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1.
Braz. j. biol ; 84: e250936, 2024. graf
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1345557

RESUMEN

Abstract This study was carried out to evaluate the effect of Glutamine, as a dipeptide or a free amino acid form, on the progression of burn injuries in rats. Thirty male Wistar rats were burned with a comb metal plate heated in boiling water (98 °C) for three minutes, creating four rectangular full-thickness burn areas separated by three unburned interspaces (zone of stasis) in both dorsum sides. The animals were randomized into three groups (n=10): saline solution (G1-Control) and treated groups that orally received Glutamine as dipeptide (G2-Dip) or free amino acid (G3-FreeAA). Two and seven days after burn injury, lesions were photographed for unburned interspaces necrosis evolution assessment. Seven days after injury, glutathione seric was measured and histopathological analysis was performed. By photographs, there was a significant reduction in necrosis progression in G3-Free-AA between days two and seven. Histopathological analysis at day 7 showed a significantly higher stasis zone without necrosis and a higher number of fibroblasts in G2-Dip and G3-FreeAA compared with G1-Control. Also, glutathione serum dosage was higher in G2-Dip. The plasmatic glutathione levels were higher in the G2-Dip than the G1-Control, and there was a trend to higher levels in G3-FreeAA. The reduction in histological lesions, greater production of fibroblasts, and greater amounts of glutathione may have benefited the evolution of burn necrosis, which showed greater preservation of interspaces.


Resumo Este estudo foi realizado para avaliar o efeito da Glutamina, como um dipeptídeo ou forma de aminoácido livre, na progressão de queimaduras em ratos. Trinta ratos Wistar machos foram queimados com um pente de metal aquecido em água fervente (98 °C) por três minutos, criando quatro áreas retangulares queimadas separadas por três interesespaços não queimados (zona de estase) em ambos os lados do dorso. Os animais foram randomizados em três grupos (n = 10): solução salina (G1-Controle) e grupos tratados que receberam glutamina via oral como dipeptídeo (G2-Dip) ou aminoácido livre (G3-FreeAA). Dois e sete dias após a queimadura, as lesões foram fotografadas para avaliação da evolução da necrose entre os espaços não queimados. Sete dias após a lesão, foi dosada a glutationa sérica e realizada análise histopatológica. Pelas fotografias, houve uma redução significativa na progressão da necrose no G3-Free-AA entre os dias dois e sete. A análise histopatológica no dia 7 mostrou uma zona de estase significativamente maior sem necrose e número mais elevado de fibroblastos em G2-Dip e G3-FreeAA em comparação com G1-Controle. Os níveis plasmáticos de glutationa foram maiores no G2-Dip em relação ao G1-Controle, e houve tendência a níveis mais elevados no G3-FreeAA. A redução das lesões histológicas, maior produção de fibroblastos, maior quantidade de glutationa podem ter beneficiado a evolução da necrose da queimadura, que mostrou maior preservação dos interespaços.


Asunto(s)
Animales , Masculino , Ratas , Quemaduras/tratamiento farmacológico , Glutamina , Ratas Wistar , Dipéptidos , Modelos Animales de Enfermedad , Aminoácidos
2.
Braz. j. biol ; 84: e252575, 2024. tab
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1355869

RESUMEN

Abstract Increased anxiety and depressive symptoms have reported to be its association with long term illness. Because of having unwanted effects of newly available drugs, patients administering anxiolytic drugs usually discontinue the treatment before they are completely recovered. Therefore, there is a serious need to develop new anxiolytic drugs. The anxiolytic effect of hydro-alcoholic extract of Agaricus blazei in animal models was assessed. 24 male mice (Mus musculus genus) were included in the study. Four groups were prepared and each group contained six animals. The groups were vehicle control, positive control (diazepam 1.0 mg/kg, i.p.) as well as two treatment groups receiving Agaricus blazei hydro-alcoholic extract at a dose of 136.50 mg/kg and 273.0 mg/kg orally. The Marble burying test, Nestlet shredding test and Light and Dark box test used to assess anxiolytic activity. Mice administered with diazepam 1.0 mg/kg, i.p. while hydro-alcoholic extract of AbM (136.50 and 273.0 mg/kg, respectively) was administered via oral route which exhibited marked reduction in number of marbles-burying as compared to vehicle control group. Mice administered with diazepam 1.0 mg/kg, i.p. and Oral administration of hydro-alcoholic extract of AbM (136.50 and 273.0 mg/kg, respectively) exhibited significant decrease in nestlet shredding in comparison to vehicle control group. The oral administration of hydro-alcoholic extract at a dose of 136.5mg/kg and 273mg/kg showed elevation in time spent in light box and was comparable to standard treated group while time spent by mice following oral administration of hydro-alcoholic extract of Agaricus blazei at a dose of 273.0 mg/kg also showed elevation and was found to be more near to standard treated group (diazepam 1 mg/kg, i.p.).


Resumo O aumento da ansiedade e dos sintomas depressivos têm relatado sua associação com doenças de longa duração. Por causa dos efeitos indesejáveis dos novos medicamentos disponíveis, os pacientes que administram medicamentos ansiolíticos geralmente interrompem o tratamento antes de estarem completamente recuperados. Portanto, há uma necessidade séria de desenvolver novos medicamentos ansiolíticos. Foi avaliado o efeito ansiolítico do extrato hidroalcoólico de Agaricus blazei em modelos animais. Vinte e quatro camundongos machos (gênero Mus musculus) foram incluídos no estudo. Quatro grupos foram preparados, e cada grupo continha seis animais. Os grupos foram controle de veículo, controle positivo (diazepam 1,0 mg/kg, i.p.), bem como dois grupos de tratamento recebendo extrato hidroalcoólico de Agaricus blazei na dose de 136,50 mg/kg e 273,0 mg/kg por via oral. O teste de enterrar Marble, o teste de retalhamento Nestlet e o teste de caixa clara e escura são usados ​​para avaliar a atividade ansiolítica. Camundongos foram administrados com diazepam 1,0 mg/kg, i.p., enquanto o extrato hidroalcoólico de AbM (136,50 e 273,0 mg/kg, respectivamente) foi administrado por via oral, que exibiu redução acentuada no número de mármores enterrados em comparação com o grupo de controle de veículo. Camundongos administrados com diazepam 1,0 mg/kg, i.p. e a administração oral de extrato hidroalcoólico de AbM (136,50 e 273,0 mg/kg, respectivamente) exibiu diminuição significativa na trituração de ninhos em comparação ao grupo de controle de veículo. A administração oral de extrato hidroalcoólico na dose de 136,5mg/kg e 273mg/kg mostrou elevação no tempo gasto na caixa de luz e foi comparável ao grupo tratado padrão, enquanto o tempo gasto por camundongos após a administração oral de extrato hidroalcoólico de Agaricus blazei na dose de 273,0 mg/kg também mostrou elevação e foi mais próximo do grupo tratado padrão (diazepam 1 mg/kg, ip).


Asunto(s)
Animales , Masculino , Conejos , Agaricus , Conducta Exploratoria , Modelos Animales de Enfermedad
3.
Braz. j. biol ; 84: e253616, 2024. tab, graf
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1355880

RESUMEN

Abstract This study evaluated the effect of the volatile oil of Alpinia zerumbet (VOAz) on caveolin-1 gene expression and muscular fibrosis. The rats were immobilized to induce fibrosis of the gastrocnemius muscle, and they were treated with VOAz. Collagen quality was assessed by histology and the expression of the caveolin-1 (CAV-1) gene was evaluated using qPCR. Histomorphological analysis indicated a significant reduction in the perimeter, width, and intensity of collagen in the treated groups, thus showing that the oil was effective in regulating the quality of collagen at the three concentrations. The results of expression levels suggested a decrease in the lesioned group and in two treatment groups (0.0115 µg/g and 0.009 µg/g). However, with the lowest concentration (0.0065 µg/g), no significant difference was observed, with levels similar to those found in healthy tissue. Therefore, the results showed that VOAz has the potential to be a non-invasive and low-cost alternative to aid in the treatment of muscular fibrosis.


Resumo Este estudo avaliou o efeito do óleo volátil de Alpinia zerumbet (OVAz) na expressão do gene da caveolina-1 e na fibrose muscular. Os ratos foram imobilizados para induzir a fibrose do músculo gastrocnêmio, e foram tratados com OVAz. A qualidade do colágeno foi avaliada com histologia e à expressão do gene caveolina-1 (CAV-1) foi avaliada usando qPCR. A análise histomorfológica indicou uma redução significativa no perímetro, largura e intensidade do colágeno nos grupos tratados. Os resultados dos níveis de expressão sugeriram diminuição nos grupos de lesão e em dois grupos de tratamento (0,0115 µg/g e 0,009 µg/g). No entanto, com a menor concentração (0,0065 µg/g), não foi observada diferença significativa, apresentando níveis semelhantes aos encontrados em tecido saudável. O uso do OVAz foi eficaz para reverter as alterações do colágeno causadas pela fibrose, e sua menor concentração apresentou uma possível tendência de aumento na expressão do CAV-1. Portanto, os resultados mostraram que o OVAz tem potencial para ser uma alternativa não invasiva e de baixo custo para auxiliar no tratamento da fibrose muscular.


Asunto(s)
Animales , Ratas , Aceites Volátiles/farmacología , Colágeno/metabolismo , Alpinia/química , Caveolina 1/metabolismo , Músculos/efectos de los fármacos , Fibrosis , Aceites Vegetales/farmacología , Brasil , Ratas Wistar , Modelos Animales de Enfermedad , Músculos/patología
4.
Methods Mol Biol ; 2587: 55-66, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36401024

RESUMEN

Duchenne muscular dystrophy (DMD) (the most common form of muscular dystrophy) is caused by a lack of dystrophin protein. Currently, although many therapeutic strategies are under investigation, there is no cure for DMD and unfortunately, patients succumb to respiratory and/or cardiac failure in their second or third decade of life. Preclinical work has focused on the mouse model C57BL/10ScSn-Dmdmdx/J (BL10/mdx), which does not exhibit a robust pathophenotype. More recently, the D2.B10-Dmdmdx/J (D2/mdx) mouse has been utilized, which presents a more severe pathology and therefore more closely mimics the human pathophenotype, particularly in the heart. Here, we outline important considerations when utilizing the D2/mdx model by highlighting the differences between these models in addition to describing histological and immunohistochemical methods utilized in Kennedy et al. (Mol Ther Methods Clin Dev 11:92-105, 2018) for both cardiac and skeletal muscle, which can quantify these differences. These considerations are particularly important when investigating treatment strategies that may be affected by regeneration; such is the case for upregulation of the dystrophin paralogue, utrophin.


Asunto(s)
Distrofina , Distrofia Muscular Animal , Humanos , Ratones , Animales , Ratones Endogámicos mdx , Utrofina/genética , Distrofina/genética , Distrofia Muscular Animal/genética , Ratones Endogámicos C57BL , Músculo Esquelético/metabolismo , Modelos Animales de Enfermedad
5.
Behav Brain Res ; 437: 114128, 2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36174841

RESUMEN

While SSRIs are the current first-line pharmacotherapies against post-traumatic stress disorder (PTSD), they suffer from delayed onset of efficacy and low remission rates. One solution is to combine SSRIs with other treatments. Neuronal nitric oxide synthase (nNOS) has been shown to play a role in serotonergic signaling, and there is evidence of synergism between nNOS modulation and SSRIs in models of other psychiatric conditions. Therefore, in this study, we combined subchronic fluoxetine (Flx) with 7-nitroindazole (NI), a selective nNOS inhibitor, and evaluated their efficacy against anxiety-related behavior in an animal model of PTSD. We used the underwater trauma model to induce PTSD in rats. Animals underwent the open field (OFT) and elevated plus maze tests on days 14 (baseline) and 21 (post-treatment) after PTSD induction to assess anxiety-related behaviors. Between the two tests, the rats received daily intraperitoneal injections of 10 mg/kg Flx or saline, and were injected intraperitoneally before the second test with either 15 mg/kg NI or saline. The change in behaviors between the two tests was compared between treatment groups. Individual treatment with both Flx and NI had anxiogenic effects in the OFT. These effects were associated with modest increases in cFOS expression in the hippocampus. Combination therapy with Flx + NI did not show any anxiogenic effects, while causing even higher expression levels of cFOS. In conclusion, addition of NI treatment to subchronic Flx therapy accelerated the abrogation of Flx's anxiogenic properties. Furthermore, hippocampal activity, as evidenced by cFOS expression, was biphasically related to anxiety-related behavior.


Asunto(s)
Ansiolíticos , Inhibidores Enzimáticos , Óxido Nítrico Sintasa de Tipo I , Inhibidores de la Captación de Serotonina , Trastornos por Estrés Postraumático , Animales , Ratas , Ansiedad/metabolismo , Modelos Animales de Enfermedad , Fluoxetina/farmacología , Fluoxetina/uso terapéutico , Hipocampo/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo I/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo I/metabolismo , Inhibidores de la Captación de Serotonina/farmacología , Inhibidores de la Captación de Serotonina/uso terapéutico , Trastornos por Estrés Postraumático/tratamiento farmacológico , Trastornos por Estrés Postraumático/metabolismo , Quimioterapia Combinada , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Ansiolíticos/farmacología , Ansiolíticos/uso terapéutico
6.
Methods Mol Biol ; 2587: 467-478, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36401044

RESUMEN

In vivo testing of glucocorticoid steroids in dystrophic mice offers important insights in benefits and risks of those drugs in the pathological context of muscular dystrophy. Frequency of dosing changes the spectrum of glucocorticoid effects on muscle and metabolic homeostasis. Here, we describe a combination of non-invasive and invasive methods to quantitatively discriminate the specific effects of intermittent (once-weekly) versus mainstay (once-daily) regimens on muscle fibrosis, muscle function, and metabolic homeostasis in murine models of Duchenne and limb-girdle muscular dystrophies.


Asunto(s)
Distrofia Muscular de Cinturas , Distrofia Muscular de Duchenne , Ratones , Animales , Glucocorticoides/farmacología , Glucocorticoides/metabolismo , Modelos Animales de Enfermedad , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/patología , Distrofia Muscular de Cinturas/tratamiento farmacológico , Distrofia Muscular de Cinturas/patología
7.
Methods Mol Biol ; 2587: 527-536, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36401048

RESUMEN

For cell therapy toward Duchenne muscle dystrophy (DMD), muscle progenitor cells derived from human-induced pluripotent stem cell (hiPSC-MuPCs) are recognized as a good candidate, and currently, cell transplantation of hiPSC-MuPCs is being tested with several DMD animal models. In this article, we describe an efficient method to dissociate, purify by cell sorting, transplant, and evaluate the transplantation efficacy of hiPSC-MuPCs.


Asunto(s)
Células Madre Pluripotentes Inducidas , Distrofia Muscular de Duchenne , Ratones , Humanos , Animales , Distrofia Muscular de Duchenne/terapia , Mioblastos , Trasplante de Células Madre , Modelos Animales de Enfermedad , Músculos
8.
Methods Mol Biol ; 2587: 557-568, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36401050

RESUMEN

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset rare muscle disease affecting approximately 1 in 80,000 individuals worldwide. However, it can affect as much as 1:600 individuals in some populations due to a strong founder effect. The muscle pathology is characterized by progressive eyelid drooping (ptosis), swallowing difficulties (dysphagia), and limb weakness at later stages of disease progression. The genetic defect is associated with significant fibrotic deposition and atrophy in affected muscles. No treatments are available to cure the disease. Only surgical techniques to correct ptosis and swallowing are currently possible, though they carry a risk of recurrence. Myostatin is a negative regulator of muscle growth, and several strategies to downregulate its expression have been developed with the aim of improving muscle mass and strength in muscular pathologies. We recently showed that weekly systemic treatment of the A17 murine model of OPMD with a monoclonal antibody for myostatin improves body and muscle mass, increases muscle strength, and reduces muscle fibrosis. Here, we describe the methodology for repeated intraperitoneal delivery of myostatin antibody in the murine model. Furthermore, we detail the most relevant analyses to assess histopathological and functional improvements of this treatment in this mouse model.


Asunto(s)
Distrofia Muscular Oculofaríngea , Ratones , Animales , Distrofia Muscular Oculofaríngea/genética , Distrofia Muscular Oculofaríngea/patología , Miostatina , Anticuerpos Monoclonales/uso terapéutico , Modelos Animales de Enfermedad , Inmunoterapia
9.
Mol Med Rep ; 27(1)2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36331022

RESUMEN

Stroke is one of the leading causes of death from diseases. When the blood supply to the brain tissue is interrupted, neuronal core death occurs due to the lack of glucose and oxygen in min. Blood pressure lowering after ischemic stroke was proven to be an effective strategy to achieve neurovascular protection and reduce the risk of recurrent stroke. Astragaloside IV is a pure small molecular compound isolated from Radix Astragali, and it is well documented that astragaloside IV has neuroprotective effect on cerebral ischemia reperfusion (CIR) injury through many mechanisms, including antioxidant, anti­inflammatory and anti­apoptotic. The present study adopted mean arterial pressure (MAP) monitoring, neurological scoring, 2,3,5­triphenyltetrazolium chloride staining, enzyme­linked immuno­sorbent assay, western blotting and other experimental methods to investigate the effect of astragaloside IV on systemic blood pressure during CIR in a middle cerebral artery occlusion animal model. It was demonstrated that astragaloside IV pretreatment significantly alleviated CIR injury as previously reported. In addition, the elevation of MAP during CIR was significantly inhibited by astragaloside IV administration. Moreover, it was revealed that the expression of Na+­K+­2Cl­ cotransporter isoform 1 in the hypothalamus was inhibited and the subsequent synthesis of vasopressin was reduced by astragaloside IV pretreatment in the CIR animal model. In conclusion, astragaloside IV may alleviate CIR injury partially by lowering systemic blood pressure.


Asunto(s)
Isquemia Encefálica , Daño por Reperfusión , Saponinas , Triterpenos , Ratas , Animales , Ratas Sprague-Dawley , Saponinas/farmacología , Saponinas/uso terapéutico , Triterpenos/farmacología , Triterpenos/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Reperfusión , Infarto de la Arteria Cerebral Media , Modelos Animales de Enfermedad
10.
Mol Med Rep ; 27(1)2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36367174

RESUMEN

Alzheimer's disease (AD) is a common neurodegenerative disorder. Amyloid ß (Aß) deposition is considered an important pathological feature of AD. Growing evidence has linked neuroinflammation and autophagy to Aß deposition in the progression of AD. However, there are few drug options for inhibiting neuroinflammation and autophagy to prevent AD. Ginsenoside Rg1 (Rg1), a steroidal saponin extracted from ginseng, has been reported to possess multiple neuroprotective effects. The present study aimed to evaluate whether Rg1 treatment could attenuate cognitive disorders and neuronal injuries by inhibiting NLRP1 inflammasome and autophagy dysfunction in an AD model of APP/PS1 mice. The results of behavioral tests indicated that Rg1 treatment for 12 weeks could significantly improve olfactory dysfunction as well as learning and memory impairments. The results of histopathological tests indicated that Rg1 treatment could reduce Aß deposition and neuronal damages in APP/PS1­9M mice. Additionally, the results of immunoblot, reverse transcription­quantitative PCR or immunohistochemistry demonstrated that Rg1 treatment significantly downregulated the expression levels of inflammation­related proteins of NLRP1, caspase1, IL­1ß and TNF­α, as well as autophagy­related proteins of p­AMPK/AMPK, Beclin1 and LC3 II/LC3 I, and increased the expression levels of p­mTOR/mTOR and P62 in APP/PS1­9M mice. In addition, the molecular docking analysis showed that there was favorable binding result between Rg1 and NLRP1. The present study suggested that Rg1 may alleviate learning and memory impairments and Aß disposition by inhibiting NLRP1 inflammasome and improving autophagy dysfunction, suggesting that Rg1 may be a potential therapeutic agent for delaying AD.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Ratones , Animales , Péptidos beta-Amiloides/metabolismo , Inflamasomas/metabolismo , Simulación del Acoplamiento Molecular , Proteínas Quinasas Activadas por AMP , Modelos Animales de Enfermedad , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Trastornos de la Memoria/tratamiento farmacológico , Autofagia , Serina-Treonina Quinasas TOR , Ratones Transgénicos , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo
11.
Methods Mol Biol ; 2582: 309-321, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36370359

RESUMEN

Approximately 45% of the deaths in the developed world result from conditions with a fibrotic component. Although no specific, focused anti-fibrotic therapies have been approved for clinical use, a long-standing concept is that targeting CCN proteins may be useful to treat fibrosis. Herein, we summarize current data supporting the concept that targeting CCN2 may be a viable anti-fibrotic approach to treat scleroderma. Testing this hypothesis has been made possible by using a mouse model of inflammation-driven skin and lung fibrosis.


Asunto(s)
Fibrosis Pulmonar , Esclerodermia Sistémica , Animales , Bleomicina/efectos adversos , Factor de Crecimiento del Tejido Conjuntivo/genética , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Fibrosis , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Piel/metabolismo , Modelos Animales de Enfermedad , Esclerodermia Sistémica/inducido químicamente , Esclerodermia Sistémica/metabolismo
12.
Methods Mol Biol ; 2582: 335-342, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36370361

RESUMEN

Skeletal fractures are most common large-organ traumatic injuries that impact the functions and esthetic outcomes and quality of life. Unfortunately, infection during the fracture healing process and inadequate blood supply to the bone impede reduced ability to produce cartilage and effective bone callus formation, leading to nonunion or delayed union fracture. Therefore, studying the mechanism of fracture healing is an important task in solving the problem of fracture healing failure. Animal models of bone fracture healing are important tools to investigate the pathogenesis and develop treatment strategies. This protocol introduces researchers to a bone repair model utilizing the ribs of rats and the immunohistological expression of cellular communication network factor/connective tissue growth factor (CTGF/CCN2) during the fracture healing processes.


Asunto(s)
Fracturas Óseas , Fracturas Cerradas , Ratas , Animales , Curación de Fractura , Factor de Crecimiento del Tejido Conjuntivo , Calidad de Vida , Fracturas Óseas/terapia , Fracturas Óseas/patología , Callo Óseo , Modelos Animales de Enfermedad
13.
Methods Mol Biol ; 2582: 343-353, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36370362

RESUMEN

Bone metastasis and bone destruction are common occurrences in human malignancies, including breast, prostate, and lung cancer, and are associated with a high morbidity rate because of intractable bone pain, pathological fractures, hypercalcemia, and nerve compression. Animal models of bone metastasis and bone destruction are important tools to investigate the pathogenesis and develop treatment strategies. However, there are few models of spontaneous bone metastasis despite the fact that animals often spontaneously develop cancer. Here, we describe methods for developing a mouse model of breast cancer bone metastasis achieved by injection of MDA-MB-231 breast cancer cells into the left cardiac ventricle. In addition, we introduce mouse model of the bone destruction by injection of SAS oral squamous cell carcinoma cells into the bone marrow space of the right tibial metaphysis. These assays can be applied to studies on roles of cellular communication network factor/connective tissue growth factor (CTGF/CCN2) protein in tumor metastasis and development of treatment strategies targeting CCN proteins.


Asunto(s)
Neoplasias Óseas , Neoplasias de la Mama , Carcinoma de Células Escamosas , Neoplasias de la Boca , Ratones , Masculino , Animales , Humanos , Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/patología , Neoplasias Óseas/patología , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Huesos/metabolismo , Proteínas , Modelos Animales de Enfermedad , Neoplasias de la Mama/patología , Línea Celular Tumoral
14.
Carbohydr Polym ; 300: 120226, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36372471

RESUMEN

Radical pelvic surgery is commonly accompanied by the risk of postoperative erectile dysfunction induced by cavernous nerve injury (CNI-ED). The strategy of using adipose mesenchymal stem cell-derived exosomes (ADSC-Exo) to treat neurodegenerative diseases has shown promising results. However, it remains challenging to prolong the retention of unbound ADSC-Exo in damaged tissues to exert therapeutic effects. Herein, we develop a novel injectable thermo-sensitive hydroxyethyl chitosan/sodium ß-glycerophosphate hydrogel (HG) encapsulating ADSC-Exo (HG@Exo) to manage CNI-ED. The HG exhibits excellent injectability, structural stability, and body temperature sensitivity. In vivo assessment demonstrates that the designed ADSC-Exo-loaded HG hydrogel enhances the retention of ADSC-Exo and displays a slow release. Furthermore, when HG@Exo is applied to the site of nerve injury, erectile function in the bilateral cavernous nerve injury rat model is significantly improved. Thus, our finding indicates that the developed bioactive hydrogel presents a promising strategy for the effective management of CNI-ED.


Asunto(s)
Exosomas , Masculino , Ratas , Animales , Pene/lesiones , Pene/inervación , Hidrogeles/uso terapéutico , Ratas Sprague-Dawley , Modelos Animales de Enfermedad
15.
Methods Mol Biol ; 2597: 1-9, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36374409

RESUMEN

Hindlimb suspension is a well-established rodent model of disuse-induced atrophy and is commonly used to simulate the effects of bed rest and space flight on humans. Over the decades, this method has undergone many changes to reduce the stress response on the animals and improve the reliability of the data. Here, we detail our method of performing hindlimb suspension in mice that minimizes stress, maximizes the replicability of the data, and uses space efficiently.


Asunto(s)
Suspensión Trasera , Músculo Esquelético , Humanos , Ratones , Animales , Suspensión Trasera/efectos adversos , Suspensión Trasera/métodos , Reproducibilidad de los Resultados , Músculo Esquelético/patología , Modelos Animales de Enfermedad , Roedores , Atrofia , Miembro Posterior
16.
Methods Mol Biol ; 2597: 39-58, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36374413

RESUMEN

Chemokine-glycosaminoglycan (GAG) interactions direct immune cell activation and invasion, e.g., directing immune cells to sites of infection or injury, and are central to initiating immune responses. Acute innate and also adaptive or antibody-mediated immune cell responses both drive damage to kidney transplants. These immune responses are central to allograft rejection and transplant failure. While treatment for acute rejection has advanced greatly, ongoing or chronic immune damage from inflammation and antibody-mediated rejection remains a significant problem, leading to transplant loss. There are limited numbers of organs available for transplant, and preventing chronic graft damage will allow for longer graft stability and function, reducing the need for repeat transplantation. Chemokine-GAG interactions are the basis for initial immune responses, forming directional gradients that allow immune cells to traverse the vascular endothelium and enter engrafted organs. Targeting chemokine-GAG interactions thus has the potential to reduce immune damage to transplanted kidneys.Mouse models for renal transplant are available, but are complex and require extensive microsurgery expertise. Here we describe simplified subcapsular and subcutaneous renal allograft transplant models, for rapid assessment of the roles of chemokine-GAG interactions during allograft surgery and rejection. These models are described, together with treatment using a unique chemokine modulating protein (CMP) M-T7 that disrupts chemokine-GAG interactions.


Asunto(s)
Trasplante de Riñón , Ratones , Animales , Trasplante de Riñón/efectos adversos , Rechazo de Injerto , Glicosaminoglicanos/metabolismo , Quimiocinas/metabolismo , Modelos Animales de Enfermedad , Complicaciones Posoperatorias , Aloinjertos
17.
Methods Mol Biol ; 2597: 19-24, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36374411

RESUMEN

Corneal transplantation is the most common form of organ transplantation worldwide. Transplant survival depends on various factors, many of which are not fully understood. Due to the existence of many genetically defined strains, mouse models of corneal transplantation are most commonly used. Here, we describe a method for a mouse corneal transplantation.


Asunto(s)
Trasplante de Córnea , Ratones , Animales , Trasplante de Córnea/métodos , Supervivencia de Injerto , Modelos Animales de Enfermedad , Rechazo de Injerto
18.
Behav Brain Res ; 437: 114100, 2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36075399

RESUMEN

INTRODUCTION: Non-motor symptoms (NMS) have high prevalence in patients with Parkinson's disease (PD). These symptoms are mainly the result of increased oxidative stress and neuronal damage. In this study we investigated the possible neuroprotective effects of anethole as a potent antioxidant on rotenone-induced behavioral deficits, hippocampal neuronal death, and oxidative stress profile in rats. METHODS: Male Wistar rats were administered with anethole (62.5, 125, and 250 mg/kg, i.g) concomitantly with rotenone (2 mg/kg, s.c) for 35 days. Shuttle box and novel object recognition tests were performed to determine cognitive functions, and tail flick test was used to measure pain sensitivity. The levels of BDNF, MDA, SOD, and GPx were assayed in the hippocampus. Hippocampal neuronal damage was evaluated using cresyl violet staining technique. RESULTS: Chronic administration of rotenone induced cognitive deficit and reduced thermal pain threshold. Rotenone also decreased SOD and GPx activities, increased MDA level, and reduced the expression of BDNF in the hippocampus. In addition, hippocampal neuronal loss was increased in rotenone treated rats. Treatment with high dose of anethole (250 mg/kg) improved cognitive function and increased pain threshold in all three doses (62.5, 125, and 250 mg/kg). Despite the unchanged SOD and GPx activities, hippocampal levels of MDA was significantly decreased after high-dose anethole treatment. Moreover, High dose of anethole increased the number of surviving neurons in the hippocampus, but couldn't increase the BDNF expression. CONCLUSION: Our findings indicated that anethole has antioxidant and neuroprotective effects against non-motor disorders induced by rotenone toxicity.


Asunto(s)
Fármacos Neuroprotectores , Enfermedad de Parkinson , Animales , Ratas , Masculino , Rotenona/farmacología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Enfermedad de Parkinson/metabolismo , Antioxidantes/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ratas Wistar , Estrés Oxidativo , Superóxido Dismutasa/metabolismo , Modelos Animales de Enfermedad
19.
Behav Brain Res ; 437: 114111, 2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36100009

RESUMEN

Autism spectrum disorder (ASD) presents with two core symptoms, impairments in social communication and the presence of restricted, repetitive behaviors (RRBs). RRBs are commonly linked to a lack of behavioral flexibility, having a significant negative impact on daily functioning for ASD individuals and their caregivers. Commonly utilized tests of behavioral flexibility employ a traditional deterministic reward approach where choices are either correct or incorrect throughout testing. The incorporation of an 80 %/20 % probabilistic reversal learning paradigm allows for the examination of flexible behavior in the face of variable outcomes, a more ecologically relevant approach. In this task, one specific choice is reinforced on 80 % of trials and the opposite or incorrect choice is reinforced on 20% of trials. Upon successful discrimination learning, the reward contingencies are switched so that the correct choice is now reinforced 20% of trials and the incorrect choice reinforced 80 % of trials, making it the new optimal choice. This translational task has been previously validated in ASD individuals and animal models of ASD, including the BTBR T + tf/J strain. Our lab and others have demonstrated that male BTBR T + tf/J mice have higher expression of lower order RRBs and display deficits in spatial probabilistic reversal learning tasks using a T-maze apparatus. Instead, female BTBR mice do not express the same lower order RRBs and results are mixed on whether females demonstrate similar probabilistic reversal learning deficits in a T-maze. Therefore, the purpose of this study was to assess the validity of using operant chambers to examine BTBR mouse performance on an 80 %/20 % probabilistic reversal learning task and to also examine the sex-specific differences in reversal learning performance in both mouse strains. Results show that BTBR mice, irrespective of sex, were impaired on the reversal learning, requiring more days and trials to reach reversal criterion compared to C57BL/6J mice. These results parallel previous strain findings in the spatial dependent T-maze task in male mice. Further error analysis showed that the impaired behavioral flexibility was due to elevated regressive errors and lose-shift probabilities. BTBR mice have more difficulty maintaining new choice patterns compared to C57BL/6J mice, which supports findings utilizing a spatial T-maze task. Together, these findings further support the use of the BTBR mouse as preclinical models of ASD due to their validity as an ASD model.


Asunto(s)
Trastorno del Espectro Autista , Aprendizaje Inverso , Ratones , Animales , Masculino , Femenino , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Ratones Endogámicos , Conducta Social
20.
Behav Brain Res ; 437: 114132, 2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36181946

RESUMEN

Autism spectrum disorder (ASD) is characterized by deficits in social communication and repetitive behaviors/restricted interests. One mouse model of ASD is the BTBR T+Itprtf/J (BTBR) mice which display low levels of social behavior in several tests. The social approach test is used to examine the preference for social interaction between a stranger mouse or a novel object. While female BTBR mice have been used in the social approach test, no one has examined the degree to which the strain of the stranger mouse will affect social behavior. The current experiment tested female BTBR subject mice in the social approach test with stranger mice from different strains including the BTBR, 129S1/SvImJ (129), and C57BL/6J (B6) mice, of which the B6 mice are most social. The results show that female BTBR mice overall spent significantly more time in the stranger mouse chamber. However, further analysis revealed that the subject mice spent significantly more time in the stranger mouse chamber when the stranger was from the B6 strain, but not the BTBR or 129 strains. The BTBR female mice also sniffed the B6 and 129 stranger mice more than the novel object. This suggests that BTBR females are more social with mice that display high levels of social behavior, but less so with less social mice.


Asunto(s)
Trastorno del Espectro Autista , Ratones , Femenino , Animales , Ratones Endogámicos C57BL , Ratones Endogámicos , Conducta Social , Modelos Animales de Enfermedad
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