although the lattice mismatch between the AlxGa1-xN and the buffer layer AlN gets smaller. A reduction in the lateral coherence lengths and an increase in the edge and screw dislocations are seen as the AlxGa1-xN composition is varied from GaN to AlN, exhibiting a clear dependence of the crystal properties of AlxGa1-xN on the Al content. The bandgap of the epitaxial layers is slightly lower than predicted value due to a larger tensile strain effect on the a-axis compared to the compressive strain on the c-axis. Raman characteristics of the AlxGa1-xN samples exhibit a shift in the phonon peaks with the Al composition. The effect of strain on the optical phonon energies of the epitaxial layers is also discussed.

16.
ACS Appl Mater Interfaces ; 11(30): 27402-27409, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31288511

RESUMO

In this study, we have prepared a novel superhydrophilic fabric that has underwater directional oil-transport capability. The fabric was prepared using a two-step process consisting of dip-coating of a cross-linkable polymer, which comprises both oleophilic and hydrophilic groups, onto the fabric substrate and single-side UV irradiation of the coated fabric. The fabric had in-air superhydrophilicity on both sides, and it can be wetted easily once immersed in water. The treated fabric showed underwater oleophobicity on the UV-exposed surface, whereas the unexposed back side still maintained underwater oleophilicity. At the optimized condition, the fabric in water transports oil automatically from the UV-exposed to the unexposed back side but stops oil transport in the opposite direction. Such a directional oil transport takes place without the need for oil prewetting or formation of a plastron layer on fabric. The UV irradiation time showed an effect on oil-transport ability. We further showed that the underwater directional oil-transport fabric had a novel "oil trapping" ability. When used to seal a container, the fabric can trap oil into the container, and once trapped, the oil was kept without releasing. This underwater directional oil-transport fabric may be useful for the development of high-efficiency oil recovery systems.

17.
Medicine (Baltimore) ; 98(27): e16351, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277192

RESUMO

RATIONAL: How to manage patients with prostate cancer (PCa) with biochemical recurrence (BCR) following primary curative treatment is a controversial issue. Multiple disciplinary team (MDT) mechanism may propose an appropriate treatment plan for patients and can effectively improve patient prognosis and survival, reduce patient diagnosis and treatment waiting time, and greatly improve patient satisfaction. PATIENT CONCERNS: Here, we presented a case of a 77-year-old man with a persistently elevated serum level of prostate-specific antigen (PSA), who had a history of radical prostatectomy (RP) and of 9 years endocrine therapy. DIAGNOSES: Castration-resistant prostate cancer and locally recurrent prostate cancer. INTERVENTIONS: Androgen-deprivation therapy was first utilized 2 months after RP, due to the consideration of BCR on May 5, 2007. And during the next 9 years, he was treated with different endocrine agents but failed to maintain serum levels of PSA stable. Finally, the MDT suggested patient to perform salvage radiation therapy (SRT). Under MDT mechanism, we avoid secondary surgery, so as to reduce the patients' mental suffering and cost of patient care. OUTCOMES: EPIC26 scale assessment revealed leak-free urine, good urine control, no defecation abnormalities or blood in the stool, no breast tenderness and breast enlargement significantly improved. The patient now has no adjuvant therapy, including endocrine therapy. The patient achieved good prognosis through local RT. LESSONS: Pelvic SRT for patients with locally recurrent PCa may restore the same radical effect as RP. And more importantly, MDT mechanism plays an important role in making the most appropriate decisions for patients.


Assuntos
Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/terapia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/terapia , Idoso , Terapia Combinada , Humanos , Masculino , Prostatectomia , Terapia de Salvação
18.
Int J Mol Sci ; 20(11)2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31146362

RESUMO

BACKGROUND: To investigate the expression of vascular adhesion protein-1 (VAP-1) in joint tissues and serum in symptomatic knee osteoarthritis (SKOA) patients and examine whether VAP-1 levels predict increased risk of disease severity in a cross-sectional study. METHODS: Baseline VAP-1 expression and soluble VAP-1 (sVAP-1) levels were assessed in the synovium synovial fluid and in the serum in cohorts of patients with tibiofemoral medial knee OA and healthy subjects. Standardized fixed-flexion poster anterior knee radiographs scored for Kellgren-Lawrence (KL) grade (0-4) and medial joint space width (JSW). KL1/2 vs. KL3/4 scores defined early and advanced radiographic severity, respectively. Biochemical markers assessed in serum or synovial fluids (SF) comprised sVAP-1, interleukin 1 receptor antagonist (IL-1Ra), interleukin 6 (IL-6), soluble receptor for advanced glycation end-products (sRAGE), C-C motif chemokine ligand 2 (CCL2), C-C motif chemokine ligand 4 (CCL4), cluster of differentiation 163 (CD163), high sensitivity C-reactive protein (hsCRP), and matrix metalloproteinases (MMPs)-1,-3,-9. Associations between biomarkers and radiographic severity KL1/2 vs. KL3/4 (logistic regression controlling for covariates) and pain (Spearman correlation) were evaluated. RESULTS: Elevated levels of sVAP-1 observed in OA synovial fluid and VAP-1 expression in synovium based on immunohistochemical, microarray, and real-time quantitative polymerase chain reaction (qRT-PCR) analyses. However, serum sVAP-1 levels in OA patients were lower than in controls and inversely correlated with pain and inflammation markers (hsCRP and soluble RAGE). Soluble VAP-1 levels in serum were also lower in radiographically advanced (KL3/4) compared with early KL1/2 knee SKOA patients. CONCLUSION: Local (synovial fluid) semicarbazide-sensitive amine oxidase (SSAO)/sVAP-1 levels were elevated in OA and correlated with radiographic severity. However, systemic (serum) sVAP-1 levels were lower in SKOA patients than normal and inversely correlated with pain and inflammation markers. Serum sVAP-1 levels were higher in early (KL1/2) compared with advanced (KL3/4) SKOA patients.

19.
ACS Appl Mater Interfaces ; 11(25): 22878-22884, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31199607

RESUMO

Previous fabrics with directional fluid transport capability typically have a single function to transport liquid. Multifunctional directional fluid fabrics are highly desirable for making "smart" textiles but remain a challenge to develop. In this study, we have for the first time prepared a multifunctional, directional water transport fabric. By using a two-step coating process, we applied polypyrrole (PPy), a conducting polymer, on one side of a hydrophilic fabric (cotton). We showed that the single-side PPy-coated fabrics had reasonable conductivity (surface resistance in the range of 43-54 kΩ/□) and a one-way water transport function. We further showed that by integrating metal-plated nylon wires on the two sides, the fabric can be used as a capacitive sensor to sense water content in the fabric. The conducting layer enables the sensor device to have a sufficient capacitance response. Reasonable integration of the metal electrodes allows the device to have a minimal effect on the directional water transport and breathability of the fabric. Such a novel multifunctional fabric may find applications in making "smart" clothing.

20.
Neural Netw ; 117: 163-178, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31170576

RESUMO

With the rapid development of multimedia technology, massive unlabelled data with high dimensionality need to be processed. As a means of dimensionality reduction, unsupervised feature selection has been widely recognized as an important and challenging pre-step for many machine learning and data mining tasks. Traditional unsupervised feature selection algorithms usually assume that the data instances are identically distributed and there is no dependency between them. However, the data instances are not only associated with high dimensional features but also inherently interconnected with each other. Furthermore, the inevitable noises mixed in data could degenerate the performances of previous methods which perform feature selection in original data space. Without label information, the connection information between data instances can be exploited and could help select relevant features. In this work, we propose a robust unsupervised feature selection method which embeds the latent representation learning into feature selection. Instead of measuring the feature importances in original data space, the feature selection is carried out in the learned latent representation space which is more robust to noises. The latent representation is modelled by non-negative matrix factorization of the affinity matrix which explicitly reflects the relationships of data instances. Meanwhile, the local manifold structure of original data space is preserved by a graph based manifold regularization term in the transformed feature space. An efficient alternating algorithm is developed to optimize the proposed model. Experimental results on eight benchmark datasets demonstrate the effectiveness of the proposed method.

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