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1.
Cell Death Dis ; 11(3): 163, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32123166

RESUMO

While B cells in the tumor microenvironment (TME) might play important roles in cancer progression, their impacts on the renal cell carcinoma (RCC) metastasis remained unclear, which drew our attention to further explore. We found that RCC tissues could recruit more B cells than the surrounding normal renal tissues from human clinical RCC samples. Wound healing assay, transwell assay and 3D invasion assays demonstrated that recruited B cells, also known as tumor-educated B cells (TEB), could significantly increase the RCC cell migration and invasion. In addition, in vivo data from xenograft RCC mouse model also confirmed that TEB could enhance RCC cell invasive and metastatic capability. Mechanism dissection revealed that TEB activated IL-1ß/HIF-2α signals in RCC cells that could induce the downstream Notch1 signaling pathway. The above results demonstrated the key roles of TEB within renal cancer associated tumor microenvironment were metastasis-promotor and might help us to develop the potential therapies via targeting these newly identified IL-1ß/HIF-2α/Notch1 signals in RCC progression.

2.
BMC Genomics ; 21(1): 211, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32138648

RESUMO

BACKGROUND: Plant height, mainly decided by main stem height, is the major agronomic trait and closely correlated to crop yield. A number of studies had been conducted on model plants and crops to understand the molecular and genetic basis of plant height. However, little is known on the molecular mechanisms of peanut main stem height. RESULTS: In this study, a semi-dwarf peanut mutant was identified from 60Co γ-ray induced mutant population and designated as semi-dwarf mutant 2 (sdm2). The height of sdm2 was only 59.3% of its wild line Fenghua 1 (FH1) at the mature stage. The sdm2 has less internode number and short internode length to compare with FH1. Gene expression profiles of stem and leaf from both sdm2 and FH1 were analyzed using high throughput RNA sequencing. The differentially expressed genes (DEGs) were involved in hormone biosynthesis and signaling pathways, cell wall synthetic and metabolic pathways. BR, GA and IAA biosynthesis and signal transduction pathways were significantly enriched. The expression of several genes in BR biosynthesis and signaling were found to be significantly down-regulated in sdm2 as compared to FH1. Many transcription factors encoding genes were identified as DEGs. CONCLUSIONS: A large number of genes were found differentially expressed between sdm2 and FH1. These results provide useful information for uncovering the molecular mechanism regulating peanut stem height. It could facilitate identification of causal genes for breeding peanut varieties with semi-dwarf phenotype.

3.
Sci Total Environ ; 721: 137740, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32163736

RESUMO

Recently, two-dimensional black phosphorus (BP) nanomaterial has captured much attention due to its superb physiochemical and electronic properties and various promising biomedical applications. However, relatively few studies have explored its antimicrobial properties, particularly for targeting antibiotic-resistant pathogens. A comprehensive understanding of the bactericidal mechanisms of BP is essential for application of this material as an antimicrobial. This review discusses the physicochemical and electronic properties of BP that are relevant for antimicrobial applications, especially the unique characteristics that may play a role in overcoming drug resistance. The literature is discussed in the context of what is known and what information is missing. We also highlight the differences and advantages of BP over other two-dimensional nanomaterials (i.e., graphene oxide and molybdenum disulfide) for bactericidal activity. Finally, we analyze existing challenges and note topics that require future investigation to overcome current inadequacies, aiming to assist the safe development of BP-based nanotechnology for pathogen control.

4.
J Colloid Interface Sci ; 569: 114-127, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32105899

RESUMO

The use of stabilizer with designer structures can effectively promote graphite exfoliation in common solvents to render functionalized graphene desirable for their various applications. Herein, a hyperbranched polyethylene copolymer, HBPE@Py@Acryl, simultaneously bearing multiple pyrene terminal groups and pendant acryloyl moieties has been successfully synthesized from ethylene with a Pd-diimine catalyst based on unique chain walking mechanism. The unique structural design of the HBPE@Py@Acryl makes it capable of effectively promote graphite exfoliation in a series of common, low-boiling-point organic solvents, e.g. CHCl3, to render stable graphene dispersions with concentrations effectively adjustable by changing feed concentrations of graphite and polymer or sonication time. Meanwhile, it can be irreversibly adsorbed on the exfoliated graphene surface based on the π-π interactions between them to concurrently render acryloyl-functionalized graphene free of structural defects, with majority (92.7%) of them having a thickness of 2-3 layers. This allows us to obtain graphene electrothermal films simply by filtration and UV irradiation, which exhibit outstanding stability in use. The action mechanism of the HBPE@Py@Acryl as stabilizer for promoting graphite exfoliation and the role of UV irradiation on improving the stability in use of resulting graphene films have been elucidated.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32045316

RESUMO

Objective: This study aimed to investigate the application of nanocarbon in surgical endoscopy in patients with thyroid cancer for the clinical tracing of level VI sentinel lymph nodes (SLNs) and for parathyroid gland protection. Materials and Methods: Ninety-three patients with papillary thyroid carcinoma (PTC) who underwent an endoscopic thyroid cancer operation were included. We randomly divided these patients into a control group (n = 42) and a nanocarbon group (n = 51). For the nanocarbon group, after thyroid exposure, nanocarbon was injected into the thyroid gland, and the SLNs were resected and subjected to frozen sectioning and routine pathological examination. In addition, the postoperative calcium and parathyroid hormone (PTH) levels of both groups were analyzed to compare the features of the nanocarbon application. Results: The number of central lymph (level VI) nodes dissected and the number of metastatic lymph nodes identified were analyzed in both groups. The number of dissected lymph nodes from both unilateral and bilateral thyroid surgeries was significantly larger in the nanocarbon group than in the control group. At the same time, the number of identified metastasis lymph nodes dissected were higher in the nanocarbon group than in the control group. We assessed the postoperative calcium and PTH level to evaluate the parathyroid function. Our results show that the nanocarbon group had a better protective effect on parathyroid function than the control group. Conclusions: As a lymph node trace agent, nanocarbon could better evaluate and permit a more clear lymph dissection for patients with PTC. Nanocarbon contributes to a decrease in the incidence rate of parathyroid damage, which has great clinical value.

6.
J Gen Intern Med ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32016703

RESUMO

BACKGROUND: No studies have evaluated the cost-effectiveness of single and two-step different diagnostic test strategies for Clostridioides difficile infection (CDI), including direct and indirect costs. OBJECTIVE: To evaluate the cost-effectiveness of commonly available diagnostic tests for CDI including nucleic acid amplification testing (NAAT) alone, glutamate dehydrogenase followed by enzyme immunoassay for toxin (GDH/EIA), GDH then NAAT (GDH/NAAT), and NAAT then EIA (NAAT/EIA). DESIGN: Decision tree model from the US societal perspective with inputs derived from the literature. Willingness-to-pay threshold was set at $150,000 per quality-adjusted life year (QALY) gained. To assess the impact of uncertainty in model inputs on the findings, we performed one-way and probabilistic sensitivity analyses. PARTICIPANTS: We conducted the analysis to represent a population aged 65 years old with diarrhea who received a CDI diagnostic test. MAIN MEASURES: Incremental cost-effectiveness ratios (ICER) and incremental net monetary benefits (INMB). KEY RESULTS: NAAT alone was the most cost-effective approach overall; GDH/NAAT was the most cost-effective two-step option. NAAT alone led to the highest QALYs gained, at an incremental cost of $54,547 (vs. GDH/NAAT), $55,410 (vs. GDH/EIA), and $50,231 (vs. NAAT/EIA) per QALY gained. NAAT/EIA was not cost-effective compared to any other strategy. GDH/NAAT resulted in a higher QALY compared to GDH/EIA, at an incremental cost of $96,841 per QALY gained. Variability in the likelihood of comorbidities, CDI probability, and age at disease onset did not substantially change the results. One-way sensitivity analyses showed that results were most sensitive to likelihood of recurrence, followed by CDI mortality rate and probability of severe CDI. Probabilistic sensitivity analyses explored known uncertainties in the base case and confirmed the robustness of the results. CONCLUSIONS: NAAT alone and GDH/NAAT (among the two-step options) were the most cost-effective diagnostic test approaches for CDI.

7.
Sci Rep ; 10(1): 252, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937837

RESUMO

As a new plant biostimulant, poly-γ-glutamic acid (γ-PGA) may be an effective anti-drought agent that can efficiently alleviate the damage to plants under drought stress. In this study, the effects of γ-PGA on the physiological responses of oilseed rape (Brassica napus L.) seedlings under drought stress were investigated using hydroponics. Growth and development of the rape seedlings were significantly inhibited in a polyethylene glycol-simulated drought environment. However, 12 d after application of γ-PGA under drought stress, the fresh weight, chlorophyll content, and relative water content of rape seedlings all markedly increased. Moreover, proline content and antioxidant enzyme activity were all markedly enhanced, and the malondialdehyde content was significantly reduced in rape seedlings treated with γ-PGA. Furthermore, the content of the important anti-drought response hormone, abscisic acid (ABA), as well as the expression levels of the ABA metabolism regulation genes BnNCED3, BnZEP, and BnAAO4, significantly increased. These results indicate that γ-PGA may induce elements of a tolerance system to drought stress by promoting ABA accumulation in B. Napus.

8.
Chem Commun (Camb) ; 56(14): 2087-2090, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31967623

RESUMO

A dual-emissive tris-heteroleptic ruthenium complex is designed, synthesized and applied for the ratiometric photoluminescent detection of amyloid-ß (Aß) aggregation in both steady and transient states. The Aß aggregation is supported by transmission electron microscopy and confocal laser scanning microscopy analysis. In addition, molecular docking calculations have been performed to gain insights into the interaction mode between the ruthenium complex and Aß fibrils.


Assuntos
Peptídeos beta-Amiloides/análise , Complexos de Coordenação/química , Rutênio/química , Complexos de Coordenação/síntese química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Agregados Proteicos
9.
Plant Biotechnol J ; 18(1): 96-105, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31131506

RESUMO

Peanut (Arachis hypogaea. L) is an important oil crop worldwide. The common testa colours of peanut varieties are pink or red. But the peanut varieties with dark purple testa have been focused in recent years due to the potential high levels of anthocyanin, an added nutritional value of antioxidant. However, the genetic mechanism regulating testa colour of peanut is unknown. In this study, we found that the purple testa was decided by the female parent and controlled by a single major gene named AhTc1. To identify the candidate gene controlling peanut purple testa, whole-genome resequencing-based approach (QTL-seq) was applied, and a total of 260.9 Gb of data were generated from the parental and bulked lines. SNP index analysis indicated that AhTc1 located in a 4.7 Mb region in chromosome A10, which was confirmed by bulked segregant RNA sequencing (BSR) analysis in three segregation populations derived from the crosses between pink and purple testa varieties. Allele-specific markers were developed and demonstrated that the marker pTesta1089 was closely linked with purple testa. Further, AhTc1 encoding a R2R3-MYB gene was positional cloned. The expression of AhTc1 was significantly up-regulated in the purple testa parent YH29. Overexpression of AhTc1 in transgenic tobacco plants led to purple colour of leaves, flowers, pods and seeds. In conclusion, AhTc1, encoding a R2R3-MYB transcription factor and conferring peanut purple testa, was identified, which will be useful for peanut molecular breeding selection for cultivars with purple testa colour for potential increased nutritional value to consumers.

10.
Transl Androl Urol ; 8(5): 442-447, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807421

RESUMO

Background: Although immunosuppressive agents used in recipients of organ transplants can suppress T cell immune responses, type I allergy to ingested or inhaled allergens after organ transplantation have frequently been reported in pediatric patients. This study aims to investigate the relationship between the use of immunosuppressive agents and the transplant-acquired allergy (TAA) in adult renal transplant recipients (RTRs). Methods: Seventy-nine RTRs treated in our hospital from February 2015 to February 2016 were interviewed for allergic diseases by using a standard questionnaire. UniCAP allergen screening tests were performed to detect total IgE and specific IgE levels before and after renal transplantation after the use of calcineurin inhibitor tacrolimus (FK506) or cyclosporin A (CsA). The follow-up visits were scheduled for 6 months, 1 year, 2 years, and 3 years after transplantation. Results: Allergen sensitization occurred in 9 of 79 patients. Among them, the sensitization occurred in 2 cases within 6 months after renal transplantation, in 1 case from 6 months to 1 year, in 3 cases from 1 to 2 years, and in 3 cases from 2 to 3 years. The majority of sensitization was induced by inhaled allergens (n=7), among whom 3 patients (3/79, 3.8%) had a history of type I allergy, which occurred within 6 months after transplantation in 2 cases (allergic dermatitis) and from 2 to 3 years in 1 case (diarrhea after peanut allergy). The total IgE levels of RTRs using immunosuppressive agents at different time points including 6 months, 1 year, 2 years, and 3 years after renal transplantation were significantly lower than that before surgery (all P<0.05). Sensitization occurred in 8 RTRs using FK506 and in 1 patient treated with CsA (P=0.432), and allergies occurred in 3 RTRs using FK506 and were not found among CsA users (P=0.561). Conclusions: Administration of immunosuppressive agents in adult RTRs cannot wholly prevent allergy or sensitization. Studies with larger sample sizes and more extended follow-up periods are still required to further explore the potential association between the use of FK506 and CSA and the allergies or sensitization.

11.
Transl Androl Urol ; 8(5): 457-466, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807423

RESUMO

Background: Carcinoembryonic antigen related cell adhesion molecule 6 (CEACAM6) is a versatile glycoprotein and a member of the CEACAM family. Studies suggested that it served as a diagnostic and prognostic biomarker in some malignancies. In addition, it is involved in tumorigenesis by stimulating proliferation, suppressing apoptosis, facilitating migration and invasion, promoting angiogenesis, and inducing drug resistance. In the present study, we demonstrated the oncogenic effects of CEACAM6 in clear cell renal cell carcinoma (ccRCC). Methods: CEACAM6 expression was detected by quantitative real-time PCR (qRT-PCR), immunohistochemical staining and western blot in ccRCC tumor tissues and cell lines. Survival analysis was performed using the data of TCGA database. Cell proliferation and migration were detected by CCK-8 and transwell assays with the overexpression or silencing of CEACAM6. LY294002 was used to block the activation of PI3K/AKT pathway. Associated pathway proteins were detected by western blot. Results: CEACAM6 was upregulated in ccRCC cell lines and tumor tissues. Longer overall survival was observed in patients with relatively low CEACAM6 levels. Furthermore, overexpression of CEACAM6 promoted the proliferation and migration of ccRCC cells. Conversely, shRNA-mediated CEACAM6 depletion modulated those changes. Further investigation demonstrated that the ERK/AKT signaling pathway activation played a pivotal role. In addition, PI3K/AKT pathway blockade abrogated the effects of CEACAM6 overexpression. Conclusions: Aberrantly high expression of CEACAM6 is a stimulus for the formation and progression of ccRCC.

12.
Ann Transl Med ; 7(20): 538, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807520

RESUMO

Background: The high incidence of post-transplant diabetes mellitus (PTDM) necessitates the identification of new factors to explain its pathogenesis. This study aimed to clarify the association between the C-peptide index (CPI) and PTDM. Methods: A total of 290 non-diabetic kidney transplant patients were analyzed. All subjects underwent a 75 g oral glucose tolerance test (OGTT). Plasma glucose concentrations, serum C-peptide levels, hemoglobin A1c (HbA1c), and other biochemical indicators were measured. CPI was calculated as the ratio of serum C-peptide to plasma glucose. Results: Among the 290 patients, 36 (12.4%) developed PTDM at the end of 1 year. Patients with PTDM had older age (P<0.001), higher levels of body mass index (BMI) (P=0.004) and HbA1c (P=0.001), a higher proportion of deceased donors (P=0.045), and lower levels of 2 h-CPI (P=0.02) than those without PTDM. The OGTT 2 h-CPI was positively correlated with BMI, HbA1c, type of calcineurin inhibitor, albumin, and triglyceride. Multivariate logistic regression and Cox hazard model analysis showed that pre-transplant OGTT 2 h-CPI was an independent predictor for the development of PTDM, together with age, BMI, and HbA1c. Conclusions: Of the pre-transplant factors studied, OGTT 2 h-CPI proved to be an independent predictor of PTDM.

13.
Front Plant Sci ; 10: 1118, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552080

RESUMO

Seed germination and formation are the beginning and ending, respectively, of a plant life cycle. These two processes are under fine regulation by the internal genetic information. Previously, we demonstrated that Arabidopsis MIDASIN 1 (MDN1) is required for ribosome biogenesis, and its dysfunction leads to pleiotropic developmental phenotypes, including impaired embryogenesis and slow seed germination. In this study, we further found that the weak mutant of MDN1, mdn1-1, exhibits an increased seed size phenotype. Seed proteomic analysis reveals that a number of proteins involved in seed development and response to external environments are mis-regulated by the MDN1 dysfunction. Many 2S seed storage proteins (SSPs) and late embryogenesis abundant (LEA) proteins are over-accumulated in the dry seeds of mdn1-1. Further, some genes encoding seed storage reserves are also upregulated in mdn1-1 seedlings. More interestingly, abscisic acid-insensitive 5 (ABI5) is over-accumulated in mdn1-1 seeds, and the loss of its function partially rescues the low seed germination rate of mdn1-1. Together, this study further demonstrates that MDN1 is essential for establishing a normal seed proteome, and its mutation triggers ABI5-mediated repression of seed germination.

14.
Transl Androl Urol ; 8(4): 292-296, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31555552

RESUMO

Background: In this paper, the regular flow of ultrasound-guided renal allograft biopsies was established by analyzing complications and clinical management principle of ultrasound-guided renal allograft biopsies, to increase the safety of ultrasound-guided renal allograft biopsies. Methods: The purpose of this study was to analyze the cases of ultrasound-guided renal allograft biopsies in our hospital from January 2006 to October 2018 because of abnormal renal function (including symptoms of albuminuria and elevated serum creatinine). The type of puncture needle used in renal allograft biopsies, the number of puncture needle and the relationship between puncture needle and complication were counted, and the treatment measures were analyzed. Results: From January 2006 to October 2018, a total of 487 patients underwent ultrasound-guided renal allograft biopsies in our hospital. Among them, the successful sampling rate was 98.8%, and the average number of glomeruli per specimen was 15.24±2.26. The complications of the patient after puncture included: perirenal hematomas, subcapsular hematomas, acute ureter obstruction caused by hematuria, gross hematuria, and microscopic hematuria. Among them, two patients were treated with open surgery to save the function of renal transplantation, and the primary treatment measures were to increase the absolute bed rest time. The symptoms of the patients were relieved after treatment. Conclusions: The analysis showed that ultrasound-guided renal allograft biopsies are safe and feasible, and the analysis of the biopsies of patients can provide meaningful pathological information for the clinic.

15.
Mol Med Rep ; 20(3): 2245-2257, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31257514

RESUMO

Chronic kidney disease (CKD) is a highly heterogeneous nephrosis that occurs when the structure and function of the kidney is damaged. Gene expression studies have been widely used to elucidate various biological processes; however, the gene expression profile of CKD is currently unclear. The present study aimed to identify diagnostic biomarkers and therapeutic targets using renal biopsy sample data from patients with CKD. Gene expression data from 30 patients with CKD and 21 living donors were analyzed by weighted gene co­expression network analysis (WGCNA), in order to identify gene networks and profiles for CKD, as well as its specific characteristics, and to potentially uncover diagnostic biomarkers and therapeutic targets for patients with CKD. In addition, functional enrichment analysis was performed on co­expressed genes to determine modules of interest. Four co­expression modules were constructed from the WGCNA. The number of genes in the constructed modules ranged from 269 genes in the Turquoise module to 60 genes in the Yellow module. All four co­expression modules were correlated with CKD clinical traits (P<0.05). For example, the Turquoise module, which mostly contained genes that were upregulated in CKD, was positively correlated with CKD clinical traits, whereas the Blue, Brown and Yellow modules were negatively correlated with clinical traits. Functional enrichment analysis revealed that the Turquoise module was mainly enriched in genes associated with the 'defense response', 'mitotic cell cycle' and 'collagen catabolic process' Gene Ontology (GO) terms, implying that genes involved in cell cycle arrest and fibrogenesis were upregulated in CKD. Conversely, the Yellow module was mainly enriched in genes associated with 'glomerulus development' and 'kidney development' GO terms, indicating that genes associated with renal development and damage repair were downregulated in CKD. The hub genes in the modules were acetyl­CoA carboxylase α, cyclin­dependent kinase 1, Wilm's tumour 1, NPHS2 stomatin family member, podocin, JunB proto­oncogene, AP­1 transcription factor subunit, activating transcription factor 3, forkhead box O1 and v­abl Abelson murine leukemia viral oncogene homolog 1, which were confirmed to be significantly differentially expressed in CKD biopsies. Combining the eight hub genes enabled a high capacity for discrimination between patients with CKD and healthy subjects, with an area under the receiver operating characteristic curve of 1.00. In conclusion, this study provided a framework for co­expression modules of renal biopsy samples from patients with CKD and living donors, and identified several potential diagnostic biomarkers and therapeutic targets for CKD.


Assuntos
Redes Reguladoras de Genes , Insuficiência Renal Crônica/genética , Transcriptoma , Perfilação da Expressão Gênica , Ontologia Genética , Humanos
16.
Bioresour Technol ; 291: 121841, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31349173

RESUMO

Soybean dregs are restricted as feed additives because they contain anti-nutrient factors. Herein, soybean dreg was bio-transformed by solid-state fermentation (SSF) using a poly γ-glutamic acid (γ-PGA) producing stain Bacillus amyloliquefaciens NX-2S. The maximum γ-PGA production of 65.79 g/kg was reached in a 5 L fermentation system while the conditions are 70% initial moisture of soybean dregs with addition of molasses meal, 12% inoculum size, 30 °C fermentation temperature, initial pH of 8, and 60 h fermentation time. Meanwhile, continuous batch fermentation was proved feasible. After SSF, the anti-nutritional factors such as trypsin inhibitor, phytic acid and tannin were reduced by 98.7%, 97.8%, and 63.2%, respectively. Compared with unfermented soybean dregs, adding fermented soybean dregs to feed increased the average weight gain of rats by 15.6% and reduced the ratio of feed to meat by 11.3%. Therefore, this study provided a feasible strategy for processing soybean dregs as feed additive.


Assuntos
Bacillus amyloliquefaciens/metabolismo , Comportamento Aditivo , Fermentação , Soja/metabolismo , Ração Animal , Animais , Comportamento Animal , Ácido Poliglutâmico/análogos & derivados , Ácido Poliglutâmico/biossíntese , Ratos
17.
Immunity ; 51(1): 169-184.e5, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31231035

RESUMO

Naive CD4+ T cells differentiate into functionally diverse T helper (Th) cell subsets. Th2 cells play a pathogenic role in asthma, yet a clear picture of their transcriptional profile is lacking. We performed single-cell RNA sequencing (scRNA-seq) of T helper cells from lymph node, lung, and airways in the house dust mite (HDM) model of allergic airway disease. scRNA-seq resolved transcriptional profiles of naive CD4+ T, Th1, Th2, regulatory T (Treg) cells, and a CD4+ T cell population responsive to type I interferons. Th2 cells in the airways were enriched for transcription of many genes, including Cd200r1, Il6, Plac8, and Igfbp7, and their mRNA profile was supported by analysis of chromatin accessibility and flow cytometry. Pathways associated with lipid metabolism were enriched in Th2 cells, and experiments with inhibitors of key metabolic pathways supported roles for glucose and lipid metabolism. These findings provide insight into the differentiation of pathogenic Th2 cells in the context of allergy.


Assuntos
Asma/imunologia , Hipersensibilidade Respiratória/imunologia , Sistema Respiratório/imunologia , Subpopulações de Linfócitos T/imunologia , Células Th2/imunologia , Animais , Antígenos de Dermatophagoides/imunologia , Modelos Animais de Doenças , Humanos , Metabolismo dos Lipídeos/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Orexina/genética , Pyroglyphidae/imunologia , Análise de Sequência de RNA , Análise de Célula Única , Transcriptoma
18.
J Exp Clin Cancer Res ; 38(1): 233, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159832

RESUMO

BACKGROUND: Previous study demonstrated that extracellular ATP could promote cell migration and invasion in multiple human cancers. Till now, the pro-invasive mechanisms of ATP and P2RX6, a preferred receptor for ATP, are still poorly studied in RCC. METHODS: Bioinformatics analysis was performed to identify the differentially expressed genes during RCC different stages. Tissue microarray, IHC staining and survival analysis was respectively used to evaluate potential clinical function. In vitro and in vivo assays were performed to explore the P2RX6 biological effects in RCC progression. RESULTS: We found that ATP might increase RCC cells migration and invasion through P2RX6. Mechanism dissection revealed that ATP-P2RX6 might modulate the Ca2+-mediated p-ERK1/2/MMP9 signaling to increase the RCC cells migration and invasion. Furthermore, METTL14 implicated m6A modification in RCC and down-regulated P2RX6 protein translation. In addition, human clinical survey also indicated the positive correlation of this newly identified signaling in RCC progression and prognosis. CONCLUSIONS: Our findings revealed that the newly identified ATP-P2RX6-Ca2+-p-ERK1/2-MMP9 signaling facilitates RCC cell invasion and metastasis. Targeting this novel signaling pathway with small molecules might help us to develop a new approach to better suppress RCC progression.


Assuntos
Trifosfato de Adenosina/metabolismo , Cálcio/metabolismo , Metilação de DNA , Metaloproteinase 9 da Matriz/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Receptores Purinérgicos P2/genética , Animais , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Biologia Computacional/métodos , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Neoplasias Renais/metabolismo , Camundongos , Modelos Biológicos , Metástase Neoplásica , Estadiamento de Neoplasias , Fosforilação , Prognóstico , Transdução de Sinais
19.
BMC Med Educ ; 19(1): 223, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31226989

RESUMO

BACKGROUND: Osteoporosis is inadequately treated in primary care settings. Under-recognition of the condition among male Veterans may contribute to this problem. In order to improve understanding of bone health in older male patients, we developed the "Musculoskeletal (MSK) Education Week", a multidisciplinary clinical training initiative within a primary care ambulatory rotation for internal medicine (IM) residents at the Salt Lake City VA Medical Center. The objective of this study was to evaluate the impact of this program on trainees' recognition of osteoporosis or treatment of this condition following the training experience. METHODS: We examined several clinical behaviors of post-graduate year 1 (PGY-1) IM trainees following their participation in the MSK Education Week between July 1-April 30, 2014. To determine the prevalence of these clinical behaviors, we conducted an observational study of patients age 50 and older enrolled at the Salt Lake City VA Healthcare System from July 1, 2013 to May 31, 2014. We used time-dependent multivariable Cox proportional hazard models to evaluate the impact of the training program on 4 osteoporosis-related outcomes: (1) completion of dual energy X-ray absorptiometry (DXA) scan, (2) diagnosis of osteopenia, (3) diagnosis of osteoporosis, and (4) initiation of osteoporosis medications. RESULTS: Twenty-six PGY-1 IM residents participated in the MSK Education Week, and 43,678 Veterans were identified over these periods of observation. In the Veterans cohort, 1154 had an encounter with a provider who had completed the training (and were therefore "exposed" to the training) and 42,524 Veterans did not. After adjusting for confounders, the effect of the provider training program was significant for DXA (HR = 1.78, 95% CI: 1.11, 2.87), osteoporosis diagnosis (HR = 3.90, 95% CI: 2.09, 7.29), and initiation of medications (HR = 2.87, 95% CI: 2.02, 4.09) outcomes. CONCLUSIONS: We have shown that IM residents' participation in the MSK Education Week was associated with significantly improvements in their completion of DXA scans, diagnosis of osteoporosis, and initiation of fracture-reducing medications in a population of US Veterans. Long-term follow up is needed to determine whether these initial results are followed by actual reductions in osteoporotic fractures.


Assuntos
Medicina Interna/educação , Internato e Residência , Osteoporose/diagnóstico , Padrões de Prática Médica/estatística & dados numéricos , Atenção Primária à Saúde/normas , Absorciometria de Fóton/estatística & dados numéricos , Competência Clínica , Humanos , Modelos de Riscos Proporcionais , Encaminhamento e Consulta/estatística & dados numéricos
20.
Electrophoresis ; 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31087687

RESUMO

Currently, the global healthcare market is increasing at high speed with the impendent global aging issue. Healthcare Industry 4.0 has emerged as an efficient solution towards the aging issue since it was integrated with ubiquitous medical sensors, big health processing platform, high bandwidth, speed technologies, and medical services, etc. It is believed to fulfil the requirement of the tremendously growing health market. The acquisition of medical data acts as the dominant precondition to implement the Healthcare Industry 4.0. In the same way, the widely available smartphone could serve as the best biomedical information collect station. In this study, a smartphone-powered photochemical dongle is demonstrated to precisely estimate blood creatinine from the fingertip blood, which works as a highly compact reflectance spectral analyzer with an enzymatically dry chemical test strip. Comparing with conventional laboratory facility for the evaluation and treatment of chronic kidney disease (CKD), it implemented the platform of point care with agreed accuracy. In order to estimate the efficiency of treatment and recovery of the CKD, the proposed photochemical dongle would provide a flexible and rapid platform for point of care. Furthermore, the proposed measured technology is very promising method for remote CKD management.

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