Early posterior vitreous detachment is associated with LAMA5 dominant mutation

Background: Extracellular matrix molecular components, previously linked to multisystem syndromes include collagens, fibrillins and laminins. Recently, we described a novel multisystem syndrome caused by the c.9418G>A p.(V3140M) mutation in the laminin alpha-5 (LAMA5) gene, which affects connective tissues of all organs and apparatus in a three generation family. In the same family, we have also reported a myopic trait, which, however, was linked to the Prolyl 4-hydroxylase subunit alpha-2 (P4HA2) gene. Results of investigation on vitreous changes and their pathogenesis are reported in the present study.Materials and Methods: Nineteen family individuals underwent complete ophthalmic examination including best-corrected visual acuity (BCVA), fundus examination, fundus photography, intraocular pressure measurement, axial length measurement using ocular biometry, Goldmann visual field examination, standard electroretinogram, SD-OCT. Segregation analysis of LAMA5 and P4HA2 mutations was performed in enrolled members.Results: The vitreous alterations fully segregated with LAMA5 mutation in both young and adult family members. Slight reduction of retinal thickness and peripheral retinal degeneration in only two patients were reported.Conclusions: In this work we showed that PVD is a common trait of LAMA5 multisystem syndrome, therefore occurring as an age-unrelated trait. We hypothesize that the p.(V3140M) mutation results in a reduction of retinal inner limiting membrane (ILM) stability, leading to a derangement in the macromolecular structure of the vitreous gel, and PVD. Further investigations will be necessary to elucidate the role of wild type and mutated LAMA5 in the pathogenesis of PVD.     

人前磨牙牙髓牙本质复合体层粘连蛋白受体的免疫组织化学研究

目的研究层粘连蛋白受体在牙髓牙本质复合体内的表达,探讨其分布与功能的关系.方法收集新鲜健康人前磨牙60个,固定,脱钙,石蜡包埋,层粘连蛋白受体SABC免疫组织化学染色.结果层粘连蛋白受体免疫反应物(LNR-IR)普遍存在于牙髓牙本质复合体的神经纤维膜、血管内皮细胞、成牙本质细胞及成纤维细胞上,以牙髓的神经纤维膜、血管内皮细胞最为丰富.结论层粘连蛋白受体一般见于牙髓牙本质复合体的各种细胞膜上,它与层粘连蛋白一起在支持、固定牙髓牙本质复合体各结构的正常位置、形态和功能的发挥上可能起了重要作用.     

Biological Changes on the Compressing Side of Orthodontic Teeth Stimulating by Soft laser

目的：研究在弱激光作用下接受正畸力作用的牙齿的压力侧出现的生物学变化，为临床应用弱激光加速牙齿移动提供理论依据。方法：实验动物分2组，每组20只。A组动物接受正畸力，B组动物除接受正畸力之外，还接受弱激光照射。采用免疫组化检测层连蛋白的组间表达变化，采用原位杂交检测RANKL(receptor activator of NF-kB ligand)mRNA的组间表达变化。结果：免疫组化结果表明，新生血管活跃的高峰期出现在接受正畸力的第7d。与A组相比，接受弱激光照射的B组呈现层连蛋白的高表达。同样，与A组相比，原位杂交检测发现在接受弱激光照射的B组中，正畸牙压力侧呈现RANKL mRNA的高表达。结论：弱激光照射后能够促进正畸牙压力侧血管新生(呈现层连蛋白高表达)，从而促进破骨细胞的分化激活。此外弱激光还能够促进破骨细胞活化因子RANKL的表达，增强正畸牙压力侧的破骨细胞的活性，加快骨改建。     

自体微粒皮与异体脱细胞微粒真皮混合移植对大鼠创面纤维连接蛋白和层粘连蛋白表达的影响

目的 探讨自体微粒皮与异体脱细胞微粒真皮混合移植对创面愈合的影响,并对有关机制做进一步研究.方法 Wistar大鼠作为供体,SD大鼠为受体,在SD大鼠背部建立全层皮肤损伤模型.90只SD大鼠分为5组,每组18只,第1组为自体微粒皮组;第2组为异体脱细胞微粒真皮移植组;第3、4、5组为混合移植组.混合移植组中自异体微粒皮的面积比例分别为:1∶1、1∶0.5、1∶0.25.术后第2、3、4周分别测量每组创面的愈合率,采集创面标本,做HE染色,检测纤维连接蛋白(FN)和层粘连蛋白(LN)、进行组间比较.结果 混合移植组与自体微粒皮移植组比较,混合移植组创面愈合率及FN、LN均高于自体微粒皮组,其中1∶0.25混合移植组最高,差异有统计学意义(P＜0.05或P＜0.01).结论 混合移植创面愈合率高于自体微粒皮移植,且自体微粒皮与异体脱细胞微粒真皮混合移植的面积比例按1∶0.25效果最佳,这可能与创面纤维连接蛋白和层粘连蛋白升高有关.     

67‐kDa Laminin receptor contributes to hypoxia‐induced migration and invasion of trophoblast‐like cells by mediating matrix metalloproteinase‐9

Insufficient trophoblast invasion often occurs in patients experiencing preeclampsia. The 67‐kDa laminin receptor (LR1) is a multifunctional protein that binds to laminin and interacts with the extracellular matrix. We recently demonstrated that LR1 is implicated in trophoblast migration and invasion. However, whether LR1 is involved in hypoxia‐mediated trophoblastic invasion remains unclear and requires further investigation. This study demonstrates that two trophoblast‐like cell lines (JEG3 and BeWo cells) cultured at 3% oxygen exerted enhanced migratory and invasive capabilities as compared with their counterparts exposed to 20% oxygen. LR1 expression was increased in hypoxic JEG3 cells but decreased after transfection with hypoxia‐inducible factor 1 alpha (HIF‐1α) specific siRNA. Moreover, shRNA targeting LR1 mRNA significantly inhibited hypoxia‐induced increase in matrix metalloproteinase (MMP)‐9 activity in JEG3 cells. Forced overexpression of LR1 augmented JEG3 cell migration and invasion, and enhanced MMP‐9 expression and activity. Additionally, the blockade of the MMP‐9 effect with its neutralizing antibody reduced LR1 elevation‐promoted trophoblastic invasion. In summary, this study demonstrates that LR1 contributes to hypoxia‐induced migration and invasion of trophoblast cells at least partly by mediating MMP‐9 in vitro.     

Effect of laminin environments and tumor factors on the biology of myeloid dendritic cells

Dendritic cells (DCs) are immune cells that surveil the organism for infections or malignancies and activate specific T lymphocytes initiating specific immune responses. Contrariwise, DCs have been show to participate in the development of diseases, among them some types of cancer by inducing angiogenesis or immunosuppression. The ultimate fate of DC functions regarding their role in disease or health is prompted by signals from the microenvironment. We have previously shown that the interaction of DCs with various extracellular matrix components modifies the immune properties and angiogenic potential of these cells.The objective of the current studies was to investigate the angiogenic and immune profile of murine myeloid DCs upon interaction with laminin environments, with a particular emphasis on ovarian cancer.Our results show that murine ovarian tumors produce several types of laminins, as determined by PCR analysis, and also that tumor-associated DCs, both from ascites or solid tumors express adhesion molecules capable of interacting with these molecules as determined by flow cytometry and PCR analysis. Further, we established that DCs cultured on laminin upregulate both AKT and MEK signaling pathways, and that long-term culture on laminin surfaces decreases the immunological capacities of these cells when compared to the same cells cultured on synthetic substrates. In addition, we observed that tumor conditioned media was able to modify the metabolic status of these cells, and also reprogram the development of DCs from bone marrow precursors towards the generation of myeloid-derived suppressor cells.Overall, these studies demonstrate that the interaction between soluble factors and extracellular matrix components of the ovarian cancer microenvironment shape the biology of DCs and thus help them become co-conspirators of tumor growth.     

Biofunctionalized peptide-based hydrogel as an injectable scaffold for BDNF delivery can improve regeneration after spinal cord injury

Background

The complex pathophysiological events occurring after traumatic spinal cord injuries (TSCI) make this devastating trauma still incurable. Peptide amphiphile (PA) hydrogels are nanobiomaterials displaying desirable properties for application in regenerative medicine because they are absorbable, injectable, allowing biofunctionalization, controlling release of trophic factors and mimic extracellular matrix (ECM). In this study, we explored the potentiality of the IKVAV-functionalized PA hydrogel to provide a permissive environment for cell migration and growth as well as sustained release of BDNF at the lesion after severe compression injury model.

Serum surrogate markers of liver fibrosis in primary biliary cirrhosis

Background

Hyaluronan, leptin, laminin and collagen IV have been used extensively for the assessment of liver fibrosis. The aim of this study was to assay these markers in the peripheral and hepatic vein blood of primary biliary cirrhosis (PBC) patients and to study their ability to discriminate early from advanced disease.

Methods

Sera from 62 PBC patients were compared to 60 controls, 44 chronic Hepatitis C, 38 hepatocellular carcinoma and 34 viral cirrhosis patients. Serum from the hepatic vein of 15 cirrhotic PBC patients and 17 patients with viral cirrhosis was also assayed.

Results

All disease groups had significantly increased levels of hyaluronan and collagen IV, compared to controls, while laminin was significantly increased only in viral cirrhosis. Hyaluronan levels were statistically different between early (54.5 ng/ml; 95%CI 27.3-426.9) and late PBC (154.5 ng/ml; 95%CI 55.3-764.4, p < 0.05). The area under the curve (AUC) for the identification of late PBC was 0.74 for hyaluronan, 0.63 for leptin, 0.59 for laminin and 0.70 for collagen IV. Hyaluronan had high sensitivity and NPV in identifying late stages of PBC (96% and 90%, respectively). Short term UDCA had no effect on these markers.

Conclusion

No single measurement can differentiate between advanced and early fibrosis in PBC. However serum hyaluronan is a promising single serum marker for longitudinal studies in PBC.     

神经精神狼疮患者脑脊液层粘蛋白透明质酸测定的临床意义

目的探讨神经精神狼疮(NPLE)患者脑脊液(CSF)中层粘蛋白(LN)、透明质酸(HA)含量变化及临床意义.方法采用放射免疫法测定了系统性红斑狼疮(SLE)患者67例(其中NPLE 31例,非NPLE 36例)CSF中LN、HA水平;同时检测非SLE所致的脑血管病23例、正常对照组39例脑脊液中LA、HA含量.结果NPLE组CSF中LN、HA明显高于正常对照组、非NPLE-SLE组和非SLE所致的脑血管病组(P＜0.01).治疗有效的NPLE患者CSF中LN、HA较治疗前明显下降(P＜0.05).NPLE患者血清LN、HA与CSF中的LN、HA经直线相关分析,二者呈正相关(P＜0.05).CSF中LN、HA与CSF压力、蛋白、细胞数呈正相关(P＜0.05).结论SLE患者CSF中LN、HA的测定对临床诊断及预测NPLE提供了帮助.GSF中LN、HA含量的改变在一定程度上反映了SLE患者神经系统损害的程度,其动态监测可作为NPLE疗效和预后判断的参考指标.     

肾衰宁对糖尿病大鼠肾脏损伤的保护作用

目的 探讨肾衰宁对糖尿病大鼠肾脏的保护作用及可能机制.方法 雄性Vista大鼠24只,随机选取8只作为正常对照组(N组),其余16只注射链脲佐茵素(STZ)制成糖尿病模型,并随机分为糖尿病肾病组(DN组,n=8)和肾衰宁治疗组(S组,n=8),给药8周.检测血糖、肾功能、24 h尿蛋白定量等指标,并进行肾脏病理学检查及...