ABSTRACT
ObjectiveTo investigate the changes of differential metabolites in the serum of mice at different stages of bleomycin sulfate（BLM）-induced pulmonary fibrosis modeling and administration， and the mechanism of Wenfei Huaxian granules（WHG）against idiopathic pulmonary fibrosis. MethodMice were randomly divided into control group， control group of 14 days， model group， model group of 14 days， low-dose WHG group and high-dose WHG group. BLM（0.04 U per mouse）was injected into the trachea of mice in the model group， model group of 14 days， low-dose WHG group and high-dose WHG group， and sterile normal saline was injected into the trachea of mice in the control group and control group of 14 days. Mice of low-dose WHG group and high-dose WHG group were given different doses of WHG by gavage every day after injection of BLM， and mice of control group， control group of 14 days， model group and model group of 14 days were given sterile water by gavage every day. The peripheral blood of mice in the control group of 14 days and model group of 14 days were taken to prepare serum after injection of BLM for 14 days， and the peripheral blood and other materials of mice in the other groups were taken after continuous administration for 28 days. The bronchoalveolar lavage fluid（BALF）was collected for leucocyte differential count， the pathological examination and hydroxyproline（HYP）content determination of lung tissues of mice were performed， and the small molecule metabolites in serum samples of mice in each group were determined by ultra-high performance liquid chromatography-mass spectrometry（UHPLC-MS）. Principal component analysis（PCA）and orthogonal partial least squares-discriminant analysis（OPLS-DA）were conducted to screen differential metabolites and their biological functions were analyzed. ResultCompared with the control group， a large number of continuous fibrotic foci appeared in the lung tissue of mice in the model group， the alveolitis score， fibrosis degree score and HYP content increased significantly（P<0.01）， and the total number of leukocytes， macrophages and lymphocytes in BALF increased significantly（P<0.05）. A total of 33 differential metabolites were screened between the control group of 14 days and model group of 14 days， mainly lipid metabolites， which were mainly involved in oxidative damage and inflammatory process. A total of 34 differential metabolites， mainly amino acid metabolites， were screened between the control group and model group， mainly involving nucleic acid damage and inflammatory process. Compared with the model group， the HYP content， fibrosis score and alveolitis score in the lung tissue of mice from high-dose WHG group decreased significantly（P<0.05， P<0.01）， and the total number of lymphocytes in BALF decreased significantly（P<0.05）. Compared with the model group， 27， 40 differential metabolites were identified in the serum of mice from the low-dose WHG group and high-dose WHG group separately. There were totally 9 common differential metabolites between the model group and low-dose WHG group/high-dose WHG group， which mainly involved in the metabolic pathways of inflammation related lipids metabolism， arginine and tryptophan metabolism， and the change trends in low-dose WHG group and high-dose WHG group were significantly back-regulated compared with the model group. ConclusionWHG can alleviate BLM-induced pulmonary fibrosis， collagen deposition and inflammatory reaction in mice， and its anti-fibrotic effect may be related to the adjusting of inflammatory factors， nitric oxide and oxidative stress related metabolic pathways.
ABSTRACT
BACKGROUND: The osteoinduction by biomaterials has been proven in various animal experiments. OBJECTIVE: To investigate the osteoinduction of porous calcium phosphate cement on bone marrow mesenchymal stem cel s. METHODS: Bone marrow mesenchymal stem cel s were isolated from rabbits aged 1 week in vitro and labeled by PKH-67 or PKH-26, respectively. Forty-eight adult New Zealand white rabbits were randomized into four groups and porous calcium phosphate cement was implanted into both sides of gluteus maximus in each rabbit. Then, 1 mL PKH-26-labeled bone barrow mesenchymal stem cel s (1×1010/L) were injected into the superior gluteal artery branch at each side of gluteus maximus near the femur, and 1 mL PKH-67-labeled bone barrow mesenchymal stem cel s (1×1010/L) injected into tissues around the cement (group A); 1 mL PKH-26-labeled bone barrow mesenchymal stem cel s (1×1010/L) were injected into the each side of superior gluteal artery branch (group B); 1 mL PKH-67-labeled bone barrow mesenchymal stem cel s (1×1010/L) were injected into tissues around the cement (group C); the same amount of normal saline was injected into tissues around the cement (group D). At 3, 7 and 12 weeks after implantation, the cement and its surrounding tissues were extracted and detected by fluorescence microscope and Massion staining. Expression of bone morphogenetic protein 2 was analyzed by RT-PCR. RESULTS AND CONCLUSION: Under fluorescence microscope, PKH-26-labeled bone barrow mesenchymal stem cel s attached fast and distributed homogeneously; however, PKH-67-labeled bone barrow mesenchymal stem cel s attached slowly and exhibited a gradual y homogeneous distribution. Massion staining showed that ectopic new bone formation appeared to have an upward trend in al groups, and the area of new bones in groups A, B and C were larger than that of group D at different time points after implantation. There was a significantly higher expression of bone morphogenetic protein 2 in groups A, B and C compared with the group D at different time points after implantation (P < 0.05), and the expression was the highest in the group A (P < 0.05). In conclusion, the porous calcium phosphate cement can induce bone barrow mesenchymal stem cel s chemotaxis and osteogenetic differentiation. Besides, osteoblasts are differentiated from both the surrounding capil aries and body fluid, and capil ary-derived mesenchymal stem cel s occupy the important position.
ABSTRACT
Abnormal uric acid metabolism is closely associated with the development and progression of nonalcoholic fatty liver disease (NAFLD). This article describes the relationship between uric acid and the prevalence and severity of NAFLD, and point out that uric acid metabolic disorders directly affect the development and progression of NAFLD through complicated pathways such as insulin resistance, oxidative stress, direct influence on the expression of lipid synthetase, and inflammatory response. Control of uric acid is expected to become one of the multimodality therapies for NAFLD.
ABSTRACT
Studying effects of 50 Hz sinusoidal electromagnetic fields (SEMFs) with different intensities on peak bone mass (PBM) of rats may provide a theoretical basis for application of electromagnetic clinical field. 30 female SD rats, 6 weeks of age, were randomly divided into three groups: the control group, 0.1 mT electromagnetic field group (EMFs) and 0.6 mT EMFs. The EMFs groups were treated for 3 h/day. After 8 weeks, we examined their bone mineral densities (BMD) , measured their bone biomechanical properties, and made serum levels of osteocalcin (OC), tartrate-resistant acid phosphatase 5b (TRACP 5b), and histomorphometry. It was found that the BMD (P < 0.01), maximum mechanical load (P < 0.01) in the 0.1 mT group were significantly higher than those in the control group, and Yield strength (P < 0.05), the analyses of serum bone turnover markers and histomorphometric parameters were better than those in the control group (P < 0.05). However, the 0.6 mT group did not have significantly difference comparing with that in the control group. This study proved that 50 Hz 0.1 mT SEMFs can increased BMD, bone strength, and bone tissue microstructure. Therefore, 50 Hz 0.1 mT SEMFs can improve peak bone mass of rats.