Novel azulene-based derivatives as potent multi-receptor tyrosine kinase inhibitors.

A series of azulene-based derivatives were synthesized as potent inhibitors for receptor tyrosine kinases such as FMS-like tyrosine kinase 3 (FLT-3). Systematic side chain modification of prototype 1a was carried out through SAR studies. Analogue 22 was identified from this series and found to be one of the most potent FLT-3 inhibitors, with good pharmaceutical properties, superior efficacy, and tolerability in a tumor xenograft model.

Publisher Correction: Non-Toxic Gold Nanoclusters for Solution-Processed White Light-Emitting Diodes.

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[An experimental study on percutaneous autologous bone marrow mesenchymal stem cell grafting for bone defect].

OBJECTIVES: To investigate in vive osteogenic potential in size-critical bone defect after percutaneous autologous grafting of culture-expanded rabbit autologous BMSCs, osteo-induced BMSCs and combination of both. METHODS: BMSCs were cultured and then induced with osteogenic supplement (OS) medium. BMSCs with and without OS induction were collected and percutaneously autologously injected respectively into the 15 mm bone defect of 20 experimental rabbit model. The grafts were BMSCs, osteo-induced BMSCs, BMSCs and osteo-induced BMSCs, BMP combined with fibrin sealant, and 0.9% NaCl solution. Osteogenesis at the defect areas were observed by regular radiography, histology and biomechanics. RESULTS: The group transplanted with BMSCs + osteo-induced BMSCs achieved complete bone healing with medullary cavity united, which showed the largest quantity of new bone measured by X-ray analysis, and also their maximal load were better than those in other groups. CONCLUSION: The bone-forming ability of rabbit osteo-induced BMSCs combined with BMSCs in bone defect is superior to those of BMSCs and osteo-induced BMSCs.

Non-Toxic Gold Nanoclusters for Solution-Processed White Light-Emitting Diodes.

Solution-processed optoelectronic devices are attractive because of the potential low-cost fabrication and the compatibility with flexible substrate. However, the utilization of toxic elements such as lead and cadmium in current optoelectronic devices on the basis of colloidal quantum dots raises environmental concerns. Here we demonstrate that white-light-emitting diodes can be achieved by utilizing non-toxic and environment-friendly gold nanoclusters. Yellow-light-emitting gold nanoclusters were synthesized and capped with trioctylphosphine. These gold nanoclusters were then blended with the blue-light-emitting organic host materials to form the emissive layer. A current efficiency of 0.13 cd/A was achieved. The Commission Internationale de l'Eclairage chromaticity coordinates of (0.27, 0.33) were obtained from our experimental analysis, which is quite close to the ideal pure white emission coordinates (0.33, 0.33). Potential applications include innovative lighting devices and monitor backlight.

Alterations of scapular kinematics and associated muscle activation specific to symptomatic dyskinesis type after conscious control.

BACKGROUND: Scapular orientation and movements can affect the function of the shoulder. However, evidence is limited on whether symptomatic subjects can actively maintain the scapula in a neutral position through conscious control. OBJECTIVE: To investigate whether symptomatic subjects with scapular dyskinesis can achieve optimal scapular movements and associated muscle activities through conscious control. DESIGN: A cross-sectional study. METHODS: Sixty subjects with scapular dyskinesis (16 inferior angle pattern I, 16 medial border pattern II, and 28 mixed pattern) performed 3 selected exercises (arm elevation, side-lying elevation, and side-lying external rotation) with and without conscious control. Three-dimensional electromagnetic motion and electromyography were used to record the scapular kinematics and muscle activation during the exercises. RESULTS: For scapular kinematics, significant increases in scapular external rotation (4.6 ± 3.2°, p < 0.0125) were found with conscious control during arm elevation and side-lying elevation in three groups. Significant increases in activation of the middle and lower trapezius (MT: 4.9 ± 2.4% MVIC; LT: 10.2 ± 6.8% MVIC, p < 0.0 25) were found with conscious control in 3 exercises among the 3 dyskinesis groups. Increased serratus anterior activation (SA: 11.2 ± 4.8% MVIC, p < 0.0 25) was found in the concentric phase of side-lying external rotation in the pattern I and I + II groups. CONCLUSION: Conscious control of the scapula can alter scapular orientation and MT, LT, and SA activation during 3 selected exercises in subjects with symptomatic dyskinesis. Specifically, conscious control during side-lying external rotation can be applied to increase SA activity in pattern I and I + II dyskinesis.

[Case-control study on bone-setting manipulation for the treatment of isolated systolic hypertension combined with cervical spondylosis].

OBJECTIVE: To investigate clinical effect and safety of bone-setting manipulation in treating isolated systolic hypertension combined with cervical spondylosis. METHODS: From January 2012 to January 2015, 320 patients suffered from isolated systolic hypertension combined with cervical spondylosis were randomly divided into treatment group and control group. In treatment group, there were 160 patients including 84 males and 76 females with an average age of (39.82 ± 10.33) years old, average blood pressure was (149.61 ± 10.75)/(81.01± 8.25) mmHg, NPQ score was 24.61 ± 8.14; treated with flexion top spin and lock bone-setting manipulation of cervical spine, once every two days for 20 days. While in control group, there were 160 patients including 90 males and 70 females with an average age of(41.37 ± 9.42) years old, average blood pressure was (151.48 ± 11.32)/ (79.65 ± 9.32) mmHg, NPQ score was 25.78 ± 9.53; treated with manipulation of reposition cervical spine by rotation, once every two days for 20 days. Blood pressure and NPQ score were tested and compared for evaluating clinical effects. RESULTS: Before and after a period treatment, systolic pressure in treatment group was (149.61 ± 10.75) mmHg and (129.67 ± 12.26) mmHg; (151.48 ± 11.32) mmHg and (132.02 ± 11.73) mmHg in control group. After treatment, systolic pressure in both two groups was obviously decreased, and treatment group was better than control group. Before and after a period treatment, diastolic pressure in treatment group was (80.01 ± 8.25) mmHg and (78.15 ± 10.34) mmHg, (79.65 ± 9.32) mmHg and (76.89 ± 9.79) mmHg in control group, and there was no significant difference between two groups. NPQ score in treatment group was 24.61 ± 8.14 before treatment, 12.46 ± 7.94 after treatment, while in control group was 25.78 ± 9.53, 14.17 ± 8.86; NPQ score of the two groups after treatment was better than before treatment, while there was no obviously significance between two groups after treatment. The whole clinical effect in treatment group was better than control group. CONCLUSION: Bone-setting manipulation for isolated systolic hypertension combined with cervical spondylosis at early stage could receive good clinical result, and flexion top spin and lock bone-setting manipulation of cervical spine was better and safety than manipulation of reposition cervical spine by rotation.

[Extracellular splitting pattern of mitochondria and the depressant effects of CsA on the process].

OBJECTIVE: To investigate extracellular splitting pattern of mitochondria and the depressant effects of CsA on the process and explore the mechanism of post-traumatic SIRS and its therapeutic strategy. METHODS: Ten male SD rats with 60 to 70 days age and 240 to 280 g weight were used for mitochondrial isolation. Freshly isolated mitochondria were randomly divided into two groups, which were cultured in blood plasma with or without CsA respectively for 8 h. COX and MDH were assayed by ELISA every 30 min. Meanwhile, Rat macrophage cell line NR8383 were treated as follows, control (group A): cultivation with normal medium; NR8383+CsA co-culture group (group B): culture medium was supplemented with CsA of 10 mmol/L; NR8383+intact mitochondria co-culture group (group C): culture medium was supplemented with intact mitochondria (mtDNA=5 g/ml); NR8383+intact mitochondria+CsA co-culture group (group D): culture medium was supplemented with intact mitochondria (mtDNA=5 µg/ml)and CsA of 10 mmol/L; NR8383+disrupted mitochondria co-culture group (group E): culture medium was supplemented with disrupted mitochondria (mtDNA=5 µg/ml); NR8383+disrupted mitochondria+CsA co-culture group (group F): culture medium was supplemented with disrupted mitochondria (mtDNA=5 µg/ml)and CsA of 10 mmol/L. TNF-α and IL-6 concentrations in supernatant were assessed at 1, 3, 5 h after culture. RESULTS: In the mitochondria plasma cultures, MDH and COX levels were increased with the time and peaked at about 3 h and 3.5 h; CsA can delay the appearance of peak to 4.5 h. Among different treated groups,there was no significant difference in TNF-α and IL-6 between group A and group B; there was significant difference in TNF-α and IL-6 other groups. After 1 h culture, compared with group C, no significant difference of TNF-α and IL-6 was observed in group D, while TNF-α and IL-6 were significant higher in group E; after 3 h culture, compared with group C, TNF-α and IL-6 were significantly lower in group D, while TNF-α and IL-6 were significantly higher in group E; after 5 h culture, compared with group C, TNF-α and IL-6 were significantly lower in group D, while no significant difference of TNF-α and IL-6 were observed in group E. At each time point, there was no significant difference in TNF-α and IL-6 between group F and group E. CONCLUSION: Mitochondria can split in serum with time, which will further activate macrophages. CsA has depressant effect to mitochondrial splitting on the process and will therefore inhibit the activation of macrophages.

Ischemic stroke in Williams-Beuren syndrome: a case report.

A 15-year-old girl was admitted because of an acute onset of facial palsy and right hemiparesis. The patient had a history of moderate mental retardation and developmental delay. On admission, her vital signs were stable, except for high blood pressure. Magnetic resonance imaging demonstrated an infarct involving the left internal capsule and putamen. Because of the patient's young age, an extensive stroke survey was performed. Williams-Beuren syndrome was finally confirmed by fluorescent in situ hybridization. Compared with the previously reported cases, no evidence of cerebral arterial stenosis or cardiac abnormalities was found by noninvasive imaging techniques. Because Williams-Beuren syndrome is a complex, multiple congenital anomaly syndrome with prominent cardiovascular features, regular assessment and antihypertensive treatment are necessary to minimize the lifelong cardiovascular risk in patients with this syndrome.

Fluoxetine up-regulates expression of cellular FLICE-inhibitory protein and inhibits LPS-induced apoptosis in hippocampus-derived neural stem cell.

Fluoxetine is a widely used antidepressant compound which inhibits the reuptake of serotonin in the central nervous system. Recent studies have shown that fluoxetine can promote neurogenesis and improve the survival rate of neurons. However, whether fluoxetine modulates the proliferation or neuroprotection effects of neural stem cells (NSCs) needs to be elucidated. In this study, we demonstrated that 20 microM fluoxetine can increase the cell proliferation of NSCs derived from the hippocampus of adult rats by MTT test. The up-regulated expression of Bcl-2, Bcl-xL and the cellular FLICE-inhibitory protein (c-FLIP) in fluoxetine-treated NSCs was detected by real-time RT-PCR. Our results further showed that fluoxetine protects the lipopolysaccharide-induced apoptosis in NSCs, in part, by activating the expression of c-FLIP. Moreover, c-FLIP induction by fluoxetine requires the activation of the c-FLIP promoter region spanning nucleotides -414 to -133, including CREB and SP1 sites. This effect appeared to involve the phosphatidylinositol-3-kinase-dependent pathway. Furthermore, fluoxetine treatment significantly inhibited the induction of proinflammatory factor IL-1beta, IL-6, and TNF-alpha in the culture medium of LPS-treated NSCs (p<0.01). The results of high performance liquid chromatography coupled to electrochemical detection further confirmed that fluoxentine increased the functional production of serotonin in NSCs. Together, these data demonstrate the specific activation of c-FLIP by fluoxetine and indicate the novel role of fluoxetine for neuroprotection in the treatment of depression.