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3.
Cancer Immunol Res ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32047024

RESUMO

The ability of focal radiotherapy to promote priming of tumor-specific CD8+ T cells and increase responses to immunotherapy is dependent on infiltration of the tumor by Batf3-dependent conventional dendritic cell type 1 (cDC1) cells. Such infiltration is driven by radiotherapy-induced IFN type I (IFN-I). Other signals may also modulate cDC1 infiltration of irradiated tumors. Here we found increased expression of adenosine-generating enzymes CD38 and CD73 in irradiated mouse and human breast cancer cells and increased adenosine in mouse tumors following radiotherapy. CD73 blockade alone had no effect. CD73 blockade with radiotherapy restored radiotherapy-induced cDC1 infiltration of tumors in settings where radiotherapy induction of IFN-I was suboptimal. In the absence of radiotherapy-induced IFN-I, blockade of CD73 was required for rejection of the irradiated tumor and for systemic tumor control (abscopal effect) in the context of CTLA-4-blockade. These results suggest that CD73 may be a radiation-induced checkpoint, and that CD73 blockade in combination with radiotherapy and immune checkpoint blockade might improve patient response to therapy.

4.
Neuroradiology ; 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32008047

RESUMO

PURPOSE: To recommend a new simple and explicit index termed the anteroposterior diameter of the lateral ventricle index (ALVI) for assessing brain ventricular size in neuroimaging and to compare Evans index (EI) between idiopathic normal pressure hydrocephalus (iNPH) patients and age-matched healthy elderly subjects. METHODS: Retrospective measurements of ventricular volume (VV), relative VV (RVV), the EI, and the ALVI were taken from thin-section CT scans for 23 pre-shunt-insertion iNPH patients and 62 age-matched healthy elderly volunteers. The area under the receiver operating characteristic (ROC) curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to assess the effectiveness of ALVI scores for predicting VV. RESULTS: The correlations between VV or RVV and ALVI scores (VV, r = 0.957; RVV, r = 0.983) were significantly stronger than the corresponding correlations with EI scores (VV, r = 0.843; RVV, r = 0.840). The AUC for ALVI scores was significantly greater than the AUC for EI scores. Furthermore, with the inclusion of the ALVI, the NRI value was 0.14 and the IDI value was 0.14; these improvements were also statistically significant. CONCLUSION: The ALVI is a more accurate and more explicitly defined marker of VV than the EI and assesses ventricular enlargement effectively. We suggest that ventricular enlargement of the healthy elderly be defined by ALVI > 0.50.

5.
Sci Adv ; 6(6): eaax7989, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32076641

RESUMO

Mosquito-borne flaviviruses infect both mammals and mosquitoes. RNA interference (RNAi) has been demonstrated as an anti-flavivirus mechanism in mosquitoes; however, whether and how flaviviruses induce and antagonize RNAi-mediated antiviral immunity in mammals remains unknown. We show that the nonstructural protein NS2A of dengue virus-2 (DENV2) act as a viral suppressor of RNAi (VSR). When NS2A-mediated RNAi suppression was disabled, the resulting mutant DENV2 induced Dicer-dependent production of abundant DENV2-derived siRNAs in differentiated mammalian cells. VSR-disabled DENV2 showed severe replication defects in mosquito and mammalian cells and in mice that were rescued by RNAi deficiency. Moreover, NS2As of multiple flaviviruses act as VSRs in vitro and during viral infection in both organisms. Overall, our findings demonstrate that antiviral RNAi can be induced by flavivirus, while flavivirus uses NS2A as a bona fide VSR to evade RNAi in mammals and mosquitoes, highlighting the importance of RNAi in flaviviral vector-host life cycles.

6.
Med Sci Sports Exerc ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32079925

RESUMO

PURPOSE: This study was to investigate the mechanism of intestinal physical and immune barriers in the occurrence of high-intensive exercise-induced gastrointestinal symptoms (GIS). METHODS: An over-training model of male C57BL/6 mice was established by running-to-exhaustive exercise. Then, the mice were sacrificed and a series of evaluation indicators, including the routine blood analysis as well as histological examinations, inflammatory factors, ultrastructure observation and intestinal permeability of the gut were measured based on this model. The expressions of inflammatory factors TNF-α, IFN-γ and IL-6 as well as the tight junction and adherence junction proteins ZO-1, Occludin, Claudin-1 and E-cadherin were measured, respectively. Furthermore, the mRNA level of IL-22 and the proportion of ILC3, IL-22 produced in CD4 T cells in lamina propria lymphocytes (LPLs) were analyzed by flow cytometry. Besides, the liver glycogen and the expressions of SIRT3 and HIF-1a which were associated with the intestinal metabolism phenotype were analyzed by western blotting. RESULTS: Exhaustive exercise induced a disrupted intestinal barrier integrity, an aggravated intestinal inflammation, increased gut permeability and the reduced IL-22 mRNA level. Compared to the non-exercise mice, the IL-22 produced in LPLs was reduced followed by exhaustive exercise, whereas the proportion of IL-22 produced in CD4 T cells was still unchanged. Significantly, the proportion of ILC3 in the LPLs was decreased obviously, including the NCR ILC3. Furthermore, the intestinal metabolism phenotype assessment showed lower liver glycogen and blood glucose as well as higher blood lactic acid and HIF-1a, respectively. CONCLUSIONS: The data indicated that the acute high-intensity running-induced GIS is closely associated with a reduced percentage of ILC3 and IL-22 level in the LPLs, possibly due to the glycogen exhaustion and intestinal mucosa hypoperfusion.

7.
Medicine (Baltimore) ; 99(5): e18643, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000368

RESUMO

INTRODUCTION: Metastatic mesenchymal chondrosarcoma of the spine is a highly unusual disease without standard curative managements yet. The objective of this case report is to present a very rare case of metastatic chondrosarcoma to the spine successfully operated by surgical treatment. The management of these unique cases has yet to be well-documented. PATIENT CONCERNS: A 34-year-old woman presented with a 4-month history of continuous and progressive back pain and a 1-month history of radiating pain of bilateral lower extremities. The patient, who had been diagnosed of mesenchymal chondrosarcoma of maxillary sinus for 3 years, received surgical treatment of palliative endoscopic-assisted total left maxillary resection via mini Caldwell-Luc approach, and palliative enlarged resection due to the progress of residual lesions, followed by no adjuvant therapy. Multiple lytic, expanding lesions of the spine and paraspinal region with severe epidural spinal cord compression was identified. DIAGNOSIS: CT, MRI and bone scan of spine showed spinal cord compression secondary to the epidural component of the metastatic lesions. Post-operative pathology confirmed the diagnosis of metastatic spinal mesenchymal chondrosarcomas. INTERVENTIONS: The patient underwent posterior spinal canal decompression, resection of T12 and L3 lesions, internal fixation of T11-L5 pedicles, and cement augmentation of T12 and L3. OUTCOMES: The patient's neurological deficits improved significantly after the surgery, and the postoperative period was uneventful at the 1-year follow-up visit. There were no complications associated with the spinal surgery during the follow-up period. CONCLUSION: Metastatic spinal mesenchymal chondrosarcoma, although rare, should be part of the differential diagnosis when the patient presents with back pain and radiculopathy. We recommend the posterior approach for spinal decompression and total resection of the metastatic chondrosarcoma when the tumor has caused neurological deficits or other severe symptoms. Osteoplasty by cement augmentation is also a good choice for surgical treatment in some patients.


Assuntos
Condrossarcoma Mesenquimal/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Adulto , Condrossarcoma Mesenquimal/diagnóstico por imagem , Condrossarcoma Mesenquimal/secundário , Feminino , Humanos , Neoplasias do Seio Maxilar/diagnóstico por imagem , Neoplasias do Seio Maxilar/patologia , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/secundário
8.
Int J Biol Macromol ; 147: 1-9, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31917976

RESUMO

Cellulose based hydrogels with a relatively high stretchability were fabricated in the NaOH/urea system via sequential chemical crosslinking and dual network fabrication. The first step involved crosslinking of cellulose using epichlorohydrin as a crosslinker. Cryo-electron microscopy analysis revealed the utilization of diluted acid to treat hydrogels significantly affected the morphology of the first network and improved the mechanical properties. After diffusion of precursors into the first network, the dual network hydrogels were generated after the UV light-initiated polymerization. Raman spectroscopy demonstrated a spatial distribution of second networks within the first network. The compression strength of hydrogels synthesized under the optimized conditions was effectively enhanced from 0.04 MPa to 10.9 MPa. In addition, the tensile properties of hydrogels were easily adjusted via copolymerization of acrylic acid with acrylamide. The highest strain could reach 219.5% with a tensile strength of 1.4 MPa. This work provides a promising and simple strategy to develop a cellulose based hydrogel with enhanced and tunable mechanical properties for wide applications.

10.
Medicine (Baltimore) ; 99(1): e18575, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895803

RESUMO

This was a meta-analysis of epidemiological articles that aimed to estimate the association of garlic intake with the risk of colorectal cancer (CRC).Electronic databases, including the Cochrane Database of Systematic Reviews, PubMed, and EMBASE, were systemically searched from inception to May 2019 to identify related articles. In addition, a random model was used to pool the included evidence based on heterogeneity. Additionally, subgroup analyses were carried out to examine the differences between different groups. The stability of our findings was tested through sensitivity analyses. Publication bias was also assessed by Egger and Begg tests. Moreover, all enrolled studies were ordered according to the publication year for a cumulative meta-analysis.A total of 11 studies (involving 12,558 cases) were included in the current meta-analysis. Our integrated relative risk (RR) of CRC was 0.80 (95% confidence interval [CI], 0.69-0.91) for the highest versus the lowest garlic consumption categories (RR: 0.71 [95% CI, 0.60-0.84] for controls and RR: 0.99 [95% CI, 0.80-1.23] for cohorts). There was significant heterogeneity across all enrolled studies (I = 68.3%, P < .01). The sensitivity analysis revealed no notable alterations of the integrated results. According to the funnel plot regarding garlic intake and the risk of CRC, together with the Egger test (P = .1) and Begg test (P = .064) results, there was no notable evidence of publication bias. The cumulative meta-analysis suggested that the 95% CIs became narrower with the increase in sample size.Based on the existing evidence, garlic intake could reduce the risk of CRC.


Assuntos
Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Dieta/efeitos adversos , Alho , Adulto , Idoso , Ingestão de Alimentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
11.
J Cell Biochem ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31898842

RESUMO

This study aimed to identify the association between lnc-LAMC2-1:1 polymorphism rs2147578 and the recurrence of ovary cancer, as well as to study the underlying mechanism of rs2147578 in ovary cancer. Real-time polymerase chain reaction, Western blot analysis, immunohistochemistry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Logrank test, and Kaplan-Meier analysis were carried out to explore the role of rs2147578 in ovary cancer. No obvious difference was observed concerning all clinical characteristics among 90 patients genotyped as CC (N = 28), CG (N = 38), and GG (N = 24) in their rs2147578 polymorphism. In addition, the subjects carrying the CC genotype had longer recurrence-free survival time and showed a lower level of malignancy compared with those carrying CG and GG genotypes. Lnc-LAMC2-1:1 and miR-128 were lowly expressed in the CC group, while deleted in colorectal cancer (DCC) was highly expressed in the CC group. Furthermore, DCC was identified as a target gene of miR-128, and miR-128 mimics decreased the luciferase activity of cells cotransfected with wild-type DCC 3'-untranslated region. Lnc-LAMC2:1-1 directly targeted and affected miR-128 expression, and the G allele in lnc-LAMC2-1:1 rs2147578 upregulated miR-128 expression. Transfection with a miR-128 precursor evidently downregulated the expression of lnc-LAMC2-1:1, miR-128, and DCC expression, but did not affect the expression of ABCC5 and body mass index. Finally, miR-128 precursor promoted cell proliferation and inhibited cell apoptosis. Compared with lnc-LAMC2-1:1 rs2147578C allele, the G allele increases the risk of ovarian cancer by reducing the binding between lnc-LAMC2-1:1 and miR-128-3p, which in turn further decreases the expression of DCC and inhibits cell apoptosis.

13.
14.
Medicine (Baltimore) ; 99(4): e18603, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977851

RESUMO

RATIONALE: Tumor-induced osteomalacia (TIO) is a highly unusual disease with enormous difficulties in clinical diagnosis and curative managements. The objective of this study is to report a very rare case who underwent surgical treatment of recurrent spinal phosphaturic mesenchymal tumor. The management of these unique cases has yet to be further elucidated. PATIENT CONCERNS: A 52-year-old man presented with a 3-year history of back pain and 1-year history of continuous and progressive systemic bone pain. The patient, who had been diagnosed of TIO for 3 years, received surgical treatment of extended resection of spinal phosphaturic mesenchymal tumor at L5. Somatostatin receptor tomography revealed the expression of somatostatin in the spine increased significantly, with high suspicion of recurrent phosphaturic mesenchymal tumor. DIAGNOSIS: Magnetic resonance imaging of spine and positron emission tomography-computed tomography showed the mass in L5, which was highly indicative of the recurrent pathogenic tumor. Postoperative pathology confirmed the diagnosis of phosphaturic mesenchymal tumor in the spinal region. INTERVENTIONS: The patient underwent posterior L5 tumor resection, bone cement reconstruction, L4-S1 spinal canal decompression, and L3-S2 internal fixation. OUTCOMES: The patient's symptoms improved significantly after the surgery, and we noticed that his hypophosphatemia was successfully corrected after the 2nd operation. Follow-up at 1 month after surgery revealed no recurrence, and the serum phosphorus level of the patient turned to be normal postoperatively. There were no complications associated with the operation during the follow-up period. LESSONS: Taken together, the lesion's clinical features, imaging results, and pathologic characteristics are unique. Combined efforts of specialists from orthopedics, endocrinology, nuclear medicine, radiology, pathology, and medical oncology led to the successful diagnosis and management of this patient. TIO, although rare, should be part of the differential diagnosis when the patient has a history of hypophosphatemia and systemic multiple bone pain. We recommend surgical treatment of the phosphaturic mesenchymal tumor in the spinal region. Osteoplasty by bone cement may be a treatment option for patients with TIO who cannot undergo appropriate surgery or decline open surgery.


Assuntos
Neoplasias de Tecido Conjuntivo/etiologia , Neoplasias da Coluna Vertebral/complicações , Descompressão Cirúrgica/métodos , Humanos , Hipofosfatemia/etiologia , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias de Tecido Conjuntivo/diagnóstico , Neoplasias de Tecido Conjuntivo/cirurgia
15.
Int J Biochem Cell Biol ; 118: 105644, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31712163

RESUMO

Although the early diagnosis of prostate cancer (PCa) enhances life expectancy with a 5-year survival rate of 100 %, metastasized-PCa is the fundamental reason for death by PCa, hence requires an advanced and target-directed treatment strategy. Metastasis is considered to be initiated with the epithelial-mesenchymal transition (EMT) event in which tumor cells change their epithelial characteristics into mesenchymal form and exacerbates the cancer progression. Herein, we investigated the effect and mechanism of resveratrol function in PCa cell proliferation and migration and reported that TNF-receptor associated factor 6 (TRAF6), an unconventional E3 ligase, is a key mediator of resveratrol function to inhibit PCa cell growth and proliferation and targeted for lysosomal degradation by resveratrol. MTT and cell counting demonstrated that resveratrol inhibited the viability and proliferation in DU145 and PC3 cells. Resveratrol (50 µM) mediated the degradation of TRAF6 which in turn facilitated repression of the NF-κB pathway. Also, wound healing and transwell migration assays and level of EMT-related proteins showed that resveratrol used TRAF6, at least in part to inhibit cell migration. Overexpression of TRAF6 augmented EMT in PCa by upregulating the expression of transcription factor SLUG. Moreover, TRAF6 overexpression was closely associated with EMT process through the NF-κB pathway. Our exploration exhibited that resveratrol may inhibit EMT through the TRAF6/NF-κB/SLUG axis. Altogether, this study represents that TRAF6 acts as an intermediary of resveratrol action to suppress PCa cell proliferation and migration, and concerns future attention to obtain as a therapeutic target for the treatment of PCa.

16.
J Virol ; 94(3)2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31694940

RESUMO

RNA interference (RNAi) is a conserved antiviral immune defense in eukaryotes, and numerous viruses have been found to encode viral suppressors of RNAi (VSRs) to counteract antiviral RNAi. Alphaviruses are a large group of positive-stranded RNA viruses that maintain their transmission and life cycles in both mosquitoes and mammals. However, there is little knowledge about how alphaviruses antagonize RNAi in both host organisms. In this study, we identified that Semliki Forest virus (SFV) capsid protein can efficiently suppress RNAi in both insect and mammalian cells by sequestrating double-stranded RNA and small interfering RNA. More importantly, when the VSR activity of SFV capsid was inactivated by reverse genetics, the resulting VSR-deficient SFV mutant showed severe replication defects in mammalian cells, which could be rescued by blocking the RNAi pathway. Besides, capsid protein of Sindbis virus also inhibited RNAi in cells. Together, our findings show that SFV uses capsid protein as VSR to antagonize RNAi in infected mammalian cells, and this mechanism is probably used by other alphaviruses, which shed new light on the knowledge of SFV and alphavirus.IMPORTANCE Alphaviruses are a genus of positive-stranded RNA viruses and include numerous important human pathogens, such as Chikungunya virus, Ross River virus, Western equine encephalitis virus, etc., which create the emerging and reemerging public health threat worldwide. RNA interference (RNAi) is one of the most important antiviral mechanisms in plants and insects. Accumulating evidence has provided strong support for the existence of antiviral RNAi in mammals. In response to antiviral RNAi, viruses have evolved to encode viral suppressors of RNAi (VSRs) to antagonize the RNAi pathway. It is unclear whether alphaviruses encode VSRs that can suppress antiviral RNAi during their infection in mammals. In this study, we first uncovered that capsid protein encoded by Semliki Forest virus (SFV), a prototypic alphavirus, had a potent VSR activity that can antagonize antiviral RNAi in the context of SFV infection in mammalian cells, and this mechanism is probably used by other alphaviruses.

17.
Talanta ; 208: 120359, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816689

RESUMO

A versatile protocol has been developed for highly sensitive magnetic relaxation detection of the analyte based on the fabrication of MnO nanoparticles (NPs) assemblies. Based on the strategy that positively charged analyte could induce the assembly of negatively charged MnO NPs through electrostatic interaction, which will generate the change of magnetic relaxation rate of MnO NPs, we achieved highly sensitive and convenient detection of the analytes. By applying the detection of melamine as an example, we found that the detection limit can be as low as 0.733 ppb. Furthermore, this strategy has been applied for the initially detection of commercially available milk spiked with melamine as proof of its potential applicability of detection in complicated food samples.

18.
Talanta ; 208: 120453, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816768

RESUMO

Herein, a turn-on fluorescence assay was introduced for alkaline phosphatase (ALP) detection based on ThT/G-quadruplex system. The basis of the method is that chelation of guanine bases at the binding sites by Ag+ blocks G-quadruplex formation and decreases the fluorescence intensity sharply. In the presence of ALP, ascorbic acid 2-phosphate (AAP) is hydrolyzed to form ascorbic acid (AA) which in turn reduces Ag+ to Ag0. As a result, the blockage ability of Ag+ is disrupted which augments the fluorescence intensity and relies on the concentration of ALP. Under the optimized parameters (500 nM DNA probe; 6 µM Ag+; 1 mM AAP; 30 min for Ag+ and DNA probe reaction time), fluorescence intensity correlates linear range between 1 and 100 U/L of ALP concentration with the detection limit of 0.503 U/L. In the inhibition assay, 50% of ALP inhibition is caused by Na3VO4 with a concentration of 0.254 mM. Furthermore, the assay was used to detect ALP activity in human serum samples in which the results were significant. Above all, the proposed strategy is potential, facile, and sensitive for analyzing ALP activity and screening ALP inhibitor.

19.
20.
Medicine (Baltimore) ; 98(49): e18259, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804360

RESUMO

RATIONALE: Adrenocortical carcinoma is a rare aggressive type of cancer whose prognosis is poor, particularly for metastatic entities. Metastatic adrenocortical carcinoma in the spine is a rare disease with no standard curative managements yet. The objective of this study is to report a very rare case of spinal metastases of adrenocortical carcinoma successfully managed by combination of cement augmentation, radiotherapy together with adjuvant programmed cell death 1 (PD-1) therapy. The management of these unique cases has yet to be well-documented. PATIENT CONCERNS: A 42-year-old woman presented with a 3-month history of continuous and progressive back pain. The patient, who had been diagnosed of right pheochromocytoma, received surgical treatment of right adrenalectomy 14 months ago in another hospital, followed by no further treatment. DIAGNOSIS: Magnetic resonance imaging of spine showed vertebral pathological fracture of L1, spinal cord compression secondary to the epidural component of the L1 mass, with increased metastatic marrow infiltration of the right L1 vertebral body, which presented as a solid tumor. Postoperative pathology confirmed the diagnosis of spinal metastases of adrenocortical carcinoma. INTERVENTIONS: The patient underwent cement augmentation via a posterior approach, radiotherapy, radiofrequency ablation of psoas major muscle occupying lesions, right chest wall, liver and kidney recess together with adjuvant PD-1 therapy. OUTCOMES: The patient's neurological deficits improved significantly after the surgery, and the postoperative period was uneventful at the 6-month and 1-year follow-up visit. There were no complications associated with the operation during the follow-up period. LESSONS: Combined efforts of specialists from orthopedics, urology, interventional radiology, radiotherapy, pathology, endocrinology, and medical oncology led to the successful diagnosis and management of this patient. Metastatic adrenocortical carcinoma of the spine, although rare, should be part of the differential diagnosis when the patient has a history of adrenal carcinoma and presents with back pain, myelopathy, or radiculopathy. We recommend the posterior approach for total excision of the spinal metastatic adrenocortical carcinoma when the tumor has caused neurological deficits. Osteoplasty by cement augmentation, radiotherapy, and targeted PD-1 therapy may also be good choices for treatment.


Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/secundário , Carcinoma Adrenocortical/terapia , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/terapia , Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia , Adulto , Terapia Combinada , Feminino , Humanos , Imagem por Ressonância Magnética
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