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1.
Cancer Immunol Immunother ; 73(1): 18, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38240856

RESUMEN

Hepatocellular carcinoma (HCC) is the most prevalent malignant tumor worldwide. Within HCC's tumor microenvironment, focal adhesion kinase (FAK) plays a critical role. Regulatory T cells (Treg) modulate the polarization of tumor-associated macrophages , but the relationship between FAK, Treg cells, and macrophages remains underexplored. Phellinus linteus (PL) shows promise as a treatment for HCC due to its pharmacological effects. This study aimed to explore the relationship between FAK and Treg-macrophages and to assess whether PL could exert a protective effect through the FAK process in HCC. Initially, C57BL/6-FAK-/- tumor-bearing mice were utilized to demonstrate that FAK stimulates HCC tumor development. High dosages (200 µM) of FAK and the FAK activator ZINC40099027 led to an increase in Treg (CD4+CD25+) cells, a decrease in M1 macrophages (F4/80+CD16/32+, IL-12, IL-2, iNOS), and an increase in M2 macrophages (F4/80+CD206+, IL-4, IL-10, Arg1, TGF-ß1). Additionally, FAK was found to encourage cell proliferation, migration, invasion, and epithelial-mesenchymal transition while inhibiting apoptosis in HepG2 and SMMC7721 cells. These effects were mediated by the PI3K/AKT1/Janus Kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinase (p38 MAPK)/Jun N-terminal Kinase (JNK) signaling pathways. Furthermore, PL exhibited a potent antitumor effect in vivo in a dose-dependent manner, reducing FAK, Treg cells, and M2 macrophages, while increasing M1 macrophages. This effect was achieved through the inhibition of the PI3K/AKT/JAK/STAT3, and p38/JNK pathways. Overall, our findings suggest that FAK promotes HCC via Treg cells that polarize macrophages toward the M2 type through specific signaling pathways. PL, acting through FAK, could be a protective therapy against HCC.


Asunto(s)
Basidiomycota , Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Ratones , Carcinoma Hepatocelular/patología , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Linfocitos T Reguladores/metabolismo , Neoplasias Hepáticas/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones Endogámicos C57BL , Macrófagos/metabolismo , Línea Celular Tumoral , Microambiente Tumoral
2.
Artículo en Inglés | MEDLINE | ID: mdl-32629087

RESUMEN

Oral administration of sucralose has been reported to stimulate food intake through inducing hypothalamic neuropeptide Y (NPY) in mice and fruit flies. However, the underlying mechanisms of action of sucralose in hypothermia and NPY and monoamine regulation remain unknown. The aim of the present study was to investigate central effects of sucralose on body temperature, NPY, and monoamine regulation, as well as its peripheral effects, in chicks. In Experiment 1, 5-day-old chicks were centrally injected with 1 µmol of sucralose, other sweeteners (erythritol and glucose), or saline. In Experiment 2, chicks were centrally injected with 0.2, 0.4, and 1.6 µmol of sucralose or saline. In Experiment 3, chicks were centrally injected with 0.8 µmol of sucralose or saline, with a co-injection of 100 µg fusaric acid (FA), an inhibitor of dopamine-ß-hydroxylase, to examine the role dopamine in sucralose induced hypothermia. In Experiment 4, 7-16-day-old chicks were orally administered with 75, 150, and 300 mg/2 ml distilled water or sucralose, daily. We observed that the central injection of sucralose, but not other sweeteners, decreased body temperature (P < .05) in chicks; however, the oral injection did not influence body temperature, food intake, and body weight gain. Central sucralose administration decreased dopamine and serotonin and stimulated dopamine turnover rate in the hypothalamus significantly (P < .05). Notably, sucralose co-injection with FA impeded sucralose-induced hypothermia. Sucralose decreases body temperature potentially via central monoaminergic pathways in the hypothalamus.


Asunto(s)
Dopamina/análisis , Hipotálamo/metabolismo , Hipotermia/metabolismo , Serotonina/análisis , Sacarosa/análogos & derivados , Administración Oral , Animales , Temperatura Corporal , Encéfalo/metabolismo , Pollos , Eritritol/análisis , Ácido Fusárico/química , Glucosa/análisis , Infusiones Intraventriculares , Masculino , Neuropéptido Y/metabolismo , Sacarosa/química
3.
Kidney Int ; 95(6): 1347-1358, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30799025

RESUMEN

Neointima formation is a major contributor to arteriovenous fistula (AVF) failure. We have previously shown that activation of the Notch signaling pathway contributes to neointima formation by promoting the migration of vascular smooth muscle cells (VSMCs) into the venous anastomosis. In the current study we investigated the mechanisms underlying the dedifferentiation and migration of VSMCs, and in particular the role of bone marrow-derived fibroblast specific protein 1 (FSP-1)+ cells, another cell type found in models of vascular injury. Using VSMC-specific reporter mice, we found that most of the VSMCs participating in AVF neointima formation originated from dedifferentiated VSMCs. We also observed infiltration of bone marrow-derived FSP-1+ cells into the arterial anastomosis where they could interact with VSMCs. In vitro, conditioned media from FSP-1+ cells stimulated VSMC proliferation and phenotype switching. Activated Notch signaling transformed FSP-1+ cells into type I macrophages and stimulated secretion of cytokines and growth factors. Pretreatment with a Notch inhibitor or knockout of the canonical downstream factor RBP-Jκ in bone marrow-derived FSP1+ cells decreased FSP1+ cell infiltration into murine AVFs, attenuating VSMC dedifferentiation and neointima formation. Our results suggest that targeting Notch signaling could provide a new therapeutic strategy to improve AVF patency.


Asunto(s)
Derivación Arteriovenosa Quirúrgica/efectos adversos , Miocitos del Músculo Liso/patología , Neointima/patología , Receptores Notch/metabolismo , Diálisis Renal/efectos adversos , Animales , Desdiferenciación Celular/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Humanos , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/genética , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Noqueados , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Neointima/etiología , Neointima/prevención & control , Cultivo Primario de Células , Receptores Notch/antagonistas & inhibidores , Diálisis Renal/métodos , Insuficiencia Renal Crónica/terapia , Proteína de Unión al Calcio S100A4/metabolismo , Transducción de Señal/efectos de los fármacos , Grado de Desobstrucción Vascular/efectos de los fármacos
4.
J Therm Biol ; 81: 1-11, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30975405

RESUMEN

Heat-stress exposure increased the expression of heat-shock proteins (HSPs), B-cell lymphoma 2 (BCL-2) and anti-oxidative enzymes to maintain normal cellular function by attenuating the oxidative reaction and apoptosis. Reducing the stress response or enhancing anti-stress capability is an important goal in animal production. Our previous study indicated a protective role of flavangenol, a pine bark extract, in chicks after three hours of high-temperature exposure. However, the cellular mechanism of flavangenol was not clarified ex vivo. In the current study, we investigated the effect of flavangenol on cellular apoptosis and oxidation in heat-stressed treated chick brain cells (mixed neurons and glia cells). The primary brain cells were isolated from the diencephalon of 14-day-old chicks and cultured at 41.5 °C (to mimic the body temperature of young chicks), and were treated with flavangenol from day 3 of isolation to day 8. Cells were kept bathed in the cell culture dish under a high temperature (HT: 45 °C, 20 or 60 min) on day 8 and were then collected for analysis of cell viability as well as for HSP and other related gene expression. Flavangenol treatment significantly increased cell viability and BCL-2 mRNA expression, and attenuated HSP-70 and BCL-2-associated X protein mRNA expression. Moreover, flavangenol treatment elevated the mRNA expression of glutathione peroxidase in the HT group, which indicates that cellular anti-oxidative ability was strengthened by flavangenol. In conclusion, flavangenol may play a protective role in cells damaged or killed by heat stress by increasing cellular anti-oxidative pathways.


Asunto(s)
Antioxidantes/administración & dosificación , Apoptosis/efectos de los fármacos , Biflavonoides/administración & dosificación , Encéfalo/efectos de los fármacos , Pollos/genética , Regulación de la Expresión Génica/efectos de los fármacos , Respuesta al Choque Térmico/efectos de los fármacos , Fármacos Neuroprotectores/administración & dosificación , Proantocianidinas/administración & dosificación , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Aviares/metabolismo , Encéfalo/metabolismo , Supervivencia Celular/efectos de los fármacos , Pollos/metabolismo , Proteínas de Choque Térmico/metabolismo , Respuesta al Choque Térmico/genética , Calor , Masculino , Cultivo Primario de Células , ARN Mensajero/metabolismo
5.
Fish Physiol Biochem ; 45(4): 1343-1354, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31001753

RESUMEN

Water temperature directly affects the body temperature in fish, so increasing water temperatures in oceans and rivers will lead to increases in fish body temperatures. Whilst a range of responses of fish to increases in water temperature have been measured, amino acid metabolism in a fish under high water temperature (HT) conditions has not been investigated. The aim of this study was to determine the effects of an acute increase in water temperature on oxygen consumption, plasma cortisol concentrations, and free amino acid concentrations in plasma and several tissues in goldfish (Carassius auratus). Oxygen consumption and plasma cortisol concentrations were increased in goldfish exposed to HT (30 ± 1 °C) for 200 min compared with goldfish at a control water temperature (CT 17 ± 1 °C). Oxygen consumption and plasma cortisol concentrations in both groups of fish combined were positively correlated. When goldfish were exposed to HT for 300 min oxygen consumption and plasma concentrations of 15 free amino acids were increased compared with goldish at CT. Concentrations of several free amino acids were increased to varying extents in the brain, liver, and muscle tissues. In conclusion, an acute increase in water temperature affected amino acid metabolism differently in the brain, liver, and muscle tissues. Goldfish will be a useful species for further studies of the possible roles of various amino acids in the brain, muscle, and liver during acute increases in water temperature in fish.


Asunto(s)
Aminoácidos/metabolismo , Carpa Dorada/metabolismo , Temperatura , Aminoácidos/sangre , Animales , Encéfalo/metabolismo , Carpa Dorada/sangre , Hidrocortisona/sangre , Hígado/metabolismo , Músculos/metabolismo , Consumo de Oxígeno , Agua
6.
Asian-Australas J Anim Sci ; 32(6): 842-848, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30381734

RESUMEN

OBJECTIVE: Heat stress poses an increasing threat for poultry production. Some amino acids have been found to play critical roles in affording thermotolerance. Recently, it was found that in ovo administration of L-leucine (L-Leu) altered amino acid metabolism and afforded thermotolerance in heat-exposed broiler chicks. METHODS: In this study, two doses (35 and 70 µmol/egg) of L-Leu were administered in ovo on embryonic day 7 to determine their effect on rectal temperature (RT), body weight (BW) and thyroid hormones at hatching. Changes in RT, BW, and thermotolerance in post-hatched chicks were also analyzed. RESULTS: It was found that in ovo administration of L-Leu dose-dependently reduced RT and plasma thyroxine (T4) level just after hatching. In post-hatched neonatal broiler chicks, however, the higher dose of L-Leu administered in ovo significantly increased RT without affecting BW gain. In chicks that had been exposed to heat stress, the RT was significantly lowered by in ovo administration of L-Leu (high dose) in comparison with the control chicks under the same high ambient temperature (HT: 35°C±1°C, 120 min). CONCLUSION: In ovo administration of L-Leu in a high dose contributed to an increased daily body temperature and afforded thermotolerance under HT in neonatal broiler chicks.

7.
Clin Nephrol ; 90(2): 106-111, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29932407

RESUMEN

BACKGROUND: Residual renal function (RRF) is a crucial factor that plays an important role in peritoneal dialysis (PD) patients, but whether RRF influences the quality of life (QOL) of PD patients is still controversial. The aims of this study were to explore the effects of RRF on QOL in patients with continuous ambulatory peritoneal dialysis (CAPD) and analyze the related factors that might affect patients' QOL. MATERIALS AND METHODS: All 120 adult patients in this study received regular CAPD treatment for at least 3 months. Patients were divided into two groups: an RRF group (residual glomerular filtration (rGFR) ≥ 1 mL×min-1×(1.73m2)-1) and a non-RRF group (rGFR ≥ 1 mL×min-1×(1.73m2)-1). The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was used as a reference to calculate the scores of CAPD patients for assessing their QOL. Multiple- and single-linear regression analysis was performed to analyze correlation degree of several SF-36-related indexes. RESULTS: The indexes of age, gender, cause of disease, complication, body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP), hemoglobin (HB), cholesterol, triglycerides, high- and low-density lipoprotein, normalized protein catabolic rate (nPCR), and cardiothoracic ratio (CTR) showed no difference between the two groups (RRF and non-RRF). Comparing with RRF group, the patients without RRF showed a significant difference on indexes of PD duration, urine volume, ultrafiltration volume, dialysis dose, serum albumin, potassium, Kt/V (urea reduction ratio), creatinine, calcium, phosphate, C-reactive protein (CRP), and parathyroid hormone (PTH). Single-linear regression analysis that achieved total score of SF-36 showed no correlation with rGFR, but there was a correlation of SF-36 score with CRP, creatinine, CTR, albumin, and ultrafiltration volume. CONCLUSION: These results suggested that there was no correlation between RRF and QOL in CAPD patients, but chronic inflammation, fluid overload, and malnutrition were considered as the main factors that affect patients' QOL.
.


Asunto(s)
Fallo Renal Crónico/terapia , Riñón/fisiopatología , Diálisis Peritoneal Ambulatoria Continua , Calidad de Vida , Anciano , Índice de Masa Corporal , Proteína C-Reactiva , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular/fisiología , Hemoglobinas , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Albúmina Sérica , Triglicéridos/sangre , Desequilibrio Hidroelectrolítico
8.
J Therm Biol ; 71: 74-82, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29301703

RESUMEN

Thermal manipulation declined embryonic brain and liver concentrations of leucine (Leu). L-Leu in ovo injection afforded thermotolerance in male broiler chicks. This study aimed to examine the role of in ovo injection of L-Leu in metabolic functions, and differences between male and female broiler chicks in thermotolerance. L-Leu injection was performed in ovo on embryonic day (ED) 7 to reveal its role in metabolic activity in embryos and in post-hatch male and female broiler chicks under heat stress. To examine the metabolic activity of embryos, oxygen (O2) consumption, carbon dioxide (CO2) production, heat production and plasma metabolites were analyzed. Rectal temperature, food intake and plasma metabolites were also analyzed in heat-exposed (35 ± 1°C for 180min) male and female broiler chicks. It was found that O2 consumption, heat production, and plasma triacylglycerol (TG) and non-esterified fatty acid (NEFA) concentrations in ED 14 embryos were significantly increased by in ovo injection of L-Leu in comparison with the controls. Plasma glucose concentration was significantly increased in both male and female chicks under heat stress, but in ovo injection of L-Leu attenuated the increase in male chicks. In contrast, plasma TG, NEFA, and ketone body concentrations were significantly higher in male chicks injected in ovo with L-Leu, but not in similarly injected female chicks, compared with control chicks, all under heat stress. Rectal temperature and food intake were significantly lower in male, but not female, chicks under heat stress injected in ovo with L-Leu. In conclusion, in ovoL-Leu administration enhanced the prenatal metabolic rate and lipid metabolisms, which possibly appeared as sex-dependent fashion to facilitate thermotolerance in males. A reduction in heat production through lowered food intake in heat-exposed male, but not female chicks injected in ovo with L-Leu may help to afford thermotolerance in male broiler chicks under heat stress.


Asunto(s)
Pollos/fisiología , Leucina/farmacología , Metabolismo de los Lípidos , Termotolerancia , Animales , Metabolismo Basal , Embrión de Pollo/efectos de los fármacos , Pollos/crecimiento & desarrollo , Pollos/metabolismo , Ingestión de Energía , Femenino , Respuesta al Choque Térmico , Leucina/administración & dosificación , Masculino , Factores Sexuales
9.
Artículo en Inglés | MEDLINE | ID: mdl-27840178

RESUMEN

Thermal manipulation (TM) of incubation temperature causes metabolic alterations and contributes to improving thermotolerance in chicks post hatching. However, there has been no report on amino acid metabolism during TM and the part it plays in thermotolerance. In this study, we therefore first analyzed free amino acid concentrations in the embryonic brain and liver during TM (38.6°C, 6h/d during embryonic day (ED) 10 to ED 18). It was found that leucine (Leu), phenylalanine and lysine were significantly decreased in the embryonic brain and liver. We then chose l-Leu and other branched-chain amino acids (l-isoleucine (L-Ile) and l-valine (l-Val)) for in ovo injection on ED 7 to reveal their roles in thermoregulation, growth, food intake and thermotolerance in chicks. It was found that in ovo injection of l-Leu, but not of l-Ileu or l-Val, caused a significant decline in body temperature at hatching and increased food intake and body weight gain in broiler chicks. Interestingly, in ovo injection of l-Leu resulted in the acquisition of thermotolerance under high ambient temperature (35±1°C for 180min) in comparison with the control thermoneutral temperature (28±1°C for 180min). These results indicate that the free amino acid concentrations during embryogenesis were altered by TM. l-Leu administration in eggs caused a reduction in body temperature at hatching, and afforded thermotolerance in heat-exposed young chicks, further suggesting that l-Leu may be one of the key metabolic factors involved in controlling body temperature in embryos, as well as in producing thermotolerance after hatching.


Asunto(s)
Regulación de la Temperatura Corporal , Pollos/fisiología , Leucina/metabolismo , Animales , Embrión de Pollo , Conducta Alimentaria , Crecimiento
10.
J Therm Biol ; 69: 163-170, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29037378

RESUMEN

Recently we demonstrated that L-citrulline (L-Cit) causes hypothermia in chicks. However, the question of how L-Cit mediates hypothermia remained elusive. Thus, the objective of this study was to examine some possible factors in the process of L-Cit-mediated hypothermia and to confirm whether L-Cit can also afford thermotolerance in young chicks. Chicks were subjected to oral administration of L-Cit along with intraperitoneal injection of a nitric oxide synthase (NOS) inhibitor, NG-nitro-l-arginine methyl ester HCl (L-NAME), to examine the involvement of NO in the process of hypothermia. Food intake and plasma metabolites were also analyzed after oral administration of L-Cit in chicks. To examine thermotolerance, chicks were orally administered with a single dose of L-Cit (15mmol/10ml/kg body weight) or the same dose twice within a short interval of 1h (dual oral administration) before the exposure to high ambient temperature (35 ± 1°C) for 180min. Although the rectal temperature was reduced following administration of L-Cit, L-NAME caused a greater reduction. L-NAME reduced total NO2 and NO3 (NOx) in plasma, which confirmed its inhibitory effect on NO. A single oral administration of L-Cit mediated a persistent state of hypothermia for the 300min of the study without affecting food intake. It was further found that plasma glucose was significantly lower in L-Cit-treated chicks. Dual oral administration of L-Cit, but not a single oral administration, afforded thermotolerance without a significant change in plasma NOx in chicks. In conclusion, our results suggest that L-Cit-mediated hypothermia and thermotolerance may not be involved in NO production. L-Cit-mediated thermotolerance further suggests that L-Cit may serve as an important nutritional supplement that could help in coping with summer heat.


Asunto(s)
Pollos/fisiología , Citrulina/metabolismo , Termotolerancia , Administración Oral , Animales , Glucemia/metabolismo , Citrulina/administración & dosificación , Citrulina/farmacología , Suplementos Dietéticos/análisis , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/farmacología , Hipotermia/inducido químicamente , Hipotermia/metabolismo , Masculino , NG-Nitroarginina Metil Éster/administración & dosificación , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Termotolerancia/efectos de los fármacos
11.
J Therm Biol ; 60: 140-8, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27503726

RESUMEN

Exposure to a high ambient temperature (HT) can cause heat stress, which has a huge negative impact on physiological functions. Cellular heat-shock response is activated upon exposure to HT for cellular maintenance and adaptation. In addition, antioxidants are used to support physiological functions under HT in a variety of organisms. Flavangenol, an extract of pine bark, is one of the most potent antioxidants with its complex mixture of polyphenols. In the current study, chronic (a single daily oral administration for 14 days) or acute (a single oral administration) oral administration of flavangenol was performed on chicks. Then the chicks were exposed to an acute HT (40±1°C for 3h) to examine the effect of flavangenol on the mRNA expression of heat-shock protein (HSP) in the brain and liver. Rectal temperature, plasma aspartate aminotransferase (AAT), a marker of liver damage, and plasma corticosterone as well as metabolites were also determined. HSP-70 and -90 mRNA expression, rectal temperature, plasma AAT and corticosterone were increased by HT. Interestingly, the chronic, but not the acute, administration of flavangenol caused a declining in the diencephalic mRNA expression of HSP-70 and -90 and plasma AAT in HT-exposed chicks. Moreover, the hepatic mRNA expression of HSP-90 was also significantly decreased by chronic oral administration of flavangenol in HT chicks. These results indicate that chronic, but not acute, oral administration of flavangenol attenuates HSP mRNA expression in the central and peripheral tissues due to its possible role in improving cellular protective functions during heat stress. The flavangenol-dependent decline in plasma AAT further suggests that liver damage induced by heat stress was minimized by flavangenol.


Asunto(s)
Antioxidantes/uso terapéutico , Biflavonoides/uso terapéutico , Pollos/fisiología , Proteínas de Choque Térmico/genética , Respuesta al Choque Térmico/efectos de los fármacos , Proantocianidinas/uso terapéutico , Administración Oral , Animales , Antioxidantes/administración & dosificación , Aspartato Aminotransferasas/sangre , Biflavonoides/administración & dosificación , Pollos/sangre , Regulación de la Expresión Génica/efectos de los fármacos , Trastornos de Estrés por Calor/sangre , Trastornos de Estrés por Calor/metabolismo , Trastornos de Estrés por Calor/prevención & control , Trastornos de Estrés por Calor/veterinaria , Masculino , Pinus/química , Corteza de la Planta/química , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Enfermedades de las Aves de Corral/sangre , Enfermedades de las Aves de Corral/metabolismo , Enfermedades de las Aves de Corral/prevención & control , Proantocianidinas/administración & dosificación , ARN Mensajero/genética
12.
Kidney Int ; 88(3): 490-502, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25786100

RESUMEN

A major factor contributing to failure of arteriovenous fistulas (AVFs) is migration of smooth muscle cells into the forming neointima. To identify the source of smooth muscle cells in neointima, we created end-to-end AVFs by anastomosing the common carotid artery to the jugular vein and studied neural crest-derived smooth muscle cells from the carotid artery, which are Wnt1-positive during development. In Wnt1-cre-GFP mice, smooth muscle cells in the carotid artery but not the jugular vein are labeled with GFP. About half of the cells were GFP-positive in the neointima, indicating their migration from the carotid artery to the jugular vein in AVFs created in these mice. As fibroblast-specific protein-1 (FSP-1) regulates smooth muscle cell migration, we examined FSP-1 in failed AVFs and polytetrafluoroethylene grafts from patients with end-stage kidney disease or from AVFs in mice with chronic kidney disease. In smooth muscle cells of AVFs or polytetrafluoroethylene grafts, FSP-1 and activation of Notch1 are present. In smooth muscle cells, Notch1 increased RBP-Jκ transcription factor activity and RBP-Jκ stimulated FSP-1 expression. Conditional knockout of RBP-Jκ in smooth muscle cells or general knockout of FSP-1 suppressed neointima formation in AVFs in mice. Thus, the artery of AVFs is the major source of smooth muscle cells during neointima formation. Knockout of RBP-Jκ or FSP-1 ameliorates neointima formation and might improve AVF patency during long-term follow-up.


Asunto(s)
Derivación Arteriovenosa Quirúrgica/efectos adversos , Implantación de Prótesis Vascular/efectos adversos , Movimiento Celular , Oclusión de Injerto Vascular/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Neointima , Receptor Notch1/metabolismo , Insuficiencia Renal Crónica/terapia , Anciano , Animales , Implantación de Prótesis Vascular/instrumentación , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Arteria Carótida Común/metabolismo , Arteria Carótida Común/patología , Arteria Carótida Común/cirugía , Células Cultivadas , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/patología , Oclusión de Injerto Vascular/fisiopatología , Humanos , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/genética , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/metabolismo , Venas Yugulares/cirugía , Masculino , Ratones Transgénicos , Persona de Mediana Edad , Modelos Animales , Músculo Liso Vascular/patología , Músculo Liso Vascular/fisiopatología , Músculo Liso Vascular/cirugía , Miocitos del Músculo Liso/patología , Interferencia de ARN , Receptor Notch1/genética , Diálisis Renal , Proteína de Unión al Calcio S100A4 , Proteínas S100/genética , Proteínas S100/metabolismo , Transducción de Señal , Transfección , Grado de Desobstrucción Vascular
13.
J Am Soc Nephrol ; 25(4): 773-83, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24480830

RESUMEN

Neointima formation causes the failure of 60% of arteriovenous fistulas (AVFs) within 2 years. Neointima-forming mechanisms are controversial but possibly linked to excess proinflammatory responses and dysregulated Notch signaling. To identify how AVFs fail, we anastomosed the carotid artery to the internal jugular vein in normal and uremic mice and compared these findings with those in failed AVFs from patients with ESRD. Endothelial cells (ECs) of AVFs in uremic mice or patients expressed mesenchymal markers (FSP-1 and/or α-SMA) and exhibited increased expression and nuclear localization of Notch intracellular domain compared with ECs of AVFs in pair-fed control mice. Furthermore, expression of VE-Cadherin decreased, whereas expression of Notch1 and -4, Notch ligands, the downstream transcription factor of Notch, RBP-Jκ, and Notch target genes increased in ECs of AVFs in uremic mice. In cultured ECs, ectopic expression of Notch ligand or treatment with TGF-ß1 triggered the expression of mesenchymal markers and induced endothelial cell barrier dysfunction, both of which were blocked by Notch inhibition or RBP-Jκ knockout. Furthermore, Notch-induced defects in barrier function, invasion of inflammatory cells, and neointima formation were suppressed in mice with heterozygous knockdown of endothelial-specific RBP-Jκ. These results suggest that increased TGF-ß1, a complication of uremia, activates Notch in endothelial cells of AVFs, leading to accelerated neointima formation and AVF failure. Suppression of Notch activation could be a strategy for improving AFV function in uremia.


Asunto(s)
Derivación Arteriovenosa Quirúrgica/efectos adversos , Células Endoteliales/fisiología , Receptores Notch/fisiología , Insuficiencia Renal Crónica/fisiopatología , Actinas/análisis , Anciano , Animales , Proteínas de Unión al Calcio/análisis , Humanos , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/fisiología , Masculino , Ratones , Persona de Mediana Edad , Neointima , Insuficiencia Renal Crónica/patología , Proteína de Unión al Calcio S100A4 , Transducción de Señal , Factor de Crecimiento Transformador beta1/fisiología
14.
Biotechnol Lett ; 36(3): 667-76, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24338158

RESUMEN

Human adipose-derived stem cells (hASCs) improve renal function in acute kidney injury. Hypoxia-inducible factor-1α (HIF-1α) was transfected into hASCs. hASCs modified by lentivirus-mediated empty-vector and HIF-1α maintained their stem cell characteristics. The expression of the renal-protective gene, heme oxygenase-1 and vascular endothelial growth factor were significantly increased in hASCs modified by HIF-1α, compared to hASCs modified by empty-vector. Cellular ultra-structure and TUNEL staining revealed that hASCs modified by HIF-1α promoted the recovery of apoptotic morphology in cisplatin-treated human kidney-2 cells (HK-2 cells) when compared to hASCs modified by empty-vector. Additionally, hASCs modified by empty-vector inhibited caspase-3 expression and up-regulated Bcl-2 expression in cisplatin-treated HK-2 cells, an effect even more pronounced with hASCs modified by HIF-1α. Thus, HIF-1α gene-modified ASCs could be an effective way to enhance the renal-protective effect.


Asunto(s)
Lesión Renal Aguda/terapia , Trasplante de Células/métodos , Cisplatino/toxicidad , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Células Madre/fisiología , Apoptosis , Línea Celular , Células Epiteliales/fisiología , Vectores Genéticos , Hemo-Oxigenasa 1/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Técnicas In Vitro , Lentivirus/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
15.
Materials (Basel) ; 17(11)2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38893864

RESUMEN

A solid-state repair technique based on surface friction welding is investigated in depth to achieve excellent mechanical properties of damaged 7A52 aluminum alloy. The results show that the yield strength and tensile strength along the repair direction are 436 MPa and 502 MPa, respectively, at a rotational speed of 1400 rpm and a travel speed of 300 mm/min, which are about 157.9% and 129.7% of those before the defects were repaired, respectively, while the elongation is 17.2% compared to the base material. Perpendicular to the repair direction, the yield strength and tensile strength are 254 MPa and 432 MPa, which are 111.4% and 129.7% of those before the defects were repaired, respectively, while the elongation is 11.8% compared to the base material. The mechanical properties of the repaired areas are still improved compared to those of the defect-free sheets. On the one hand, this is attributed to the dynamic recrystallization of the nugget zone due to the thermo-mechanical coupling, resulting in the formation of a fine, equiaxed grain structure; on the other hand, the precipitated Mg2Si phase, which is incoherent within the base material, transforms into the Al12(Fe, Mn)3Si phase, as well as the precipitation of the Al6Mn phase and η' phase, resulting in the enhancement of the properties. The material fracture at the junction of the nugget zone and the heat-affected zone occurs after repair, which is attributed to the significant difference in the texture of the nugget zone and the heat-affected zone, as well as to the stress concentration at the junction.

16.
Am J Physiol Renal Physiol ; 304(12): F1413-20, 2013 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-23576636

RESUMEN

Hemodialysis patients depend on arteriovenous fistulas (AVF) for vascular access. Unfortunately, their 2-yr primary patency rate is only 60% because of AVF clog due to intimal hyperplasia at the venous anastomosis. Chronic kidney disease (CKD) can increase neointima formation by unknown mechanisms. A new AVF mouse model was created, and the mechanisms of CKD on neointima formation in AVFs were investigated. We created AVFs in mice by anastomosing the common carotid artery to the internal jugular vein. CKD was induced [BUN (blood urea nitrogen) in control and CKD mice, 33.3 ± 3.9 vs. 114.2 ± 12.1 mg/dl, P < 0.05]. After 1 day, there was endothelial cell loss and CD41-positive platelet aggregation, especially in the venous anastomosis. An invasion of macrophages and neutrophils peaked at 1 wk after surgery. Neointima formation (smooth muscle cell accumulation and extracellular matrix deposition) increased progressively over 4 wk. Mice with CKD had ~45% (P < 0.05) more neointima formation than control mice. CKD decreased vascular endothelial-cadherin expression in endothelial cells and delayed regeneration of the endothelium. CKD also increased inflammatory cells (Mac-2-positive or CD45-positive) in AVFs at 2 wk. Finally, AVFs were "leakier" (increased accumulation of Evans blue) in CKD mice at 7 and 14 days than control mice. We find that CKD increases neointima formation and endothelial barrier dysfunction. We have created a mouse model of AVF with characteristics similar to failed AVFs in patients. The model will allow testing of strategies directed at improving AVF function in CKD patients.


Asunto(s)
Derivación Arteriovenosa Quirúrgica , Endotelio/fisiopatología , Neointima/etiología , Insuficiencia Renal Crónica/fisiopatología , Animales , Fístula Arteriovenosa/fisiopatología , Derivación Arteriovenosa Quirúrgica/efectos adversos , Arteria Carótida Común/cirugía , Venas Yugulares/cirugía , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Animales , Insuficiencia Renal Crónica/complicaciones
17.
Cytotherapy ; 15(5): 578-85, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23415920

RESUMEN

Kidney disease has reached epidemic proportions and is associated with high mortality and morbidity rates. Stem cell-based therapy may effectively treat kidney damage by cell transplantation. The breakthrough discovery using a combination of four transcription factors to reprogram genetically somatic cells into induced pluripotent stem (iPS) cells was a milestone in stem cell therapy. The lentivirus was packaged containing OCT4, SOX2, c-MYC and KLF4 transcription factors and then transfected mouse renal tubular epithelial cells (RTECs). The colonies were picked up at 21 days and were tested by cytochemistry, immunofluorescence assay and quantitative real-time polymerase chain reaction. Viral transgene expression levels were also assessed by quantitative analysis. Additionally, embryoid bodies from iPS cells were formed, and immunofluorescence and teratoma assays were performed. Karyotype analysis of mouse RTEC-derived iPS cells was also performed. The iPS cells were indistinguishable from mouse embryonic stem cells with respect to colony morphology, the expression of pluripotency-associated transcription factors and surface markers, embryoid body-mediated differentiation potential and teratoma assays. Quantitative polymerase chain reaction demonstrated that the lentiviral transgenes were largely silenced. The mouse RTEC-derived iPS cells exhibited a normal karyotype of 40,XY. iPS cells can be produced using mouse RTECs, which would be helpful in investigations to ameliorate the symptoms of kidney disease and to slow the progression of kidney disease by in vitro and in vivo animal studies.


Asunto(s)
Diferenciación Celular , Reprogramación Celular , Células Epiteliales/citología , Células Madre Pluripotentes Inducidas/citología , Túbulos Renales/citología , Animales , Tratamiento Basado en Trasplante de Células y Tejidos , Células Madre Embrionarias/citología , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/genética , Lentivirus , Ratones , Factor 3 de Transcripción de Unión a Octámeros/genética , Proteínas Proto-Oncogénicas c-myc/genética , Factores de Transcripción SOXB1/genética , Transfección
18.
Physiol Behav ; 268: 114230, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37169121

RESUMEN

The Djungarian hamster (Phodopus sungorus) shows calm behavior, while the Roborovskii hamster (P. roborovskii) exhibits hyperactivity. Even though they belong to the same genus, Phodopus, these two species are quite different. The current study investigated the relationship between energy expenditure and the markedly different levels of activity shown by these hamsters. Roborovskii hamsters showed significantly higher energy expenditure than Djungarian hamsters under both feeding and fasting conditions during darkness. Roborovskii hamsters showed a repeated increase and decrease in energy expenditure under the feeding condition; however, this changed under the fasting condition, during which the repeated increase and decrease in energy expenditure corresponded to the repeated active and sleeping conditions. Djungarian hamsters had a tendency to keep their energy expenditure constant during the fasting condition, while Roborovskii hamsters moved around a lot to find food. The respiratory quotient (RQ) values in Djungarian hamsters were relatively constant. However, Roborovskii hamsters showed a wide variation in RQ. In particular, the RQ value declined immediately before a dark phase commenced, indicating a switchover from the utilization of glucose to that of lipids as a substrate for energy production. In conclusion, Djungarian hamsters and Roborovskii hamsters showed different behavioral patterns that were related to differences in energy metabolism.


Asunto(s)
Actividad Motora , Phodopus , Cricetinae , Animales , Metabolismo Energético
19.
Animals (Basel) ; 13(22)2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-38003138

RESUMEN

The regulation of duck physiology and behavior through the photoperiod holds significant importance for enhancing poultry farming efficiency. To clarify the impact of the photoperiod on group-raised duck activeness and quantify duck activeness, this study proposes a method that employs a multi-object tracking model to calculate group-raised duck activeness. Then, duck farming experiments were designed with varying photoperiods as gradients to assess this impact. The constructed multi-object tracking model for group-raised ducks was based on YOLOv8. The C2f-Faster-EMA module, which combines C2f-Faster with the EMA attention mechanism, was used to improve the object recognition performance of YOLOv8. Furthermore, an analysis of the tracking performance of Bot-SORT, ByteTrack, and DeepSORT algorithms on small-sized duck targets was conducted. Building upon this foundation, the duck instances in the images were segmented to calculate the distance traveled by individual ducks, while the centroid of the duck mask was used in place of the mask regression box's center point. The single-frame average displacement of group-raised ducks was utilized as an intuitive indicator of their activeness. Farming experiments were conducted with varying photoperiods (24L:0D, 16L:8D, and 12L:12D), and the constructed model was used to calculate the activeness of group-raised ducks. The results demonstrated that the YOLOv8x-C2f-Faster-EMA model achieved an object recognition accuracy (mAP@50-95) of 97.9%. The improved YOLOv8 + Bot-SORT model achieved a multi-object tracking accuracy of 85.1%. When the photoperiod was set to 12L:12D, duck activeness was slightly lower than that of the commercial farming's 24L:0D lighting scheme, but duck performance was better. The methods and conclusions presented in this study can provide theoretical support for the welfare assessment of meat duck farming and photoperiod regulation strategies in farming.

20.
Animals (Basel) ; 13(18)2023 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-37760278

RESUMEN

In breeding ducks, obtaining the pose information is vital for perceiving their physiological health, ensuring welfare in breeding, and monitoring environmental comfort. This paper proposes a pose estimation method by combining HRNet and CBAM to achieve automatic and accurate detection of duck's multi-poses. Through comparison, HRNet-32 is identified as the optimal option for duck pose estimation. Based on this, multiple CBAM modules are densely embedded into the HRNet-32 network to obtain the pose estimation model based on HRNet-32-CBAM, realizing accurate detection and correlation of eight keypoints across six different behaviors. Furthermore, the model's generalization ability is tested under different illumination conditions, and the model's comprehensive detection abilities are evaluated on Cherry Valley ducklings of 12 and 24 days of age. Moreover, this model is compared with mainstream pose estimation methods to reveal its advantages and disadvantages, and its real-time performance is tested using images of 256 × 256, 512 × 512, and 728 × 728 pixel sizes. The experimental results indicate that for the duck pose estimation dataset, the proposed method achieves an average precision (AP) of 0.943, which has a strong generalization ability and can achieve real-time estimation of the duck's multi-poses under different ages, breeds, and farming modes. This study can provide a technical reference and a basis for the intelligent farming of poultry animals.

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