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1.
J Chem Phys ; 150(6): 064313, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30769993

RESUMO

Two independent methods, namely, Binary-encounter Bethe (BEB) and complex scattering potential-ionization contribution (CSP-ic) methods, are employed to calculate the total ionization cross section (Qion) for cyclic organic molecules from ionization threshold to 5 keV for which there is a paucity of data in the literature. The Qion calculated with the (BEB/ωB97X) combination is found to give good agreement with the experimental results, the CSP-ic method, and the Qion calculated from Irikura orbital energies. The Qion for most of the targets are calculated for the first time over such a wide energy range. Hence, to check the consistency and reliability of the present data, we have also computed the static polarizability for all the targets and the variation of maximum ionization cross section (Qion,max) with polarizability is studied. A linear relationship is observed between these quantities indicating the consistency and reliability of the present Qion data. The targets studied are important for industrial applications, radiation biology, and astrophysics.

2.
J Prosthodont ; 28(1): e210-e215, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28598530

RESUMO

PURPOSE: To evaluate the effect of temporary cement cleaning methods on the retention of cemented crowns using zinc phosphate cement and resin-modified glass ionomer cement. MATERIALS AND METHODS: Forty titanium specimens were fabricated to simulate prepared molars with minimally retentive taper. The Ni-Cr cast crowns were fabricated, temporarily cemented, and separated. The specimens were divided into four groups according to the temporary cement cleaning method (n = 10) as follows: control group (no temporary cementation), orange solvent group, ultrasonic cleaning group, and air-abrasion group. After the cleaning procedures, the specimens were cemented with definitive cements (zinc phosphate cement and resin-modified glass ionomer, RMGI, cement) and subjected to thermocycling (5000 cycles, 5-55°C, dwell time, 10 seconds). The tensile bond strength of each specimen was measured using a universal testing machine, and the results were analyzed using the Kruskal-Wallis and Mann-Whitney U test (α = 0.05). RESULTS: When cemented with zinc phosphate cement, the statistical analysis showed that the value of the air-abrasion group was significantly higher than those of the other groups (p < 0.01). There was no statistically significant difference among the other groups. When cemented with RMGI cement, the air-abrasion group showed the lowest value, and the control group showed the highest value (p < 0.01). The difference between the ultrasonic cleaning group and the orange solvent group was not statistically significant. CONCLUSION: The use of temporary cement did not have a significant influence on retention of permanently cemented crowns when zinc phosphate cement was used for permanent cementation. Airborne-particle abrasion after provisional cementation improved retention of crowns cemented with zinc phosphate cement; however, the use of temporary cement significantly decreased retention of permanently cemented crowns when RMGI cement was used regardless of the temporary cement cleaning method.


Assuntos
Cimentação/métodos , Cimentos Dentários/química , Retenção em Prótese Dentária/métodos , Cimentos de Ionômeros de Vidro/química , Teste de Materiais , Abrasão Dental por Ar/métodos , Coroas , Materiais Dentários/efeitos adversos , Análise do Estresse Dentário , Detergentes/uso terapêutico , Humanos , Resistência à Tração , Terapia por Ultrassom/métodos , Cimento de Fosfato de Zinco/química
3.
J Allergy Clin Immunol ; 137(5): 1466-1476.e3, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26824999

RESUMO

BACKGROUND: Psoriasis is one of the most common chronic inflammatory diseases of the skin. Recently, IL-17-producing T cells have been shown to play a critical role in psoriatic inflammation. Programmed cell death 1 (PD-1) is a coinhibitory receptor expressed on T cells in various chronic inflammatory diseases; however, the expression and function of PD-1 during psoriatic inflammation have not previously been characterized. OBJECTIVE: We examined PD-1 expression on IL-17A-producing T cells from imiquimod-treated mice and patients with psoriasis. Additionally, we investigated the therapeutic effect of recombinant programmed cell death ligand 1 (PD-L1) protein on imiquimod-induced psoriatic inflammation. METHODS: PD-1 expression on IL-17A-producing γδ T cells from imiquimod-treated mice was examined by means of multicolor flow cytometric analysis. In the psoriatic skin of patients, PD-1 and IL-17A expression was analyzed by using immunofluorescence. The therapeutic effect of PD-L1-Fc fusion protein (PD-L1-Fc) was assessed in imiquimod-treated mice ex vivo and in vivo. RESULTS: During imiquimod-induced psoriatic inflammation, PD-1 is overexpressed on CD27(-)Vγ1(-) γδ T cells. Furthermore, PD-1 expression on IL-17A(+) T cells was confirmed in psoriatic skin tissues from patients and imiquimod-treated mice. In the CD27(-)Vγ1(-) γδ T-cell population, Vγ4(-) γδ T cells with Vγ6 mRNA expression showed a high level of PD-1 expression. Furthermore, these PD-1(hi)Vγ4(-) (Vγ6(+)) γδ T cells were specialized for anti-CD3-induced IL-17A production, which was inhibited by PD-L1-Fc treatment. In imiquimod-treated mice PD-L1-Fc reduced psoriatic inflammation when given alone and enhanced the therapeutic effect of anti-p40 when given in combination. CONCLUSION: PD-1 is overexpressed in IL-17A-producing T cells in both imiquimod-treated mice and patients with psoriasis. Moreover, recombinant PD-L1-Fc alleviates psoriatic inflammation in imiquimod-treated mice.


Assuntos
Interleucina-17/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Psoríase/metabolismo , Subpopulações de Linfócitos T/metabolismo , Adjuvantes Imunológicos , Aminoquinolinas , Animais , Antígeno B7-H1/farmacologia , Antígeno B7-H1/uso terapêutico , Humanos , Imiquimode , Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Pele/efeitos dos fármacos , Pele/metabolismo
4.
Molecules ; 21(7)2016 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-27399667

RESUMO

Skin is the outermost layer of the human body that is constantly exposed to environmental stressors, such as UV radiation and toxic chemicals, and is susceptible to mechanical wounding and injury. The ability of the skin to repair injuries is paramount for survival and it is disrupted in a spectrum of disorders leading to skin pathologies. Diabetic patients often suffer from chronic, impaired wound healing, which facilitate bacterial infections and necessitate amputation. Here, we studied the effects of gallic acid (GA, 3,4,5-trihydroxybenzoic acid; a plant-derived polyphenolic compound) on would healing in normal and hyperglucidic conditions, to mimic diabetes, in human keratinocytes and fibroblasts. Our study reveals that GA is a potential antioxidant that directly upregulates the expression of antioxidant genes. In addition, GA accelerated cell migration of keratinocytes and fibroblasts in both normal and hyperglucidic conditions. Further, GA treatment activated factors known to be hallmarks of wound healing, such as focal adhesion kinases (FAK), c-Jun N-terminal kinases (JNK), and extracellular signal-regulated kinases (Erk), underpinning the beneficial role of GA in wound repair. Therefore, our results demonstrate that GA might be a viable wound healing agent and a potential intervention to treat wounds resulting from metabolic complications.


Assuntos
Antioxidantes/farmacologia , Ácido Gálico/farmacologia , Glucose/antagonistas & inibidores , Queratinócitos/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Ácido Ascórbico/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Catalase/genética , Catalase/metabolismo , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Regulação da Expressão Gênica , Glucose/metabolismo , Glucose/toxicidade , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Queratinócitos/citologia , Queratinócitos/metabolismo , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Modelos Biológicos , Picratos/antagonistas & inibidores , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
5.
Gut ; 64(2): 260-71, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24902766

RESUMO

OBJECTIVE: Programmed death-ligand 1 (PD-L1) has been shown to negatively regulate immune responses via its interaction with PD-1 receptor. In this study, we investigated the effects of PD-L1-Fc treatment on intestinal inflammation using two murine models of inflammatory colitis induced by dextran sulfate sodium (DSS) and T-cell transfer. DESIGN: The anti-colitis effect of adenovirus expressing Fc-conjugated PD-L1 (Ad/PD-L1-Fc) and recombinant PD-L1-Fc protein was evaluated in DSS-treated wild-type and Rag-1 knockout (KO) mice. We examined differentiation of T-helper cells, frequency of innate immune cells, and cytokine production by dendritic cells (DCs) in the colon from DSS-treated mice after PD-L1-Fc administration. In Rag-1 KO mice reconstituted with CD4 CD45RB(high) T cells, we assessed the treatment effect of PD-L1-Fc protein on the development of colitis. RESULTS: Administration of Ad/PD-L1-Fc significantly ameliorated DSS-induced colitis, which was accompanied by diminished frequency of interleukin (IL)-17A-producing CD4 T cells and increased interferon-γ-producing CD4 T cells in the colon of DSS-fed mice. The anti-colitic effect of PD-L1-Fc treatment was also observed in DSS-treated Rag-1 KO mice, indicating lymphoid cell independency. PD-L1-Fc modulated cytokine production by colonic DCs and the effect was dependent on PD-1 expression. Furthermore, PD-L1-Fc protein could significantly reduce the severity of colitis in CD4 CD45RB(high) T-cell-transferred Rag-1 KO mice. CONCLUSIONS: Based on the protective effect of PD-L1-Fc against DSS-induced and T-cell-induced colitis, our results suggest that PD-1-mediated inhibitory signals have a crucial role in limiting the development of colonic inflammation. This implicates that PD-L1-Fc may provide a novel therapeutic approach to treat inflammatory bowel disease.


Assuntos
Antígeno B7-H1/uso terapêutico , Colite Ulcerativa/prevenção & controle , Fatores Imunológicos/uso terapêutico , Doença Aguda , Adenoviridae/genética , Animais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Antígeno B7-H1/farmacologia , Diferenciação Celular/efeitos dos fármacos , Colite Ulcerativa/etiologia , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Colo/imunologia , Citocinas/biossíntese , Células Dendríticas/imunologia , Sulfato de Dextrana , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Vetores Genéticos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Imunidade Inata , Imunidade nas Mucosas , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/metabolismo , Fragmentos Fc das Imunoglobulinas/farmacologia , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Fatores Imunológicos/genética , Fatores Imunológicos/metabolismo , Fatores Imunológicos/farmacologia , Mucosa Intestinal/imunologia , Transfusão de Linfócitos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Recombinantes de Fusão/farmacologia , Proteínas Recombinantes de Fusão/uso terapêutico , Linfócitos T Auxiliares-Indutores/imunologia , Células Th17/imunologia
6.
Biochem Biophys Res Commun ; 466(3): 300-5, 2015 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-26361146

RESUMO

Uncontrolled endoplasmic reticulum (ER) stress activates members of the NOD-like receptor family, which are involved in the pyrin domain containing 3 (NLRP3) inflammasome pathway. This pathway has been proposed to contribute to ß-cell dysfunction and death. However, the connection between ER stress and NLRP3 inflammasome activation remains controversial. Here we generated Akita/KO (Ins2(+/C96Y); NLRP3(-/-)) mice by crossing Akita (Ins2(+/C96Y); NLRP3(+/+)) mice with NLRP3 KO (Ins2(+/+); NLRP3(-/-)) mice. We then compared the metabolic phenotypes of the different strains. Knockout of the NLRP3 inflammasome did not affect the onset or the severity of diabetes in Akita/KO mice at any point of the study. Histological observations of pancreatic islets supported these findings. Tunicamycin-exposed islets from NLRP3 KO mice exhibited similar levels of ER stress and apoptosis induction as islets from WT (Ins2(+/+); NLRP3(+/+)) mice. Furthermore, NLRP3 deletion did not prevent tunicamycin-mediated reduction of glucose-stimulated insulin secretion. In conclusion, deletion of the NLRP3 inflammasome did not protect against ER stress-induced diabetes development or ß-cell damage, indicating that ß cell death in Akita mice is not mediated via activation of the NLRP3 inflammasome.


Assuntos
Proteínas de Transporte/metabolismo , Estresse do Retículo Endoplasmático , Células Secretoras de Insulina/citologia , Animais , Apoptose , Retículo Endoplasmático/metabolismo , Deleção de Genes , Glucose/metabolismo , Inflamassomos , Inflamação/metabolismo , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR , Fenótipo , Polimorfismo de Fragmento de Restrição , Desnaturação Proteica , Tunicamicina/química
7.
Bioorg Med Chem ; 23(13): 3322-36, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-25982078

RESUMO

A series of alkoxy-3-indolylacetic acid analogs has been discovered as peroxisome proliferator-activated receptor (PPAR) agonists. Structure-activity relationship study indicated that PPARα/γ/δ activities were dependent on the nature of the hydrophobic group, the attachment position of the alkoxy linker to the indole ring, and N-alkylation of indole nitrogen. Some compounds presented significant PPARγ/δ activity and molecular modeling suggested their putative binding modes in the ligand binding domain of PPARγ. Of these, compound 51 was selected for in vivo study via an evaluation of microsomal stability in mouse and human liver. Compound 51 lowered the levels of fasting blood glucose, insulin, and HbA1c without gain in body weight in db/db mice. When compound 51 was treated, hepatic triglycerides level and the size of adipocytes in white adipose tissue of db/db mice were also reduced as opposed to treatment with rosiglitazone. Taken together, compound 51 shows high potential warranting further studies in models for diabetes and related metabolic disorders and may be in use as a chemical tool for the understanding of PPAR biology.


Assuntos
Álcoois/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Ácidos Indolacéticos/farmacologia , PPAR delta/agonistas , PPAR gama/agonistas , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/patologia , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Desenho de Fármacos , Jejum , Regulação da Expressão Gênica , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/síntese química , Ácidos Indolacéticos/síntese química , Insulina/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Microssomos Hepáticos/patologia , PPAR delta/genética , PPAR delta/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Rosiglitazona , Transdução de Sinais , Tiazolidinedionas/farmacologia
8.
Int J Pharm ; : 124415, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960340

RESUMO

The human colorectal adenocarcinoma cell line Caco-2, widely used for studying intestinal drug permeability, is typically grown on permeable filter supports and matures in 21 days with frequent media changes. The process is labor-intensive, prone to contamination, and has low throughput, contributing to the overall high utilization cost. Efforts to establish a low-cost, high-throughput, short-duration model have encountered obstacles, such as weaker tight junctions causing monolayer leaks, incomplete differentiation resulting in low transporter expression, intricate and challenging protocols, and cytotoxicity, limiting the usability. Hence, this study aimed to develop a low-cost, efficient, and short-duration model by addressing the aforementioned concerns by customizing the media and finding a safe differentiation inducer. We generated a new rapid model using sodium valerate, which demonstrated sufficient transporter activity, improved monolayer integrity, and higher levels of differentiation markers than the 21-day model. Furthermore, this model exhibited consistent and reliable results when used to evaluate drug permeability over multiple days of repeated use. This study demonstrates the potential of a sodium valerate-assisted abbreviated model for drug permeability assessment with economic and practical advantages.

9.
Nutrients ; 15(12)2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37375700

RESUMO

It was recently found that glutamine (Gln) supplementation activates glutamatergic neurotransmission and prevents chronic-stress-induced mild cognitive impairment (MCI). In this study, we evaluated the effects of Gln on glutamatergic activity in the medial prefrontal cortex and the onset of cognitive impairment in a triple-transgenic Alzheimer's disease mouse model (3×Tg-AD). Female 3×Tg-AD mice were fed a normal diet (3×Tg) or a Gln-supplemented diet (3×Tg+Gln) from 2 to 6 months of age. Glutamatergic neuronal activity was analyzed at 6 months, and cognitive function was examined at 2, 4, and 6 months. 3×Tg mice exhibited a decrease in glutamatergic neurotransmission in the infralimbic cortex, but 3×Tg+Gln mice did not. The 3×Tg group showed MCI at 6 months of age, but the 3×Tg+Gln group did not. The expressions of amyloid peptide, inducible nitric oxide synthase, and IBA-1 were not elevated in the infralimbic cortex in the 3×Tg+Gln group. Therefore, a Gln-supplemented diet could delay the onset of MCI even in a mouse model predisposed to cognitive impairment and dementia through genetic modification.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Camundongos , Feminino , Animais , Glutamina/farmacologia , Proteínas tau/metabolismo , Doença de Alzheimer/metabolismo , Camundongos Transgênicos , Disfunção Cognitiva/prevenção & controle , Suplementos Nutricionais , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
10.
Clin Immunol ; 144(3): 190-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22836084

RESUMO

IL-12p40 homodimer is a natural antagonist of IL-12 and IL-23, which are potent pro-inflammatory cytokines required for Th1 and Th17 immune responses, respectively. It has been reported that Th17 response is involved in inflammatory bowel disease (IBD), a chronic disorder of the digestive system with steadily increasing incidence. Here, we investigated the effects of IL-12p40 delivered via recombinant adenovirus (rAd/IL-12p40) or mesenchymal stem cells (MSC/IL-12p40) in a dextran sulfate sodium salt (DSS)-induced colitis model. Injection of rAd/IL-12p40 or MSC/IL-12p40 efficiently attenuated colitis symptoms and tissue damage, leading to an increased survival rate. Moreover, IL-12p40 delivery suppressed IL-17A, but enhanced IFN-γ production from mesenteric lymph node cells, supporting the preferential suppression of IL-23 by IL-12p40 homodimer in vitro and the suppression of Th17 responses in vivo. Our results demonstrate that IL-12p40 delivery ameliorates DSS-induced colitis by suppressing IL-17A production and inflammation in the intestinal mucosa, providing an effective new therapeutic strategy for IBDs.


Assuntos
Colite/imunologia , Inflamação/imunologia , Doenças Inflamatórias Intestinais/imunologia , Subunidade p40 da Interleucina-12/imunologia , Interleucina-17/imunologia , Mucosa Intestinal/imunologia , Adenoviridae/imunologia , Animais , Colite/induzido quimicamente , Sulfato de Dextrana , Modelos Animais de Doenças , Feminino , Interferon gama/imunologia , Interleucina-12/imunologia , Interleucina-23/imunologia , Linfonodos/imunologia , Células-Tronco Mesenquimais/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley , Células Th17/imunologia
11.
Nat Commun ; 13(1): 1808, 2022 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379817

RESUMO

Expanding the exercise capacity of skeletal muscle is an emerging strategy to combat obesity-related metabolic diseases and this can be achieved by shifting skeletal muscle fibers toward slow-twitch oxidative type. Here, we report that Sirt6, an anti-aging histone deacetylase, is critical in regulating myofiber configuration toward oxidative type and that Sirt6 activator can be an exercise mimetic. Genetic inactivation of Sirt6 in skeletal muscle reduced while its transgenic overexpression increased mitochondrial oxidative capacity and exercise performance in mice. Mechanistically, we show that Sirt6 downregulated Sox6, a key repressor of slow fiber specific gene, by increasing the transcription of CREB. Sirt6 expression is elevated in chronically exercised humans, and mice treated with an activator of Sirt6 showed an increase in exercise endurance as compared to exercise-trained controls. Thus, the current study identifies Sirt6 as a molecular target for reprogramming myofiber composition toward the oxidative type and for improving muscle performance.


Assuntos
Músculo Esquelético , Sirtuínas , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Camundongos , Mitocôndrias/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Oxirredução , Estresse Oxidativo , Fatores de Transcrição SOXD , Sirtuínas/genética , Sirtuínas/metabolismo
12.
Nutrients ; 14(19)2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36235564

RESUMO

The purpose of this study was to examine whether Limonium tetragonum, cultivated in a smart-farming system with LED lamps, could increase exercise capacity in mice. C57BL/6 male mice were orally administered vehicle or Limonium tetragonum water extract (LTE), either 30 or 100 mg/kg, and were subjected to moderate intensity treadmill exercise for 4 weeks. Running distance markedly increased in the LTE group (100 mg/kg) by 80 ± 4% compared to the vehicle group, which was accompanied by a higher proportion of oxidative fibers (6 ± 6% vs. 10 ± 4%). Mitochondrial DNA content and gene expressions related to mitochondrial biogenesis were significantly increased in LTE-supplemented gastrocnemius muscles. At the molecular level, the expression of PGC-1α, a master regulator of fast-to-slow fiber-type transition, was increased downstream of the PKA/CREB signaling pathway. LTE induction of the PKA/CREB signaling pathway was also observed in C2C12 cells, which was effectively suppressed by PKA inhibitors H89 and Rp-cAMP. Altogether, these findings indicate that LTE treatment enhanced endurance exercise capacity via an improvement in mitochondrial biosynthesis and the increases in the formation of oxidative slow-twitch fibers. Future study is warranted to validate the exercise-enhancing effect of LTE in the human.


Assuntos
Condicionamento Físico Animal , Extratos Vegetais , Plumbaginaceae , Corrida , Animais , DNA Mitocondrial/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Biogênese de Organelas , Estresse Oxidativo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Condicionamento Físico Animal/fisiologia , Resistência Física , Extratos Vegetais/farmacologia , Plumbaginaceae/química
13.
Exp Mol Med ; 54(12): 2148-2161, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36473937

RESUMO

The clinical progression of neurodegenerative diseases correlates with the spread of proteinopathy in the brain. The current understanding of the mechanism of proteinopathy spread is far from complete. Here, we propose that inflammation is fundamental to proteinopathy spread. A sequence variant of α-synuclein (V40G) was much less capable of fibril formation than wild-type α-synuclein (WT-syn) and, when mixed with WT-syn, interfered with its fibrillation. However, when V40G was injected intracerebrally into mice, it induced aggregate spreading even more effectively than WT-syn. Aggregate spreading was preceded by sustained microgliosis and inflammatory responses, which were more robust with V40G than with WT-syn. Oral administration of an anti-inflammatory agent suppressed aggregate spreading, inflammation, and behavioral deficits in mice. Furthermore, exposure of cells to inflammatory cytokines increased the cell-to-cell propagation of α-synuclein. These results suggest that the inflammatory microenvironment is the major driver of the spread of synucleinopathy in the brain.


Assuntos
Doenças Neurodegenerativas , Sinucleinopatias , Camundongos , Animais , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Encéfalo/metabolismo , Inflamação , Modelos Animais de Doenças
14.
Eur J Immunol ; 40(2): 351-8, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19950168

RESUMO

IL-7 plays a crucial role in the homeostatic proliferation, differentiation and survival of T cells, as well as in the survival and proliferation of precursor B cells. Here, we demonstrated that utilizing nonlytic Fc-fused IL-7 (IL-7-Fc(m)) as a genetic adjuvant significantly enhanced not only CD4(+) but also CD8(+) T-cell responses by E7 DNA immunization, in addition to improving protection against TC-1-induced tumors in comparison to IL-7 alone. Similar results were obtained in OT-1 adoptive transfer experiments with OVA DNA injection, suggesting independence from antigenic nature and experimental conditions. In particular, the increased frequency of CD8(+) T cells was mainly due to enhanced T-cell proliferation in T-cell priming, and not to decreased cellular apoptosis. Interestingly, the enhanced adjuvant effect was not seen in the co-delivery of lytic Fc-fused IL-7 (IL-7-Fc) which increases T-cell apoptosis as well as T-cell proliferation, suggesting that the T-cell proliferative effect may be neutralized by T-cell apoptosis. Thus, our findings suggest that nonlytic Fc, in contrast to lytic Fc, fusion to cytokines may provide an insight in designing a potent genetic adjuvant for inducing CD4(+) and CD8(+) T-cell responses.


Assuntos
Antígenos/imunologia , Fragmentos Fc das Imunoglobulinas/imunologia , Interleucina-7/imunologia , Linfócitos T/imunologia , Adjuvantes Imunológicos , Animais , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Feminino , Citometria de Fluxo , Humanos , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/metabolismo , Imunoterapia Adotiva , Interleucina-7/genética , Interleucina-7/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Neoplasias Experimentais/terapia , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/imunologia , Proteínas Oncogênicas Virais/metabolismo , Ovalbumina/imunologia , Proteínas E7 de Papillomavirus , Linfócitos T/citologia , Linfócitos T/metabolismo , Vacinação/métodos , Vacinas de DNA/imunologia
15.
Bioinformatics ; 26(18): 2359-60, 2010 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-20647520

RESUMO

UNLABELLED: We are constructing an ontology for traditional Korean medicine, and we started with medicinal materials to express the relationships between patients' symptoms, diseases and treatments. Biological materials and mineral resources have been used traditionally for patient treatments. The ontology includes various data related to these materials, such as their scientific names, parts of materials used, effectiveness and related oriental organ of the human body. AVAILABILITY: http://tkm.kiom.re.kr/ontology/TraditionalKoreanMedicine.rdf-xml.owl (10-20 s using Internet Explorer.)


Assuntos
Medicina Tradicional Coreana , Doença , Humanos , Internet
16.
Biol Pharm Bull ; 34(7): 1026-31, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21720008

RESUMO

The generation of nitric oxide (NO) via inducible NO synthase (iNOS) and reactive oxygen species plays a key role in cytokine-mediated pancreatic ß-cell damage. Oxidative stress due to reactive oxygen species activates the nuclear factor-κB (NF-κB) transcription factor, which regulates iNOS expression. In this regard, suppression of the NF-κB pathway is a novel strategy for protecting ß-cells from damage. This study was performed to explore the effects of kazinol U, a prenylated flavan from Broussonetia kazinoki, on the NF-κB activation pathway in interleukin-1ß (IL-1ß)- and interferon-γ (IFN-γ)-treated ß-cells. The cytotoxic effects of cytokines were completely abolished when RINm5F cells or islets were pretreated with kazinol U. Kazinol U inhibited the nuclear translocation and DNA binding of NF-κB subunits, which correlated with the inhibitory effects on IκB kinase (IKK) phosphorylation and IκBα degradation. In addition, kazinol U suppressed NO and hydrogen peroxide production and apoptotic cell death by cytokines in RINm5F cells. The protective effects of kazinol U were further demonstrated by normal insulin secretion of cytokine-treated islets in response to glucose. Taken together, these results suggest that using kazinol U to block the NF-κB pathway in pancreatic ß-cells reduces cell damage. Therefore, kazinol U may have therapeutic value in delaying pancreatic ß-cell destruction in type 1 diabetes.


Assuntos
Apoptose/efeitos dos fármacos , Broussonetia/química , Citocinas/antagonistas & inibidores , Flavonoides/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Animais , Linhagem Celular , Citocinas/fisiologia , Flavonoides/isolamento & purificação , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Prenilação , Ratos
17.
Biol Pharm Bull ; 34(1): 97-102, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21212525

RESUMO

Butein (3,4,2',4'-tetrahydroxychalcone), a plant polyphenol, is a major component in isolate of Rhus verniciflua STOKES (Anacardiaceae). It is shown to exert various potent effects such as antioxidant, antiinflammatory induction of apoptosis among many properties. In this study, we investigated the effect of butein on cytokine-induced ß-cell damage. Pre-treatment with butein is shown to increase the viability of cytokine-treated INS-1 cells at concentrations of 15-30 µM. Butein prevented cytokine-mediated cell death, as well as nitric oxide (NO) production, and these effects correlated well with reduced levels of protein expression of the inducible nitric oxide synthase (iNOS). Furthermore, the molecular mechanisms by which butein inhibits iNOS gene expression appeared to be through the inhibition of nuclear factor-κB (NF-κB) translocation. In a second set of experiments, rat islets were used to demonstrate the protective effects of butein and the results were essentially the same as those observed in Beutin pretreated INS-1 cells. Butein prevented cytokine-induced NO production, iNOS expression, and NF-κB translocation and inhibition of glucose-stimulated insulin secretion (GSIS). In conclusion, these results suggest that butein can be used for the prevention of functional ß-cell damage and preventing the progression of Type 1 diabetes mellitus (T1DM).


Assuntos
Chalconas/farmacologia , Citocinas/toxicidade , Células Secretoras de Insulina/efeitos dos fármacos , Óxido Nítrico/metabolismo , Rhus/química , Animais , Linhagem Celular , Chalconas/química , Regulação Enzimológica da Expressão Gênica , Estrutura Molecular , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Sprague-Dawley
18.
Mitochondrial DNA B Resour ; 6(4): 1330-1331, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33889742

RESUMO

The complete mitochondrial genome of a bagrid catfish, Tachysurus nitidus was completely analyzed by the primer walking method. It was composed of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a control region with a total length of 16,537 bp. In the phylogenetic tree, using mitochondrial genome of 13 related sequences revealed that T. nitidus (MW451217) of Korea is clustered with T. nitidus (KC822643) of China. This complete mitochondrial genome provides an important resource for reviewing the phylogenetic relationships and taxonomic status of the bagrid species.

19.
Nutrients ; 13(12)2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34959956

RESUMO

Hovenia dulcis, known as the oriental raisin tree, is used for food supplements and traditional medicine for the liver after alcohol-related symptoms. However, little information exists about the use of its leaves and branches. In this study, we established a method to use the leaves and branches to develop anti-hangover treatment and elucidated the underlying mechanisms. Oxidation-treated leaves (OL) exhibited high antioxidant content comparable to that of the peduncles and showed an anti-hangover effect in male mice. The branch extract (BE) was enriched in the flavonoid catechin, approximately five times more than OL extract. The mixture of OL and BE (OLB) was formulated in a 2:1 ratio with frozen-dried extract weight and was tested for anti-hangover effects and protective properties against binge alcohol-induced liver injury. OLB showed better anti-hangover effect than OL. In addition to this anti-hangover effect, OLB protected the liver from oxidative/nitrosative damage induced by binge alcohol intake.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Bebidas Alcoólicas/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Suplementos Nutricionais , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Caules de Planta/química , Rhamnaceae/química , Animais , Catequina/análise , Composição de Medicamentos , Masculino , Camundongos Endogâmicos ICR , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Água
20.
G3 (Bethesda) ; 11(9)2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-33944944

RESUMO

Pond smelt (Hypomesus nipponensis) is a cold-freshwater fish species and a winter economic aquaculture resource in South Korea. Because of its high susceptibility to abnormal water temperature from global warming, a large number of smelt die in hot summers. Here, we present the first draft genome of H. nipponensis and transcriptomic changes in molecular mechanisms or intracellular responses under heat stress. We combined Illumina and PacBio sequencing technologies to generate the draft genome of H. nipponensis. Based on the reference genome, we conducted transcriptome analysis of liver and muscle tissues under normal (NT, 5°C) vs. warm (HT, 23°C) conditions to identify heat stress-induced genes and gene categories. We observed a total of 1987 contigs with N50 of 0.46 Mbp, with the largest contig (3.03 Mbp) in the assembled genome. A total of 20,644 protein-coding genes were predicted, and 19,224 genes were functionally annotated: 15,955 genes for Gene Ontology terms and 11,560 genes for KEGG Orthology. We conducted the lost and gained genes analysis compared with three species that: human, zebrafish, and salmon. In the lost genes analysis, we detected that smelt lost 4461 (22.16%), 2825 (10.62%), and 1499 (3.09%) genes compare with above three species, respectively. In the gained genes analysis, we observed that smelt gained 1133 (5.49%), 1670 (8.09%), and 229 (1.11%) genes compared with the above species, respectively. From transcriptome analysis, a total of 297 and 331 differentially expressed genes (DEGs) with a false discovery rate <0.05 were identified in the liver and muscle tissues, respectively. Gene enrichment analysis of DEGs indicates that upregulated genes were significantly enriched for lipid biosynthetic process (GO:0008610, P < 0.001) and regulation of apoptotic process (GO:0042981, P < 0.01), and genes were downregulated by immune responses such as myeloid cell differentiation (GO:0030099, P < 0.001) in the liver under heat stress. In muscle tissue, upregulated genes were enriched for hypoxia (GO:0001666, P < 0.05), transcription regulator activity (GO:0140110, P < 0.001), and calcium-release channel activity (GO:0015278, P < 0.01), and genes were downregulated for a nicotinamide nucleotide biosynthetic process (GO:0019359, P < 0.01). The results of KEGG pathway analysis were similar to that of gene enrichment analysis. The draft genome and transcriptomic of H. nipponensis will be a useful genetic resource for functional and evolutionary studies. Our findings will improve understanding of molecular mechanisms and heat responses and be useful for predicting survival of the smelt and its closely related species under global warming.


Assuntos
Osmeriformes , Animais , Perfilação da Expressão Gênica , Resposta ao Choque Térmico/genética , Humanos , Fígado , Músculos , Osmeriformes/genética , República da Coreia , Transcriptoma , Peixe-Zebra
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