RESUMO
BACKGROUND: Angiogenesis is an effective method for promoting neurological function recovery after cerebral ischemia (CI). Buyang Huanwu decoction (BHD) is a traditional Chinese medicinal recipe that is frequently employed for CI treatment. Previous investigations have validated that it promotes angiogenesis following CI. Nevertheless, the precise mechanism by which it does this has yet to be completely understood. OBJECTIVE: This study aims to examine the underlying mechanism through which BHD facilitates angiogenesis following CI by regulating the exosomal MALAT1/YAP1/HIF-1α signaling axis, specifically via the involvement of caveolin-1 (Cav1), an endocytosis-associated protein. METHODS: A CI model was created using middle cerebral artery occlusion (MCAO). Following the administration of multiple doses of BHD, various parameters, including the neurobehavioral score, pathological damage, and angiogenesis, were assessed in each group of mice to identify the optimal dosage of BHD for treating CI. The molecular processes underlying the angiogenic implications of BHD following CI were investigated exhaustively by employing single-cell sequencing. Finally, the involvement of Cav1 was confirmed in Cav1 knockout mice and Cav1-silenced stably transfected strains to validate the mechanism by which BHD increases angiogenesis following CI. RESULTS: BHD could promote angiogenesis after CI. Single-cell sequencing results suggested that its potential mechanism of action might be connected with Cav1 and the exosomal MALAT1/YAP1/HIF-1α signaling axis. BHD could promote angiogenesis after CI by regulating the exosomal MALAT1/YAP1/HIF-1α axis through Cav1, as validated in vivo and in vitro experiments. Accordingly, Cav1 may be a key target of BHD in promoting angiogenesis after CI. CONCLUSION: This investigation represents the initial attempt to comprehensively ascertain the underlying mechanism of action of BHD in treating CI using single-cell sequencing, gene-knockout mice, and stable transfected cell lines, potentially associated with the modulation of the exosomal MALAT1/YAP1/HIF-1α axis by Cav1. Our findings offer novel empirical evidence for unraveling the regulatory pathways through which Cav1 participates in angiogenesis following CI and shed light on the potential mechanisms of BHD.
Assuntos
Isquemia Encefálica , Caveolina 1 , Medicamentos de Ervas Chinesas , Exossomos , Subunidade alfa do Fator 1 Induzível por Hipóxia , RNA Longo não Codificante , Proteínas de Sinalização YAP , Animais , RNA Longo não Codificante/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Caveolina 1/metabolismo , Camundongos , Masculino , Exossomos/metabolismo , Exossomos/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Modelos Animais de Doenças , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Humanos , AngiogêneseRESUMO
Rhabdomyolysis refers to the destruction or disintegration of striated muscles. This syndrome is characterized by muscle breakdown and necrosis, resulting in the leakage of intracellular muscle constituents into the circulation and extracellular fluid. We report a rare case of rhabdomyolysis complicating multi-organ failure caused by T-cell lymphoma in a 32-year-old woman. The final diagnosis was rhabdomyolysis caused by peripheral T-cell lymphoma based on bone marrow aspirate and biopsy.
Assuntos
Neoplasias da Medula Óssea/complicações , Linfoma de Células T/complicações , Rabdomiólise/etiologia , Injúria Renal Aguda/etiologia , Adulto , Biópsia por Agulha , Medula Óssea/patologia , Neoplasias da Medula Óssea/patologia , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica , Linfoma de Células T/patologiaRESUMO
Rhabdomyolysis refers to the destruction or disintegration of striated muscles. This syndrome is characterized by muscle breakdown and necrosis, resulting in the leakage of intracellular muscle constituents into the circulation and extracellular fluid. We report a rare case of rhabdomyolysis complicating multi-organ failure caused by T-cell lymphoma in a 32-year-old woman. The final diagnosis was rhabdomyolysis caused by peripheral T-cell lymphoma based on bone marrow aspirate and biopsy.
Assuntos
Humanos , Feminino , Adulto , Rabdomiólise/etiologia , Linfoma de Células T/complicações , Neoplasias da Medula Óssea/complicações , Biópsia por Agulha , Medula Óssea/patologia , Imuno-Histoquímica , Linfoma de Células T/patologia , Evolução Fatal , Neoplasias da Medula Óssea/patologia , Injúria Renal Aguda/etiologiaRESUMO
PURPOSE: The aim of this study is to determine whether vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) could increase the survival of xenografted human ovarian tissue in an experimental rabbit model. METHODS: Fresh human ovarian tissue was xenotransplanted into the back muscle of 25 castrated female New Zealand rabbits for 6 weeks with the immunosuppression of FTY720 (2 mg/kg/d). Rabbits were randomly divided into five experimental groups: (A) graft and host treatment with VEGF (50 ng/ml); (B) graft and host treatment with bFGF (100 ng/ml); (C) graft and host treatment with VEGF(50 ng/ml) + bFGF (100 ng/ml); (D) graft and host treatment with normal saline; (E) control group, no treatment. 4 weeks after transplantation, human menopausal gonadotropin (HMG) 10 IU was administered every second day in group A, group B, group C and group D for 2 weeks. Graft survival was assessed by graft recovery rate, histological analysis, immunohistochemical staining for CD31 and Ki-67expression, TUNEL assay. RESULTS: After 6 weeks of grafting, the number of CD31-positive stained cells increased significantly in group A, group B and group C compared to the control group. All groups showed strong Ki-67 immunostaining in ovarian stroma. Only one rabbit in group C retained the grafts' follicles. Grafting resulted in relative lower fibrosis in group A and group C compared to the control group. Apoptosis was significantly lower in group C compared to the control group. CONCLUSIONS: Fresh human ovarian cortex grafted into the back muscle of rabbit can sustain part of ovarian tissue function with the immunosuppression of FTY720, although follicle number diminishes significantly after grafting. The administration of VEGF and bFGF, especially the combination of them, may trigger angiogenesis, reduce apoptosis and fibrosis, increase survival in transplanted human ovarian tissue.