RESUMEN
BACKGROUND: We administered Bushen Huoxue Huazhuo Formula (BSHXHZF) and transplanted bone marrow mesenchymal stem cells (BMSCs) into mice with Wilson's disease (WD)-related liver fibrosis to evaluate the liver-protecting mechanism of this prescription. METHODS: Mice, randomly divided into different treatment groups, showed histopathological changes and degree of hepatocyte apoptosis. For hepatic hydroxyproline (Hyp) determination, transforming growth factor-ß1 (TGF-ß1) and bone morphogenetic protein-7 (BMP-7) mRNA and protein were measured. Chemical profiling of the extract of BSHXHZF using The liquid chromatography-mass spectrometry (LC-MS/MS) and revealing its antifibrosis mechanism using metabolomics. RESULTS: TCM+BMSC group livers exhibited few inflammatory cells. TUNEL revealed abundant brown apoptotic cells in model control groups, while the TCM+BMSC groups showed a significant increase in blue negative expression of liver cells. Hyp in toxic milk (TX) mice groups was significantly lower than that in model control groups (MG). Compared with MG, TGF-ß1 expression was significantly lower than all other groups, while BMP-7 expression was significantly higher. Metabolic analysis identified 20 potential biomarkers and 10 key pathways, indicating that BSHXHZF+BMSC intervention has a significant regulatory effect on metabolic disorders of these small molecule substances. CONCLUSION: BSHXHZF combined with BMSCs can inhibit liver fibrosis and hepatocyte apoptosis by improving related metabolic disorders, and achieving therapeutic effects in WD-related liver fibrosis.
Asunto(s)
Proteína Morfogenética Ósea 7 , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Degeneración Hepatolenticular , Cirrosis Hepática , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Metabolómica , Factor de Crecimiento Transformador beta1 , Animales , Cirrosis Hepática/metabolismo , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/patología , Metabolómica/métodos , Medicamentos Herbarios Chinos/farmacología , Ratones , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Degeneración Hepatolenticular/terapia , Degeneración Hepatolenticular/metabolismo , Degeneración Hepatolenticular/tratamiento farmacológico , Proteína Morfogenética Ósea 7/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Masculino , Trasplante de Células Madre Mesenquimatosas/métodos , Apoptosis/efectos de los fármacos , Medicina Tradicional China/métodos , Espectroscopía de Protones por Resonancia Magnética , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Hepatocitos/metabolismo , Hepatocitos/efectos de los fármacos , Hidroxiprolina/metabolismoRESUMEN
Objective: To evaluate the therapeutic effect of a novel air-cooled Nd:YAG laser in the venous lakes of the lips (VLL). Background: The thermal injury is one of the most important issues during laser therapy for venous lakes. Methods: Six pieces of fresh pork livers were used to provide 30 regions with a diameter of 6 mm for experiment in vitro, among which 15 regions were treated by Nd:YAG laser with air cooling until the tissue turned gray-white, whereas the rest were treated without air cooling as control. The operation time of laser irradiation, the degree of temperature increase, and the depth of coagulation tissue were compared between two groups. Then, 60 VLL patients were selected for Nd:YAG laser treatment with or without air cooling. The operation time of laser irradiation, the degree of temperature increase, the postoperative pain visual analog scale (VAS) score, and the percentage of lesions removed within 1 month were compared. Results: In tissue studies, the treated group showed a longer operation time of laser irradiation (p < 0.01), a lower degree of temperature increase (p < 0.01), and there was no significant statistical difference in the depth of coagulation tissue (p = 0.624). In clinical studies, the treated group showed a longer operation time of laser irradiation (p < 0.01), a lower degree of temperature increase (p < 0.01), and a lower VAS score on the 1st and 2nd day, compared with the control group (p < 0.01). Conclusions: Air cooling during Nd:YAG laser for the treatment of VLL can prolong the surgical time, but lowered tissue temperature and reduced patient pain within 2 days under the premise of ensuring the treatment effect.
Asunto(s)
Terapia por Láser , Láseres de Estado Sólido , Terapia por Luz de Baja Intensidad , Humanos , Láseres de Estado Sólido/uso terapéutico , Labio/cirugía , TemperaturaRESUMEN
In traditional Chinese medicine, Radix Astragali has played a vital role in treating progressive fibrotic diseases. One of its main active components, astragaloside IV, is a promising anti-fibrotic treatment despite its extremely low bioavailability. Our study aimed to optimize sodium astragalosidate (SA) by salt formation to improve solubility and oral absorption for anti-fibrotic therapy in vivo. Isoproterenol-induced myocardial fibrosis rat models and obese BKS-db mice presenting diabetic kidney fibrosis were used in this study. Daily oral administration of SA (20 mg/kg) for 14 days ameliorated cardiac fibrosis by reducing collagen accumulation and fibrosis-related inflammatory signals, including TNF-α, IL-1ß, and IL-6. In db/db mice, SA (5,10, and 20 mg/kg per day for 8 weeks) dose-dependently alleviated lipid metabolism impairment and renal dysfunction when administered orally. Furthermore, Western blot and immunohistochemistry analyses demonstrated that SA treatment inhibited renal fibrosis by suppressing TGF-ß1/Smads signaling. Taken together, our findings provide the oral-route medication availability of SA, which thus might offer a novel lead compound in preclinical trial-enabling studies for developing a long-term therapy to treat and prevent fibrosis.