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1.
Artigo em Inglês | MEDLINE | ID: mdl-31721382

RESUMO

We report, for the first time, utilizing a rotating ring-disc electrode (RRDE) assembly for detecting changes in the local pH during aqueous CO2 reduction reaction (CO2RR). Using Au as a model catalyst where CO is the only product, we show that the CO oxidation peak shifts by -86 ± 2 mV/pH during CO2RR, which can be used to directly quantify the change in the local pH near the catalyst surface during electrolysis. We then applied this methodology to investigate the role of cations in affecting the local pH during CO2RR and find that during CO2RR to CO on Au in a MHCO3 buffer (where M is an alkali metal), the experimentally measured local basicity decreased in the order Li+ > Na+ > K+ > Cs+, which agreed with an earlier theoretical prediction by Singh et al. Our results also reveal that the formation of CO is independent of the cation. In summary, RRDE is a versatile tool for detecting local pH change over a diverse range of CO2RR catalysts. Additionally, using the product itself (i.e. CO) as the local pH probe allows us to investigate CO2RR without the interference of additional probe molecules introduced to the system. Most importantly, considering that most CO2RR products have pH-dependent oxidation, RRDE can be a powerful tool for determining the local pH and correlating the local pH to reaction selectivity.

2.
Sci Data ; 6(1): 209, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31624267

RESUMO

Tea is the most popular non-alcoholic caffeine-containing and the oldest beverage in the world. In this study, we de novo assembled the chloroplast (cp) and mitochondrial (mt) genomes of C. sinensis var. assamica cv. Yunkang10 into a circular contig of 157,100 bp and two complete circular scaffolds (701719 bp and 177329 bp), respectively. We correspondingly annotated a total of 141 cp genes and 71 mt genes. Comparative analysis suggests repeat-rich nature of the mt genome compared to the cp genome, for example, with the characterization of 37,878 bp and 149 bp of long repeat sequences and 665 and 214 SSRs, respectively. We also detected 478 RNA-editing sites in 42 protein-coding mt genes, which are ~4.4-fold more than 54 RNA-editing sites detected in 21 protein-coding cp genes. The high-quality cp and mt genomes of C. sinensis var. assamica presented in this study will become an important resource for a range of genetic, functional, evolutionary and comparative genomic studies in tea tree and other Camellia species of the Theaceae family.

3.
Anal Chem ; 91(21): 14036-14042, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31603308

RESUMO

Cancer imaging with minimal background signal and targeted intracellular drug delivery are of vital importance in clinical cancer diagnosis and therapy. Herein, we developed a biomimetic nanoprobe for activated fluorescence imaging and targeted drug delivery. pH-responsive porous coordination polymer nanoparticles (PCP NPs) were first synthesized by a codeposition method, anticancer drug doxorubicin (DOX) was then loaded into PCP NPs through physical and electrostatic adsorption (PCP-DOX), and finally the cell membranes extracted from Bel-7402 cancer cells were coated on the DOX-loaded PCP NPs (PCP-DOX-CM). The fluorescence of DOX was quenched due to the fluorescence resonance energy transfer between DOX and PCP NPs. Under acidic environment inside cancer cells, PCP NPs degraded, DOX was released from PCP-DOX-CM, and the fluorescence of DOX was activated, which was very specific for cancers with a high signal-to-noise ratio. Benefited from immune escaping and homologous targeting ability from cancer cell membranes, compared with PCP-CM and PCP-DOX, PCP-DOX-CM significantly enhanced the cellular endocytosis of DOX in Bel-7402 cancer cells and exhibited excellent cancer therapy effect in vitro. Together, our work provides a useful platform for an activated cancer imaging system and personalized cancer treatment.

4.
J Investig Med ; 67(8): 1103-1109, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31575668

RESUMO

Although significant improvements have been achieved in the renal replacement therapy of acute kidney injury (AKI), the mortality of patients with AKI remains high. The aim of this study is to prospectively investigate the capacity of Acute Physiology and Chronic Health Evaluation version II (APACHE II), Simplified Acute Physiology Score version II (SAPS II), Sepsis-related Organ Failure Assessment (SOFA) and Acute Tubular Necrosis Individual Severity Index (ATN-ISI) to predict in-hospital mortality of critically ill patients with AKI. A prospective observational study was conducted in a university teaching hospital. 189 consecutive critically ill patients with AKI were selected according Risk, Injury, Failure, Loss, or End-stage kidney disease criteria. APACHE II, SAPS II, SOFA and ATN-ISI counts were obtained within the first 24 hours following admission. Receiver operating characteristic analyses (ROCs) were applied. Area under the ROC curve (AUC) was calculated. Sensitivity and specificity of in-hospital mortality prediction were calculated. In this study, the in-hospital mortality of critically ill patients with AKI was 37.04% (70/189). AUC of APACHE II, SAPS II, SOFA and ATN-ISI was 0.903 (95% CI 0.856 to 0.950), 0.893 (95% CI 0.847 to 0.940), 0.908 (95% CI 0.866 to 0.950) and 0.889 (95% CI 0.841 to 0.937) and sensitivity was 90.76%, 89.92%, 90.76% and 89.08% and specificity was 77.14%, 70.00%, 71.43% and 71.43%, respectively. In this study, it was found APACHE II, SAPS II, SOFA and ATN-ISI are reliable in-hospital mortality predictors of critically ill patients with AKI. Trial registration number: NCT00953992.

5.
World J Surg Oncol ; 17(1): 163, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31526392

RESUMO

BACKGROUND: Pancreatic carcinoma (PC) is one of the most lethal malignancies, and its poor prognosis is strongly associated with invasion and metastasis. CA19.9 is considered to be the most sensitive serum marker for PC in clinical practice; however, the detection of CA19.9 in PC has a certain false positive and false negative rate. The expression of the calcium-binding protein S100A4 has been reported to be associated with poor prognosis in various cancers. This study aimed to investigate the relationship between S100A4 and CA19.9 and its prognostic significance in PC. METHODS: We performed immunohistochemical staining for S100A4 in formalin-fixed, paraffin-embedded blocks of 128 PC tissues. The levels of S100A4 expression and pre-operative serum CA19.9 were correlated with clinicopathological parameters. The possible correlation between S100A4 protein expression and pre-operative serum CA19.9 levels were evaluated using the chi-square test and Spearman correlation. Survival was assessed by Kaplan-Meier analysis together with a single variable or multivariate Cox analysis. RESULTS: A significant positive correlation between S100A4 expression and pre-operative serum CA19.9 level was observed in PC tissues (ρ = 0.202, P = 0.022). The co-expression of both proteins correlated significantly with tumor differentiation (ρ = - 0.280, P = 0.001), TNM stage (ρ = - 0.389, P = 0.000), and lymph node metastasis (ρ = 0.254, P = 0.008). Upregulation of S100A4 was identified as a significant, independent predictor of poor overall survival (P = 0.000). Moreover, higher serum CA19.9 levels (≥ 35 U/mL) were also recognized as an independent predictor of inferior overall survival (P = 0.001). Additionally, upregulation of S100A4 and higher pre-operative serum CA19.9 levels (≥ 35 U/mL) in patients with PC contributed to a significant decrease in overall survival (P = 0.000). CONCLUSIONS: The expression levels of S100A4 in PC tissues were positively correlated with pre-operative serum CA19.9 levels. S100A4 expression and pre-operative serum CA19.9 levels were significant, independent prognostic factors for the overall survival of patients with PC. S100A4 expression/pre-operative serum CA19.9 levels may prove useful as dual prognostic biomarkers for PC. Analysis of CA19.9 in combination with S100A4 can better predict the prognosis of PC.

6.
Anal Chem ; 91(17): 11200-11208, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31403276

RESUMO

Multidrug resistance is a major cause of failure in the clinical cancer therapy, in which the overexpression of P-glycoprotein (P-gp) plays a crucial role. Herein, we fabricate a theranostic nanoprobe with the function of simultaneous detection and inhibition of P-gp to diagnose and combat multidrug-resistant cancer in vitro and in vivo. For constructing the nanoprobe, elacridar modified quantum dots (QDs-Ela), acting as a gatekeeper, are grafted onto the doxorubicin (DOX) loaded, folic acid (FA) decorated mesoporous silica nanoparticles (MSNs). Upon targeted uptake by multidrug-resistant cancer cells, Bel-7402/ADR are used as a model, the acidic environment results in QDs-Ela removal from the nanoprobe, and subsequent DOX release. The removed QDs-Ela could specifically combine with P-gp in the cancer cell membrane and inhibit their active sites, which prevents the efflux of intracellular DOX and increases the retention of DOX. Another way, the fluorescence intensity of the binding QDs-Ela quantifies the P-gp expression level. Subsequently, in vitro and in vivo experiments both demonstrate the enhanced multidrug-resistant cancer therapy efficacy, i.e., nanoprobe has 10 times better curative effect than free DOX. In addition, due to the conjugation of FA, the nanoprobe exhibits a selective cell targeting ability to Bel-7402/ADR cells. This nanoplatform paves a new avenue for the accurate treatment of multidrug-resistant cancers.

7.
Medicine (Baltimore) ; 98(28): e16297, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305414

RESUMO

AIM: Accumulating evidence has explored the effect of mesalazine on irritable bowel syndrome (IBS). However, these studies remain inconsistent. Thus, a meta-analysis was conducted to estimate the role of mesalazine on IBS. METHODS: PubMed, Medline, Embase, Web of Science, and the Cochrane Library Database were searched for all relevant randomized, controlled, blinded trials on mesalazine in patients with IBS between January 1980 and October 2018. All statistical analyses were performed using Revman 5.3 software. A fixed-effects model was adopted, 95% confidence intervals for SMD was calculated. Heterogeneity was evaluated by χ test and I statistic. RESULTS: Five studies involving 387 participants were finally included in this meta-analysis. The results showed that the SMD for clinical efficacy on abdominal pain in IBS patients treated with mesalazine in comparison to placebo was 0.19 (95% CI = -0.01 to 0.39, P = .06), which was statistically non-significant but clinically important. For beneficial effect of abdominal bloating, the SMD was 0.05 (95% CI = -0.20 to 0.30, P = .70), which was statistically non-significant. In regard to clinical efficacy on defecation frequency per day, the results revealed that the SMD was 0.29 (95% CI = -0.14 to 0.73, P = .18), which was statistically non-significant but clinically important. As for beneficial effect of general well-being, we found that the SMD was 0.41 (95% CI = -0.75 to 1.58, P = .49), which was statistically non-significant. With respect to stool consistency, the SMD was 0.01 (95% CI = -0.31 to 0.33, P = .96), which was statistically non-significant. For the effect of defecation urgency severity in IBS patients treated with mesalazine in comparison to placebo, we detected a surprising result with an SMD of 0.54 (95% CI = 0.05-1.04, P = .03), which was statistically significant. There was no significant difference between mesalazine group and placebo group on total mucosal immune cell counts of the patients with IBS with an SMD of -1.64 (95% CI = -6.17 to 2.89, P = .48) and there was also no significant difference in adverse reactions between two groups with an SMD of 1.05 (95% CI = 0.76-1.46 P = .77). CONCLUSION: Mesalazine is not superior to placebo in relieving clinical symptoms of abdominal pain, abdominal bloating, and general well-being of IBS and has no advantage of reducing defecation frequency per day and immune cell infiltration and improving stool consistency though without adverse reactions of mesalazine compared with placebo. For defecation urgency severity, placebo is even superior to mesalazine for IBS patients. Thus, mesalazine might be a cost burden to patients without providing good effectiveness. In view of the small sample size of the current study and the differences in every experimental designs, this study has high heterogeneity and requires subsequent verification.


Assuntos
Fármacos Gastrointestinais/uso terapêutico , Síndrome do Intestino Irritável/tratamento farmacológico , Mesalamina/uso terapêutico , Humanos , Falha de Tratamento
8.
Diagn Pathol ; 14(1): 79, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31311568

RESUMO

AIMS: Pseudomyogenic hemangioendothelioma (PHE)/epithelioid sarcoma-like hemangioendothelioma (ES-H) is a rare vascular tumor of intermediate malignancy that commonly occurs in soft tissue of distal extremities of young adults. PHE typically has a multifocal presentation and can involve several tissue planes, including the dermis, subcutis, muscle and bone. METHODS AND RESULTS: We present here a unique case of PHE/ESH that arose in the breast as well as a review of the published literature. The initial biopsy was interpreted as a metaplastic carcinoma. However, complete resection largely revealed plump epithelioid cells, and a more spindled cell component was also noted. The cells displayed abundant eosinophilic cytoplasm and central vesicular nuclei arranged in loose fascicles, with a mild, mixed acute and chronic inflammatory infiltrate. Overall, linear membranous staining of CD31 and lack of CD34 expression were highly suggestive of PHE. At the same time, FOSB immunoreactivity was observed, which supported PHE/ESH instead of metaplastic carcinoma. The patient has not shown recurrence in the half year follow up after total mastectomy. CONCLUSION: To our knowledge, this is the first report of breast involvement in this neoplasm. Recognition of its histopathological features and immunohistochemical reactivity will prevent misdiagnosis of breast lesions.

9.
Sci Total Environ ; 689: 434-443, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31279190

RESUMO

How leaf traits vary with environmental and climatic variables in cold and arid environments is an essential issue in environmental ecology. Here, we analyzed the variations in leaf nitrogen (N) and phosphorus (P) stoichiometry and leaf dry matter content (LDMC) in Qilian juniper (Juniperus przewalskii Kom.) growing in 14 environmentally different plots on the northeastern Tibetan Plateau. The results showed that the N and P concentrations, N:P ratio and LDMC of Qilian juniper were 10.89 mg.g-1, 1.04 mg.g-1, 10.80 and 483.06 mg.g-1, respectively. The spatial coefficients of the variations in leaf N and P stoichiometry were significantly higher than the seasonal ones, and the correlations of leaf N and P concentrations with spatial variables were stronger than their correlations with the season. During the growing season, only the leaf N concentration and N:P ratio significantly increased. Soil nutrients were highly positively significantly correlated with leaf P concentrations but negatively correlated with the N:P ratio and LDMC. However, leaf N concentrations showed no significant correlations with soil nutrients. We suggest that the effects of temperature on the N concentration and LDMC were stronger than the effects of drought, while those on the P concentration and N:P ratio were weaker. Drought reduced leaf N and P concentrations and increased the N:P ratio and LDMC. In the arid region, with an increasing mean annual temperature (MAT), leaf N concentration significantly decreased, and LDMC significantly increased. In the semi-arid region, as MAT increased, leaf N and P concentrations significantly increased and LDMC and the N:P ratio significantly decreased. These opposite results supported the growth rate hypothesis that plant N and P concentrations increase while the N:P ratio and LDMC decrease as the growth rate increases.


Assuntos
Clima Desértico , Juniperus/fisiologia , Folhas de Planta/fisiologia , China , Temperatura Baixa , Juniperus/química , Juniperus/crescimento & desenvolvimento , Nitrogênio/metabolismo , Fósforo/metabolismo , Folhas de Planta/química , Folhas de Planta/crescimento & desenvolvimento
10.
Fish Shellfish Immunol ; 92: 519-527, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31202967

RESUMO

Antibiotic-resistant bacteria are severe threats to aquaculture industry. Boosting and modulating host immune responses has been proved to be an effective strategy to combat with bacterial infections and there is an urgent need for novel immunomodulators. Cathelicidins is an important family of host defense peptides (HDPs) that possess direct antimicrobial activities and potent immunomodulatory properties. Several cathelicidins have been identified and characterized from diverse fish species. Considering the relatively conserved immune systems between different fish species, it is reasonable to speculate that cathelicidins from different fish species possess immunomodulating functions on the other fish species. In the present study, two fish-derived cathelicidins (CATH_BRALE and codCath1) were selected to investigate their protective effect on zebrafish with bacterial infections. They exhibited potent and broad-spectrum antimicrobial activities against the tested aquatic Gram-positive and Gram-negative pathogenic bacteria, with MIC values ranging 2.34-18.75 µg/ml for CATH_BRALE and 2.34-37.5 µg/ml for codCath1. And their antimicrobial effect is so rapid that they killed the bacteria within 60 min. Unlike conventional antibiotics, they kill bacteria by inducing bacterial membrane permeabilization and cell disruption. Besides direct antimicrobial activity, CATH_BRALE and codCath1 exhibited potent immunomodulatory functions by both inhibiting bacteria induced zebrafish pro-inflammatory cytokine gene (TNF-α, IL-1ß, and IL-6) expression and stimulating zebrafish chemokine gene IL-8 expression. In vivo challenge test proved that they could significantly decrease the bacterial numbers and enhance the survival rates of zebrafish. All the results above imply the great potential of CATH_BRALE and codCath1 as novel peptide immunomodulators in fish aquaculture industry.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31212664

RESUMO

Paraquat (PQ) is a toxic non-selective herbicide. To date, the effect of PQ on memory immune response is still unknown. We investigated the impact of PQ on memory immune response. Adult C57BL/6 mice were subcutaneously injected with 2 mg/kg PQ, 20 mg/kg PQ or vehicle control every three days for two weeks. A single injection of keyhole limpet hemocyanin (KLH) at day four after the initial PQ treatment was used to induce a primary immune response; a second KLH challenge was performed at three months post the first KLH immunization to induce a secondary immune response. In steady state, treatment with 20 mg/kg PQ reduced the level of serum total IgG, but not that of IgM; treatment with 20 mg/kg PQ decreased the number of effector and memory lymphocytes, but not naïve or inactivated lymphocytes. During the primary immune response to KLH, treatment with 20 mg/kg PQ did not influence the proliferation of lymphocytes or expression of co-stimulatory molecules. Instead, treatment with 20 mg/kg PQ increased the apoptosis of lymphocytes at late stage, but not early stage of the primary immune response. During the secondary immune response to KLH, treatment with 20 mg/kg PQ reduced the serum anti-KLH IgG and KLH-responsive CD4 T cells and B cells. Moreover, effector or activated lymphocytes were more sensitive to PQ-induced apoptosis in vitro. Treatment with 2 mg/kg PQ did not impact memory immune response to KLH. Thus, treatment with 20 mg/kg PQ increased apoptosis of late stage effector cells to yield less memory cells and thereafter impair memory immune response, providing a novel understanding of the immunotoxicity of PQ.

12.
Zoolog Sci ; 36(1): 68-76, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31116540

RESUMO

The cathelicidins represent an important family of host defense peptides (HDPs) found exclusively in vertebrates, which serve as a critical effector in host immune response against microbial infections. To date, a large number of cathelicidins has been identified from diverse vertebrates, such as mammals, birds, reptiles, amphibians and fishes. Sixteen cathelicidins have been identified from snakes in the Elapidae, Viperidae, and Biodae families. However, no cathelicidin has been discovered from a snake of the Colubrinae family. In the present study, we report the identification and characterization of a novel cathelicidin, SA-CATH, from the Colubrinae family snake, Sinonatrix annularis. The cDNA sequence encoding SA-CATH precursor is 735 bp in length, and the mature peptide (SA-CATH) is composed of 30 amino acid residues. Sequence alignment result indicated that SA-CATH precursor possesses relatively high sequence similarity with the cathelicidins from Elapidae and Viperidae family snakes. Similar as the cathelicidins from Elapidae, Viperidae, and Biodae family snakes, SA-CATH mainly assumes an amphipathic alpha-helical conformation, and possesses potent antimicrobial, biofilm inhibitory and anti-inflammatory activities. The results in the present study imply that cathelicidins serve as a kind of conserved effectors with similar structures in the immune systems of Colubrinae, Boidae, Elapidae and Viperidae family snakes. The identification of SA-CATH provides novel clues for the understanding of function and evolution of snake immune systems. The potent antimicrobial, biofilm inhibitory, anti-inflammatory, and slight cytotoxic activities of SA-CATH imply that it is a potential drug candidate in novel antimicrobial agent development.


Assuntos
Catelicidinas/isolamento & purificação , Colubridae , Sequência de Aminoácidos , Animais , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Bactérias/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Catelicidinas/química , Catelicidinas/farmacologia , Feminino , Fungos/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Camundongos Endogâmicos C57BL , Filogenia , Análise de Sequência de DNA
13.
Dev Comp Immunol ; 98: 189-204, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31121185

RESUMO

Cathelicidins are a family of gene-encoded immune effectors in vertebrate innate immunity. Here, we reported the diversity and biological activity of cathelicidins in green sea turtle, a marine reptile species known for long lifespan and disease resistance. Four novel cathelicidins (Cm-CATH1-4) were identified from green sea turtle. All of them, especially Cm-CATH2, exhibited potent, broad-spectrum and rapid bactericidal and anti-biofilm activities by inducing the disruption of cell membrane integrity. Additionally, Cm-CATH2 effectively induced the macrophages/monocytes and neutrophils trafficking to the infection site, and inhibited the LPS-induced production of inflammatory cytokines, by blocking TLR4/MD2 complex and the downstream signaling pathway activation. In mouse peritonitis and pneumonia models, Cm-CATH2 exhibited evident protection against drug-resistant bacterial infections. Taken together, the diverse structures and functions of Cm-CATHs indicated their pleiotropic role in innate immunity of green sea turtle, and the potent antimicrobial, anti-biofilm and immunomodulatory properties make them ideal candidates for the development of novel anti-infective drugs.

14.
J Colloid Interface Sci ; 547: 309-317, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30965229

RESUMO

Magnesium (Mg) alloys have received considerable attentions as the emerging biodegradable implant materials in orthopedic surgery applications. However, the rapid corrosion rate and the susceptibility to bacterial infection have prevented their wide spread applications to date. In this work, the gentamicin-loaded multilayers have been constructed on Mg alloys through spin-assisted layer-by-layer (SLbL) assembly. Heat treatment is applied for improving the corrosion resistance and prolonging the drug release profile. In addition, the treated multilayer can promote the formation of hydroxyapatite (HA) during the long-time immersion in Hank's balanced salt solution (HBSS).


Assuntos
Ligas/química , Gentamicinas/química , Temperatura Alta , Magnésio/química , Polieletrólitos/química , Liberação Controlada de Fármacos , Resistência a Medicamentos , Hidroxiapatitas/síntese química , Hidroxiapatitas/química , Estrutura Molecular , Tamanho da Partícula , Propriedades de Superfície
15.
Leukemia ; 33(10): 2454-2465, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30953029

RESUMO

New prognostic factors are needed to establish indications for haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) for T-cell lymphoblastic lymphoma (T-LBL) patients. We used microarray to compare T-LBL tissue samples (n = 75) and fetal thymus tissues (n = 20), and identified 35 differentially expressed miRNAs. Using 107 subjects as the training group, we developed a five-miRNA-based classifier to predict patient survival with LASSO Cox regression: lower risk was associated with better prognosis (disease-free survival (DFS): hazard ratio (HR) 4.548, 95% CI 2.433-8.499, p < 0.001; overall survival (OS): HR 5.030, 95% CI 2.407-10.513, p < 0.001). This classifier displayed good performance in the internal testing set (n = 106) and the independent external set (n = 304). High risk was associated with more favorable response to HSCT (DFS: HR 1.675, 95% CI 1.127-2.488, p = 0.011; OS: HR 1.602, 95% CI 1.055-2.433, p = 0.027). When combined with ECOG-PS and/or NOTCH1/FBXW7 status, this classifier had even better prognostic performance in patients receiving HSCT (DFS: HR 2.088, 95% CI 1.290-3.379, p = 0.003; OS: HR 1.996, 95% CI 1.203-3.311, p = 0.007). The five-miRNA classifier may be a useful prognostic biomarker for T-LBL adults, and could identify subjects who could benefit from HSCT.

16.
Gut ; 68(7): 1169-1179, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30842211

RESUMO

OBJECTIVE: The pathogenesis of UC relates to gut microbiota dysbiosis. We postulate that alterations in the viral community populating the intestinal mucosa play an important role in UC pathogenesis. This study aims to characterise the mucosal virome and their functions in health and UC. DESIGN: Deep metagenomics sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on the rectal mucosa of 167 subjects from three different geographical regions in China (UC=91; healthy controls=76). Virome and bacteriome alterations in UC mucosa were assessed and correlated with patient metadata. We applied partition around medoids clustering algorithm and classified mucosa viral communities into two clusters, referred to as mucosal virome metacommunities 1 and 2. RESULTS: In UC, there was an expansion of mucosa viruses, particularly Caudovirales bacteriophages, and a decrease in mucosa Caudovirales diversity, richness and evenness compared with healthy controls. Altered mucosal virome correlated with intestinal inflammation. Interindividual dissimilarity between mucosal viromes was higher in UC than controls. Escherichia phage and Enterobacteria phage were more abundant in the mucosa of UC than controls. Compared with metacommunity 1, metacommunity 2 was predominated by UC subjects and displayed a significant loss of various viral species. Patients with UC showed substantial abrogation of diverse viral functions, whereas multiple viral functions, particularly functions of bacteriophages associated with host bacteria fitness and pathogenicity, were markedly enriched in UC mucosa. Intensive transkingdom correlations between mucosa viruses and bacteria were significantly depleted in UC. CONCLUSION: We demonstrated for the first time that UC is characterised by substantial alterations of the mucosa virobiota with functional distortion. Enrichment of Caudovirales bacteriophages, increased phage/bacteria virulence functions and loss of viral-bacterial correlations in the UC mucosa highlight that mucosal virome may play an important role in UC pathogenesis.


Assuntos
Colite Ulcerativa/virologia , Disbiose/virologia , Microbioma Gastrointestinal , Mucosa Intestinal/virologia , Reto/virologia , Adulto , Estudos de Casos e Controles , China , Colite Ulcerativa/patologia , Disbiose/patologia , Feminino , Humanos , Masculino , Reto/patologia
17.
Molecules ; 24(3)2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30717241

RESUMO

Theanine, a unique amino acid in Camellia sinensis, accounts for more than 50% of total free amino acids in tea and has a significant contribution to the quality of green tea. Previous research indicated that theanine is synthesized from glutamic acid (Glu) and ethylamine mainly in roots, and that theanine accumulation depends on the availability of ethylamine which is derived from alanine (Ala) decarboxylation catalyzed by alanine decarboxylase (AlaDC). However, the specific gene encoding AlaDC protein remains to be discovered in tea plants or in other species. To explore the gene of AlaDC in tea plants, the differences in theanine contents and gene expressions between pretreatment and posttreatment of long-time nitrogen starvation were analyzed in young roots of two tea cultivars. A novel gene annotated as serine decarboxylase (SDC) was noted for its expression levels, which showed high consistency with theanine content, and the expression was remarkably high in young roots under sufficient nitrogen condition. To verify its function, full-length complementary DNA (cDNA) of this candidate gene was cloned from young roots of tea seedlings, and the target protein was expressed and purified from Escherichia coli (E. coli). The enzymatic activity of the protein for Ala and Ser was measured in vitro using ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS). The results illustrated that the target protein could catalyze the decarboxylation of Ala despite of its high similarity with SDC from other species. Therefore, this novel gene was identified as AlaDC and named CsAlaDC. Furthermore, the gene expression levels of CsAlaDC in different tissues of tea plants were also quantified with quantitative real-time PCR (qRT-PCR). The results suggest that transcription levels of CsAlaDC in root tissues are significantly higher than those in leaf tissues. That may explain why theanine biosynthesis preferentially occurs in the roots of tea plants. The expression of the gene was upregulated when nitrogen was present, suggesting that theanine biosynthesis is regulated by nitrogen supply and closely related to nitrogen metabolism for C. sinensis. The results of this study are significant supplements to the theanine biosynthetic pathway and provide evidence for the differential accumulation of theanine between C. sinensis and other species.


Assuntos
Alanina/metabolismo , Camellia sinensis/genética , Carboxiliases/genética , Regulação da Expressão Gênica de Plantas , Glutamatos/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/genética , Camellia sinensis/enzimologia , Carboxiliases/metabolismo , Clonagem Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Etilaminas/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Nitrogênio/deficiência , Nitrogênio/farmacologia , Especificidade de Órgãos , Filogenia , Folhas de Planta/enzimologia , Folhas de Planta/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/enzimologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Plântula/enzimologia , Plântula/genética , Serina/metabolismo , Chá
18.
Mediators Inflamm ; 2019: 5160694, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30718973

RESUMO

Background: Acute exacerbation of IPF (AE-IPF) is associated with high mortality. We studied changes in pathogen involvement during AE-IPF and explored a possible role of infection in AE-IPF. Objectives: Our purpose is to investigate the role of infection in AE-IPF. Methods: Overall, we recruited 170 IPF patients (48 AE-IPF, 122 stable) and 70 controls at Shanghai Pulmonary Hospital. Specific IgM against microbial pathogens and pathogens in sputum were assessed. RNA sequences of pathogens in nasopharyngeal swab of IPF patients were detected by PathChip. A panel of serum parameters reflecting immune function were assessed. Results: Antiviral/bacterial IgM was higher in IPF vs. controls and in AE-IPF vs. stable IPF. Thirty-eight different bacterial strains were detected in IPF patient sputum. Bacteria-positive results were found in 9/48 (18.8%) of AE-IPF and in 26/122 (21.3%) stable IPF. Fifty-seven different viruses were detected in nasopharyngeal swabs of IPF patients. Virus-positive nasopharyngeal swabs were found in 18/30 (60%) of tested AE-IPF and in 13/30 (43.3%) of stable IPF. AE-IPF showed increased inflammatory cytokines (IL-6, IFN-γ, MIG, IL-17, and IL-9) vs. stable IPF and controls. Mortality of AE-IPF in one year (39.5%) was higher compared to stable IPF (28.7%).Conclusions. IPF patients had different colonization with pathogens in sputum and nasopharyngeal swabs; they also displayed abnormally activated immune response, which was exacerbated during AE-IPF.


Assuntos
Fibrose Pulmonar Idiopática/sangue , Fibrose Pulmonar Idiopática/complicações , Infecção/sangue , Infecção/complicações , Idoso , China , Citocinas/sangue , Feminino , Humanos , Imunoglobulina M/imunologia , Imunossupressão , Inflamação , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/isolamento & purificação , Análise de Sequência de RNA , Escarro/microbiologia , Escarro/virologia
20.
Am J Physiol Lung Cell Mol Physiol ; 316(3): L519-L524, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30652492

RESUMO

We use the simultaneous application and testing method to detect Mycobacterium tuberculosis rRNA (SAT-TB) with the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy specimens to differentiate sputum-negative tuberculosis from sarcoidosis. In the first part, we validated the SAT-TB on the bronchial or EBUS-TBNA biopsy specimens from sputum smear-positive pulmonary tuberculosis. In the second part, all EBUS-TBNA specimens for sputum smear-negative intrathoracic tuberculous lymphadenopathies or sarcoidosis were tested with the SAT-TB, acid-fast bacilli smear, and culture. In the 16 sputum-positive tuberculosis cases, 5 showed negative SAT (2 nontuberculous mycobacteria and 3 had anti-tuberculosis therapies previously); the remaining 11 were positive. Of the 41 sputum-negative tuberculosis cases in the second part, five other diseases were negative. In the remaining 36 cases, 27 sarcoidosis cases were negative; 7 in 9 with sputum-negative tuberculosis were positive (77.78%). In these 36 patients, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the SAT method were 77.78, 100, 100, 93.10, and 94.44%, respectively. The SAT distinguished sputum-negative tuberculosis from sarcoidosis significantly ( P < 0.0001) and identified cases with active M. tuberculosis as accurately as the conventional methods (κ = 0.912, P < 0.0001). We conclude that the SAT-TB may be an effective method for using biopsy specimens to differentiate sputum-negative tuberculosis from sarcoidosis.

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