Skeletal unloading induces resistance to insulin-like growth factor-I (IGF-I) by inhibiting activation of the IGF-I signaling pathways.

We showed that unloading markedly diminished the effects of IGF-I to activate its signaling pathways, and the disintegrin echistatin showed a similar block in osteoprogenitor cells. Furthermore, unloading decreased alphaVbeta3 integrin expression. These results show that skeletal unloading induces resistance to IGF-I by inhibiting activation of the IGF-I signaling pathways at least in part through downregulation of integrin signaling. INTRODUCTION: We have previously reported that skeletal unloading induces resistance to insulin-like growth factor-I (IGF-I) with respect to bone formation. However, the underlying mechanism remains unclear. The aim of this study was to clarify how skeletal unloading induces resistance to the effects of IGF-I administration in vivo and in vitro with respect to bone formation. MATERIALS AND METHODS: We first determined the response of bone to IGF-I administration in vivo during skeletal unloading. We then evaluated the response of osteoprogenitor cells isolated from unloaded bones to IGF-I treatment in vitro with respect to activation of the IGF-I signaling pathways. Finally we examined the potential role of integrins in mediating the responsiveness of osteoprogenitor cells to IGF-I. RESULTS: IGF-I administration in vivo significantly increased proliferation of osteoblasts. Unloading markedly decreased proliferation and blocked the ability of IGF-I to increase proliferation. On a cellular level, IGF-I treatment in vitro stimulated the activation of its receptor, Ras, ERK1/2 (p44/42 MAPK), and Akt in cultured osteoprogenitor cells from normally loaded bones, but these effects were markedly diminished in cells from unloaded bones. These results were not caused by altered phosphatase activity or changes in receptor binding to IGF-I. Inhibition of the Ras/MAPK pathway was more impacted by unloading than that of Akt. The disintegrin echistatin (an antagonist of the alphaVbeta3 integrin) blocked the ability of IGF-I to stimulate its receptor phosphorylation and osteoblast proliferation, similar to that seen in cells from unloaded bone. Furthermore, unloading significantly decreased the mRNA levels both of alphaV and beta3 integrin subunits in osteoprogenitor cells. CONCLUSION: These results indicate that skeletal unloading induces resistance to IGF-I by inhibiting the activation of IGF-I signaling pathways, at least in part, through downregulation of integrin signaling, resulting in decreased proliferation of osteoblasts and their precursors.     

肝络通对门静脉高压症大鼠肝组织α7-烟碱样乙酰胆碱受体的影响

目的:分析肝络通对门静脉高压症大鼠肝组织中α7-烟碱样乙酰胆碱受体表达的影响特征,探讨肝络通治疗门静脉高压症的可能机制.方法:取体重240～260g的清洁级雄性SD大鼠40只,根据体重随机分为假手术组、2周模型组、2周肝络通组、4周模型组、4周肝络通组.模型组及给药组采用胆总管结扎术(CBDL)对大鼠进行造模,分别于造模2周、4周测量门静脉压力,并用免疫印迹法检测α7-烟碱样乙酰胆碱受体(nAchRα7)在肝组织中的表达.结果:胆总管结扎后2周和4周门静脉压力均显著升高,模型组nAchRα7的表达较假手术组明显增多,门静脉压力和nAchRα7的表达具有随术后时间延长而加重的一致性趋势.肝络通组门静脉压力显著低于模型组,术后4周作用最为显著;2周肝络通组nAchRα7的表达与2周模型组比较无显著差异,4周肝络通组较4周模型组显著减少.结论:肝组织nAchRα7的表达变化与门静脉压力变化具有一致性趋势,肝络通降低门静脉压力的作用可能与调节肝组织内nAchRα7的表达有关.     

Pseudoangiomatous stromal hyperplasia of the breast: A case report

Pseudoangiomatous stromal hyperplasia (PASH) is a rare benign breast entity scarcely reported in the medical literature. Its pathogenesis, etiology, and optimal treatment are still unknown. PASH tumors have a broad spectrum of clinical presentations and might be mistaken for malignancies. The authors present six patients diagnosed with PASH.     

Regulation of Th17 cells by P. UF1 against systemic Listeria monocytogenes infection

Regulation of Th17 and Th1 cell responses against intracellular pathogens, including Listeria monocytogenes (L. m), is critical to limit inflammation-induced tissue damage. We recently demonstrated the ability of P. UF1 bacterium derived from the intestinal bacterial commensals of preterm infants fed human breast milk to significantly mitigate pathogen-induced inflammation limiting colonic tissue damage. Here we further elucidated the potential of P. UF1 to also regulate innate and T cells, particularly Th17 and Th1 cells, against systemic L. m infection. Data demonstrate that P. UF1 not only robustly regulated protective Th17 and Th1 cells, but also sustained regulatory T cells (Treg cells) resulting in accelerated L. m clearance. Together, regulation of pathogenic inflammation by a novel probiotic bacterium such as P. UF1 may illuminate a new strategy to specifically control Th17-Th1 cells via IL-10⁺ Treg cells to limit systemic tissue damage induced by intracellular pathogens, including L. m.     

Silver nanoparticles production by two soil isolated bacteria,Bacillus thuringiensis and Enterobacter cloacae,and assessment of their cytotoxicity and wound healing effect in rats

Production of silver nanoparticles by Bacillus thuringiensis and Enterobacter cloacae was performed and confirmed through UV–visible spectrophotometry, transmission electron microscopy (TEM), and x‐ray diffraction (XRD) analyses. The 3‐(4,5‐dimethylthiazol‐2‐yl)?2,5‐diphenyltetrazolium bromide (MTT) assay using mouse fibroblast cell line NIH‐3T3 D4 was carried out and IC_50s of AgNPs were obtained. The nontoxic dose of each AgNPs solution was selected for wound healing assay. Thirty‐two rats were divided into four groups; two were used as the controls and two were treated by AgNPs that were produced by two bacterial strains. Results revealed that the produced AgNPs were amorphous, spherical in shapes, and had sizes under 100 nm. Histological analysis showed that AgNPs had better wound healing efficacy than the control groups. In conclusion, when the biologically produced AgNPs were used in vivo, they induced the epithelization, formation of the collagen bundles and fibroplasia and reduced the duration of completion of the epithelization and the angiogenesis.     

Non-invasive endotracheal delivery of paclitaxel-loaded alginate microparticles

Aerosolized chemotherapeutics leads to higher, localized and continuous concentrations of active agents in lung tissue with lower side effects for other organs. The present study was performed on jugular vein cannulated rats which endothracheally received 4 mg/kg of free paclitaxel powder (Free-PTX), paclitaxel-loaded alginate microparticles (PTX-ALG-MPs) and i.v. paclitaxel (Anzatax^®). Pharmacokinetic parameters for Free-PTX and PTX-ALG-MPs contain higher AUC, mean residence time (MRT),half-life and bioavailability, with lower elimination constant (k_e). Statistical analysis showed that the amount of paclitaxel per gram of lung tissue after 0.5, 6 and 24 h after administration of Free-PTX was lower than PTX-ALG-MPs. Lung tissue AUC for Free-PTX was lower than PTX-ALG-MPs. According to the obvious advantages obtained, such as dose lowering and increasing paclitaxel residence time and half-life. It should be noted that cell cytotoxicity test on normal airway cell lines was not examined in this study but due to previous reports on safety of inhaled paclitaxel, it can be suggested that pulmonary delivery of paclitaxel can be a useful non-invasive route of administration compared with i.v administration.     

Cervical myelopathy secondary to omovertebral bone in the pediatric patient with Sprengel deformity

Sprengel deformity is a congenital anomaly arising mainly in the shoulder girdle, associated with elevation of dysplastic scapula. skeletal anomalies, mainly Klippel-Feil syndrome, hemivertebrae, and omovertebral bone may be present along Sprengel anomaly. The omovertebral bone is an abnormal bone that originates from the superomedial edge of the scapula with different insertion points along the posterior cervical spine, seen in about third of the patients with Sprengel anomaly. While cosmetic to functional impairment is a common presentation to the omovertebral bone, cervical myelopathy is a rare presentation. Here, we described our experience, management and follow up of 13-year-old boy presented with cervical myelopathy secondary to the omovertebral bone.

Sprengel deformity is a complex anomaly of the shoulder girdle, associated with elevation of dysplastic scapula.1-4 Clinically, it is associated with disfigurement and limitation of shoulder movement. Other skeletal anomalies – mainly, Klippel–Feil syndrome, hemivertebrae, and omovertebral bone may be present.4 The omovertebral bone is an abnormal bone that originates from the superomedial edge of the scapula with different insertion points along the posterior cervical spine, seen in about a third of patients with Sprengel anomaly.2,5 The clinical presentation ranges from cosmetic to functional impairment, while cervical myelopathy is a rare presentation related to omovertebral bone. The management and follow up is less described in the literature contributed to its rare occurance.6 Here, the author described a 13-year- old boy diagnosed with Sprengel deformity presented with myelopathic manifestation, where cervical magnetic resonance imaging (MRI) showed signal cord changes secondary to compression by intraspinal extension of the omovertebral bone. The patient underwent uneventful resection of the abnormal bone, and spinal cord decompression.