透骨消痛胶囊及其拆方对退变软骨细胞Wnt/β-catenin信号通路的影响

BACKGROUND: Previous studies have showed that Tougu Xiaotong Capsule (TGXTC) exerts better effects on osteoarthritis, by regulating Rho/Rock signaling pathway, inhibiting signal transduction of chondrocyte mitochondrial apoptosis pathway, varying the rate and pattern of subchondral bone remodeling and improving the arrangement of subchondral bone collagen fibers and calcium-phosphate crystallization. OBJECTIVE: To observe the effects of the serum containing TGXTC and its disassembled recipes on chondrocyte degeneration of rats via Wnt/β-catenin signal pathway, and to explore the main therapeutic method for osteoarthritis in the TGXTC. METHODS:Forty Sprague-Dawley rats were randomly assigned to receive the treatment of TGXTC, Bushen Rougan (BSRG), Huoxue Qufeng (HXQF) and normal saline, respectively, according to the dose conversion methods of animal to animal and animal to human. Then various drug-containing serums were prepared for the following cellular experiment. After culture and passage, chondrocytes from Sprague-Dawley rats at passage 3 were divided into five groups: blank control, model, TGXTC, BSRG, HXQF groups. Cells in the latter four groups were cultured in appropriate drug-containing serums (normal saline serum for the model group) for 72 hours, following intervention with interleukin-1β for 24 hours. Cells in the blank control group were cultured in normal saline serum. Afterwards, cells in all the five groups were collected for detecting expression of Wnt 4, β-catenin and matrix metalloproteinase 13 at mRNA and protein levels using real-time PCR and western blot assay, respectively. RESULTS AND CONCLUSION: Compared with the blank control group, the expression of Wnt 4, β-catenin, matrix metalloproteinase 13 was significantly increased in the model group. Compared with the model group, the expression of Wnt 4, β-catenin, matrix metalloproteinase 13 in the TGXTC, BSRG and HXQF groups were decreased significantly, sequenced as TGXTC group < BSRG group < HXQF group. These results indicate that TGXTC plays a synergistic protection against interleukin-1β induced degeneration of chondrocytes. In addition, BSRG as a disassembled recipe of TGXTC is the main therapeutic method for osteoarthritis. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

阿伐他汀激活wnt/β-catenin信号通路促进骨质疏松模型大鼠移植物的骨整合

BACKGROUND: Atorvastatin has been shown to reduce bone loss and fracture, but its effects on implant osseointegration remain unknown. OBJECTIVE: To investigate the effects of atorvastatin on implant osseointegration in osteoporotic rats and the underlying mechanisms. METHODS: Forty-eight Sprague-Dawley rats were randomized into sham-surgery, ovariectomy, and atorvastatin (10 and 20 mg/kg per day) treatment groups, respectively. All rats received ovariectomy and implant surgery except those in the sham-surgery group. Bone mineral density of the lumbar vertebra, osseointegration ratio and pull-out strength of implants were measured after 12-week treatment. Levels of bone formation and resorption markers in osteoblasts treated with atorvastatin were determined by ELISA. Wnt pathway-related gene expression was detected by RT-PCR. RESULTS AND CONCLUSION: Bone mineral density, osseointegration ratio and pull-out strength of implants were significantly increased in 20 mg/kg per day of atorvastatin treatment group compared with ovariectomy group (P < 0.05). Levels of alkaline phosphatase, osteocalcin and osteoprotegerin were significantly increased in osteoblasts treated with atorvastatin in vitro (P < 0 .05), and the level of osteoclast differentiation factor RANKL was significantly inhibited (P < 0.05). Meanwhile, atorvastatin significantly promoted the mRNA expression of low-density lipoprotein associated protein 5 and β-catenin, and inhibited the mRNA expression of dickkopf Wnt signal pathway inhibitor 1 and sclerostin. Our results suggest that atorvastatin promotes implant osseointegration in osteoporotic rats by activating Wnt/β-catenin signal pathway. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

佛手柑内酯对双氧水诱导人脐静脉内皮细胞衰老的影响

BACKGROUND: The effective treatment of traditional Chinese medicine can alleviate the aging of endothelial cells. Traditional Chinese medicine is difficult to extract, and in contrast, Bergapten is cheap and easily purified, but its antisenescence is little reported. OBJECTIVE: To explore the effect of Bergapten on H2O2-induced senescence of human umbilical vein endothelial cells. METHODS: Human umbilical vein cell aging model was induced by H2O2, and pretreated with 0.1, 1 and 10 μmol/L Bergapten, respectively. Expressions of pRb, pAmpk, pS6, LC3-II, and Beclin-1 protein in each group were detected by western blot assay, and the number of aging cells and pS6-positive cells was determined by β-galactosidase staining and immunofluorescence, respectively. ESULTS AND CONCLUSION: After Bergapten pretreatment, pS6 and pRb protein expressions were significantly downregulated, and the number of cells positive for β-galactosidase and pS6 was significantly decreased, while protein expressions of pAmpk, Beclin-1and LC3-II were significantly increased (P < 0.05). These findings suggest that Bergapten is able to delay the H2O2-induced aging of human umbilical vein endothelial cells 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

宁夏枸杞叶对去势模型大鼠雌激素受体表达的影响

BACKGROUND: Lycium barbarum polysaccharide, the main active component of leaves of lycium barbarum, has a remarkable therapeutic effect on osteoporosis in adult ovariectomized female rats. OBJECTIVE: To explore effects of leaves of Lycium barbarum on serum estradiol and bone estrogen receptor expressions in adult oxariectomized female rats． METHODS: Thirty-two 6-month-od female rats were randomized into sham-surgery, model, and treatment groups, respectively. Rat models of postmenopausal osteoporosis were induced by ovariotomy followed by orally administration of water solution of leaves of Lycium barbarum (500 or 1 000 mg/kg) or distilled water once daily for consecutive 12 weeks in treatment and model groups, respectively. Serum estradiol level was detected by radiation immunoassay method. Estrogen receptor α, β immunoreactivities in bone tissue were determined by immunohistochemical staining． RESULTS AND CONCLUSION: Serum estradiol level in the model group was significantly decreased compared with the sham-surgery group (P < 0.01), but that was significantly increased in the treatment groups, particularly at high dose, compared with the model group (P < 0.01). Estrogen receptor α, β immunoreactivities were weaker in the model group than the sham-surgery group (P < 0.01), and those were stronger in the treatment groups than the model group (P < 0.01). Our results suggest that leaves of Lycium barbarum treat osteoporosis through enhancing serum estradiol and estrogen receptor expressions in adult ovariectomized rats． 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

人骨形成蛋白7重组腺病毒载体的构建及其在牙周膜细胞中的表达

Objective To investigate the expression of adenovirus-transfected human bone morphogenetic protein-7 (BMP-7) in human periodontal ligament cells(PDLCs) and its effect on PDLCs proliferation after transfection. Methods The BMP-7 fragment was amplified by PCR according to the pCMV-SPORT6-BMP-7, and the fragment was cloned into pShuttle-CMV-BMP-7, then it was homogenously recombined with pBHGE3 in 293 cells to obtain adenovirus expression vector containing BMP-7 (Ad-BMP-7). Ad-BMP-7 was identified and the titer of virus was measured after amplification and purification. Ad-RMP-7 transfected human PDLCs in vitro. The BMP-7 protein expression and proliferation of transfected PDLCs were detected by Western blot and MTT assay respectively. Results PCR analysis confirmed that the human BMP-7 gene was successfully inserted into the adenovirus vector. The titer of the recombinant adenovirus was 1.785×1012 pfu/ml. Expression of BMP-7 protein was detected in PDLCs transfected with Ad-BMP-7. The MTT test showed no significant difference between PDLCs transfected with or without Ad-BMP-7. Conclusions Adenovirus expression vector containing BMP-7 can transfect human PDLCs successfully with high expresion of BMP-7 in PDLCs in vitro.     

Sema7A干预钛微粒诱导鼠MC3T3-E1成骨细胞的凋亡

BACKGROUND: Semaphorin7A (Sema7A) is a kind of cell surface protein, which can promote the fusion of osteoclasts and the migration of osteoblasts at the same time, affecting the dynamic balance of the bone. It is speculated that Sema7A siRNA may inhibit osteoblast apoptosis induced by titanium particles.OBJECTIVE: To study the effect of Sema7A on the preosteoblast activity inhibited by titanium particles.METHODS:Mouse MC3T3-E1 preosteoblasts at passages 6 and 7 were divided into four groups: in blank control group, MC3T3-E1 cells were cultured alone; in standard control group, cell were cultured with titanium particles; in experimental groups 1 and 2, the cells were cultured with titanium particles+Sema7A overexpression plasmids and titanium particles+Sema7A siRNA, respectively. Apoptotic rate of MC3T3-E1 cells was detected by flow cytometry; the mRNA expression of bone sialoprotein, osteocalcin and type I collagen was detected by Q-PCR; western blot assay was adopted to detect the protein expression of bone sialoprotein, osteocalcin and type I collagen; alizarin red calcium nodule staining was taken to detect the degree of osteoblast mineralization.RESULTS AND CONCLUSION: The expressions of bone sialoprotein, osteocalcin and type I collagen were decreased in the standard control group and experimental group 1, but these expression were significantly increased in the experimental group 2 compared with the standard control group (P < 0.05). Flow cytometry results suggested that the apoptotic rate of osteoblasts in the experimental group 1 was significantly higher than that in the other groups (P < 0.05), and the apoptotic rate in the experimental group 2 was lower than that in the standard control group (P < 0.05). Alizarin red staining showed that there were no obvious mineralized nodules in the experimental group 1, but mineralized nodules formed in the experimental group 2. In brief, the genetic interference technique that inhibits the activity of Sema7A can interfere the process of mouse MC3T3-E1 preosteoblast differentiation inhibited by titanium particles, and thus provide a feasible way for the clinical treatment of wear particles-induced osteolysis using biotechnology.  中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

白细胞介素1β对软骨细胞miR-27b和基质金属蛋白酶13蛋白表达的影响

BACKGROUND: Matrix metalloproteinase-13 is most active in the degradation of collagen type II in the extracellular matrix of cartilage. Interleukin-1 (IL-1) is thought to be the inducer of matrix metalloproteinases, and participates in the degradation and degeneration of articular cartilage. OBJECTIVE: To study the influence of IL-1β on microRNA-27b (miR-27b) and matrix metalloproteinase-13 expression of chondrocytes in rats. METHODS: Chondrocytes isolated from seven male Wistar rats were cultured and divided into IL-1β stimulation group and control group. No stimulus was given in the control group; 10 μg/L of serum free medium was used to culture rat chondrocytes in the IL-1β stimulation group. Cell growth was observed at 0, 24, and 48 hours under an inverted microscope. miR-27b and matrix metalloproteinase-13 expression in the cultured chondrocytes were detected. RESULTS AND CONCLUSION:The relative expression of matrix metalloproteinase-13 in rat chondrocytes was gradually increased when induced by IL-1β at 0, 24, and 48 hours (P < 0.05). Expression of miR-27b and miR-31 in rat chondrocytes at 24 and 48 hours induced by IL-1β gradually decreased (P < 0.05); conversely, expression of MiR-26a, miR-26b, miR-23, and miR-204 gradually increased (P < 0.05). After 48 hours of IL-1β induction, expression of miR-27b was the lowest in rat chondrocytes (P < 0.05). These findings suggest that IL-1β inhibits miR-27b expression, strengthens the expression of matrix metalloproteinase-13, and damages chondrocytes, contributing to both the onset and progression of osteoarthritis. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Phenylephrine effects on the morphology of osteoblasts and expression of nicotinamide phosphoribosyltransferase under oxidative stress北大核心

BACKGROUND: Phenylephrine has been proved to exert a protective effect on radiant-induced salivary gland and epithelial cell injuries, but its effect on hydrogen peroxide (H2O2)-induced oxidative stress in osteoblasts are not fully understood. OBJECTIVE: To explore the effect of phenylephrine on H2O2-induced oxidative stress in osteoblasts, and to explore the mechanism underlying the regulation by the expression level of nicotinamide phosphoribosyltransferase (Nampt). METHODS: Primary osteoblasts were cultured and randomly divided into four groups: blank control group, H2O2 group, phenylephrine group, and combination group (0.5 hour pretreatment of 1×10-5 mol/L phenylephrine, and then given 300 µmol/L H2O2). The morphology of osteoblasts was observed at different time points. Osteoblasts were collected after 24-hour culture, and total RNA and protein were then extracted to detect the mRNA and protein expression levels of Nampt by RT-PCR and western blot assay, respectively. RESULTS AND CONCLUSION: Compared with the blank control group, reduced osteoblasts and evident cell shrinks were observed in the H2O2 group, while the number of osteoblasts significantly increased in the combined group compared with the H2O2 group at 12, 24 and 48 hours of culture. RT-PCR results showed that the mRNA level of Nampt in the H2O2 group was reduced by 31.23% of that in the blank control group, while the mRNA level of Nampt in the combination group was dramatically increased by 206.20% of that in the H2O2 group at 24 hours of culture (both P < 0.05). Furthermore, western blot assay findings revealed that the protein level of Nampt in the H2O2 group was reduced by 67.98% of that in the blank control group, while the protein level of Nampt in the combination group was increased by 152.25% of that in the H2O2 group at 24 hours of culture (both P < 0.05). Our results indicate that phenylephrine can alleviate the shrink and atrophy of osteoblasts caused by H2O2, thereby exerting protective effect by up-regulating the mRNA and protein levels of Nampt that may be a regulatory gene. © 2018, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

hIL-24基因通过调控转化生长因子β/Smad通路影响瘢痕疙瘩的生物学特性

BACKGROUND:hIL-24, a tumor suppressor gene, can stimulate immune responses, inhibit the growth of tumor cells, and the formation of tumor vessels, and induce cell apoptosis. OBJECTIVE: To explore the effects of hIL-24 gene on the proliferation and apoptosis of fibroblasts in the keloid and the underlying mechanisms. METHODS: All the keloid specimens collected from 13 patients were used for fibroblast culture and indentification. Fibroblast of the keloid was transfected with or without hlL-24 lentivirus. Subsequently, mRNA expressions of transforming growth factor-β, Smad3, proliferating cell nuclear antigen, matrix metalloproteinase-2, -9, and metallopeptidase inhibitor 1 were determined. RESULTS AND CONCLUSION:Immunofluorescent staining and flow cytometry showed that vimentin antibody was expressed positively in cytoplasma of fibroblast cultures, and the purity was more than 97.8%. Western blot assay showed that hIL-24 expression was significantly increased in the transfected fibroblasts. Quantitative PCR showed that the overexpression rate of hIL-24 in fibroblasts was 81.7% and mRNA expressions of transforming growth factor-β, Smad3, proliferating cell nuclear antigen, matrix metalloproteinase-2, and -9 were significantly decreased, while metallopeptidase inhibitor 1 mRNA expression was significantly increased in hIL-24 transfection group compared with control group (P < 0.05). These findings suggest that hIL-24 gene inhibits the expressions of proliferating cell nuclear antigen, matrix metalloproteinase-2, and -9 in fibroblasts, and the underlying mechanism may involves TGF-β/Smad3 pathway. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

骨髓间充质干细胞修复系膜增生性肾炎：作用及机制

BACKGROUND: Bone marrow mesenchymal stem cells are likely to repair renal injury by differentiating into renal parenchymal cells. OBJECTIVE: To explore the effect and mechanism of bone marrow mesenchymal stem cells in the renal repair after mesangial proliferative glomerulonephritis. METHODS: Thirty Sprague-Dawley rats were randomized into normal group, model group and treatment group (n=10 per group). Model group and treatment group were treated with tail vein injection of mouse anti-rat monoclonal antibody Thy1.1 to prepare mesangial proliferative glomerulonephritis models. One week after modeling, rats in the treatment group were given 2×106 bone marrow mesenchymal stem cells via the tail vein, and rats in the other two groups were given the same volume of normal saline. Two weeks after transplantation, urinary protein, urea nitrogen, creatinine levels were detected; hematoxylin-eosin staining was used for observing pathological changes of the renal tissue under microscope; and the expression of transforming growth factor beta 1 was detected by immunohistochemistry method. RESULTS AND CONCLUSION: The levels of urinary protein, urea nitrogen and creatinine as well as the expression of transforming growth factor beta 1 in the renal tissue arranged in descending order were listed as follows: model group > treatment group > control group, and there were significant differences among three groups (P < 0.05). In the model group, diffuse glomerular hyperplasia was observed with the presence of increased extracellular matrix, partial glomerular sclerosis, and interstitial infiltration of inflammatory cells; in the treatment group, glomerular hyperplasia, mesangial proliferation and inflammatory cell infiltration were all mitigated compared with the model group. Therefore, bone marrow mesenchymal stem cell transplantation may contribute to renal repair after mesangial proliferative glomerulonephritis, by inhibiting overexpression of transforming growth factor beta 1 in the kidney. 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程      

Analysis of plasminogen activator inhibitor-1, integrin beta3, beta fibrinogen, and methylenetetrahydrofolate reductase polymorphisms in Iranian women with recurrent pregnancy loss

Citation
Jeddi‐Tehrani M, Torabi R, Zarnani AH, Mohammadzadeh A, Arefi S, Zeraati H, Akhondi MM, Chamani‐Tabriz L, Idali F, Emami S, Zarei S. Analysis of plasminogen activator inhibitor‐1, integrin beta3, beta fibrinogen and methylenetetrahydrofolate reductase polymorphisms in Iranian women with recurrent pregnancy loss. Am J Reprod Immunol 2011; 66: 149–156 Problem To identify the associations of the plasminogen activator inhibitor‐1 (PAI‐1) ?675 4G/5G, beta fibrinogen (BF) ?455G/A, integrin beta 3 (ITGB3) 1565T/C, and methylenetetrahydrofolate reductase (MTHFR) 677C/T and 1298A/C polymorphisms with recurrent pregnancy loss (RPL). Method of study Polymerase chain reaction and restriction fragment length polymorphism (PCR‐RFLP) were performed to assess the frequency of five candidate genetic risk factors for RPL, and the frequencies of the polymorphisms were calculated and compared between case and control groups. Results The BF ?455G/A, MTHFR 677C/T, and 1298A/C polymorphisms were found to be positively, and ITGB3 1565T/C polymorphism negatively, associated with RPL. Homozygosity but not heterozygosity for PAI‐1 ?675 4G/5G polymorphism was significantly higher in patients with RPL than in the control group. The presence of both mutations of MTHFR genes highly increased the risk of RPL. Conclusion The data highlight the importance of thrombophilia screening in patients with RPL.     

Interactions and molecular structure of cardiolipin and beta 2-glycoprotein 1 (beta 2-GP1).

beta 2-GP1 is a serum protein which influences binding of anticardiolipin antibodies to cardiolipin, may influence induction of these antibodies in animals and may play a role in anticardiolipin-mediated thrombosis. Various investigators have proposed that when beta 2-GP1 binds cardiolipin, structural alterations occur in one or both molecules, resulting in exposure of new epitopes for anticardiolipin binding, but there has been no proof that such alterations occur. Utilizing Fourier transform infrared spectroscopy, this study analysed the structure of cardiolipin and beta 2-GP1 alone, then mixed with each other. For pure cardiolipin, analysis of the CH2 stretching, scissoring and carbonyl bands suggested this molecule assumes a hexagonal crystal lattice packing structure in both anhydrous and aqueous samples. Based on the second derivative analysis of the amide 1 band from the beta 2-GP1 protein backbone, as well as Fourier self-deconvolution and curve fit algorithms, beta 2-GP1 was calculated to contain 18% turns, 37% alpha-helix, and 45% beta-sheet structure. beta 2-GP1 binding with cardiolipin results in a significant change in the conformation as well as geometry of the lipid and protein components. This is indicated by a broadening of the CH stretching band and a marked shift in intensity of the carbonyl band of cardiolipin, indicating less hydrogen bonding. There was a decrease in beta-sheet structure of beta 2-GP1 from 46% to 23% and appearance of 26% to 28% random structure. These findings indicate that mixing beta 2-GP1 with cardiolipin results in profound changes in both molecules which might explain the effect of beta 2-GP1 on anticardiolipin binding activity.     

The role of LTBPs in TGF beta signaling

The purpose of this review is to discuss the transforming growth factor beta (TGFB) binding proteins (LTBP) with respect to their participation in the activity of TGFB. We first describe pertinent aspects of the biology and cell function of the LTBPs. We then summarize the physiological consequences of LTBP loss in humans and mice. Finally, we consider a number of outstanding questions relating to LTBP function.     

多巴胺β羟化酶基因多态性与帕金森病遗传易感性

目的 探讨多巴胺β羟化酶(dopamine beta hydroxylase,DBH)基因内含子5Taq I多态性与帕金森病遗传易感性的关系。方法 用聚合酶链反应—限制性长度片段多态性技术检测了144例原发性帕金森病患者和年龄及性别相匹配的188名健康人多巴胺β羟化酶基因内含子5Taq I多态性。结果 与健康人比较，帕金森病患者DBH基因内含子5Taq I基因型(A1／A2，A2／A2)或等位基因(A1，A2)的分布不同，两组之间的差异有显著性(基因型：A1／A2 OR＝0．45，Z＝10．11，P＜0．015 A2／A2 OR＝2．11，Z＝10．66，P＜0．01；等位基因：A1 OR＝0．54，Z＝10．20，P＜0．01；A2 OR＝1．82，Z＝10．89，P＜0．01)。结论 DBH基因Taq I多态性可能在帕金森病的遗传易感性中起作用。     

辛伐他汀对小鼠胰腺β细胞功能的影响及机制研究

 目的：观察辛伐他汀对小鼠胰腺β细胞株MIN6胰岛素分泌功能的影响并探讨其可能机制。方法：将MIN6细胞随机分为正常对照组和低、中、高浓度辛伐他汀组,分别用含0、2、5、10 μmol/L辛伐他汀和15%胎牛血清的高糖DMEM培养基培养48 h。采用放射免疫分析法检测辛伐他汀对MIN6细胞胰岛素分泌功能的影响;生物化学发光法测定细胞内ATP含量;用实时荧光定量PCR检测内向整流钾离子通道62（Kir62）、电压依赖性钙离子通道12（CaV12）及葡萄糖转运体2（GLUT2）mRNA表达水平;用Western印迹检测Kir62、CaV12及GLUT2蛋白表达水平。结果：5和10 μmol/L的辛伐他汀能够明显减少MIN6细胞胰岛素的合成及分泌（P<005）;辛伐他汀处理组MIN6细胞内ATP水平较正常对照组明显降低（P<005）;辛伐他汀各处理组MIN6细胞Kir62 mRNA表达水平较正常对照组明显上调（均P<001）,5和10 μmol/L辛伐他汀组CaV12 mRNA水平明显下调（均P<001）,GLUT2 mRNA表达水平明显下调（P<005）;5和10 μmol/L辛伐他汀处理组Kir62蛋白表达较正常对照组明显升高（均P<001）,10 μmol/L辛伐他汀处理组CaV12及GLUT2蛋白表达水平明显下降（均P<001）,5 μmol/L辛伐他汀组CaV12蛋白表达水平较正常对照组亦有明显下降（P<001）。结论：辛伐他汀对小鼠胰腺β细胞株MIN6胰岛素的合成和分泌具有一定的抑制作用。辛伐他汀可能通过抑制MIN6细胞内ATP的生成以及上调MIN6细胞Kir62、下调CaV12和GLUT2的表达从而影响其胰岛素的合成和分泌。     

Beta lactam allergy and resensitization in children with suspected beta lactam allergy

Background In patients who were clinically diagnosed as having beta lactam allergy and had negative skin tests, the rates of reported resensitization to beta lactams after subsequent exposures, vary significantly. Some allergists advocate skin testing before every exposure to beta lactams.
Objective We sought to determine the true rate of beta lactam allergy and of resensitization in children with a positive history for suspected beta lactam allergy.
Methods The study was conducted from July 1998 to May 2004, with follow-up during 2007. Beta lactam allergy tests with the major determinant and freshly prepared minor determinant mixtures were offered to history positive children. Negative skin tests were followed by oral challenge. The tests were performed again 1–5 months later in order to address the possibility of resensitization.
Results Tests were performed on 166 children: 150 for penicillins alone, 14 for penicillin in combination with cephalosporins, and an additional 2 patients solely for cephalosporins. Only 10 children (6%) were positive in the initial evaluation, four by skin test and six by oral challenge. A second set of tests was performed in 98 children with a negative initial evaluation; only two children (2%) were resensitized. On a follow-up survey of 71 of the 96 patients, 59 (83%) had received beta lactams; only one had developed a minor rash after subsequent exposure to amoxicillin.
Conclusions Most children with suspected beta lactam allergy were not allergic to beta lactams. Resensitization to beta lactam antibiotics in children in this study was infrequent. In children with a clinical diagnosis of beta lactam allergy and negative skin tests, repeated skin testing before every exposure is usually unnecessary.     

Immunosuppressive role of transforming growth factor beta in breast cancer

Transforming growth factor beta (TGF-β) is a multifunctional cytokine, whose myriad of functions include its ability to potently suppress the immune system. Because of its ability to negatively modulate the inductive and effector phases of the immune response, TGF-β is thought to contribute to tumor progression and metastases formation. Immunosuppression by tumor-derived TGF-β is increasingly becoming recognized as an important factor in tumor progression and may, in part, explain the low response rates achieved in cancer patients undergoing immunotherapy for their disease. This review will focus on the immunosuppressive role of tumor-derived TGF-β in breast cancer. Due to the paucity of human studies, it will specifically address the actions of tumor-derived TGF-β on cells of the immune system in preclinical animal models, as well as discuss strategies to negate the deleterious effects of TGF-β in order to improve the anti-tumor immune response.     

胚胎干细胞向胰岛细胞诱导分化的研究

胚胎干细胞(embryonicstemcell熏ESC)因具有全能分化潜能而有望成为组织工程和细胞治疗中的重要种子细胞来源。如能将其诱导分化为能分泌胰岛素的细胞,将有助于解决胰岛素绝对或相对缺乏引起的糖尿病代谢失调状态。目前已有研究者诱导分化出能分泌胰岛素的细胞,有的将之应用于糖尿病鼠模型并取得了可喜的效果。本文对这一领域的研究现状进行综述。     

Differential recognition of vascular and parenchymal beta amyloid deposition

By phage display, llama-derived heavy chain antibody fragments were selected from non-immune and immune libraries and tested for their affinity and specificity for beta amyloid by phage-ELISA, immunohistochemistry and surface plasmon resonance.We identified eight distinct heavy chain antibody fragments specific for beta amyloid. While three of them recognized vascular and parenchymal beta amyloid deposits, the remaining five heavy chain antibody fragments recognized vascular beta amyloid specifically, failing to bind to parenchymal beta amyloid.These heavy chain antibody fragments, selected from different libraries, demonstrated differential affinity for different epitopes when used for immunohistochemistry. These observations indicate that the llama heavy chain antibody fragments are the first immunologic probes with the ability to differentiate between parenchymal and vascular beta amyloid aggregates. This indicates that vascular and parenchymal beta amyloid deposits are heterogeneous in epitope presence/availability. The properties of these heavy chain antibody fragments make them potential candidates for use in in vivo differential diagnosis of Alzheimer disease and cerebral amyloid angiopathy. Continued use and characterization of these reagents will be necessary to fully understand the performance of these immunoreagents.