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1.
BMC Med Imaging ; 20(1): 30, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183731

RESUMO

BACKGROUND: Osteoporosis (OP) is a systemic metabolic bone disorder identified as an essential health issue worldwide. Orthopedic imaging approaches were commonly used with some limitations. Thus, our study aimed to investigate the diagnostic value of magnetic resonance spectroscopy (1-H MRS) and m-Dixon-Quant in OP. METHODS: A total of 76 subjects were enrolled in the study and bone mineral density (BMD) was measured using quantitative computed tomography (QCT). Then, the subjects were divided into three groups according to BMD: normal control group, osteopenia group and OP group. The following parameters were recorded for each patient: gender, age, height, body weight, waist circumference, and hip circumference. Further, the fat fraction percentage (FF%) values were determined by 1-H MRS and m-Dixon-Quant methods. RESULTS: In both 1-H MRS and magnetic resonance Imaging (MRI) m-Dixon-Quant, the FF% exhibited a negative correlation with BMD (P < 0.05). The FF% value of the OP group was significantly higher than that of the control group (P < 0.05). In addition, the FF% value in the m-Dixon scans was positively related to age, while BMD showed a negative linear relationship with age (P < 0.0001). Further, females had a significantly higher FF% value compared to males (P < 0.01), and height was correlated with BMD (P < 0.05) but not with FF% (P > 0.05). CONCLUSIONS: MRI investigations especially FF% value in the m-Dixon-Quant imaging system is correlated with OP. Its diagnostic value remains to be demonstrated on a large prospective cohort of patients. Besides, parameters such as age, gender, and height are important factors for predicting and diagnosing OP.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31987928

RESUMO

BACKGROUND & AIMS: Alcohol abuse is the major cause of experimental and human pancreatitis but the molecular mechanisms remain largely unknown. We investigated the role of transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, in the pathogenesis of alcoholic pancreatitis. METHODS: Using a chronic plus acute alcohol binge (referred to as Gao-binge) mouse model, we analyzed pancreas injury, autophagic flux, zymogen granule removal, TFEB nuclear translocation and lysosomal biogenesis in GFP-LC3 transgenic mice, acinar cell-specific Atg5 knockout (KO) and TFEB KO mice as well as their matched wild type mice. RESULTS: We found that Gao-binge alcohol induced typical features of pancreatitis in mice with increased serum amylase and lipase activities, pancreatic edema, infiltration of inflammatory cells, accumulation of zymogen granules (ZGs) and expression of inflammatory cytokines. While Gao-binge alcohol increased the number of autophagosomes, it also concurrently inhibited TFEB nuclear translocation and TFEB-mediated lysosomal biogenesis resulting in insufficient autophagy. Acinar cell-specific Atg5 KO and acinar cell-specific TFEB KO mice developed severe inflammatory and fibrotic pancreatitis in both Gao-binge alcohol and control diet-fed mice. In contrast, TFEB overexpression inhibited alcohol-induced pancreatic edema, accumulation of zymogen granules and serum amylase and lipase activities. In line with our findings in mice, decreased LAMP1 and TFEB nuclear staining were also observed in human alcoholic pancreatitis tissues. CONCLUSIONS: our results indicate that TFEB plays a critical role in maintaining pancreatic acinar cell homeostasis. Impairment of TFEB-mediated lysosomal biogenesis by alcohol may lead to insufficient autophagy and promote alcohol-induced pancreatitis.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31794395

RESUMO

Intravascular ultrasound (IVUS) is one of the most useful tools available today to assist intravascular stenting procedures. Having higher resolution is very important for helping doctors to evaluate the nature of atherosclerosis plaques. Current commercial IVUS systems have a spatial resolution of 70-200 µm in axial direction and 200-400 µm in lateral direction, which are insufficient for accurate diagnosis. We report here a three-matching-layer design IVUS transducer using 0.72Pb(Mg1/3Nb2/3)O3 0.28PbTiO3 single crystal, which can improve the axial resolution to 40 µm without sacrificing the penetration depth. Wire phantom imaging and in vitro porcine coronary artery imaging show noticeably better axial resolution and similar penetration depth compared to that of a commercial IVUS transducer.

4.
BMC Plant Biol ; 19(1): 379, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455203

RESUMO

BACKGROUND: Metabolic pathways are interconnected and yet relatively independent. Genes involved in metabolic modules are required for the modules to run. Study of the relationships between genes and metabolic modules improves the understanding of metabolic pathways in plants. The WIN transcription factor activates the cuticle biosynthesis pathway and promotes cuticle biosynthesis. The relationship between the WIN transcription factor and other metabolic pathways is unknown. Our aim was to determine the relationships between the main genes involved in cuticle biosynthesis and those involved in other metabolic pathways. We did this by cloning a cotton WIN gene, GhWIN2, and studying its influence on other pathways. RESULTS: As with other WIN genes, GhWIN2 regulated expression of cuticle biosynthesis-related genes, and promoted cuticle formation. Silencing of GhWIN2 resulted in enhanced resistance to Verticillium dahliae, caused by increased content of salicylic acid (SA). Moreover, silencing of GhWIN2 suppressed expression of jasmonic acid (JA) biosynthesis-related genes and content. GhWIN2 positively regulated the fatty acid biosynthesis pathway upstream of the JA biosynthesis pathway. Silencing of GhWIN2 reduced the content of stearic acid, a JA biosynthesis precursor. CONCLUSIONS: GhWIN2 not only regulated the cuticle biosynthesis pathway, but also positively influenced JA biosynthesis and negatively influenced SA biosynthesis.


Assuntos
Ciclopentanos/metabolismo , Gossypium/genética , Oxilipinas/metabolismo , Doenças das Plantas/genética , Proteínas de Plantas/genética , Ácido Salicílico/metabolismo , Verticillium/fisiologia , Sequência de Aminoácidos , Resistência à Doença/genética , Gossypium/metabolismo , Gossypium/microbiologia , Reguladores de Crescimento de Planta/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Alinhamento de Sequência
6.
Plant Sci ; 284: 127-134, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31084865

RESUMO

Avr9/Cf-9-INDUCED F-BOX1 (ACIF1) was first identified during screening of Avr9/Cf-9-elicited genes in tobacco. Further analysis revealed that ACIF1 was required for hypersensitive responses triggered by various elicitors in tobacco and tomato, indicating that it may be involved in various disease resistance. Here, we cloned its cotton (Gossypium hirsutum) homolog GhACIF1, which encodes an F-box protein. We show that GhACIF1 interacts with the putative SKP1-like protein, named GhSKP1. Disease resistance assays show that GhACIF1 enhances resistance to Verticillium dahliae in Arabidopsis plants, while silencing of GhACIF1 confers sensitivity to V. dahliae in cotton. Further analysis show that PevD1 elicitor activates hypersensitive and acquired immune response mediated by GhACIF1. Collectively, these results indicate that GhACIF1 contributes to protection against V. dahliae infection.


Assuntos
Resistência à Doença , Proteínas F-Box/fisiologia , Gossypium/imunologia , Doenças das Plantas/microbiologia , Proteínas de Plantas/fisiologia , Verticillium , Resistência à Doença/fisiologia , Proteínas F-Box/genética , Inativação Gênica , Gossypium/genética , Gossypium/microbiologia , Doenças das Plantas/imunologia , Reguladores de Crescimento de Planta/metabolismo , Proteínas de Plantas/genética , Ácido Salicílico/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNA , Técnicas do Sistema de Duplo-Híbrido , Verticillium/metabolismo
7.
Mol Pharm ; 16(5): 2199-2213, 2019 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-30974945

RESUMO

Tumor targeting agents are being developed for early tumor detection and therapeutics. We previously identified the peptide SNFYMPL (SNF*) and demonstrated its specific binding to human esophageal specimens of high-grade dysplasia (HGD) and adenocarcinoma with imaging ex vivo. Here, we aim to identify the target for this peptide and investigate its potential applications in imaging and drug delivery. With SNF* conjugated affinity chromatography, mass spectrum, Western blot, enzyme-linked immunosorbent assay (ELISA), and molecular docking, we found that the epithelial cell adhesion molecule (EpCAM) was the potential target of SNF*. Next, we showed that FITC-labeled SNF* (SNF*-FITC) colocalized with EpCAM antibody on the surface of esophageal adenocarcinoma cells OE33, and SNF*-FITC binding patterns significantly changed after EpCAM knockdown or exogenous EpCAM transfection. With the data from TCGA, we demonstrated that EpCAM was overexpressed in 17 types of cancers. Using colon and gastric adenocarcinoma cells and tissues as examples, we found that SNF*-FITC bound in a pattern was colocalized with EpCAM antibody, and the SNF* binding did not upregulate the EpCAM downstream Wnt signals. Subsequently, we conjugated SNF* with our previously constructed poly(histidine)-PEG/DSPE copolymer micelles. SNF* labeling significantly improved the micelle binding with colon and gastric adenocarcinoma cells in vitro, and enhanced the antitumor effects and decreased the toxicities of the micelles in vivo. In conclusion, we identified and validated SNF* as a specific peptide for EpCAM. The future potential use of SNF* peptide in multiple tumor surveillance and tumor-targeted therapeutics was demonstrated.

8.
Redox Biol ; 22: 101148, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30818124

RESUMO

Mitochondria damage plays a critical role in acetaminophen (APAP)-induced necrosis and liver injury. Cells can adapt and protect themselves by removing damaged mitochondria via mitophagy. PINK1-Parkin pathway is one of the major pathways that regulate mitophagy but its role in APAP-induced liver injury is still elusive. We investigated the role of PINK1-Parkin pathway in hepatocyte mitophagy in APAP-induced liver injury in mice. Wild-type (WT), PINK1 knockout (KO), Parkin KO, and PINK1 and Parkin double KO (DKO) mice were treated with APAP for different time points. Liver injury was determined by measuring serum alanine aminotransferase (ALT) activity, H&E staining as well as TUNEL staining of liver tissues. Tandem fluorescent-tagged inner mitochondrial membrane protein Cox8 (Cox8-GFP-mCherry) can be used to monitor mitophagy based on different pH stability of GFP and mCherry fluorescent proteins. We overexpressed Cox8-GFP-mCherry in mouse livers via tail vein injection of an adenovirus Cox8-GFP-mCherry. Mitophagy was assessed by confocal microscopy for Cox8-GFP-mCherry puncta, electron microscopy (EM) analysis for mitophagosomes and western blot analysis for mitochondrial proteins. Parkin KO and PINK1 KO mice improved the survival after treatment with APAP although the serum levels of ALT were not significantly different among PINK1 KO, Parkin KO and WT mice. We only found mild defects of mitophagy in PINK1 KO or Parkin KO mice after APAP, and improved survival in PINK1 KO and Parkin KO mice could be due to other functions of PINK1 and Parkin independent of mitophagy. In contrast, APAP-induced mitophagy was significantly impaired in PINK1-Parkin DKO mice. PINK1-Parkin DKO mice had further elevated serum levels of ALT and increased mortality after APAP administration. In conclusion, our results demonstrated that PINK1-Parkin signaling pathway plays a critical role in APAP-induced mitophagy and liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Deleção de Genes , Hepatócitos/metabolismo , Proteínas Quinases/genética , Ubiquitina-Proteína Ligases/genética , Animais , Biomarcadores , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Glutationa/metabolismo , Hepatócitos/ultraestrutura , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Camundongos , Camundongos Knockout , Mitocôndrias Hepáticas/genética , Mitocôndrias Hepáticas/metabolismo , Modelos Biológicos
9.
3 Biotech ; 9(4): 118, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30854278

RESUMO

Extracting RNA with high quality and integrity is crucial for molecular biology studies in eukaryotes. However, RNA isolation from cassava storage root raises a great concern because it contains large amounts of polysaccharides and polyphenol compounds. In the current study, four RNA extraction methods were evaluated for extracting RNA from cassava storage root. We found that the modified TM method (MTM) is timesaving and low-cost extraction method with high quality and quantities of RNA. The effectiveness of the improved method was assessed for qPCR analysis of four selected genes from total RNA of storage root. The improved protocol generated 4.18-5.94 µg RNA/g fresh weight. An A260/280 ratios of RNA samples are ranged from 2.14 to 2.17. The RIN values are ranged from 7.2 to 8.0. Importantly, isolated total RNA by MTM was successfully used for library construction and transcriptome sequencing. Therefore, we provide an efficient and low-cost method, MTM, for extracting high quality and quantities of RNA from cassava storage root.

10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(1): 292-296, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30738486

RESUMO

Chronic lymphocytic leukemia(CLL)is a malignant hematologic disease with heterogeneous clinical course, about two thirds of patients exhibit a long survival, but the remaining third of patients show aggressiveness of disease or poor response to conventional treatment even drug resistance. Studies suggested that tumor microenvironment possesses a critical effect in CLL disease progression in recent years. Monocyte/macrophage, as an important componens of tumor microenvironment, play a promotive role in the growth and drug reistance of tumor cells by direct cell-to-cell contact, secreting cytokines and suppressing antitumor responses. Therefore, exploring the monocyte/macrophage in CLL can provide theoretic basis for target treatment of CLL. In this review, the function of monocyte/macrophage and recent advances in therapy of CLL are discussed.


Assuntos
Leucemia Linfocítica Crônica de Células B , Humanos , Macrófagos , Monócitos , Microambiente Tumoral
11.
J Hazard Mater ; 368: 698-704, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30739022

RESUMO

To activate zero-valent iron (ZVI) for efficient nitrobenzene (NB) reduction, a hybrid Fe0/Fe3O4/FeCl2 microcomposite (hZVIbm) was synthesized via simple ball-milling of the ternary mixture of ZVI, Fe3O4, and FeCl2·4H2O (hZVI). SEM-EDX and time-of-flight secondary ion mass spectroscopy (ToF-SIMS) indicated the hZVIbm microcomposite (10-20 µm) consisted of Fe0 core covered by ∼3.3 µm-thick shell decorated with Fe3O4/FeCl2 fine particles (0.1-2 µm). Efficient removal (>95%) of NB (200 mg/L) was achieved by hZVIbm (2.0 g Fe/L) in 30 min over a wide pH range from 3 to 9. Notably, the NB removal efficiency of hZVIbm was over 30 times higher than the virgin ZVI or over three times higher than hZVI. The enhanced reactivity synergistically resulted from both chemical and physical aspects. Chemically, the Fe3O4/FeCl2-inlaid shell and the Fe(II) components played significant activation roles, as observed from the comparative experiments in their absence via pretreatments of hZVIbm by sonication and rinsing, respectively, with direct evidence of depassivation effect by XRD analysis. Physically, the ball-milling-induced inter-particle compaction effect was considered crucial to facilitate the interfacial mass/electron transfer processes during the reduction. The reduction pathway from NB to aniline via two intermediates was analyzed by liquid chromatography.

12.
Hepatology ; 69(5): 2164-2179, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30552702

RESUMO

Acetaminophen (APAP) overdose is one of the leading causes of hepatotoxicity and acute liver failure in the United States. Accumulating evidence suggests that hepatocyte necrosis plays a critical role in APAP-induced liver injury (AILI). However, the mechanisms of APAP-induced necrosis and liver injury are not fully understood. In this study, we found that p53 up-regulated modulator of apoptosis (PUMA), a B-cell lymphoma-2 (Bcl-2) homology domain 3 (BH3)-only Bcl-2 family member, was markedly induced by APAP in mouse livers and in isolated human and mouse hepatocytes. PUMA deficiency suppressed APAP-induced mitochondrial dysfunction and release of cell death factors from mitochondria, and protected against APAP-induced hepatocyte necrosis and liver injury in mice. PUMA induction by APAP was p53 independent, and required receptor-interacting protein kinase 1 (RIP1) and c-Jun N-terminal kinase (JNK) by transcriptional activation. Furthermore, a small-molecule PUMA inhibitor, administered after APAP treatment, mitigated APAP-induced hepatocyte necrosis and liver injury. Conclusion: Our results demonstrate that RIP1/JNK-dependent PUMA induction mediates AILI by promoting hepatocyte mitochondrial dysfunction and necrosis, and suggest that PUMA inhibition is useful for alleviating acute hepatotoxicity attributed to APAP overdose.

13.
Am J Pathol ; 189(3): 580-589, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30553835

RESUMO

Despite the growing global burden of alcoholic liver diseases, therapeutic options are limited, and novel targets are urgently needed. Accumulating evidence suggests that mitochondria adapt in response to ethanol and formation of megamitochondria in the livers of patients is recognized as a hallmark of alcoholic liver diseases. The processes involved in ethanol-induced hepatic mitochondrial changes, the impact on mitochondria-shaping proteins, and the significance of megamitochondria formation remain unknown. In this study, we investigated the mitochondrial and cellular response to alcohol in hepatoma cell line VL-17A. The mitochondrial architecture rapidly changed after 3 or 14 days of ethanol exposure with double-pronged presentation of hyperfragmentation and megamitochondria, and cell growth was inhibited. Dynamin-1-like protein (Drp1) was identified as the main mediator driving these mitochondrial alterations, and its genetic inactivation was determined to foster megamitochondria development, preserving the capacity of the cells to grow despite alcohol toxicity. The role of Drp1 in mediating megamitochondria formation in mice with liver-specific inactivation of Drp1 was further confirmed. Finally, when these mice were fed with ethanol, the presentation of hepatic megamitochondria was exacerbated compared with wild type fed with the same diet. Ethanol-induced toxicity was also reduced. Our study demonstrates that megamitochondria formation is mediated by Drp1, and this phenomenon is a beneficial adaptive response during alcohol-induced hepatotoxicity.


Assuntos
Dinaminas/metabolismo , Hepatopatias Alcoólicas/metabolismo , Mitocôndrias Hepáticas/metabolismo , Animais , Linhagem Celular Tumoral , Dinaminas/genética , Etanol/efeitos adversos , Etanol/farmacologia , Humanos , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/patologia , Camundongos , Camundongos Transgênicos , Mitocôndrias Hepáticas/genética , Mitocôndrias Hepáticas/patologia
14.
Mult Scler Relat Disord ; 28: 75-80, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30572285

RESUMO

BACKGROUND: Accumulating evidence indicates that regulatory T cells (Tregs) play an important role in the maintenance of immune tolerance. And dysfunction or deficiency of Tregs is thought to be involved in the pathogenesis of Multiple Sclerosis (MS). Nevertheless, previous studies reporting Tregs in patients were controversial due to the different markers adopted to identify Tregs. To clarify the status of Tregs in the pathogenesis of MS patients, we did a meta-analysis of the results published previously to assess the proportion of Tregs in peripheral blood (PB) in patients with MS. METHODS: We systematically searched Embase, PubMed, Cochrane, Web of Knowledge, FDA.gov, and Clinical Trials.gov for the studies reporting the proportion of Tregs in MS patients. Our main endpoints were the proportion of Tregs among CD4+ T cells in PB defined by different markers. We assessed pooled data by using a random-effects model. Our meta-analysis had been registered at International Prospective Register of Systematic Reviews (PROSPERO) (number CRD42017064906). RESULTS: Of 885 identified studies, a total 16 studies were selected in our analysis. There was no significant difference between MS patients and control subjects in Tregs identified by all Tregs definition methods [-0.07, (-0.46, 0.31, p = 0.706)] and Tregs defined by "CD4+ CD25+" [0.24, (-0.18, 0.65), p = 0.263]. Compared with control subjects, MS patients had a lower proportion of Tregs defined by "CD4+ CD25+ FOXP3+" [-0.75, (-0.46,0.31), p = 0.001]. CONCLUSION: Under random effect model of meta-analysis, the data showed that the results of Tregs in MS were different according to the definition method; and the proportion of Tregs defined by "CD4+ CD25+ FOXP3+" was decreased in MS. That result demonstrates that FOXP3 may be a vital definition of Tregs, and Tregs defined by stricter definition methods should be involved in the pathogenic mechanisms of MS.


Assuntos
Esclerose Múltipla/sangue , Esclerose Múltipla/imunologia , Linfócitos T Reguladores/imunologia , Humanos
15.
BMC Cancer ; 18(1): 1170, 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30477458

RESUMO

BACKGROUND: Increasing evidence indicates that cetuximab (CET) combined with chemoradiotherapy may be effective for patients with esophageal cancer. However, the recent results are still contradictory and no consensus has yet been reached on this issue. To evaluate the clinical effects and safety of CET, we conducted an updated meta-analysis by retrieving published data up to June 2018. METHODS: A comprehensive literature search was performed in several electronic databases, including PubMed, Embase, the Cochrane Library, CNKI database and Chinese Biomedicine Database using subject terms and free terms. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to determine the efficiency and safety of CET. RESULTS: This meta-analysis included 10 randomized controlled trials (RCTs). Five RCTs reported localized esophageal cancer and other five RCTs reported metastatic esophageal cancer. For these patients with localized esophageal cancer, CET could not significantly improve the response rate, overall survival and progression-free survival (PFS, 1-5 years). But CET treatment might increase the incidences of diarrhea (OR = 2.07; CI = 1.01-4.25) and rash (OR = 16.91; CI = 3.20-89.42). For other patients with metastatic esophageal cancer, the addition of CET significantly increased the response rate (OR = 3.34; CI = 1.90-5.88), disease control rate (OR = 2.92; CI = 1.49-5.71) and 2-year overall survival (OR = 2.78; CI = 1.20-6.46) compared with the control group. However, CET could not improve the 1-year overall survival and might make patients with metastatic esophageal cancer more susceptible to rash (OR = 5.50; CI = 2.14-14.14). No significant differences in other adverse effects were found between the two groups. CONCLUSIONS: Our findings suggested that adding CET to multimodal therapy significantly improved response rate and disease control rate for patients with metastatic esophageal cancer rather than patients with localized esophageal cancer. CET might be a safe therapeutic choice, but CET failed to significantly improve the overall survival and PFS for patients with localized or metastatic esophageal cancer.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Cetuximab/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Antineoplásicos Imunológicos/farmacologia , Cetuximab/farmacologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Humanos , Razão de Chances , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Resultado do Tratamento
16.
J Immunol Res ; 2018: 7103219, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30255107

RESUMO

Background: Accumulating evidence indicates that a deficiency in or dysfunction of regulatory T cells (Tregs) is involved in the pathogenesis of systemic lupus erythematosus (SLE). As different markers have been used to identify Tregs, recent studies on the proportions of Tregs in SLE patients have generated controversial results. To clarify the status of Tregs in such patients, we determined the proportions of Tregs present during development of the disease, with special consideration of controversial cellular markers. Methods: We identified studies reporting the proportions of Tregs in SLE patients by searching relevant databases through March 2018. Using the PRISMA guidelines, we performed a random effects meta-analysis of the frequencies of Tregs defined in different ways. Inconsistency was evaluated using the I-squared index (I2), and publication bias was assessed by examining funnel plot asymmetry using the Begger and Egger tests. Results: Forty-four studies involving 2779 participants were included in the meta-analysis. No significant difference in the proportions of Tregs was evident between 1772 patients and 1007 controls [-0.191, (-0.552, 0.362), p = 0.613, I2 = 95.7%]. We next conducted subanalyses based on individual definitions of Tregs. When the Treg definition included "FOXP3-positive" cells, the proportions did not differ between SLE patients and controls [-0.042, (-0.548, 0.632), p = 0.889, I2 = 96.6%]; this was the case when Tregs were defined as either "CD25low/-FOXP3+" or "CD25high/+FOXP3+" cells. SLE patients had lower proportions of Tregs that were "single CD25-positive" [-1.428, (-1.982, -0.873), p < 0.001, I2 = 93.4%] and "CD127-negative" [-1.093, (-2.002, -0.183), p = 0.018, I2 = 92.6%] compared to controls. Tregs defined as "CD25bright," "CD25bright/highCD127low/-," and "CD25highCD127low/-FOXP3+" did not differ in proportion between SLE patients and controls. Conclusions: The Treg proportions varied by the cellular identification method used. The proportions of Tregs that were accurately identified and functionally validated fell among patients with SLE. Stricter definitions of Tregs are necessary when evaluating the status of such patients.


Assuntos
Lúpus Eritematoso Sistêmico/imunologia , Linfócitos T Reguladores/imunologia , Citometria de Fluxo , Fatores de Transcrição Forkhead/metabolismo , Humanos , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Subunidade alfa de Receptor de Interleucina-7/metabolismo , Contagem de Linfócitos
17.
J Environ Manage ; 220: 142-148, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29777997

RESUMO

Rumen fluid, formed in rumen of ruminants, includes a complex microbial population of bacteria, protozoa, fungi and archaea, and has high ability to degrade lignocellulosic biomass. In this study, rumen fluid was used to ferment grass clipping for enhancing the hydrolysis and acidification of organic matters. Results showed that strict anaerobic condition, higher grass clipping content and smaller particle size of grass clipping were beneficial to the hydrolysis and acidification of organics. The increase of SCOD and total VFA concentration respectively reached 24.9 and 10.2 g/L with a suitable grass clipping content of 5%, a particle size <0.150 mm, and a fermentation time of 48 h. The VFA production was mainly attributed to the degradation of cellulose and hemicellulose with a total solid reduction of 55.7%. Firmicutes and Fibrobacteres were the major contributors to the degradation of cellulose and hemicellulose. The activity of carboxymethyl cellulose enzyme (CMCase), cellobiase and xylanase reached 0.027, 0.176 and 0.180 U/ml, respectively. The rumen fluid microorganisms successfully enhanced the hydrolysis and acidification of grass clipping.


Assuntos
Fermentação , Poaceae , Animais , Celulose , Hidrólise , Rúmen
18.
Mol Pharm ; 15(6): 2338-2347, 2018 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-29685037

RESUMO

The recently reported inhibitory effects of angiotensin 1-7 (Ang-(1-7)) on various cancers indicate its potential use as a therapeutic agent for primary and metastatic cancers. However, its extremely short half-life in the circulation greatly compromises its potential applications. Here, we reported an Ang-(1-7) analogue peptide with the amino and carboxy termini protected by acetylation and amination. The in vitro and in vivo degradation of the resulting analogue, Ang-AA, were determined using high-performance liquid chromatography (HPLC). At the same time, small RNA interference and competition studies were performed to evaluate the specific capacity of Ang-AA to bind to the cell surface Mas receptor. Cell Counting Kit-8 (CCK8), wound-healing, and Boyden chamber assays were performed to investigate the inhibitory effects of Ang-AA on A549 cells. Finally, the synergistic inhibitory effects of Ang-AA and paclitaxel (PTX) on A549 xenografts in mice were observed using animal imaging systems and survival observations. The toxicity of Ang-AA in mice was evaluated. Our results showed that acetylation and amination significantly inhibited the hydrolyzation of Ang-(1-7) in vitro and in vivo. The half-life of Ang-(1-7) in rats was prolonged from 2.4 ± 0.6 min to 238.7 ± 61.3 min ( p < 0.001). The specific binding of Ang-AA to the Mas receptor was well preserved, and Ang-AA exerted significantly greater inhibitory effects on the proliferation, migration, and invasion of A549 cells than Ang-(1-7). The combination of Ang-AA and PTX exhibited a significantly greater synergistic inhibitory effect on A549 xenografts than the combination of Ang-(1-7) and PTX. Ang-AA did not display obvious toxicity in mice. Our findings indicate acetylation and amination is a simple and effective method for producing Ang-(1-7) as a bioactive peptide.


Assuntos
Angiotensina I/farmacologia , Antineoplásicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Fragmentos de Peptídeos/farmacologia , Células A549 , Acetilação , Aminação , Angiotensina I/química , Angiotensina I/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Química Farmacêutica , Sinergismo Farmacológico , Meia-Vida , Humanos , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/uso terapêutico , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Int J Cardiol ; 261: 146-154, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29550018

RESUMO

BACKGROUND: Thymosin beta 4 (Tß4) is a 43-amino-acid peptide with protective properties in myocardium injury. Previously, we produced a recombinant human dimeric Tß4 (DTß4). Here, the cardioprotective effects of DTß4 and the molecular mechanisms underlying its enhanced activity were investigated. METHODS AND RESULTS: Echocardiography measurements showed that the cardioprotective effect of DTß4 in myocardial infarction mice was significantly higher than that of wild-type Tß4. Corresponding in vitro analyses demonstrated that the enhanced cardioprotection provided by DTß4 was largely due to increased stimulation of angiogenesis. HPLC analysis, western blotting and qRT-PCR indicated that the enhanced pro-angiogenesis activity of DTß4 was independent of the protein half-life and the known downstream pathways of wild-type Tß4. Transcriptome deep sequencing (RNA-seq), BrdU incorporation assays, flow cytometry analysis and RNA interference demonstrated that the enhanced angiogenic activity of DTß4 depended on MALAT1 (metastasis-associated lung adenocarcinoma transcript 1)-induced proliferation of vascular endothelial cells, which has not been reported for wild-type Tß4. Moreover, transcription factor activation screening, luciferase promoter reporter assay and immunoprecipitation assay demonstrated that DTß4 enhanced MALAT1 transcription by inhibiting the degradation of prospero-related homeobox 1 (PROX1). CONCLUSION: This study demonstrates the potential applications and the novel bioactivity of the Tß4 dimer. Moreover, to construct the dimer represents a new method for production of bioactive peptides that may have novel activities.


Assuntos
Cardiotônicos/uso terapêutico , Proliferação de Células/fisiologia , Endotélio Vascular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Isquemia Miocárdica/tratamento farmacológico , Timosina/uso terapêutico , Animais , Cardiotônicos/metabolismo , Cardiotônicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Dimerização , Endotélio Vascular/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/metabolismo , Timosina/metabolismo , Timosina/farmacologia
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