Tomentosin suppressed M1 polarization via increasing MERTK activation mediated by regulation of GAS6.

ETHNOPHARMACOLOGICAL RELEVANCE: Xanthium sibiricum Patrin ex Widder (X. sibiricum) are widely used traditional herbal medicines for arthritis treatment in China. Rheumatoid arthritis (RA) is characterized by progressive destructions of joints, which is accompanied by chronic, progressive inflammatory disorder. According to our previous research, tomentosin was isolated from X. sibiricum and revealed anti-inflammatory activity. However, the potential therapeutic effect of tomentosin on RA and the anti-inflammatory mechanism of tomentosin remain to be clarified. The present study lays theoretical support for X. sibiricum in RA treatment, also provides reference for further development of X. sibiricum in clinic. AIM OF THE STUDY: To investigate the effect of tomentosin in collagen-induced arthritis (CIA) mice and reveal its underlying mechanism. MATERIALS AND METHODS: In vivo, tomentosin (10, 20 and 40 mg/kg) was given to CIA mice for seven consecutive days, to evaluate its therapeutic effect and anti-inflammatory activity. In vitro, THP-1-derived macrophages were used to verify the effect of tomentosin on inflammation. Then, molecular docking and experiments in vitro was conducted to predict and explore the mechanism of tomentosin inhibiting inflammation. RESULTS: Tomentosin attenuated the severity of arthritis in CIA mice, which was evidenced by the swelling of the hind paws, arthritis scores, and pathological changes. Particularly, tomentosin effectively reduced the ratio of M1 macrophage and TNF-α levels in vitro and vivo. Then, molecular docking and experiments in vitro was carried out, indicating that tomentosin inhibited M1 polarization and TNF-α levels accompanied by the increase of MERTK and up-regulated GAS6 levels. Moreover, it has been proved that GAS6 was necessary for MERTK activation and tomentosin could up-regulate GAS6 levels effectively in transwell system. Further mechanistic studies revealed that tomentosin suppressed M1 polarization via increasing MERTK activation mediated by regulation of GAS6 in transwell system. CONCLUSION: Tomentosin relieved the severity of CIA mice by inhibiting M1 polarization. Furthermore, tomentosin suppressed M1 polarization via increasing MERTK activation mediated by regulation of GAS6.

Transcriptome and metabolome analyses reveal molecular mechanisms of anthocyanin-related leaf color variation in poplar (Populus deltoides) cultivars.

Introduction: Colored-leaf plants are increasingly popular for their aesthetic, ecological, and social value, which are important materials for research on the regulation of plant pigments. However, anthocyanin components and the molecular mechanisms of anthocyanin biosynthesis in colored-leaf poplar remain unclear. Consequently, an integrative analysis of transcriptome and metabolome is performed to identify the key metabolic pathways and key genes, which could contribute to the molecular mechanism of anthocyanin biosynthesis in the colored-leaf cultivars poplar. Methods: In this study, integrated metabolite and transcriptome analysis was performed to explore the anthocyanin composition and the specific regulatory network of anthocyanin biosynthesis in the purple leaves of the cultivars 'Quanhong' (QHP) and 'Zhongshanyuan' (ZSY). Correlation analysis between RNA-seq data and metabolite profiles were also performed to explore the candidate genes associated with anthocyanin biosynthesis. R2R3-MYB and bHLH TFs with differential expression levels were used to perform a correlation analysis with differentially accumulated anthocyanins. Results and discussion: A total of 39 anthocyanin compounds were detected by LC-MS/MS analysis. Twelve cyanidins, seven pelargonidins, five delphinidins, and five procyanidins were identified as the major anthocyanin compounds, which were differentially accumulated in purple leaves of QHP and ZSY. The major genes associated with anthocyanin biosynthesis, including structural genes and transcription factors, were differentially expressed in purple leaves of QHP and ZSY through RNA-sequencing (RNA-seq) data analysis, which was consistent with quantitative real-time PCR analysis results. Correlation analysis between RNA-seq data and metabolite profiles showed that the expression patterns of certain differentially expressed genes in the anthocyanin biosynthesis pathway were strongly correlated with the differential accumulation of anthocyanins. One R2R3-MYB subfamily member in the SG5 subgroup, Podel.04G021100, showed a similar expression pattern to some structural genes. This gene was strongly correlated with 16 anthocyanin compounds, indicating that Podel.04G021100 might be involved in the regulation of anthocyanin biosynthesis. These results contribute to a systematic and comprehensive understanding of anthocyanin accumulation and to the molecular mechanisms of anthocyanin biosynthesis in QHP and ZSY.

Cementless revision for infected hip arthroplasty: an 8.6 years follow-up.

OBJECTIVE: To investigate cementless revision for postoperative infection after total hip arthroplasty (THA). METHODS: From November 1997 to December 2009, 10 patients (10 hips; four males, six females) of mean age 58 years (36-73 years) with infection after THA were treated. Six of the 10 hips underwent revision total hip arthroplasty, two only received new acetabular components and two underwent stem revision. One-stage revision was performed in six cases and two-stage revision in four. Consecutive radiographs were compared to evaluate component conditions. Harris hip scores were determined before surgery and at final follow-up. Erythrocyte sedimentation rate and C-reactive protein were assessed. RESULTS: All patients were followed up for a mean duration of 8.6 years (6.5-15.6 years). The mean Harris hip score improved from 35 (18-63) points preoperatively to 89 (60-99) points at final follow-up. No re-infection occurred. Femoral component exsertion was occurred in one asymptomatic patient. Hip joint pain resolved in seven cases; three patients had mild pain when walking long distances. At final follow-up, six patients still had slight limps. Heterotopic ossification developed in two hips. Mean polyethylene liner wear was 0.08 mm per year at final follow-up. Deep vein phlebothrombosis and nerve injury did not occur. CONCLUSION: One- or two-stage revisions using cementless prosthesis can produce satisfactory clinical outcomes in patients with infection after THA. Whether the original prosthesis can be partially retained when attached tightly to the femur or acetabular bone needs further investigation.

[Biomechanical research of SOX9, CTGF in bone tendon junction healing].

AIM: To investigate the biomechanical effect of SOX9, CTGF in bone tendon junction healing. METHODS: 36 adult New Zealand rabbits were randomly divided into A, B and C groups(each group were 12 rab-bits). Group A with SOX9 inject into bone tendon junction;Group B with CTGF inject into bone tendon junction; C group was inject nothing. The animal of three groups were used surgery and all of the animals were faced with biomechanical test after 4 weeks, 8 weeks and 12 weeks; The result were used statistical analysis. RESULTS: group A and group B's cross-sectional area were lower than group C during 4 weeks, 12 weeks postoperative; there were statistical difference between each groups ( P < 0. 05). group Aand group B's pulled off load and ultimate tensile stress were higher than group C during 4 weeks, 8 weeks, 12 weeks postoperative, the result were statistical difference between each groups ( P < 0. 05). CONCLUSION: SOX9 and CTGF group can not only promote the early bone ten-don junction healing, But also increased the biomechanical strength of bone tendon junction.

The androgen receptor in hormone-refractory prostate cancer.

Advanced prostate cancer is responsive to hormone therapy that interferes with androgen receptor (AR) signalling. However, the effect is short-lived, as nearly all tumours progress to a hormone-refractory (HR) state, a lethal stage of the disease. Intuitively, the AR should not be involved because hormone therapy that blocks or reduces AR activity is not effective in treating HR tumours. However, there is still a consensus that AR plays an essential role in HR prostate cancer (HRPC) because AR signalling is still functional in HR tumours. AR signalling can be activated in HR tumours through several mechanisms. First, activation of intracellular signal transduction pathways can sensitize the AR to castrate levels of androgens. Also, mutations in the AR can change AR ligand specificity, thereby allowing it to be activated by non-steroids or anti-androgens. Finally, overexpression of the wild-type AR sensitizes itself to low concentrations of androgens. Therefore, drugs targeting AR signalling could still be effective in treating HRPC.