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1.
Clin Transplant Res ; 38(2): 150-153, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38725186

RESUMO

Xanthogranulomatous osteomyelitis (XO) is a rare chronic inflammatory bone disease characterized by the presence of cholesterol-laden foam macrophages, histiocytes, and plasma cells. We report the case of a 41-year-old man with end-stage renal disease who had undergone deceased donor kidney transplantation 4 years earlier. He presented with a chest wall mass that he had first identified 2 weeks prior to admission. Computed tomography revealed a periosseous heterogeneously enhancing soft tissue mass adjacent to the sternal end of the left clavicle, accompanied by irregular and destructive osteolytic lesions on the left side of the sternal manubrium. A total mass resection, which included partial clavicle and sternum removal, was performed. Pathological examination revealed foamy histiocytes along with numerous lymphoplasmacytic cells, confirming the diagnosis of XO. This case underscores the potential for XO to develop following kidney transplantation.

2.
Int. j. morphol ; 42(2)abr. 2024.
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1558142

RESUMO

SUMMARY: Although tacrolimus (TAC) significantly reduces allograft rejection incidence in solid-organ transplantation, its long-term use is associated with an increased risk of TAC-induced nephrotoxicity. In this study, we investigated the renoprotective effects of green tea extract (GTE) with or without the dipeptidyl peptidase 4 inhibitor, gemigliptin, by assessing serum creatinine levels, the amount of proteinuria, and histopathology in TAC-induced nephrotoxicity. TAC-induced nephrotoxicity was induced by intraperitoneal TAC injection, GTE was administered via subcutaneous injection, and gemigliptin was administered orally. Mice with TAC-induced nephrotoxicity exhibited a significant increase in both serum creatinine levels and 24-hour urine protein. However, when treated with GTE via subcutaneous injection, mice showed a decrease in serum creatinine levels and the amount of proteinuria. When GTE was combined with gemigliptin, further renoprotective effects were observed in biochemical assessments, consistent with the attenuation of TAC-induced nephrotoxicity in histopathology. The expression of p53 protein was lower in the mice treated with the combination of GTE and gemigliptin compared to mice with TAC-induced nephrotoxicity. Our results demonstrate that the combination of GTE and gemigliptin treatment reveals synergistic renoprotective effects by decreasing the expression of p53 protein. These findings suggest that the combination of GTE and gemigliptin could potentially be used as a prophylactic or therapeutic strategy for TAC-induced nephrotoxicity.


Aunque tacrolimus (TAC) reduce significativamente la incidencia de rechazo de aloinjertos en trasplantes de órganos sólidos, su uso a largo plazo se asocia con un mayor riesgo de nefrotoxicidad inducida por TAC. En este estudio, investigamos los efectos renoprotectores del extracto de té verde (GTE) con o sin el inhibidor de la dipeptidil peptidasa 4, gemigliptina, mediante la evaluación de los niveles de creatinina sérica, la cantidad de proteinuria y la histopatología en la nefrotoxicidad inducida por TAC. La nefrotoxicidad inducida por TAC se indujo mediante inyección intraperitoneal de TAC, el GTE se administró mediante inyección subcutánea y la gemigliptina se administró por vía oral. Los ratones con nefrotoxicidad inducida por TAC mostraron un aumento significativo tanto en los niveles de creatinina sérica como en la proteína en orina de 24 horas. Sin embargo, cuando se trataron con GTE mediante inyección subcutánea, los ratones mostraron una disminución en los niveles de creatinina sérica y en la cantidad de proteinuria. Cuando se combinó GTE con gemigliptina, se observaron efectos renoprotectores adicionales en las evaluaciones bioquímicas, lo que concuerda con la atenuación de la nefrotoxicidad inducida por TAC en histopatología. La expresión de la proteína p53 fue menor en los ratones tratados con la combinación de GTE y gemigliptina en comparación con los ratones con nefrotoxicidad inducida por TAC. Nuestros resultados demuestran que la combinación de tratamiento con GTE y gemigliptina revela efectos renoprotectores sinérgicos al disminuir la expresión de la proteína p53. Estos hallazgos sugieren que la combinación de GTE y gemigliptina podría usarse potencialmente como estrategia profiláctica o terapéutica para la nefrotoxicidad inducida por TAC.

3.
Nutrients ; 15(24)2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38140298

RESUMO

Chronic kidney disease (CKD) is a major public health problem and a leading cause of cardiovascular disease and death. Early recognition and management of CKD risk factors are necessary to prevent its onset and progression. Neck circumference (NC) is a non-invasive and easily accessible anthropometric measure associated with central obesity and subcutaneous fat accumulation in the upper body. Our study aimed to explore the relationship between NC and the prevalence of CKD using data from the nationally representative Korea National Health and Nutrition Examination Survey (2019-2021). We analyzed data from 10,219 subjects (age > 19 years, no missing values). CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Logistic regression analysis was performed, which revealed a significant association between NC and CKD prevalence even after adjusting for confounding factors, both when NC was considered a continuous variable (OR [95% CI], 1.11 [1.03-1.19]) and in quartiles (Q1 as reference; Q2 OR [95% CI], 1.23 [0.91-1.67]; Q3 OR [95% CI], 1.59 [1.16-2.18]; Q4 OR [95% CI], 1.70 [1.16-2.50]). Our findings suggest that NC could be a simple and effective anthropometric measurement for identifying individuals at risk for CKD.


Assuntos
Insuficiência Renal Crônica , Adulto , Humanos , Adulto Jovem , Inquéritos Nutricionais , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/complicações , Taxa de Filtração Glomerular , Coreia (Geográfico) , Fatores de Risco , República da Coreia/epidemiologia
4.
World J Clin Cases ; 11(29): 7113-7126, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37946781

RESUMO

BACKGROUND: Primary renal lymphoma (PRL) is extremely rare with an incidence of 0.7% among extranodal lymphomas. Occult renal lymphoma, which mimics medical renal disease and bilateral renal involvement, presents a diagnostic challenge to nephrologists and radiologists as the clinical and radiological findings are mostly non-specific or inconclusive. Acute kidney injury (AKI) is not an uncommon finding in renal infiltration due to malignant lymphoma. However, only 14% of cases are detected before death, and the low diagnostic rate may be due to the non-specific clinical manifestations of renal involvement, with only 0.5% of these cases presenting with AKI. Moreover, PRL is difficult to diagnose based on clinical, biochemical, and radiologic features, especially, in the case of bilateral diffuse involvement. CASE SUMMARY: Herein, we report a 74-year-old woman with primary diffuse large B-cell lymphoma who presented with AKI diagnosed by ultrasound-guided needle biopsy. We also report the clinicopathologic findings of 121 PRL cases reported since 1989, by conducting a literature review of published cases. CONCLUSION: A timely renal biopsy provides the most expedient means of establishing the diagnosis. Thus, early identification of the disease by the clinician facilitates early diagnosis toward effective treatment.

5.
Adv Sci (Weinh) ; 10(17): e2204378, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37097643

RESUMO

Immune checkpoint inhibitor (ICI) clinically benefits cancer treatment. However, the ICI responses are only achieved in a subset of patients, and the underlying mechanisms of the limited response remain unclear. 160 patients with non-small cell lung cancer treated with anti-programmed cell death protein-1 (anti-PD-1) or anti-programmed death ligand-1 (anti-PD-L1) are analyzed to understand the early determinants of response to ICI. It is observed that high levels of intracellular adhesion molecule-1 (ICAM-1) in tumors and plasma of patients are associated with prolonged survival. Further reverse translational studies using murine syngeneic tumor models reveal that soluble ICAM-1 (sICAM-1) is a key molecule that increases the efficacy of anti-PD-1 via activation of cytotoxic T cells. Moreover, chemokine (CXC motif) ligand 13 (CXCL13) in tumors and plasma is correlated with the level of ICAM-1 and ICI efficacy, suggesting that CXCL13 might be involved in the ICAM-1-mediated anti-tumor pathway. Using sICAM-1 alone and in combination with anti-PD-1 enhances anti-tumor efficacy in anti-PD-1-responsive tumors in murine models. Notably, combinatorial therapy with sICAM-1 and anti-PD-1 converts anti-PD-1-resistant tumors to responsive ones in a preclinical study. These findings provide a new immunotherapeutic strategy for treating cancers using ICAM-1.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Camundongos , Animais , Linfócitos T CD8-Positivos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Molécula 1 de Adesão Intercelular
6.
Microbiome ; 10(1): 188, 2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333752

RESUMO

BACKGROUND: Comparisons of the gut microbiome of lean and obese humans have revealed that obesity is associated with the gut microbiome plus changes in numerous environmental factors, including high-fat diet (HFD). Here, we report that two species of Bifidobacterium are crucial to controlling metabolic parameters in the Korean population. RESULTS: Based on gut microbial analysis from 99 Korean individuals, we observed the abundance of Bifidobacterium longum and Bifidobacterium bifidum was markedly reduced in individuals with increased visceral adipose tissue (VAT), body mass index (BMI), blood triglyceride (TG), and fatty liver. Bacterial transcriptomic analysis revealed that carbohydrate/nucleoside metabolic processes of Bifidobacterium longum and Bifidobacterium bifidum were associated with protecting against diet-induced obesity. Oral treatment of specific commercial Bifidobacterium longum and Bifidobacterium bifidum enhanced bile acid signaling contributing to potentiate oxidative phosphorylation (OXPHOS) in adipose tissues, leading to reduction of body weight gain and improvement in hepatic steatosis and glucose homeostasis. Bifidobacterium longum or Bifidobacterium bifidum manipulated intestinal sterol biosynthetic processes to protect against diet-induced obesity in germ-free mice. CONCLUSIONS: Our findings support the notion that treatment of carbohydrate/nucleoside metabolic processes-enriched Bifidobacterium longum and Bifidobacterium bifidum would be a novel therapeutic strategy for reprograming the host metabolic homeostasis to protect against metabolic syndromes, including diet-induced obesity. Video Abstract.


Assuntos
Bifidobacterium longum , Bifidobacterium , Humanos , Camundongos , Animais , Bifidobacterium/metabolismo , Nucleosídeos/metabolismo , Nucleosídeos/uso terapêutico , Fosforilação Oxidativa , Obesidade/microbiologia , Dieta Hiperlipídica/efeitos adversos , Tecido Adiposo Branco/metabolismo
7.
Sensors (Basel) ; 22(7)2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35408141

RESUMO

A satellite navigation system makes it simple to find and navigate to a specific position. Although a carrier measurement is required to establish a precise position due to the characteristics of the carrier observation, it is difficult to determine a robust position in a poor signal reception environment such as urban areas. Various studies are being carried out to overcome this problem, with cycle slips being the most important factor. With only a single frequency, it is very challenging to detect cycle slips in multiple satellite channels at the same time. A geometry-based technique is proposed in this study as a technical solution for detecting simultaneous cycle slips for multiple channels utilizing only a single-frequency receiver. The method could detect a half-wavelength size of cycle slip for each channel through the geometry information.

8.
Cancers (Basel) ; 13(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33668827

RESUMO

Colorectal cancer (CRC) is among the leading causes of cancer-related death in the world. The development of CRC is associated with smoking, diet, and microbial exposure. Previous studies have shown that dysbiosis of the gut microbiome affects cancer development, because it leads to inflammation and genotoxicity. Supplementation with specific microbiota induces anti-tumor effects by enhancing of anti-tumor immunity. Here, we observed that supplementation with either of two B. breve strains reduces tumor growth in MC38 colon carcinoma-bearing mice. Interestingly, only one B. breve strain boosted the efficacy of cancer therapeutics, including oxaliplatin and PD-1 blockade. Extensive immune profiling and transcriptomic analysis revealed that the boosting B. breve strain augments lymphocyte-mediated anti-cancer immunity. Our results suggest that supplementation with B. breve strains could potentially be used as a strategy to enhance the efficacy of CRC therapeutics.

9.
Commun Biol ; 4(1): 231, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608630

RESUMO

An unbalanced microbial ecosystem on the human skin is closely related to skin diseases and has been associated with inflammation and immune responses. However, little is known about the role of the skin microbiome on skin aging. Here, we report that the Streptococcus species improved the skin structure and barrier function, thereby contributing to anti-aging. Metagenomic analyses showed the abundance of Streptococcus in younger individuals or those having more elastic skin. Particularly, we isolated Streptococcus pneumoniae, Streptococcus infantis, and Streptococcus thermophilus from face of young individuals. Treatment with secretions of S. pneumoniae and S. infantis induced the expression of genes associated with the formation of skin structure and the skin barrier function in human skin cells. The application of culture supernatant including Streptococcal secretions on human skin showed marked improvements on skin phenotypes such as elasticity, hydration, and desquamation. Gene Ontology analysis revealed overlaps in spermidine biosynthetic and glycogen biosynthetic processes. Streptococcus-secreted spermidine contributed to the recovery of skin structure and barrier function through the upregulation of collagen and lipid synthesis in aged cells. Overall, our data suggest the role of skin microbiome into anti-aging and clinical applications.


Assuntos
Microbiota , Envelhecimento da Pele , Pele/microbiologia , Espermidina/metabolismo , Streptococcus/metabolismo , Adulto , Colágeno/metabolismo , Disbiose , Elasticidade , Feminino , Humanos , Lipogênese , Metagenoma , Fenótipo , Pele/metabolismo , Streptococcus/genética , Streptococcus/crescimento & desenvolvimento , Adulto Jovem
10.
Exp Mol Med ; 53(2): 223-234, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33547412

RESUMO

The identification of predictive biomarkers or models is necessary for the selection of patients who might benefit the most from immunotherapy. Seven histological features (signet ring cell [SRC], fibrous stroma, myxoid stroma, tumor-infiltrating lymphocytes [TILs], necrosis, tertiary lymphoid follicles, and ulceration) detected in surgically resected tissues (N = 44) were used to train a model. The presence of SRC became an optimal decision parameter for pathology alone (AUC = 0.78). Analysis of differentially expressed genes (DEGs) for the prediction of genomic markers showed that C-X-C motif chemokine ligand 11 (CXCL11) was high in responders (P < 0.001). Immunohistochemistry (IHC) was performed to verify its potential as a biomarker. IHC revealed that the expression of CXCL11 was associated with responsiveness (P = 0.003). The response prediction model was trained by integrating the results of the analysis of pathological factors and RNA sequencing (RNA-seq). When trained with the C5.0 decision tree model, the categorical level of the expression of CXCL11, a single variable, was shown to be the best model (AUC = 0.812). The AUC of the model trained with the random forest was 0.944. Survival analysis revealed that the C5.0-trained model (log-rank P = 0.01 for progression-free survival [PFS]; log-rank P = 0.012 for overall survival [OS]) and the random forest-trained model (log-rank P < 0.001 for PFS; log-rank P = 0.001 for OS) predicted prognosis more accurately than the PD-L1 test (log-rank P = 0.031 for PFS; log-rank P = 0.107 for OS).


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Terapia de Alvo Molecular , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Bases de Dados Genéticas , Gerenciamento Clínico , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etiologia , Análise de Sobrevida , Resultado do Tratamento
11.
Nat Microbiol ; 6(3): 277-288, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33432149

RESUMO

The gut microbiome can influence the development of tumours and the efficacy of cancer therapeutics1-5; however, the multi-omics characteristics of antitumour bacterial strains have not been fully elucidated. In this study, we integrated metagenomics, genomics and transcriptomics of bacteria, and analyses of mouse intestinal transcriptome and serum metabolome data to reveal an additional mechanism by which bacteria determine the efficacy of cancer therapeutics. In gut microbiome analyses of 96 samples from patients with non-small-cell lung cancer, Bifidobacterium bifidum was abundant in patients responsive to therapy. However, when we treated syngeneic mouse tumours with commercial strains of B. bifidum to establish relevance for potential therapeutic uses, only specific B. bifidum strains reduced tumour burden synergistically with PD-1 blockade or oxaliplatin treatment by eliciting an antitumour host immune response. In mice, these strains induced tuning of the immunological background by potentiating the production of interferon-γ, probably through the enhanced biosynthesis of immune-stimulating molecules and metabolites.


Assuntos
Bifidobacterium bifidum/fisiologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Probióticos/uso terapêutico , Carga Tumoral/efeitos dos fármacos , Animais , Bifidobacterium bifidum/classificação , Bifidobacterium bifidum/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/microbiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Combinada , Microbioma Gastrointestinal , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/microbiologia , Neoplasias Pulmonares/patologia , Metaboloma/efeitos dos fármacos , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Probióticos/administração & dosagem , Especificidade da Espécie , Transcriptoma/efeitos dos fármacos , Triptofano/metabolismo
12.
Exp Mol Med ; 52(9): 1574-1586, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32917958

RESUMO

The gut microbiota has pivotal roles in metabolic homeostasis and modulation of the intestinal environment. Notably, the administration of Lactobacillus spp. ameliorates diet-induced obesity in humans and mice. However, the mechanisms through which Lactobacillus spp. control host metabolic homeostasis remain unclear. Accordingly, in this study, we evaluated the physiological roles of Lactobacillus fermentum in controlling metabolic homeostasis in diet-induced obesity. Our results demonstrated that L. fermentum-potentiated oxidative phosphorylation in adipose tissue, resulting in increased energy expenditure to protect against diet-induced obesity. Indeed, oral administration of L. fermentum LM1016 markedly ameliorated glucose clearance and fatty liver in high-fat diet-fed mice. Moreover, administration of L. fermentum LM1016 markedly decreased inflammation and increased oxidative phosphorylation in gonadal white adipose tissue, as demonstrated by transcriptome analysis. Finally, metabolome analysis showed that metabolites derived from L. fermentum LM1016-attenuated adipocyte differentiation and inflammation in 3T3-L1 preadipocytes. These pronounced metabolic improvements suggested that the application of L. fermentum LM1016 could have clinical applications for the treatment of metabolic syndromes, such as diet-induced obesity.


Assuntos
Tecido Adiposo/metabolismo , Limosilactobacillus fermentum/fisiologia , Obesidade/etiologia , Obesidade/metabolismo , Fosforilação Oxidativa , Probióticos , Células 3T3-L1 , Animais , Biomarcadores , Peso Corporal , Dieta Hiperlipídica/efeitos adversos , Suscetibilidade a Doenças , Microbioma Gastrointestinal , Perfilação da Expressão Gênica , Fígado/metabolismo , Fígado/patologia , Metabolômica/métodos , Camundongos , Transdução de Sinais
13.
J Vet Sci ; 20(4): e44, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31364328

RESUMO

This study evaluated the feasibility of using texture analysis and machine learning to distinguish radiographic lung patterns. A total of 1200 regions of interest (ROIs) including four specific lung patterns (normal, alveolar, bronchial, and unstructured interstitial) were obtained from 512 thoracic radiographs of 252 dogs and 65 cats. Forty-four texture parameters based on eight methods of texture analysis (first-order statistics, spatial gray-level-dependence matrices, gray-level-difference statistics, gray-level run length image statistics, neighborhood gray-tone difference matrices, fractal dimension texture analysis, Fourier power spectrum, and Law's texture energy measures) were used to extract textural features from the ROIs. The texture parameters of each lung pattern were compared and used for training and testing of artificial neural networks. Classification performance was evaluated by calculating accuracy and the area under the receiver operating characteristic curve (AUC). Forty texture parameters showed significant differences between the lung patterns. The accuracy of lung pattern classification was 99.1% in the training dataset and 91.9% in the testing dataset. The AUCs were above 0.98 in the training set and above 0.92 in the testing dataset. Texture analysis and machine learning algorithms may potentially facilitate the evaluation of medical images.


Assuntos
Pulmão/diagnóstico por imagem , Aprendizado de Máquina , Radiografia/veterinária , Algoritmos , Animais , Área Sob a Curva , Gatos , Cães , Feminino , Masculino , Curva ROC , Radiografia/métodos
14.
EBioMedicine ; 39: 484-496, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30611717

RESUMO

BACKGROUND: Myofibroblasts are known to play a key role in the development of idiopathic pulmonary fibrosis (IPF). Two drugs, pirfenidone and nintedanib, are the only approved therapeutic options for IPF, but their applications are limited due to their side effects. Thus, curative IPF drugs represent a huge unmet medical need. METHODS: A mouse hepatic stellate cell (HSC) line was established that could robustly differentiate into myofibroblasts upon treatment with TGF-ß. Eupatilin was assessed in diseased human lung fibroblasts from IPF patients (DHLFs) as well as in human lung epithelial cells (HLECs). The drug's performance was extensively tested in a bleomycin-induced lung fibrosis model (BLM). Global gene expression studies and proteome analysis were performed. FINDINGS: Eupatilin attenuated disease severity of BLM in both preventative and therapeutic studies. The drug inhibited the in vitro transdifferantiation of DHLFs to myofibroblasts upon stimulation with TGF-ß. No such induction of the in vitro transdifferantiation was observed in TGF-ß treated HLECs. Specific carbons of eupatilin were essential for its anti-fibrotic activity. Eupatilin was capable of dismantling latent TGF-ß complex, specifically by eliminating expression of the latent TGF-ß binding protein 1 (LTBP1), in ECM upon actin depolymerization. Unlike eupatilin, pirfenidone was unable to block fibrosis of DHLFs or HSCs stimulated with TGF-ß. Eupatilin attenuated phosphorylation of Smad3 by TGF-ß. Eupatilin induced myofibroblasts to dedifferentiate into intermediate HCS-like cells. INTERPRETATION: Eupatilin may act directly on pathogenic myofibroblasts, disarming them, whereas the anti-fibrotic effect of pirfenidone may be indirect. Eupatilin could increase the efficacy of IPF treatment to curative levels.


Assuntos
Fibroblastos/patologia , Flavonoides/farmacologia , Fibrose Pulmonar Idiopática/tratamento farmacológico , Proteínas de Ligação a TGF-beta Latente/metabolismo , Miofibroblastos/citologia , Animais , Bleomicina/efeitos adversos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Transdiferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Flavonoides/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/metabolismo , Proteínas de Ligação a TGF-beta Latente/genética , Camundongos , Miofibroblastos/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/farmacologia
15.
Nanoscale ; 11(3): 1091-1102, 2019 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-30574649

RESUMO

Porous metal nanofoams have made significant contributions to a diverse set of technologies from separation and filtration to aerospace. Nonetheless, finer control over nano and microscale features must be gained to reach the full potential of these materials in energy storage, catalytic, and sensing applications. As biologics naturally occur and assemble into nano and micro architectures, templating on assembled biological materials enables nanoscale architectural control without the limited chemical scope or specialized equipment inherent to alternative synthetic techniques. Here, we rationally assemble 1D biological templates into scalable, 3D structures to fabricate metal nanofoams with a variety of genetically programmable architectures and material chemistries. We demonstrate that nanofoam architecture can be modulated by manipulating viral assembly, specifically by editing the viral surface coat protein, as well as altering templating density. These architectures were retained over a broad range of compositions including monometallic and bi-metallic combinations of noble and transition metals of copper, nickel, cobalt, and gold. Phosphorous and boron incorporation was also explored. In addition to increasing the surface area over a factor of 50, as compared to the nanofoam's geometric footprint, this process also resulted in a decreased average crystal size and altered phase composition as compared to non-templated controls. Finally, templated hydrogels were deposited on the centimeter scale into an array of substrates as well as free standing foams, demonstrating the scalability and flexibility of this synthetic method towards device integration. As such, we anticipate that this method will provide a platform to better study the synergistic and de-coupled effects between nano-structure and composition for a variety of applications including energy storage, catalysis, and sensing.


Assuntos
Nanoestruturas/química , Bacteriófago M13/química , Bacteriófago M13/metabolismo , Técnicas Biossensoriais , Boro/química , Catálise , Hidrogéis/química , Metais/química , Fósforo/química , Porosidade , Sais/química
16.
Angew Chem Int Ed Engl ; 57(32): 10221-10225, 2018 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-29920901

RESUMO

The dynamics of carbon monoxide on Cu surfaces was investigated during CO reduction, providing insight into the mechanism leading to the formation of hydrogen, methane, and ethylene, the three key products in the electrochemical reduction of CO2 . Reaction order experiments were conducted at low temperature in an ethanol medium affording high solubility and surface-affinity for carbon monoxide. Surprisingly, the methane production rate is suppressed by increasing the pressure of CO, whereas ethylene production remains largely unaffected. The data show that CH4 and H2 production are linked through a common H intermediate and that methane is formed through reactions among adsorbed H and CO, which are in direct competition with each other for surface sites. The data exclude the participation of solution species in rate-limiting steps, highlighting the importance of increasing surface recombination rates for efficient fuel synthesis.

17.
J Am Chem Soc ; 140(7): 2397-2400, 2018 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-29266936

RESUMO

Correlating the current/voltage response of an electrode to the intrinsic properties of the active material requires knowledge of the electrochemically active surface area (ECSA), a parameter that is often unknown and overlooked, particularly for highly nanostructured electrodes. Here we demonstrate the power of nonaqueous electrochemical double layer capacitance (DLC) to provide reasonable estimates of the ECSA across 17 diverse materials spanning metals, conductive oxides, and chalcogenides. Whereas data recorded in aqueous electrolytes generate a wide range of areal specific capacitance values (7-63 µF/real cm2), nearly all materials examined display an areal specific capacitance of 11 ± 5 µF/real cm2 when measured in weakly coordinating KPF6/MeCN electrolytes. By minimizing ion transfer reactions that convolute accurate DLC measurements, we establish a robust methodology for quantifying ECSA, enabling more accurate structure-function correlations.

18.
J Vet Sci ; 19(2): 296-300, 2018 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-29169229

RESUMO

This study was carried out to derive and evaluate reference computed tomography (CT)-based indices for normal canine spine. CT and magnetic resonance images were acquired from 12 clinically normal Beagle dogs (normal group) and 50 dogs with 56 spinal disorders (patient group). Image acquisition regions were cervical spine (C2-T1), thoracic spine (T1-T13), and lumbar spine (L1-L7). Measured indices were: the ratios of width to height of the spinal cord including the dura matter (CR) and of the vertebral foramen (FR), and the ratio of the cross-sectional area of the spinal cord to that of the vertebral foramen (CFAR). Reliability analysis was performed to evaluate intermodality agreement. Student's t-tests and receiver operating characteristic curves were used to discriminate the normal and patient groups on CT. Intermodality agreements of the normal and patient groups were acceptable to excellent. The highest discriminating levels of CR at the vertebral body level and the intervertebral disc space level were 1.25 or more and 1.44 or more, respectively. FR and CFAR had the highest discriminating level at the cervical region. This report presents quantitative information on canine spinal morphometry; the obtained indices may be helpful for CT screening of dogs with spinal disorders.


Assuntos
Doenças do Cão/diagnóstico por imagem , Doenças da Coluna Vertebral/veterinária , Coluna Vertebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/veterinária , Animais , Estudos de Casos e Controles , Cães , Feminino , Imageamento por Ressonância Magnética/veterinária , Masculino , Doenças da Coluna Vertebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos
19.
J Am Chem Soc ; 139(47): 17109-17113, 2017 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-28978199

RESUMO

We show that bicarbonate is neither a general acid nor a reaction partner in the rate-limiting step of electrochemical CO2 reduction catalysis mediated by planar polycrystalline Au surfaces. We formulate microkinetic models and propose diagnostic criteria to distinguish the role of bicarbonate. Comparing these models with the observed zero-order dependence in bicarbonate and simulated interfacial concentration gradients, we conclude that bicarbonate is not a general acid cocatalyst. Instead, it acts as a viable proton donor past the rate-limiting step and a sluggish buffer that maintains the bulk but not local pH in CO2-saturated aqueous electrolytes.

20.
Angew Chem Int Ed Engl ; 55(49): 15282-15286, 2016 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-27862743

RESUMO

An electrode's performance for catalytic CO2 conversion to fuels is a complex convolution of surface structure and transport effects. Using well-defined mesostructured silver inverse opal (Ag-IO) electrodes, it is demonstrated that mesostructure-induced transport limitations alone serve to increase the turnover frequency for CO2 activation per unit area, while simultaneously improving reaction selectivity. The specific activity for catalyzed CO evolution systematically rises by three-fold and the specific activity for catalyzed H2 evolution systematically declines by ten-fold with increasing mesostructural roughness of Ag-IOs. By exploiting the compounding influence of both of these effects, we demonstrate that mesostructure, rather than surface structure, can be used to tune CO evolution selectivity from less than 5 % to more than 80 %. These results establish electrode mesostructuring as a powerful complementary tool for tuning both catalyst selectivity and efficiency for CO2 conversion into fuels.

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