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1.
ACS Appl Energy Mater ; 7(7): 2989-3008, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38606033

RESUMO

Porous composite battery electrode performance is influenced by a large number of manufacturing decisions. While it is common to evaluate only finished electrodes when making process adjustments, one must then make inferences about the fabrication process dynamics from static results, which makes process optimization very costly and time-consuming. To get information about the dynamics of the manufacturing processes of these composites, we have built a miniature coating and drying apparatus capable of fabricating lab-scale electrode laminates while operating within an X-ray beamline hutch. Using this tool, we have collected the first radiography image sequences of lab-scale battery electrode coatings in profile, taken throughout drying processes conducted under industrially relevant conditions. To assist with interpretation of these image sequences, we developed an automated image analysis program. Here, we discuss our observations of battery electrode slurry samples, including stratification and long-term fluid flow, and their relevance to composite electrode manufacturing.

2.
Nat Commun ; 14(1): 8203, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38081869

RESUMO

Monitoring real-world battery degradation is crucial for the widespread application of batteries in different scenarios. However, acquiring quantitative degradation information in operating commercial cells is challenging due to the complex, embedded, and/or qualitative nature of most existing sensing techniques. This process is essentially limited by the type of signals used for detection. Here, we report the use of effective battery thermal conductivity (keff) as a quantitative indicator of battery degradation by leveraging the strong dependence of keff on battery-structure changes. A measurement scheme based on attachable thermal-wave sensors is developed for non-embedded detection and quantitative assessment. A proof-of-concept study of battery degradation during fast charging demonstrates that the amount of lithium plating and electrolyte consumption associated with the side reactions on the graphite anode and deposited lithium can be quantitatively distinguished using our method. Therefore, this work opens the door to the quantitative evaluation of battery degradation using simple non-embedded thermal-wave sensors.

3.
Nat Commun ; 14(1): 3229, 2023 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-37270603

RESUMO

The mass adoption of electric vehicles is hindered by the inadequate extreme fast charging (XFC) performance (i.e., less than 15 min charging time to reach 80% state of charge) of commercial high-specific-energy (i.e., >200 Wh/kg) lithium-ion batteries (LIBs). Here, to enable the XFC of commercial LIBs, we propose the regulation of the battery's self-generated heat via active thermal switching. We demonstrate that retaining the heat during XFC with the switch OFF boosts the cell's kinetics while dissipating the heat after XFC with the switch ON reduces detrimental reactions in the battery. Without modifying cell materials or structures, the proposed XFC approach enables reliable battery operation by applying <15 min of charge and 1 h of discharge. These results are almost identical regarding operativity for the same battery type tested applying a 1 h of charge and 1 h of discharge, thus, meeting the XFC targets set by the United States Department of Energy. Finally, we also demonstrate the feasibility of integrating the XFC approach in a commercial battery thermal management system.

4.
Cancer Med ; 12(2): 1461-1470, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35861406

RESUMO

BACKGROUND: Tumor treating fields (TTFields) is an FDA-approved adjuvant therapy for glioblastoma. The distribution of an applied electric field has been shown to be governed by distinct tissue structures and electrical conductivity. Of all the tissues the skull plays a significant role in modifying the distribution of the electric field due to its large impedance. In this study, we studied how remodeling of the skull would affect the therapeutic outcome of TTFields, using a computational approach. METHODS: Head models were created from the head template ICBM152 and five realistic head models. The electric field distribution was simulated using the default TTFields array layout. To study the impact of the skull on the electric field, we compared three cases, namely, intact skull, defective skull, and insulating process, wherein a thin electrical insulating layer was added between the transducer and the hydrogel. The electric field strength and heating power were calculated using the FEM (finite element method). RESULTS: Removing the skull flap increased the average field strength at the tumor site, without increasing the field strength of "brain". The ATVs of the supratentorial tumors were enhanced significantly. Meanwhile, the heating power of the gels increased, especially those overlapping the skull defect site. Insulation lightly decreased the electric field strength and significantly decreased the heating power in deep tumor models. CONCLUSION: Our simulation results showed that a skull defect was beneficial for superficial tumors but had an adverse effect on deep tumors. Skull removal should be considered as an optional approach in future TTFields therapy to enhance its efficacy. An insulation process could be used as a joint option to reduce the thermogenic effect of skull defect. If excessive increase in heating power is observed in certain patients, insulating material could be used to mitigate overheating without sacrificing the therapeutic effect of TTFields.


Assuntos
Neoplasias Encefálicas , Terapia por Estimulação Elétrica , Glioblastoma , Humanos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Encéfalo/patologia , Glioblastoma/patologia , Terapia Combinada , Terapia por Estimulação Elétrica/métodos , Crânio/patologia
5.
Front Immunol ; 13: 1029737, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505426

RESUMO

Binding of CD95, a cell surface death receptor, to its homologous ligand CD95L, transduces a cascade of downstream signals leading to apoptosis crucial for immune homeostasis and immune surveillance. Although CD95 and CD95L binding classically induces programmed cell death, most tumor cells show resistance to CD95L-induced apoptosis. In some cancers, such as glioblastoma, CD95-CD95L binding can exhibit paradoxical functions that promote tumor growth by inducing inflammation, regulating immune cell homeostasis, and/or promoting cell survival, proliferation, migration, and maintenance of the stemness of cancer cells. In this review, potential mechanisms such as the expression of apoptotic inhibitor proteins, decreased activity of downstream elements, production of nonapoptotic soluble CD95L, and non-apoptotic signals that replace apoptotic signals in cancer cells are summarized. CD95L is also expressed by other types of cells, such as endothelial cells, polymorphonuclear myeloid-derived suppressor cells, cancer-associated fibroblasts, and tumor-associated microglia, and macrophages, which are educated by the tumor microenvironment and can induce apoptosis of tumor-infiltrating lymphocytes, which recognize and kill cancer cells. The dual role of the CD95-CD95L system makes targeted therapy strategies against CD95 or CD95L in glioblastoma difficult and controversial. In this review, we also discuss the current status and perspective of clinical trials on glioblastoma based on the CD95-CD95L signaling pathway.


Assuntos
Células Endoteliais , Glioblastoma , Humanos , Transdução de Sinais , Apoptose , Microambiente Tumoral
6.
BMC Neurol ; 22(1): 411, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36333683

RESUMO

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive disease. The role of surgical resection in PCNSL has always been the center of debate. Here we investigated the clinical and follow-up data of single lesion PCNSL operated in our center, focusing on the comparison between surgical resection and biopsy. METHODS: All consecutive cases of single lesion PCNSL between October 2004 and December 2019 were retrospectively collected from the database of the Second Affiliated Hospital of Zhejiang University, School of Medicine. Patients were divided into resection group and biopsy group. Clinical information including age, gender, Karnofsky performance status, imaging features and postoperative treatment was collected from the medical records. All the patients were followed for survival analysis. RESULTS: A total of 105 patients with PCNSL were finally involved in our analysis. Neither PFS nor OS were significantly different between the resection group and biopsy group. The univariate analysis revealed that age < 60 and therapeutic treatment were significant predictors of longer PFS and OS. In the multivariate analysis, age (HR = 3.09, 95% CI 1.31-7.28, p = 0.01) and therapeutic treatment (HR = 0.25, 95% CI 0.07- 0.83, p = 0.02) were independent prognostic markers with OS. Multivariable Cox regression analyses also revealed that only age (HR = 2.29 (95% CI, 1.11-4.71, p = 0.03) was independent prognostic marker for PFS. CONCLUSIONS: In single lesion PCNSL, there was no significant difference between the resection group and biopsy group for both PFS and OS. Younger age and postoperative treatment have been proved to be indicators of better prognosis.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma , Humanos , Neoplasias do Sistema Nervoso Central/cirurgia , Neoplasias do Sistema Nervoso Central/patologia , Estudos Retrospectivos , Prognóstico , Biópsia , Linfoma/cirurgia , Linfoma/tratamento farmacológico , Sistema Nervoso Central/patologia
7.
Clin Neurol Neurosurg ; 210: 106950, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34583274

RESUMO

OBJECTIVE: Contralateral subdural effusion after decompressive craniectomy (CSEDC) is rare, and the optimal treatment is not determined. We present 11 cases of CSEDC and give an overview of the English literature pertaining to this disease. METHODS: We searched the database at our institution and performed a search of English literature in PubMed and Google Scholar. Keywords used were as follows (single word or combination): "subdural hygroma"; "subdural effusion"; "decompressive craniectomy". Only patients with CSEDC and contained adequate clinical information pertinent to the analysis were included. RESULTS: 11 cases of CSEDC were recorded at our institution. They comprised ten men and one woman with an average age of 41.9 years. All the 8 symptomatic patients underwent surgery and the CSEDC resolved gradually. 68 cases of CSEDC were found in the literature. Including ours, a total of 79 patients were analyzed. Conservative treatment was effective in the asymptomatic patients. 41.7% of the symptomatic CSEDC underwent burr hole drainage and successfully drained the CSEDC. However, 76% of them received subsequent surgery to manage the reaccumulation of CSEDC. 25% of the symptomatic patients underwent cranioplasty, while 13.3% of them received Ommaya drainage later because of CSEDC recurrence. 18.3% of the symptomatic patients underwent cranioplasty plus subduroperitoneal shunting, and all CSEDC resolved completely. CONCLUSIONS: Burr hole drainage appears to be only a temporary measure. Early cranioplasty should be performed for patients with CSEDC. CSF shunting procedures may be required for patients in whom CSEDC have not been solved or hydrocephalus manifest after cranioplasty.


Assuntos
Craniectomia Descompressiva/efeitos adversos , Hidrocefalia/cirurgia , Derrame Subdural/etiologia , Adulto , Drenagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Derrame Subdural/cirurgia , Resultado do Tratamento , Trepanação
8.
Front Immunol ; 12: 582594, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815356

RESUMO

Objective: Pediatric diffuse gliomas (pDGs) are relatively rare and molecularly distinct from pediatric pilocytic astrocytoma and adult DGs. Immunotherapy is a promising therapeutic strategy, requiring a deep understanding of tumor immune profiles. The spatial locations of brain tumors might be related to the molecular profiles. We aimed to analyze the relationship between the immune checkpoint molecules with the locations of DGs comparing pediatric with adult patients. Method: We studied 20 pDGs patients (age ≤ 21 years old), and 20 paired adult patients according to gender and histological types selected from 641 adult patients with DGs. Immune checkpoint molecules including B7-H3, CD47, and PD-L1, as well as tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs), were manifested by immunohistochemical staining. Expression difference analyses and Spearman's correlation were performed. MRI data were voxel-wise normalized, segmented, and analyzed by Fisher's exact test to construct the tumor frequency and p value heatmaps. Survival analyses were conducted by Log-rank tests. Result: The median age of pediatric patients was 16 years. 55% and 30% of patients were WHO II and III grades, respectively. The left frontal lobe and right cerebellum were the statistically significant locations for pDGs, while the anterior horn of ventricles for adult DGs. A potential association between the expression of PD-L1 and TAMs was found in pDGs (p = 0.002, R = 0.670). The right posterior external capsule and the lateral side of the anterior horn of the left ventricle were predominant locations for the adult patients with high expression of B7-H3 and low expression of PD-L1 compared to pediatric ones, respectively. Pediatric patients showed significantly improved overall survival compared with adults. The prognostic roles of immune checkpoint molecules and TILs/TAMs were not significantly different between the two groups. Conclusion: Immune checkpoint-associated locations of diffuse gliomas comparing pediatric with adult patients could be helpful for the immunotherapy decisions and design of clinical trials.


Assuntos
Antígenos B7/imunologia , Antígeno B7-H1/imunologia , Neoplasias Encefálicas/imunologia , Antígeno CD47/imunologia , Glioma/imunologia , Linfócitos do Interstício Tumoral/imunologia , Adolescente , Adulto , Idoso , Antígenos B7/metabolismo , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Antígeno CD47/metabolismo , Criança , Feminino , Glioma/metabolismo , Glioma/terapia , Humanos , Imuno-Histoquímica , Imunoterapia/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Adulto Jovem
9.
Onco Targets Ther ; 14: 1147-1159, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33642868

RESUMO

PURPOSE: LINC00466 is a newfound long non-coding RNA (lncRNA) that has been rarely explored in cancers. However, the specific role and molecular mechanism of LINC00466 in glioma remain to be further elucidated. METHODS: Bioinformatic analysis was used to screen differentially expressed genes. Quantitative real-time PCR (qRT-PCR) was used to determine the expression of LINC00466, microRNA-137 (miR-137) and protein phosphatase 1 regulatory subunit 14B (PPP1R14B). Dual-luciferase reporter gene assay and RNA binding protein Immunoprecipitation (RIP) assays were employed to verify the binding relationship among LINC00466, miR-137 and PPP1R14B. The sensitivity of glioma cells to temozolomide (TMZ) was measured by cell counting kit-8 (CCK8) assay. The xenograft nude models were used to test the effects of LINC00466 on glioma tumor growth in vivo. RESULTS: Highly expressed LINC00466 and PPP1R14B and lowly expressed miR-137 were eventually revealed in glioma tissues. Overexpression of LINC00466 could promote proliferation, metastasis and drug sensitivity to TMZ of glioma cells. LINC00466 could bind to miR-137, and up-regulation of miR-137 could attenuate the enhancing effects caused by LINC00466 overexpression. We took a further step and found that miR-137 could bind to PPP1R14B. Besides, LINC00466 could function as a sponge to miR-137 to regulate PPP1R14B. In addition, overexpression of LINC00466 could promote tumor growth in vivo. CONCLUSION: These findings validate LINC00466 could restrain the miR-137 expression to up-regulate PPP1R14B and therefore promote proliferation, metastasis and resistance to TMZ of glioma.

10.
Cell Commun Signal ; 19(1): 40, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761934

RESUMO

BACKGROUND: Lysosome-associated membrane protein type 2A (LAMP-2A) is the key component of chaperone-mediated autophagy (CMA), a cargo-selective lysosomal degradation pathway. Aberrant LAMP-2A expression and CMA activation have been demonstrated in various human malignancies. The study focusing on the intrinsic role of LAMP-2A and CMA in glioblastoma (GBM), and downstream mechanism could provide valuable insight into the pathogenesis and novel therapeutic modality of GBM. METHODS: The levels of LAMP-2A, nuclear receptor co-repressor (N-CoR), unfolded protein response (UPR) and apoptosis were examined in clinical samples. LAMP-2A siRNA and shRNA were constructed to manipulate CMA activation. The role of CMA and downstream mechanism through degradation of N-CoR and arresting UPR mediated apoptosis were explored in GBM cells and nude mouse xenograft model. RESULTS: Elevated LAMP-2A and associated decreased N-CoR expression were observed in GBM as compared with peritumoral region and low-grade glioma. Inhibited UPR and apoptosis were observed in GBM with high LAMP-2A expression. In vitro study demonstrated co-localization and interaction between LAMP-2A and N-CoR. LAMP-2A silencing up-regulated N-CoR and aroused UPR pathway, leading to apoptosis, while N-CoR silencing led to an opposite result. In vivo study further confirmed that LAMP-2A inhibition arrested tumor growth by promoting apoptosis. CONCLUSIONS: Our results demonstrated the central role of CMA in mediating N-CoR degradation and protecting GBM cells against UPR and apoptosis, and provided evidence of LAMP-2A as potential biomarker. Further research focusing on CMA with other tumorigenic process is needed and selective modulators of LAMP-2A remain to be investigated to provide a novel therapeutic strategy for GBM. Video Abstract.


Assuntos
Apoptose , Biomarcadores Tumorais/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patologia , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Correpressor 1 de Receptor Nuclear/metabolismo , Proteólise , Animais , Apoptose/genética , Caspases/metabolismo , Linhagem Celular Tumoral , Autofagia Mediada por Chaperonas/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Gradação de Tumores , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Transcrição Gênica , Resposta a Proteínas não Dobradas/genética , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Nat Commun ; 11(1): 3655, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32678100

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

12.
Front Oncol ; 10: 556575, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33585185

RESUMO

BACKGROUND: It still remains unclear whether patients with atypical meningioma (AM) could benefit from postoperative adjuvant radiotherapy (PORT) after gross-total resection (GTR). OBJECTIVE: Exploring the effectiveness of PORT on AM patients after GTR. METHODS: Literatures on PubMed, Embase, Web of science, and Scopus databases published between January 2000 and January 2019 were searched. After the selection based on the certain exclusion criteria, the Newcastle-Ottawa evaluation scale was used to evaluate the quality of the included literatures. Finally, a meta-analysis was conducted to analyze the effectiveness of PORT on local control (LC), progression-free survival (PFS) and overall survival (OS) in atypical meningioma patients after GTR. RESULTS: A total of 17 articles with 2,008 AM patients were included in the meta-analysis. The 5-year LC, 5-year PFS, and 5-year OS rates were 82.2, 84.1, and 79.0%, respectively, for AM patients receiving PORT after GTR, and they were 71.0, 71.9, and 81.5%, respectively, for those not receiving PORT after GTR. PORT could significantly improve 5-year LC rate (OR [95% Cl] = 2.59 [1.40-4.81], P = 0.002) and 5-year PFS rate (OR [95% Cl] = 1.99 [1.35-2.95], P = 0.001), but did not significantly improve 5-year OS rate (OR [95% Cl] = 1.07 [0.60-1.91], P = 0.828). CONCLUSION: PORT could improve the 5-year LC rate and 5-year PFS rate in AM patients after GTR. AM patients might benefit from PORT after GTR.

13.
Hepatol Int ; 13(6): 715-725, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31531761

RESUMO

BACKGROUND: Approximately 50% hepatocellular carcinoma (HCC) patients die within 5 year after surgical resection. The present staging systems do not fully allow to accurately predict the HCC prognosis and recurrence. This study aimed to identify clinicopathological characteristics and molecular markers to establish classifiers to predict the 5-year overall survival (OS) and the 3-year recurrence in HCC patients post-operatively. METHODS: We enrolled 647 HCC patients from two institutions, underwent surgical resection and divided the patients into one training and two validation cohorts. Clinicopathologic characteristics and tumor protein expression of 29 biomarkers by immunohistochemical (IHC) analysis were used to develop and validate a prognostic and a recurrent classifier, using the maximum relevance minimum redundancy algorithm jointly with the multivariable regression method. RESULTS: The prognostic classifier distinguished HCC patients into high- and low-probability survival groups with significant differences in 5-year OS rate in all three cohorts (training cohort: 57.36% vs. 22.97%; p < 0.0001; internal validation cohort: 61.90% vs. 28.85%; p < 0.0001; independent validation cohort: 64.28% vs. 22.45%; p < 0.0001). The recurrent classifier also demonstrated good discrimination in all three cohorts. CONCLUSION: This study presented a prognostic classifier and a recurrent classifier using clinicopathologic and IHC characteristics. The developed classifiers stratified HCC patients into high- and low-probability survival or recurrent groups, which can help clinicians judge whether adjuvant therapy is beneficial post-operatively.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , China , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Prognóstico , Análise de Regressão , Estudos Retrospectivos , Adulto Jovem
14.
J Clin Gastroenterol ; 53(7): e298-e302, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30260809

RESUMO

BACKGROUND: Well over 700,000 United States military personnel participated in the Persian Gulf War in which they developed chronic health disorders of undetermined etiology. Up to 25% of Veterans had persistent and chronic gastrointestinal (GI) symptoms, which they suspected were related to their military service in the Gulf. AIM: The overall aim of the current study was to evaluate intestinal permeability in previously deployed Gulf War Veterans who developed chronic GI symptoms during their tour in the Persian Gulf. METHODS: To accomplish this, we evaluated intestinal permeability (IP) using the urinary lactulose/mannitol test. Measurements of intestinal permeability were then correlated with mean ratings of daily abdominal pain, frequency of bowel movements, and consistency of bowel movements on the Bristol Stool Scale in all Veterans. RESULTS: A total of 73 veterans had documented chronic GI symptoms (diarrhea, abdominal pain) and were included in the study. A total of 29/73 (39%) of veterans has increased IP and had a higher average daily stool frequency (P<0.05); increased liquid stools as indicated by a higher Bristol Stool Scale (P<0.01); and a higher mean M-VAS abdominal pain rating (P<0.01). Pearson correlation coefficients revealed that there was a positive correlation between increased IP and stool frequency, Bristol Stool Scale, and M-VAS abdominal pain rating. CONCLUSIONS: Our study demonstrates that deployed Gulf War Veterans with persistent GI symptoms commonly have increased intestinal permeability that potentiates the severity of abdominal pain, diarrhea, and stool consistency. These new findings in our study are important as they may lead to novel diagnostic biomarkers for returning Gulf War Veterans who suffer from chronic functional gastrointestinal disorders. These advances are also important for an increasing number of veterans who are now serving in the Persian Gulf and are at a high risk of developing these chronic pain disorders.


Assuntos
Dor Abdominal/etiologia , Diarreia/epidemiologia , Gastroenteropatias/fisiopatologia , Intestinos/fisiopatologia , Dor Abdominal/epidemiologia , Adulto , Doença Crônica , Feminino , Gastroenteropatias/diagnóstico , Guerra do Golfo , Humanos , Lactulose/urina , Masculino , Manitol/urina , Pessoa de Meia-Idade , Permeabilidade , Estados Unidos , Veteranos
15.
Clin J Pain ; 34(10): 944-949, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29570102

RESUMO

INTRODUCTION: Over 25% of Persian Gulf War (PGW) veterans with Gulf War Illness (GWI) (chronic health symptoms of undetermined etiology) developed gastrointestinal (GI) (diarrhea and abdominal pain) and other somatic symptoms. OBJECTIVES: Our study objective was to determine if veterans with GWI and GI symptoms exhibit heightened patterns of somatic pain perception (hypersensitivity) across nociceptive stimuli modalities. METHODS: Participants were previously deployed GW Veterans with GWI and GI symptoms (n=53); veterans with GWI without GI symptom (n=47); and veteran controls (n=38). We determined pain thresholds for contact thermal, cold pressor, and ischemic stimuli. RESULTS: Veterans with GWI and GI symptoms showed lower pain thresholds (P<0.001) for each stimulus. There was also overlap of somatic hypersensitivities among veterans with GI symptoms with 20% having hypersensitivity to all 3 somatic stimuli. Veterans with GWI and GI symptoms also showed a significant correlation between mechanical visual analog scale abdominal pain ratings and heat pain threshold, cold pressor threshold, and ischemic pain threshold/tolerance. DISCUSSION: Our findings show that there is widespread somatic hypersensitivity in veterans with GWI/GI symptoms that is positively correlated with abdominal pain ratings. In addition, veterans with somatic hypersensitivity that overlap have the greatest number of extraintestinal symptoms. These findings may have a translational benefit: strategies for developing more effective therapeutic agents that can reduce and/or prevent somatic and GI symptoms in veterans deployed to future military conflicts.


Assuntos
Gastroenteropatias , Hiperalgesia , Dor Nociceptiva , Dor Abdominal/fisiopatologia , Temperatura Baixa , Feminino , Gastroenteropatias/fisiopatologia , Guerra do Golfo , Temperatura Alta , Humanos , Hiperalgesia/fisiopatologia , Hipersensibilidade/fisiopatologia , Isquemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Dor Nociceptiva/fisiopatologia , Limiar da Dor , Síndrome , Veteranos
17.
Nat Commun ; 7: 13045, 2016 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-27721471

RESUMO

How the intestinal tract develops a tolerance to foreign antigens is still largely unknown. Here we report that extracellular vesicles (EVs) with TGF-ß1-dependent immunosuppressive activity are produced by intestinal epithelial cells (IECs) under physiological conditions. Transfer of these EVs into inflammatory bowel disease (IBD) mice induced by dextran sulfate sodium salt decreases IBD severity by inducing regulatory T cells and immunosuppressive dendritic cells. In contrast, decreased endogenous EV production promotes IBD development. IECs produce EVs with increased levels of TGF-ß1 upon IBD development in an ERK-dependent manner. Furthermore, these EVs tend to localize in the intestinal tract associated with epithelial cell adhesion molecule (EpCAM). Knockdown of EpCAM in vivo increases the severity of murine IBD, and the protective effect of EVs from IECs with decreased EpCAM on murine IBD is blunted. Therefore, our study indicates that EVs from IECs participate in maintaining the intestinal tract immune balance.


Assuntos
Molécula de Adesão da Célula Epitelial/metabolismo , Células Epiteliais/metabolismo , Vesículas Extracelulares/metabolismo , Intestinos/imunologia , Intestinos/patologia , Animais , Proliferação de Células , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Células Epiteliais/ultraestrutura , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Vesículas Extracelulares/ultraestrutura , Feminino , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/prevenção & controle , Intestinos/ultraestrutura , Camundongos Endogâmicos C57BL , Fosforilação , Índice de Gravidade de Doença , Transdução de Sinais , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
18.
BMC Ophthalmol ; 15: 131, 2015 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-26464103

RESUMO

BACKGROUND: To investigate the molecular defects in a four-generation Chinese pedigree affected with Thiel-Behnke corneal dystrophy (TBCD). And to further study the relationship between genetic mutation and clinical manifestations. METHODS: Individuals of the pedigree were recruited for extensive ophthalmic examinations. Histological studies of two corneal buttons obtained from lamellar keratoplasty were conducted. Peripheral blood was collected in EDTA for genomic DNA isolation from leukocytes of all affected and unaffected members. All 17 exons of the TGFBI gene were screened for mutations by polymerase chain reaction and direct DNA sequencing. RESULTS: Clinical examinations revealed a typical pattern of honeycomb-like TBCD. Histopathology study demonstrated eosinophilic deposits that were congo-red-positive and did not stain with periodic acid Schiff or Masson's trichrome. Genetic analysis disclosed a heterozygous p. Arg555Trp mutation resulted from a missense c. 1663C > T nucleotide change in exon 12 of TGFBI gene in all affected members. Morever, a second rare variant in exon 6 of the TGFBI gene (p. Arg257Trp) also cosegregated within this family and has been confirmed to be a single nucleotide polymorphism (SNP) not previously reported. CONCLUSIONS: The p. Arg555Trp mutation of the TGFBI gene was associated with TBCD, which revealed a novel phenotype-genotype correlation within the mutational spectrum of phenotypically diverse corneal dystrophies.


Assuntos
Distrofias Hereditárias da Córnea/genética , Proteínas da Matriz Extracelular/genética , Polimorfismo de Nucleotídeo Único , Fator de Crescimento Transformador beta/genética , Adulto , Criança , Análise Mutacional de DNA , Éxons/genética , Feminino , Estudos de Associação Genética , Testes Genéticos , Humanos , Masculino , Linhagem , Reação em Cadeia da Polimerase
19.
Sci Rep ; 5: 12713, 2015 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-26234583

RESUMO

Colorectal cancer (CRC) is one of the most frequent malignant neoplasms worldwide. Up to now, no biomarker has been used to predict the prognosis and surveillance of patients with CRC. Recently, the association between osteopontin (OPN) overexpression and the prognosis of CRC was investigated widely, but the results were inconsistent. Therefore, the aim of present meta-analysis was to assess the prognostic effect of osteopontin in patients with CRC. PubMed, EMBASE, Web of Science, Scopus and Chinese Medical Database were systematically searched. A total of 15 studies containing 1698 patients were included in our meta-analysis. The pooled data of studies showed that high OPN expression was significantly associated with high tumor grades (OR = 2.24, 95% CI 1.55-3.23), lymph node metastasis (OR = 2.36, 95% CI 1.71-3.26) and tumor distant metastasis (OR = 2.38, 95% CI 1.01-5.60). Moreover, high OPN expression was significantly associated with the 2-year (HR 1.97, 95% CI 1.30-3.00), 3-year (HR 1.82, 95% CI 1.24-2.68), 5 year (HR 1.53, 95% CI 1.28-1.82) survival rates and overall survival (OS, HR 1.70, 95% CI 1.12-2.60), respectively. These results indicated that OPN could serve as a prognostic biomarker and as a potential therapeutic target for CRC.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Osteopontina/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Expressão Gênica , Humanos , Osteopontina/genética , Prognóstico , Taxa de Sobrevida
20.
Hum Pathol ; 46(6): 843-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25841304

RESUMO

The objective of the present study was to determine whether 2 proteins (nuclear erythroid 2-related factor 2 [Nrf2] and p62) can be used as the biomarkers for prognosis of gliomas. The glioma samples were from 75 glioma patients after surgery. The expression of Nrf2 and p62 in 75 samples was detected with immunohistochemical staining. The correlation between immunohistochemical results and clinicopathological parameters or prognosis was analyzed. The results indicated that high Nrf2 expression was detected in 61.3% of glioma tissue samples and was significantly correlated with age (P = .006), tumor grade (P = .002), and onset time (P = .019). The overall survival (OS) and disease-free survival (DFS) in patients with high Nrf2 expression were significantly shorter than those in patients with low Nrf2 expression (P < .001). High p62 expression was detected in 65.3% of glioma tissue samples, and p62 expression was correlated significantly with the tumor grade (P < .001) and 1-year survival (P = .024). OS and DFS in patients with high p62 expression were significantly shorter than those in patients with low p62 expression (P < .001). Spearman rank correlation test revealed a significant positive relation between Nrf2 and p62 expressions (r = 0.515, P < .001). Multivariate regression analysis showed that p62 expression and age were the significant independent prognostic factors for DFS (P < .05) and tumor grade and p62 expression were independent prognostic parameters for OS (P < .01 or P < .05). These findings indicated that p62 may be used as the prognostic biomarker in patients with gliomas.


Assuntos
Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Neoplasias Encefálicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Adulto Jovem
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