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1.
J Immunol ; 203(6): 1436-1446, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31420466

RESUMO

Therapeutic manipulation of regulatory T cells (Tregs) has been regarded as a promising approach for the treatment of immune disorders. However, a better understanding of the immunomodulatory mechanisms of Tregs and new safe and effective methods to improve the therapeutic effects of Tregs are highly desired. In this study, we have identified the key roles of a cAMP-adenosine positive feedback loop in the immunomodulatory function of Tregs. Adult male C57BL/6J mice were used for an experimental autoimmune uveitis (EAU) model, Tregs, and uveitogenic T cells (UTs). In established EAU, induced Tregs (iTregs) administration alleviated the inflammatory response. In vitro, iTregs inhibited UTs proliferation and inflammatory cytokine production. Mechanistically, cAMP is partially responsible for iTreg-mediated inhibition on UTs. Importantly, intracellular cAMP regulates CD39 expression and CD39-dependent adenosine production in iTregs, and cAMP directly participates in iTreg-derived adenosine production by a CD39 signaling-independent extracellular cAMP-adenosine pathway. Moreover, extracellular adenosine increases the intracellular cAMP level in Tregs. More importantly, increasing the cAMP level in iTregs before transfer improves their therapeutic efficacy in established EAU. Notably, the cAMP-adenosine loop exists in both iTregs and naturally occurring Tregs. These findings provide new insights into the immunosuppressive mechanisms of Tregs and suggest a new strategy for improving the therapeutic efficacy of Tregs in established autoimmune disease.

2.
Cell Commun Signal ; 17(1): 86, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358016

RESUMO

OBJECTIVE: This study aimed to investigate the function and mechanism of neddylation of HDAC1 underlying drug resistance of AML cells. METHODS: Evaluation experiments of effects of HDAC1 on drug resistance of AML cells were performed with AML cell transfected with constructs overexpressing HDAC1 or multi-drug resistance AML cells transfected with siRNA for HDAC1 through observing cell viability, percentage of apoptotic cell, doxorubicin-releasing index and multidrug resistance associated protein 1 (MRP1) expression. Neddylation or ubiquitination of HDAC1 was determined by immunoprecipitation or Ni2+ pull down assay followed by western blot. The role of HDAC1 was in vivo confirmed by xenograft in mice. RESULTS: HDAC1 was significantly upregulated in refractory AML patients, and in drug-resistant AML cells (HL-60/ADM and K562/A02). Intracellular HDAC1 expression promoted doxorubicin resistance of HL-60, K562, and primary bone marrow cells (BMCs) of remission AML patients as shown by increasing cell viability and doxorubicin-releasing index, inhibiting cell apoptosis. Moreover, HDAC1 protein level in AML cells was regulated by the Nedd8-mediated neddylation and ubiquitination, which further promoted HDAC1 degradation. In vivo, HDAC1 overexpression significantly increased doxorubicin resistance; while HDACs inhibitor Panobinostat markedly improved the inhibitory effect of doxorubicin on tumor growth. Furthermore, HDAC1 silencing by Panobinostat and/or lentivirus mediated RNA interference against HDAC1 effectively reduced doxorubicin resistance, resulting in the inhibition of tumor growth in AML bearing mice. CONCLUSION: Our findings suggested that HDAC1 contributed to the multidrug resistance of AML and its function turnover was regulated, at least in part, by post-translational modifications, including neddylation and ubiquitination.

3.
Arch Oral Biol ; 105: 5-12, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31203086

RESUMO

Alzheimer's disease (AD) is becoming a threat to aging population all over the world. The pathogenic process of AD is likely initiated many years before clinical onset, thus biomarkers for AD diagnosis are critical for the prevention and therapy for the disease at the early stage in order to reduce the global burden brought by the disease. Saliva is treated as a potential alternative and universal diagnostic fluid that can be collected noninvasively by participants with moderate training and without side effects. Several potential salivary biomarkers, which might prove to be significant diagnostic tools in AD, have been researched. We address here the present and the future of these salivary biological biomarkers for AD.

4.
Environ Pollut ; 250: 998-1009, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31085487

RESUMO

Regional specification of PM2.5 pollution characteristics is crucial for pollution control and policymaking. Spatiotemporal variations of six criteria air pollutants and influencing factors in China were studied using hourly concentrations of PM2.5, PM10, SO2, NO2, CO, and O3 from 2015 to 2016. China was categorized into eight regions: north-east, northern coastland, eastern coastland, southern coastland, Yellow River middle reaches, Yangtze River middle reaches, south-west, and north-west. The 29 exemplary cities in China were also researched. It was found that the PM2.5 concentration in the northern coastland (Beijing-Tianjin-Hebei-Shandong) was the highest (72.28 µg.m-3) among the eight regions, particularly in the city of Baoding, Hebei, which had an annual average PM2.5 concentration of 98.53 µg.m-3. Average PM2.5 concentrations in 2015 and 2016 of China were 50.16 µg.m-3 and 46.61 µg.m-3, respectively. Compared with 2015, the PM2.5 concentration decreased by 8.41% in 2016, the decline of PM2.5 in summer was the largest, followed by autumn, spring and winter. The average mean PM2.5 concentrations of the 29 exemplary cities in 2015 and 2016 were 54.66 µg.m-3 and 48.37 µg.m-3, respectively, exceeding the limit for grade 2 of the national standards (35 µg.m-3). National air pollution distribution has exploded geographically with influence of regional economic factors. Gaseous pollutant as well as geographical and socio-economic conditions influenced PM2.5 emissions. Effects of these factors on PM2.5 emissions varied across regions and decreased continuously from the northern region to the south-west and eastern coastland regions. This paper clearly identifies the regional characteristics and distribution of PM2.5, focusing on the effects of gaseous pollutant, geography and socio-economic development. Secondary transformation and vehicle exhaust across regions should be further studied.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/análise , Monitoramento Ambiental/métodos , Gases/análise , Material Particulado/análise , Emissões de Veículos/análise , Pequim , China , Cidades , Rios/química , Estações do Ano , Fatores Socioeconômicos
5.
Mol Ecol Resour ; 19(4): 1037-1051, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31012219

RESUMO

Sequence capture across large phylogenetic scales is not easy because hybridization capture is only effective when the genetic distance between the bait and target is small. Here, we propose a simple but effective strategy to tackle this issue: pooling DNA from a number of selected representative species of different clades to prepare PCR-generated baits to minimize the genetic distance between the bait and target. To demonstrate the utility of this strategy, we newly developed a set of universal nuclear markers (including 94 nuclear protein-coding genes) for Lepidoptera, a superdiverse insect group. We used a DNA pool from six lepidopteran species (representing six superfamilies) to prepare PCR baits for the 94 markers. These homemade PCR baits were used to capture sequence data from 43 species of 17 lepidopteran families, and 94% of the target loci were recovered. We constructed two data sets from the obtained data (one containing ~90 kb target coding sequences and the other containing ~120 kb target + flanking coding sequences). Both data sets yielded highly similar and well-resolved trees with 90% of nodes having >95% bootstrap support. Our capture experiment indicated that using DNA mixtures pooled from different clade-representative species of Lepidoptera to prepare PCR baits can reliably capture a large number of targeted nuclear markers across different Lepidoptera lineages. We hope that this newly developed nuclear marker set will serve as a new phylogenetic tool for Lepidoptera phylogenetics, and the PCR bait preparation strategy can facilitate the application of sequence capture techniques by researchers to accelerate data collection.


Assuntos
Lepidópteros/classificação , Lepidópteros/genética , Hibridização de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNA/métodos , Animais , Filogenia
6.
J Rheumatol ; 46(8): 912-919, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30824650

RESUMO

OBJECTIVE: To assess how the longterm outcomes have changed over the past decades in Chinese patients with lupus nephritis (LN). The trends in patient manifestation at presentation, treatment pattern, and therapeutic effects were evaluated. METHODS: A cohort of biopsy-proven patients with LN (n = 1945) from January 1994 to December 2010 was analyzed. Treatment regimens, treatment response, renal relapse, and renal outcome were compared at different time periods (1994-1998, 1999-2004, and 2005-2010). RESULTS: Patients in the later periods had shorter duration of disease, lower serum creatinine value and chronicity at biopsy, and more frequent followup. They were more likely to receive standard-of-care therapies, which included cyclophosphamide, mycophenolate mofetil, and combination therapy. Patients in the later periods had higher probabilities of achieving remission (p < 0.001) and lower probabilities of experiencing renal flare (p = 0.007). The 5-year renal survival rates were 92.6%, 90.6%, and 94.3% in 1994-1998, 1999-2004, and 2005-2010, respectively. The 5-year risk of endstage renal disease (ESRD) did not differ between 1994-1998 and 1999-2004, but was significantly lower in 2005-2010 (HR 0.40, 95% CI 0.19-0.85 vs 1999-2004). In multivariable Cox analysis, standard therapy was independently associated with lower risk of ESRD (adjusted HR 0.72, 95% CI 0.52-0.98, p = 0.04). Variables of renal damage at biopsy (renal function, activity index, and chronicity index) were independently associated with poor outcome. CONCLUSION: The outcomes of Chinese patients with LN have improved from 1994 to 2010. With the increased use of standard therapies, the remission rates have increased and renal relapse has decreased.

7.
J Pharm Biomed Anal ; 169: 1-10, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30826486

RESUMO

There is an increasing focus on the quality consistency evaluation of dispensing granule in traditional Chinese medicines (TCMs). According to the guideline from Chinese Pharmacopoeia Commission, the substantial equivalence of dispensing granule and traditional decoction should be determined, and the chromatographic fingerprint has been recommended as a comprehensive qualitative approach to assess the quality consistency between dispensing granule and traditional decoction. However, a high-degree chemical similarity does not equal a bioequivalence. Attempting to realize the quality evaluation by integrating chemical consistency and bioequivalence, we herein proposed a totality-of-the-evidence approach based on clustering analysis and equivalence evaluation taking the dispensing granule and traditional decoction of Scutellariae Radix (SR) as a typical case. Chemical fingerprints were developed by high performance liquid chromatography coupled with photodiode array detector and quadrupole time-of-flight mass spectrometry (HPLC-PDA/QTOF-MS). Subsequently, a feature selection strategy, integrated linear and nonlinear correlation analysis, was carried out to assess the correlation between chemical profiles and biological activities. Finally, quality consistency between the dispensing granule and the traditional decoction was determined by bioactive marker-guided hierarchical clustering analysis (HCA), k-means clustering method and bioequivalence evaluation. The available evidence suggested that not all the dispensing granule of SR were sufficiently similar to the traditional decoction. This study provides an applicable methodology for quality consistency evaluation of dispensing granule and traditional decoction in TCMs.


Assuntos
Medicamentos de Ervas Chinesas/química , Scutellaria baicalensis/química , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Medicina Tradicional Chinesa/métodos , Projetos Piloto , Equivalência Terapêutica
8.
Angiogenesis ; 22(3): 369-382, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30644010

RESUMO

Retinopathy of prematurity (ROP) with pathological retinal neovascularization is the most common cause of blindness in children. ROP is currently treated with laser therapy or cryotherapy, both of which may adversely affect the peripheral vision with limited efficacy. Owing to the susceptibility of the developing retina and vasculatures to pharmacological intervention, there is currently no approved drug therapy for ROP in preterm infants. Secretogranin III (Scg3) was recently discovered as a highly disease-restricted angiogenic factor, and a Scg3-neutralizing monoclonal antibody (mAb) was reported with high efficacy to alleviate oxygen-induced retinopathy (OIR) in mice, a surrogate model of ROP. Herein we independently investigated the efficacy of anti-Scg3 mAb in OIR mice and characterized its safety in neonatal mice. We developed a new Scg3-neutralizing mAb recognizing a distinct epitope and independently established the therapeutic activity of anti-Scg3 therapy to alleviate OIR-induced pathological retinal neovascularization in mice. Importantly, anti-Scg3 mAb showed no detectable adverse effects on electroretinography and developing retinal vasculature. Furthermore, systemic anti-Scg3 mAb induced no renal tubular injury or abnormality in kidney vessel development and body weight gain of neonatal mice. In contrast, anti-vascular endothelial growth factor drug aflibercept showed significant side effects in neonatal mice. These results suggest that anti-Scg3 mAb may have the safety and efficacy profiles required for ROP therapy.

9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(6): 1742-1745, 2018 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-30501714

RESUMO

OBJECTIVE: To explore the role and the mechanism of NLRP3 inflammasome in children's immune thrombocytopenia (ITP). METHODS: Twenty-one children suffered from ITP were enrolled in ITP group, 10 healthy children were selected in control group. Peripheral blood mononuclear cells (PBMNC) were isolated from ITP children and healthy controls. The mRNA levels of NLRP3, ASC, and Caspase-1 in PBMNCs were measured by quantitative real-time PCR. Moreover, the protein level of NLRP3 in PBMNCs was detected by Western blot. The plasma IL-18 level was detected by ELISA. RESULTS: The expression level of NLRP3, ASC and Caspase-1 mRNA in newly-diagnosed ITP children was dramatically higher than that in control. The plasma IL-18 level was higher than that in healthy control. Furthermore, the level of NLRP3 protein was up-regulated in ITP children. CONCLUSION: The NLRP3 inflammasome and up-regulated level of IL-18 have been found in newlydiagnosed ITP patients, and they may involve in the pathogenesis of ITP.

10.
J Ren Nutr ; 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30446269

RESUMO

OBJECTIVE(S): To explore the validity of using bioelectrical impedance analysis (BIA)-derived 50 kHz phase angle (PhA) in predicting protein-energy wasting (PEW) in Chinese maintenance hemodialysis (MHD) patients. DESIGN AND METHODS: The design was a cross-sectional study. A total of 173 of MHD patients and 173 healthy adults were enrolled in the study. The prevalence of PEW in patients was performed by the International Society of Renal Nutrition and Metabolism criteria. The PhA, body cell mass, fat mass, body fat percentage, fat-free mass, and extracellular water/total body water were measured by InBody S10 body composition analyzer. The biochemical indices and anthropometric measurements were assessed using the way published elsewhere. The PhA, other values of BIA and its relationship with age, visceral protein, anthropometric measurements of the MHD patients were compared with the healthy group. The independent variables for predicting PEW and its cutoff values were explored using logistic regression model and receiver operating characteristic curve analysis, respectively. RESULTS: The MHD patients' PhA value was significantly lower than the healthy group (4.89°± 1.19 vs. 6.32°± 2.23, P < .01). A total of 34.1% MHD patients with PEW had significantly lower PhA values compared with well-nourished patients (P < .05). The PhA decreased more significantly with age in MHD (r = -0.35, P < .001), compared with controls (r = -0.26, P < .001). The PhA values were positively associated with nutritional indices related to serum albumin, prealbumin, fat-free mass, and mid-arm muscle circumference. PhA values were not associated significantly with fat mass and body fat percentage (P > .05). Multivariate logistic regression analysis showed that PhA and body mass index were independent predictors of PEW, but the PhA was the stronger predictor (odds ratio = 4.48, P < .05). Receiver operating characteristic curve analysis suggested that the optimal PhA cutoff value to predict PEW was 4.6°. CONCLUSIONS: BIA-derived PhA appears to be a useful bioelectrical marker for predicting PEW in Chinese hemodialysis patients with a cutoff value of 4.6°.

11.
Ecol Evol ; 8(18): 9526-9535, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30377520

RESUMO

The pace-of-life hypothesis predicts no impact of urbanization on stress responses. Accordingly, several studies have been inconsistent in showing differences in breath rate (BR), a proxy of acute stress responses to handling in passerines, between rural and urban areas. However, this evidence is limited to a single bird species and a limited geographic region (SW Europe). No study addressed whether this pattern is also apparent in other species or regions, such as in tropical environments, or whether it is dependent on the level of diet specialization, given that diet restriction and change influence stress responses. Here, we tested whether there were differences in BR between habitats and diet groups using eight highly diverse passerine assemblages experiencing different levels of anthropogenic disturbance (i.e., natural, rural, and urban locations) in SW China. We predicted that insectivores and herbivores (frugivores, nectarivores, and seed-eating species) would show higher BR than omnivores. We also predicted no differences in BR among habitat types. BR was a moderately repeatable trait, which showed a negative relationship with body mass and a positive relationship with the time of the day. We also recorded a relatively strong phylogenetic bias in the expression of this trait. Confirming our predictions, our results showed no differences in BR among natural, rural, and urban locations. Similarly, within species, there were no differences in BR between rural and urban locations. However, we also found that herbivores showed higher BR than omnivores. Overall, our results provide support to the pace-of-life hypothesis, but suggest acute stress responses can be diet-mediated, which may help to explain the marked decline of specialized trophic guilds around the world in response to anthropogenic disturbance.

12.
Stem Cell Res Ther ; 9(1): 304, 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30409188

RESUMO

BACKGROUND: Autologous urothelial cells are often obtained via bladder biopsy to generate the bio-engineered urethra or bladder, while urine-derived stem cells (USC) can be obtained by a non-invasive approach. The objective of this study is to develop an optimal strategy for urothelium with permeability barrier properties using human USC which could be used for tissue repair in the urinary tract system. METHODS: USC were harvested from six healthy adult individuals. To optimize urothelial differentiation, five different differentiation methods were studied. The induced cells were assessed for gene and protein expression markers of urothelial cells via RT-PCR, Western blotting, and immunofluorescent staining. Barrier function and ultrastructure of the tight junction were assessed with permeability assays and transmission electron microscopy (TEM). Induced cells were both cultured on trans-well membranes and small intestinal submucosa, then investigated under histology analysis. RESULTS: Differentiated USC expressed significantly higher levels of urothelial-specific transcripts and proteins (Uroplakin III and Ia), epithelial cell markers (CK20 and AE1/AE3), and tight junction markers (ZO-1, ZO-2, E-cadherin, and Cingulin) in a time-dependent manner, compared to non-induced USC. In vitro assays using fluorescent dye demonstrated a significant reduction in permeability of differentiated USC. In addition, transmission electron microscopy confirmed appropriate ultrastructure of urothelium differentiated from USC, including tight junction formation between neighboring cells, which was similar to positive controls. Furthermore, multilayered urothelial tissues formed 2 weeks after USC were differentiated on intestine submucosal matrix. CONCLUSION: The present study illustrates an optimal strategy for the generation of differentiated urothelium from stem cells isolated from the urine. The induced urothelium is phenotypically and functionally like native urothelium and has proposed uses in in vivo urological tissue repair or in vitro urethra or bladder modeling.

13.
Infect Dis Poverty ; 7(1): 97, 2018 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-30305184

RESUMO

BACKGROUND: In China since the first human infection of avian influenza A (H7N9) virus was identified in 2013, it has caused serious public health concerns due to its wide spread and high mortality rate. Evidence shows that bird migration plays an essential role in global spread of avian influenza viruses. Accordingly, in this paper, we aim to identify key bird species and geographical hotspots that are relevant to the transmission of avian influenza A (H7N9) virus in China. METHODS: We first conducted phylogenetic analysis on 626 viral sequences of avian influenza A (H7N9) virus isolated in chicken, which were collected from the Global Initiative on Sharing All Influenza Data (GISAID), to reveal geographical spread and molecular evolution of the virus in China. Then, we adopted the cross correlation function (CCF) to explore the relationship between the identified influenza A (H7N9) cases and the spatiotemporal distribution of migratory birds. Here, the spatiotemporal distribution of bird species was generated based on bird observation data collected from China Bird Reports, which consists of 157 272 observation records about 1145 bird species. Finally, we employed a kernel density estimator to identify geographical hotspots of bird habitat/stopover that are relevant to the influenza A (H7N9) infections. RESULTS: Phylogenetic analysis reveals the evolutionary and geographical patterns of influenza A (H7N9) infections, where cases in the same or nearby municipality/provinces are clustered together with small evolutionary differences. Moreover, three epidemic waves in chicken along the East Asian-Australasian flyway in China are distinguished from the phylogenetic tree. The CCF analysis identifies possible migratory bird species that are relevant to the influenza A(H7N9) infections in Shanghai, Jiangsu, Zhejiang, Fujian, Jiangxi, and Guangdong in China, where the six municipality/provinces account for 91.2% of the total number of isolated H7N9 cases in chicken in GISAID. Based on the spatial distribution of identified bird species, geographical hotspots are further estimated and illustrated within these typical municipality/provinces. CONCLUSIONS: In this paper, we have identified key bird species and geographical hotspots that are relevant to the spread of influenza A (H7N9) virus. The results and findings could provide sentinel signal and evidence for active surveillance, as well as strategic control of influenza A (H7N9) transmission in China.

14.
BMC Evol Biol ; 18(1): 134, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-30180795

RESUMO

BACKGROUND: While the communities constituted by phytophageous insects and their parasites may represent half of all terrestrial animal species, understanding their diversification remains a major challenge. A neglected idea is that geographic phenotypic variation in a host plant may lead to heterogeneous evolutionary responses of the different members of the associated communities. This could result in diversification on a host plant by ecological speciation in some species, leading to geographic variation in community composition. In this study we investigated geographic variation of inflorescence receptacle size in a plant, Ficus hirta, and how the hymenopteran community feeding in the inflorescences has responded. Our predictions were: 1) Inflorescence size variation affects wasp species differently depending on how they access oviposition sites. 2) In some affected lineages of wasps, we may observe vicariant, parapatric species adapted to different inflorescence sizes. RESULTS: We show that fig (the enclosed inflorescence of Ficus) wall thickness varies geographically. The fig-entering pollinating wasp was not affected, while the parasites ovipositing through the fig wall were. Two parapatric species of Philotrypesis, exhibiting strikingly different ovipositor lengths, were recorded. One species of Sycoscapter was also present, and it was restricted, like the shorter-ovipositor Philotrypesis, to the geographic zone where fig walls were thinner. CONCLUSIONS: Previous work on fig wasps suggested that parapatric geographic ranges among congenerics were due to adaptation to variation in abiotic factors, complemented by interspecific competition. Our results show that parapatric ranges may also result from adaptation to variation in biotic factors. Within an insect community, differences among species in their response to geographic phenotypic variation of their host plant may result in geographically heterogeneous community structure. Such heterogeneity leads to heterogeneous interaction networks among sites. Our results support the hypothesis that plant geographic phenotypic variation can be a driver of diversification in associated insect communities, and can complement other diversification processes.


Assuntos
Variação Biológica da População , Ficus/parasitologia , Geografia , Parasitos/fisiologia , Vespas/fisiologia , Vespas/parasitologia , Animais , Feminino , Ficus/anatomia & histologia , Ficus/genética , Inflorescência/anatomia & histologia , Inflorescência/fisiologia , Repetições de Microssatélites/genética , Oviposição/fisiologia , Polinização , Tamanho da Amostra
15.
Protein Pept Lett ; 25(9): 830-837, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30182833

RESUMO

BACKGROUND: During recent years, a lot of experimental studies have shown that lncRNA-binding proteins play a key role in many biomedical processes. Therefore, it is important to predict the potential lncRNA-protein associations in biomedical researches. OBJECTIVE: To predict the associations between lncRNAs and proteins more reliably and more efficiently. METHOD: Considering the limitations of previous computational methods, we introduce a predictive model called Random Walk for lncRNA-Protein Associations Prediction (RWLPAP). It belongs to semi-supervised learning algorithms, and thus RWLPAP successfully avoids the difficulty of extracting negative data sets and features. RESULTS: By the leave-one-out cross validation, we compare RWLPAP with previous methods and conclude that RWLPAP has an AUC of 0.88, which is significantly higher than other three models. It suggests that RWLPAP is more reliable and effective in predicting the interactions between lncRNAs and proteins. CONCLUSION: In the case study, according to the rank of predictive scores, we can find that the scores of some lncRNA-protein associations are highly ranking by our method when is compared with other three methods. It indicates that our method is very effective and comprehensive. Therefore, we can expect that RWLPAP will be a useful bioinformatic tool in the future.

16.
Invest Ophthalmol Vis Sci ; 59(10): 3952-3962, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30073366

RESUMO

Purpose: To explore the roles of hemin in preventing corneal allograft rejection (CGR) and the underlying mechanisms. Methods: Hemin (30 mg/kg) was intraperitoneally injected into rats with a corneal allograft on alternate days, from the day of transplantation until euthanasia. The clinical signs of the corneal allografts were evaluated and recorded according to a previously published system. Corneal edema, macrophage infiltration, and phenotype, and the expression of chemokines, cytokines, and heme oxygenase (HO)-1 were detected by histology, real-time PCR, and Western blot. The rat macrophage cell line NR8383 was used to explore the mechanisms of action of hemin in vitro. Results: Treatment with hemin significantly prolonged corneal allograft survival, with decreased corneal edema and fewer macrophages. Moreover, hemin treatment alleviated inflammation in the corneal grafts, as characterized by downregulated mRNA levels of proinflammatory mediators. In addition, hemin administration reduced the proportion of proinflammatory M1 macrophages and increased the proportion of anti-inflammatory M2 macrophages in the corneal grafts. Hemin treatment induced HO-1 expression in vivo and in vitro, whereas co-administration of zinc protoporphyrin IX (ZnPP), an HO-1 inhibitor, blocked the beneficial effects of hemin in preventing CGR. Conclusions: Our results are the first to demonstrate that hemin, a Food and Drug Administration-approved drug, promotes corneal allograft survival. These findings indicate that hemin might be a potential alternative treatment for CGR.

18.
Biochem Pharmacol ; 154: 18-27, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29656117

RESUMO

Autoimmune uveitis is a sight-threatening ocular inflammatory disorder. Immunological inflammation is regarded as the key to pathogenesis in autoimmune uveitis. Baicalin, the major bioactive component of Scutellaria baicalensis, possesses immunomodulatory properties. However, the role of baicalin in uveitis and its underlying mechanisms remain unclear. In the current study, we found that baicalin treatment obviously inhibited the intraocular inflammatory process in mice with experimental autoimmune uveitis, along with clear declines in infiltrated inflammatory cells and inflammatory cytokine transcription in the retina and draining lymph nodes. Furthermore, baicalin treatment increased the frequency and number of regulatory T cells and decreased the frequency and number of effector T cells (Th1 and Th17 cells) in the draining lymph nodes of mice with experimental autoimmune uveitis. In vitro, baicalin treatment suppressed interphotoreceptor retinoid binding protein-specific CD4+ T cell proliferation and converted CD4+ T cell differentiation. Furthermore, the expression of aryl hydrocarbon receptor was activated by baicalin treatment. Baicalin-mediated modulation of CD4+ T cell differentiation was partially abrogated by the suppression of aryl hydrocarbon receptor. These findings suggest that baicalin modulates the Treg/Teff balance and CD4+ T cell proliferation to ameliorate experimental autoimmune uveitis by activating the aryl hydrocarbon receptor.

19.
Kidney Blood Press Res ; 43(2): 500-512, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29627824

RESUMO

BACKGROUND/AIMS: Evidence from our and other groups has demonstrated that zinc transporter 7 in SLC30 family (ZnT7) inhibited epithelial-to-mesenchymal transition (EMT) and apoptosis in rat peritoneal mesothelial cells (RPMCs) under high glucose (HG) concentration. In the present study, we investigated the effect of ZnT7 on EMT of renal tubular epithelial cells (RTECs) in an in vitro model of diabetic nephropathy (DN). METHODS: A dual-fluorescent staining protocol was used for detection of ZnT7 in a normal rat kidney tubular epithelial cell line (NRK-52E cells). EMT was induced with HG (30 mM). NRK-52E cells were transfected with plasmids codifying for hZnT7-EGFP and interfering RNA for determination of the effect of ZnT7 over-expression and silencing, respectively. Expression of ZnT7, activation of the MAPK/ERK and TGF-ß/Smad pathways were analyzed with by means of Western blot. RESULTS: ZnT7 was localized in the perinuclear region and Golgi apparatus. In HG-induced EMT of NRK-52E cells, ZnT7 was up-regulated. Over-expression of ZnT7 led to inhibition of HG-induced EMT, while knock-down of ZnT7 increased EMT. Furthermore, knock-down of ZnT7 and increased HG-induced EMT was accompanied by activation of the MAPK/ERK and TGF-ß/Smad pathways. CONCLUSION: The present study provides evidence that ZnT7 has a protective effect over EMT of RTECs in DN and suggests that the inhibition of HG-induced EMT may be achieved through the MAPK/ERK and TGF-ß/Smad pathways. Thereby, ZnT7 could be a potential target for translation medicine and prevention program in DN.


Assuntos
Proteínas de Transporte de Cátions/farmacologia , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glucose/farmacologia , Túbulos Renais Proximais/citologia , Animais , Proteínas de Transporte de Cátions/análise , Proteínas de Transporte de Cátions/uso terapêutico , Linhagem Celular , Nefropatias Diabéticas , Sistema de Sinalização das MAP Quinases , Ratos , Proteínas Smad/metabolismo , Transfecção , Fator de Crescimento Transformador beta/metabolismo
20.
Mol Med Rep ; 17(6): 8269-8281, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29658611

RESUMO

Smoking is a risk factor associated with bone and oral diseases, particularly periodontitis. Nicotine, the major toxic component of tobacco, is able to affect the quality and quantity of bone. Osteoblasts serve an important role in bone formation. Thus far, the effects of nicotine on metabolism­associated gene and protein expression in osteoblasts have been controversial and the mechanisms remain unclear. The present study assessed alterations in osteogenic activity by performing a Cell Counting kit­8 assay to investigate proliferation, Annexin V­fluorescein isothiocyanate/propidium iodide staining to investigate apoptosis, alizarin red staining to investigate the formation of mineralized nodules, reverse transcription­quantitative polymerase chain reaction and western blotting to investigate the mRNA and protein levels of collagen I, alkaline phosphatase, bone osteocalcin, bone sialoprotein and osteopontin; and mRNA microarray expression analysis, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis to investigate the whole genome expression profile of Sprague­Dawley (SD) rat primary osteoblasts following treatment with different concentrations of nicotine. The results demonstrated that nicotine inhibited proliferation, promoted early apoptosis and inhibited mineralized nodule formation in a dose­dependent manner by regulating alkaline phosphatase activity and the expression of osteoblast metabolism­associated genes and proteins. According to microarray analysis, several genes associated with bone metabolism and genes in the Hedgehog and Notch signaling pathways were downregulated significantly in nicotine­treated osteoblasts. The results of the present study indicated that nicotine may serve an inhibitory, dose­dependent role in SD rat primary osteoblasts that may be caused by the perturbation of genes and signaling pathways associated with bone formation. These results may provide a theoretical basis for future research regarding bone metabolism and targeted treatment of oral diseases associated with smoking.


Assuntos
Metabolismo Energético/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Nicotina/farmacologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Transcriptoma , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Biomarcadores , Proliferação de Células/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
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