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Objective: To investigate magnetic resonance longitudinal relaxation time quantitative imaging (T1rho) and transverse relaxation time quantitative imaging (T2 mapping) techniques in evaluating cartilage damage in middle-aged and elderly patients with knee osteoarthritis (OA). Methods: To carry out this investigation, the researchers enrolled 65 OA patients subjects for the study. These patients were divided into 2 groups based on the severity of their OA. Thirty healthy individuals were included as the control group. All study participants underwent magnetic resonance T1rho and T2 mapping scans. OA patient scores and values from the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), T2, and a T1rho MRI measurement indicating potential early indication of bone and joint diseases from each cartilage area were compared among the OA patients as well as the control group. Pearson correlation analysis was used to examine the relationships between T2 and T1rho values and WOMAC scores. Results: The WOMAC scores in the mild OA group were lower than the severe OA group (P < .05). There were no significant differences in T2 and T1rho values of lateral tibial cartilage among the 3 groups (P > .05). On the other hand, the T2 and T1rho values of medial femoral, lateral femoral, and medial tibial cartilage areas increased progressively in the control, mild OA, and severe OA groups (P < .05). A Pearson analysis found a positive correlation between the T2 values of medial, lateral, and medial tibial cartilages and the WOMAC scores. Similarly, the T1rho values of these cartilage areas were also positively correlated with the WOMAC scores. Conclusion: Magnetic resonance T1rho and T2 mapping offer good evaluation value for assessing cartilage injury in middle-aged and elderly patients with knee OA. The values obtained from T1rho and T2 mapping in various areas of the cartilage show a positive correlation with WOMAC scores.
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AIM: Liver fibrosis remains a great challenge in the world. Spinosin (SPI), a natural flavonoid-C-glycoside, possesses various pharmacological activities including anti-inflammatory and anti-myocardial fibrosis effects. In this study, we investigate whether SPI can be a potential lead for the treatment of liver fibrosis and explore whether the orphan nuclear receptor Nur77, a negative regulator of liver fibrosis development, plays a critical role in SPI's action. METHODS: A dual luciferase reporter system of α-SMA was established to evaluate the effect of SPI on hepatic stellate cell (HSC) activation in LX2 and HSC-T6 cells. A mouse model of CCl4-induced liver fibrosis was used to test the efficacy of SPI against liver fibrosis. The expression levels of Nur77, inflammatory cytokines and collagen were determined by Western blotting and qPCR. Potential kinase pathways involved were also analyzed. The affinity of Nur77 with SPI was documented by fluorescence titration. RESULTS: SPI can strongly suppress TGF-ß1-mediated activation of both LX2 and HSC-T6 cells in a dose-dependent manner. SPI increases the expression of Nur77 and reduces TGF-ß1-mediated phosphorylation levels of ASK1 and p38 MAPK, which can be reversed by knocking out of Nur77. SPI strongly inhibits collagen deposition (COLA1) and reduces inflammatory cytokines (IL-6 and IL-1ß), which is followed by improved liver function in the CCl4-induced mouse model. SPI can directly bind to R515 and R563 in the Nur77-LBD pocket with a Kd of 2.14 µM. CONCLUSION: Spinosin is the major pharmacological active component of Ziziphus jujuba Mill. var. spinosa which has been frequently prescribed in traditional Chinese medicine. We demonstrate here for the first time that spinosin is a new therapeutic lead for treatment of liver fibrosis by targeting Nur77 and blocking the ASK1/p38 MAPK signaling pathway.
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Células Estreladas do Fígado , Fator de Crescimento Transformador beta1 , Camundongos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Transdução de Sinais , Linhagem Celular , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Flavonoides/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Colágeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , FígadoRESUMO
Liquidambar formosana Hance is a pinene-rich deciduous plant species in the Altingiaceae family that is used as a medicinal plant in China. However, the regulatory mechanisms underlying α-pinene and ß-pinene biosynthesis in L. formosana leaves remain unknown. Here, a joint analysis of the volatile compounds and transcriptomes of L. formosana leaves was performed to comprehensively explore the terpene synthase (TPS) that may participate in α-pinene and ß-pinene biosynthesis. Headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS) jointly detected volatile L. formosana leaves. Trees with high and low levels of both α-pinene and ß-pinene were defined as the H group and L group, respectively. RNA sequencing data revealed that DXR (1-deoxy-D-xylulose-5-phosphate reductoisomerase), HDS [(E)-4-hydroxy-3-methylbut-2-eny-l-diphosphate synthase], and TPS may be the major regulators of monoterpenoid biosynthesis. We identified three TPSs (LfTPS1, LfTPS2, and LfTPS3), which are highly homologous to α-pinene and ß-pinene synthases of other species in phylogenetic analysis. Four TPS genes (LfTPS1, LfTPS2, LfTPS4, LfTPS5) may be critically involved in the biosynthesis and regulation of α-pinene and ß-pinene in L. formosana. Bioinformatic and transcriptomic results were verified using quantitative real-time PCR. We identified LfTPS1, LfTPS2 as candidate genes for α-pinene and ß-pinene biosynthesis that significantly improve the yield of beneficial terpenoids.
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Liquidambar , Transcriptoma , Transcriptoma/genética , Liquidambar/química , Liquidambar/genética , Filogenia , Folhas de Planta/fisiologiaRESUMO
BACKGROUND: Bu Shen Yi Sui capsule (BSYS) is a traditional Chinese medicine prescription that has shown antineuroinflammatory and neuroprotective effects in treating multiple sclerosis (MS) and its animal model of experimental autoimmune encephalomyelitis (EAE). Microglia play an important role in neuroinflammation. The M1 phenotype of microglia is involved in the proinflammatory process of the disease, while the M2 phenotype plays an anti-inflammatory role. Promoting the polarization of microglia to M2 in MS/EAE is a promising therapeutic strategy. This study is aimed at exploring the effects of BSYS on microglial polarization in mice with EAE. METHODS: The EAE model was established by the intraperitoneal injection of pertussis toxin and subcutaneous injection of myelin oligodendrocyte glycoprotein (MOG)35-55 in C57BL/6J mice. The mice were treated with BSYS (3.02 g/kg), FTY720 (0.3 mg/kg), or distilled water by intragastric administration. H&E and LFB staining, transmission electron microscopy, qRT-PCR, immunofluorescence, ELISA, fluorescence in situ hybridization, and western blotting were used to detect the histological changes in myelin, microglial M1/M2 polarization markers, and the expression of key genes involved in EAE. Results and Conclusions. BSYS treatment of EAE mice increased the body weight, decreased the clinical score, and reduced demyelination induced by inflammatory infiltration. BSYS also inhibited the mRNA expression of M1 microglial markers while increasing the mRNA level of M2 markers. Additionally, BSYS led to a marked decrease in the ratio of M1 microglia (iNOS+/Iba1+) and an obvious increase in the number of M2 microglia (Arg1+/Iba1+). In the EAE mouse model, miR-124 expression was decreased, and miR-155 expression was increased, while BSYS treatment significantly reversed this effect and modulated the levels of C/EBP α, PU.1, and SOCS1 (target genes of miR-124 and miR-155). Therefore, the neuroprotective effect of BSYS against MS/EAE was related to promoting microglia toward M2 polarization, which may be correlated with changes in miR-124 and miR-155 in vivo.
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Encéfalo/patologia , Doenças Desmielinizantes/genética , Medicamentos de Ervas Chinesas/farmacologia , Encefalomielite Autoimune Experimental/genética , Inflamação/patologia , MicroRNAs/metabolismo , Microglia/patologia , Animais , Peso Corporal/efeitos dos fármacos , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Cápsulas , Diferenciação Celular/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Citocinas/metabolismo , Encefalomielite Autoimune Experimental/sangue , Encefalomielite Autoimune Experimental/patologia , Exossomos/metabolismo , Feminino , Inflamação/genética , Camundongos Endogâmicos C57BL , MicroRNAs/sangue , MicroRNAs/genética , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/patologia , Fenótipo , Proteínas Proto-Oncogênicas/metabolismo , Medula Espinal/patologia , Transativadores/metabolismo , Regulação para Cima/genéticaRESUMO
Hydroquinone (HQ) is widely used in food stuffs and is an occupational and environmental pollutant. Although the hepatotoxicity of HQ has been demonstrated both in vitro and in vivo, the prevention of HQ-induced hepatotoxicity has yet to be elucidated. In this study, we focused on the intervention effect of aqueous extracts of Flos lonicerae Japonicae (FLJ) on HQ-induced cytotoxicity. We demonstrated that HQ reduced cell viability in a concentration-dependent manner by administering 160 µmol/L HQ for 12 h as the positive control of cytotoxicity. The aqueous FLJ extracts significantly increased cell viability and decreased LDH release, ALT, and AST in a concentration-dependent manner compared with the corresponding HQ-treated groups in hepatic L02 cells. This result indicated that aqueous FLJ extracts could protect the cytotoxicity induced by HQ. HQ increased intracellular MDA and LPO and decreased the activities of GSH, GSH-Px, and SOD in hepatic L02 cells. In addition, aqueous FLJ extracts significantly suppressed HQ-stimulated oxidative damage. Moreover, HQ promoted DNA double-strand breaks (DSBs) and the level of 8-hydroxy-2'-deoxyguanosine and apoptosis. However, aqueous FLJ extracts reversed HQ-induced DNA damage and apoptosis in a concentration-dependent manner. Overall, our results demonstrated that the toxicity of HQ was mediated by intracellular oxidative stress, which activated DNA damage and apoptosis. The findings also proved that aqueous FLJ extracts exerted protective effects against HQ-induced cytotoxicity in hepatic L02 cells.