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Radiation enteritis (RE) is a common syndrome in the radiotherapy of abdominal and pelvic malignant tumors, heavy influencing living quality, but no specific clinical regimens are available. Long oil (LO) is composed of the fat components from cuttlebone, safflower, walnut oil and rapeseed oil and has been clinically used for wound healing. In this study, oral LO was applied for the prevention and treatment of RE and the mechanisms were explored. Animal experiments were approved by the Ethics Committee of the Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences, and the experiments were conducted in accordance with relevant guidelines and regulations. An RE mouse model was established after single whole abdominal γ-ray radiation of 13 Gy. LO (8 mL·kg-1) was intragastrically administered to the mice 1 h pre-radiation. Compared to the models, the mice of the LO group had more regenerated intestinal crypts and longer villus on day 3.5, and remarkable increase in the abundance of gut microbiota on day 7, especially the amounts of probiotics including Eubacterium and Lactobacillus. Moreover, the mice of the LO group showed longer total movement distance, shorter immobility time, and higher speed than the model mice on day 7. On day 14, the mice of the LO group showed the high descending of proinflammatory factors including tumor necrosis factor-α and interleukin-6, close to the normal levels. Therefore, oral LO can alleviate the inflamed syndromes of RE and improve the repair of damaged intestinal tissues. Moreover, the mice of the LO group had highly low permeability of intestinal mucosa according to the fluorescence labeling experiment, which was close to the normal level. Oral LO can protect intestine mucosa and prevent RE by modification of the intestinal microenvironment, alleviation of the inflammatory response, and promotion of tissue repair.
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OBJECTIVE@#Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear.@*METHODS@#An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins.@*RESULTS@#XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons.@*CONCLUSION@#Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.
Subject(s)
Animals , Mice , AMP-Activated Protein Kinases/metabolism , Acetyl-CoA Carboxylase/metabolism , Adiponectin/metabolism , Antidepressive Agents/pharmacology , China , Depression/drug therapy , Disease Models, Animal , Drugs, Chinese Herbal/therapeutic use , Glucose , Hypothalamus/metabolism , Receptors, Adiponectin/metabolismABSTRACT
OBJECTIVE@#High-fat diet (HFD) and inflammation are two key contributors to nonalcoholic fatty liver disease (NAFLD). Shenling Baizhu powder (SLBZP), a classical herbal compound, has been successfully used to alleviate NAFLD. However, its specific mechanisms are not fully understood. In this study, we assessed the anti-NAFLD effect of SLBZP in vivo.@*METHODS@#Rats were fed an HFD with or without SLBZP or with probiotics. At the end of week 16, an echo magnetic resonance imaging (EchoMRI) body composition analyser was used to quantitatively analyse body composition; a micro-computed tomography (micro-CT) imaging system was used to evaluate whole body and liver fat; and the Moor full-field laser perfusion imager 2 was used to assess liver microcirculation, after which, all rats were sacrificed. Then, biochemical indicators in the blood and the ultrastructure of rat livers were evaluated. Protein expression related to the liver Toll-like receptor 4 (TLR4)/Nod-like receptor family pyrin domain-containing 3 (NLRP3) signalling pathway was assessed using Western blot analysis. Further, high-throughput screening of 29 related inflammatory factors in liver tissue was performed using a cytokine array.@*RESULTS@#SLBZP supplementation reduced body weight, serum free fatty acid, and insulin resistance index (P < 0.05). It also ameliorated liver microcirculation and ultrastructural abnormalities. EchoMRI and micro-CT quantitative analyses showed that treatment with SLBZP reduced fat mass and visceral fat (P < 0.05 and P < 0.01, respectively). In addition, SLBZP decreased the expression of lipopolysaccharide (LPS)-activated TLR4/NLRP3 signalling pathway-related proteins and altered the expression levels of some inflammatory cytokines in liver tissues.@*CONCLUSION@#SLBZP can inhibit NLRP3 inflammasome activation and interleukin-1β release by suppressing LPS-induced TLR4 expression in rats with HFD-induced NAFLD. Thus, SLBZP may be beneficial for the prevention and treatment of inflammatory damage and associated diseases.
Subject(s)
Animals , Rats , Liver , NLR Family, Pyrin Domain-Containing 3 Protein , Non-alcoholic Fatty Liver Disease/drug therapy , Powders , Toll-Like Receptor 4 , X-Ray MicrotomographyABSTRACT
To systematically evaluate the efficacy of traditional Chinese medicine(TCM) compounds combined with levodopa medicine in the treatment of Parkinson's disease(PD), and screen basic herbs to provide certain evidence-based medical proof and program for better guidance on clinical drug use. Six databases were searched to screen out the randomized controlled trial on the TCM compounds combined with levodopa medicine in the treatment of PD. Literature quality of the included studies was evaluated by improved Jadad rating scale, and the Meta-analysis was performed by RevMan 5.3 software. After the data of the basic TCM compounds involved were sorted out, the strong association rules were found by using Apriori algorithm of SPSS Modeler 18.0 software, and then the basic herbs for the treatment of PD could be picked out. A total of 20 studies were eventually included, involving 1 784 patients. Ten studies were of high-quality literature, Jadad score≥4 points. Meta-analysis showed that efficacy of TCM combined with levodopa medicine was better than levodopa medicine alone in lowering Unified Parkinson's Disease Rating Scale(UPDRS) score: UPDRS Ⅰ(MD=-0.43, 95%CI[-0.62,-0.24], P<0.000 1), UPDRS Ⅱ(MD=-2.72, 95%CI[-3.24,-2.21], P<0.000 01), UPDRS Ⅲ(MD =-1.97, 95%CI[-2.69,-1.25], P<0.000 01), UPDRS Ⅳ(MD=-0.28, 95%CI[-0.46,-0.11], P=0.002). And the improvement in UPDRS score reduction rate of TCM combined with levodopa medicine was better than that in levodopa medicine alone: effective rate(OR=4.81, 95%CI[3.50, 6.62], P<0.000 01). Data mining results showed that the basic prescription for treating PD consisted of Paeoniae Radix Alba-Rehmanniae Radix Praeparata-Gastrodiae Rhizoma in general. According to each part of UPDRS, the basic prescription for treating mentation, behavior and mood(UPDRS Ⅰ) consists of Paeoniae Radix Alba-Rehmanniae Radix Praeparata-Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, Among which Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle might have unique efficacy. The basic prescriptions for treating UPDRS Ⅱ and UPDRS Ⅲ consisted of Paeoniae Radix Alba-Rehmanniae Radix Praeparata, or Chuanxiong Rhizoma-Angelicae Sinensis Radix(two drug combinations). However, in the treatment of UPDRS Ⅳ, the drugs were scattered. But due to the limitations in the quantity and quality of clinical studies, the results obtained still need further research and clinical confirmation of its efficacy.
Subject(s)
Humans , China , Drugs, Chinese Herbal , Levodopa , Medicine , Medicine, Chinese Traditional , Parkinson DiseaseABSTRACT
@#【Objective】To screen survival-related differential expression of long non-coding RNA(lncRNA)and its co-expressed genes in breast cancer patients and to verify their expression in breast cancer cells.【Methods】RNA-seq data of 943 cases(837 breast cancer + 106 normal controls)by the TCGA database were screened,and found that long non-coding MAPT-AS1 highly expressed,and breast cancer patients had longer survival. The long non-coding MAPT- AS1 overexpression and interference plasmid was constructed,and the constructed plasmid was transfected into breast cancer cell line T47D,and the stably expressed T47D cell line was screened by puromycin. The expression of long non-coding MAPT-AS1 and its co-expressed genes was verified by the methods of RT-qPCR.【Results】Fluorescence microscopy and RT-qPCR confirmed that the long non-coding MAPT-AS1 overexpression and interference-transfected breast cancer cell line T47D were successfully constructed,and the long non-coding MATS-AS1 interference fragment shRNA3 with the highest interference efficiency was screened. The expression of MAPT ,MAPT- IT1 and NXNL2 in the co-expressed gene was decreased after transfection of the shRNA3 interference fragment ,which was consistent with the expression trend of the long non-coding MAPT-AS1.【Conclusion】The long non-coding MAPT-AS1 overexpression and interference plasmid transfected breast cancer cell line T47D were successfully constructed,and the expression of the co- expressed gene was consistent with the database. The study laid the foundation for further study of the mechanism of action of long non-coding MAPT-AS1 gene in breast cancer.
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Objective To obtain the ratcheting strain of articular cartilage under different loading conditions,and construct the theoretical model so as to predict the ratcheting strain of cartilage.Methods The fresh articular cartilage obtained from the trochlear of distal femur was used as experimental subject.The ratcheting strain of articular cartilage was tested under cyclic compressive loads by applying the non-contact digital image correlation technique.The theoretical model was constructed to predict the ratcheting strain of articular cartilage with different stress amplitudes and stress rates.The results from predictions were compared with the experimental results.Results The ratcheting strain of cartilage increased rapidly at initial stage and then showed the slower increase with cycles increasing.The ratcheting strain increased with stress amplitude increasing when the stress rate was constant.However,the ratcheting strain decreased with stress rate increasing when the stress amplitude was constant.When the stress rate increased,the ratcheting stain decreased.The prediction results of the established theoretical model were in good agreement with experimental results.Conclusions The ratcheting strain of articular cartilage is proportional to the stress amplitude,and inversely proportional to the stress rate.The established theoretical model can predict the ratcheting strain of articular cartilage and provide guidance for the construction of tissue engineered artificial cartilage.
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Objective To obtain the ratcheting strain of articular cartilage under different loading conditions,and construct the theoretical model so as to predict the ratcheting strain of cartilage.Methods The fresh articular cartilage obtained from the trochlear of distal femur was used as experimental subject.The ratcheting strain of articular cartilage was tested under cyclic compressive loads by applying the non-contact digital image correlation technique.The theoretical model was constructed to predict the ratcheting strain of articular cartilage with different stress amplitudes and stress rates.The results from predictions were compared with the experimental results.Results The ratcheting strain of cartilage increased rapidly at initial stage and then showed the slower increase with cycles increasing.The ratcheting strain increased with stress amplitude increasing when the stress rate was constant.However,the ratcheting strain decreased with stress rate increasing when the stress amplitude was constant.When the stress rate increased,the ratcheting stain decreased.The prediction results of the established theoretical model were in good agreement with experimental results.Conclusions The ratcheting strain of articular cartilage is proportional to the stress amplitude,and inversely proportional to the stress rate.The established theoretical model can predict the ratcheting strain of articular cartilage and provide guidance for the construction of tissue engineered artificial cartilage.
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Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor beta superfamily. GDF-15 expression is dramatically upregulated during acute brain injury, cancer, cardiovascular disease, and inflammation, suggesting its potential value as a disease biomarker. It has been suggested that GDF-15 has neurotropic effects in the nervous system. Our studies showed that GDF-15 modulated the expression of neuronal Kand Caion channels and increased the release of excitatory transmitter in the medial prefrontal cortex of mice. GDF-15 is also involved in the complex modulation of cancer and cardiovascular disease. Here, we reviewed studies involving the modulation of GDF-15 expression and its mechanisms, the primary pathological and physiological functions of GDF-15 in neurological and cardiovascular systems, and its role in cancer progression. The biological effects and the values of GDF-15 in basic research and clinical applications were also addressed.
Subject(s)
Animals , Humans , Mice , Brain Injuries , Calcium Channels , Metabolism , Cardiovascular Diseases , Disease Progression , Growth Differentiation Factor 15 , Metabolism , Inflammation , Neoplasms , Nervous System , Metabolism , Potassium Channels , Metabolism , Prefrontal Cortex , Metabolism , Transforming Growth Factor beta , Up-RegulationABSTRACT
BACKGROUND: Cancellous bone, as an important part of bone, is a kind of porous, inhomogeneous, anisotropic and viscoelastic structure, which plays a critical role in load transmission and energy absorption. Therefore,research on its mechanical properties is of great significance.OBJECTIVE: To investigate the compressive properties of cancellous bone at different stress rates and its creep behaviors at different stress levels.METHODS: The fresh cancellous bone from pig femur was used as the material, and subjected to different stress until the compressive strain of sample was up to 5%. The constant compressive stress levels were loaded on the surface of cancellous bone for 7200 s to observe its creep behaviors.RESULTS AND CONCLUSION: (1) In the uniaxial compression test, the stress values and Young's modulus increased with the stress rate increasing under the same strain value. (2) The stress-strain curves of cancellous bone were different at different loading rates, indicating that the mechanical properties of cancellous bone depend on the loading rate. (3) In the creep test, the creep strain increased with the increase of stress level, but the creep compliance decreased with the increase of stress level. (4) These results suggest that the stress rate and stress level have significant influence on compressive properties of cancellous bone, which provide reference for avoiding cancellous bone injury.
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Objective To obtain the ratcheting strain of articular cartilage under different loading conditions, and construct the theoretical model so as to predict the ratcheting strain of cartilage. Methods The fresh articular cartilage obtained from the trochlear of distal femur was used as experimental subject. The ratcheting strain of articular cartilage was tested under cyclic compressive loads by applying the non-contact digital image correlation technique. The theoretical model was constructed to predict the ratcheting strain of articular cartilage with different stress amplitudes and stress rates. The results from predictions were compared with the experimental results. Results The ratcheting strain of cartilage increased rapidly at initial stage and then showed the slower increase with cycles increasing. The ratcheting strain increased with stress amplitude increasing when the stress rate was constant. However, the ratcheting strain decreased with stress rate increasing when the stress amplitude was constant. When the stress rate increased, the ratcheting stain decreased. The prediction results of the established theoretical model were in good agreement with experimental results. Conclusions The ratcheting strain of articular cartilage is proportional to the stress amplitude, and inversely proportional to the stress rate. The established theoretical model can predict the ratcheting strain of articular cartilage and provide guidance for the construction of tissue engineered artificial cartilage.