Periostin: A Novel Prognostic and Therapeutic Target For Genitourinary Cancer?

Many of the cellular abnormalities present in solid tumors are structural in nature and involve the proteins of the extracellular matrix (ECM). Periostin is a protein produced and secreted by the fibroblasts as a component of the ECM where it is involved in regulating intercellular adhesion. The expression of periostin has an important physiological role during embryogenesis and growth, namely at the level of bone, dental, and cardiac tissues. Many studies indicate that periostin plays an important role for tumor progression in various types of cancer, such as colon, lung, head and neck, breast, ovarian, and prostate. To the best of our knowledge, a limited number of studies have investigated periostin expression in urogenital cancer, such as prostate, bladder, penile, and renal cancer, and no studies were performed in testis cancer. In this review article, we summarize the most recent knowledge of periostin, its genetic and protein structure, and the role of the different isoforms identified and sequenced so far. In particular, we focus our attention on the role of this protein in genitourinary tumors, trying to emphasize the role not only as a possible prognostic marker, but also as a possible target for the development of future anticancer therapies.     

Fetal and perinatal stem cells in cardiac regeneration: Moving forward to the paracrine era

Cardiovascular disease (CD) is a major burden for Western society. Regenerative medicine has provided encouraging results, yet it has not addressed the focal defects causing CD and mainly related to the inefficient repair programme of the heart. In this scenario, stem cells have been broadly investigated and their paracrine effect proposed as a possible working strategy to boost endogenous mechanisms of repair and regeneration from within the cardiac tissue.The scientific community is now focusing on identifying the most effective stem cell secretome, as the whole of bioactive factors and extracellular vesicles secreted by stem cells and endowed with regenerative potential. Indeed, the adult stem cell-paracrine potential for cardiac regeneration have been widely analyzed with positive outcome. Nevertheless, low yield, invasive sampling and controversial self-renewal may limit adult stem cell application. On the contrary, fetal and perinatal stem cells, which can be easily isolated from leftover sample via prenatal screening during gestation or as clinical waste material after birth, can offer an ideal alternative. These broadly multipotent immature progenitors share features with both adult and embryonic stem cells, show high self-renewal, but they are not tumorigenic neither cause any ethical concern. While fetal and perinatal stem cells demonstrated to improve cardiac function when injected in the injured heart, the comprehensive characterization of their secretome for future applications is still at its infancy.In this review, we will discuss the paracrine potential of the fetal and perinatal stem cell secretome to provide cardiac repair and resurge the dormant mechanisms of cardiac regeneration for future therapy.     

Changes in mRNA expression of MMP-2 in the Müllerian duct of chicken embryo

Although asymmetric development of the ovary and the oviduct is a unique characteristic in birds, the mechanism of asymmetric development still remains unclear. Recently, degradation of extracellular matrix has been suggested as an important factor related to the regression of the Müllerian duct in mammals. The present study was conducted to examine a possible role of metalloproteinase-2 (MMP-2) in the regression of the right Müllerian duct in the developing chicken embryo. Morphological changes in the Müllerian ducts were studied on day 15 of incubation and mRNA expresseion of MMP-2 was studied on days 12, 15, and 18 of incubation. Morphological observation demonstrated the disappearance of basement membrane in the right Müllerian duct which undergoes the regression. RT-PCR analysis showed that MMP-2 mRNA expression of the right Müllerian duct increased on days 15 and 18 of incubation coincidently with the time of regression. In the right Müllerian duct, regression was prevented by diethylstilbestrol treatment on day 4 of incubation and a coincident decrease in MMP-2 expression was observed when compared to the control group. These results suggest that MMP-2 may be involved in the regression of the right Müllerian duct in the female embryos of the chicken.     

Cardiac electrolytes and water in thyroparathyroidectomized rat

The effect of thyroparathyroidectomy (TPTX) on myocardial extracellular space (ECS), water and electrolytes was studied in young, female, Sprague-Dawley rats. Eight weeks after TPTX the ventricular ECS, measured in vivo with [³⁵S]sulfate, was found to be 0.219 ± 0.004 (g H₂O/g tissue as compared to 0.177 ± 0.006 in euthyroid control rats. Measurement of ECS in the same ventricular tissue of TPTX rat by a morphometric procedure confirmed the increase: 0.209 ± 0.004 (cm³/cm³). This increase in ECS was only relative to the size of the cellular compartment, for the absolute volume of the ECS in the ventricular myocardium fell. Thus, the relative expansion of the ECS at the expense of the cellular compartment appears to be due to a greater sensitivity of the parenchyma to the inhibitory effects of hypothyroidism on growth. This finding is compatible with a decrease in cellular size of the hearts of hypothyroid rats; a compartmental shift in water from the cellular to the extracellular compartment need not be postulated. Most or all of the enlargement of ECS is due to an expansion of the interstitial compartment. No changes in tissue water content were detected. Plasma concentrations of potassium, calcium and magnesium declined, whereas the concentrations of sodium and chloride remained constant. Depending on whether the electrolytes are predominantly intracellular or extracellular, tissue electrolyte contents showed alterations appropriate to the relative changes in compartmental volumes. Assuming homogeneous distributions of the electrolytes throughout the ECS, the calculated cellular concentrations slightly increased for sodium and potassium, decreased for magnesium, and remained unchanged for calcium and chloride.     

采用磁共振示踪法探讨大鼠脑细胞间隙内物质转运清除规律

目的 采用磁共振示踪法探讨脑细胞间隙（ECS）内物质转运规律及外界刺激对其转运能力的影响。方法 将32只雄性SD大鼠随机分为尾状核-对照组、丘脑-对照组、尾状核-运动组和丘脑-疼痛组,通过立体定位技术将示踪剂Gd-DTPA导引至尾状核和丘脑区的ECS,在示踪剂注射前和注射后不同时间点进行MR扫描,直至Gd-DTPA所致的高信号消失,通过图像后处理和数学建模技术,计算示踪剂在ECS内的半衰期,采用独立样本t检验比较各组结果。结果 尾状核ECS内的Gd-DTPA可转运至邻近皮层区,丘脑ECS内Gd-DTPA的转运局限于原位,未观察到向邻近区域进行跨区域转运。尾状核-对照组、丘脑-对照组Gd-DTPA的半衰期分别为（104.30±54.12） min和（49.93±2.11） min （t=2.839,P<0.05）。尾状核-运动组Gd-DTPA的半衰期分别为（113.42±47.32） min,与尾状核-对照组比较差异无统计学意义（t=0.359,P>0.05）。丘脑-疼痛组的Gd-DTPA的半衰期为（109.40±10.33） min,较丘脑-对照组显著延长（t=15.954,P<0.05）。结论 磁共振示踪法是研究脑ECS内物质转运规律的有效手段,外界刺激可调控相关脑区ECS内物质的转运清除。     

Fibroblasts as maestros orchestrating tissue regeneration

Fibroblasts constitute a dynamic and versatile population of cells of mesenchymal origin, implicated in both regenerative strategies and pathological conditions. Despite being frequently associated to disease development, particularly through the establishment of fibrotic tissue, fibroblasts hold great potential for tissue engineering and regenerative medicine applications. They are responsible for synthesizing and depositing extracellular matrix components, allowing other cells to settle and migrate along a three‐dimensional support and thereby generating an organ‐specific architecture. Additionally, they produce bioactive molecules that are involved in several physiological processes, including angiogenesis and tissue repair. Although there seems to be much still to unveil about these fascinating cells they have been attracting increasing interest and are now being intensively explored as a cell source to develop bioengineered tissue constructs or to improve stem cell‐based technologies. This review intends to highlight the potential of fibroblasts in orchestrating tissue regeneration, as well as to contribute to uncover uncharted prospective applications of these cells. Copyright © 2017 John Wiley & Sons, Ltd.     

Effect of tissue inhibitor of metalloproteinases-l siRNA on endothelial cells injury induced by septic serum北大核心CSCD

Objective: To investigate the effect and possible mechanism of tissue inhibitor of Metalloproteinases-l (TIMP-1) siRNA on human umbilical vein endothelial cells injury induced by serum of septic patient. Methods: Serum samples were separately collected from septic patients and healthy controls. Human umbilical vein endothelial cells (HUVECs) were randomly divided into blank group (normal culture cells), control group (culture medium with 10% control serum), septic group (culture medium with 10% septic serum), negative control group (negative siRNA + 10% septic serum), and TIMP-1 siRNA group (TIMP-1 siRNA + 10% septic serum). The survival rate of endothelial cells was detected by MTT assay. The levels of matrix Metalloproteinase-9 (MMP-9) and TIMP-1 in supernatant of culture medium were measured by enzyme-linked immunosorbent assay (ELISA). The levels of MMP-9, TIMP-1 and Thrombomoduline (TM) in endothelial cells were examined by Western blot. Results: Compared with control group, the cell survival rate of septic group decreased 12 hours after the addition of serum (P<0.05) and reached minimum 48 hours later. The levels of MMP-9 and TIMP-1 in supernatant of culture medium of septic group significantly increased (P<0.01). The levels of MMP-9 and TIMP-1 increased in the septic group (P<0.01), while the level of TM reduced at the same time in septic group (P<0.01). Compared with septic group, the cell survival rate of TIMP-1 siRNA group decreased (P<0.05). The level of MMP-9 in supernatant of culture medium of TIMP-1 siRNA group increased (P<0.05), while the level of TIMP-1 decreased (P<0.05). The level of MMP-9 increased in TIMP-1 siRNA group (P<0.01), whereas the levels of TIMP-1 and TM reduced in TIMP-1 siRNA group (P<0.01). Conclusions: TIMP-1 plays a protective role in endothelial cells injury induced by septic serum. © 2018 Chinese Medical Association. All rights reserved.     

牵张应力对退变椎间盘髓核细胞增殖凋亡及细胞外基质表达的影响

目的 探讨不同强度牵张应力刺激对体外培养的人退变髓核细胞增殖凋亡和细胞外基质表达的影响。 方法 分选并体外培养人退变的髓核细胞,使用四点弯曲细胞力学装置对细胞施加不同强度的牵张应力,根据施加牵张应力强度的不同分为对照组（未给予应力刺激）、低强度组（1000 μ）、中强度组（2000 μ）和高强度组（4000 μ）四组。采用流式细胞仪测定退变髓核细胞的增殖情况;采用实时荧光定量聚合酶链反应（qPCR）检测各组细胞的细胞增殖核抗原(PCNA)、细胞凋亡相关蛋白B淋巴细胞瘤-2基因（Bcl-2）与Bcl-2相关X蛋白（Bax）、以及Ⅱ型胶原（ColⅡ）和蛋白聚糖(Aggrecan)的基因表达情况并进行分析。 结果 在不同强度的牵张应力作用下,退变髓核细胞的增殖凋亡和细胞外基质分泌呈现不同的变化。随着施加力学强度的增加,髓核细胞的增殖指数和PCNA基因表达水平先升高而后又逐渐降低,差异有统计学意义（P<0.05）。髓核细胞凋亡相关基因Bcl-2/Bax mRNA值在1000 μ强度牵张应力作用下为对照组的1.53倍,而在2000 μ和4000 μ强度下分别为0.71和0.43,同样呈现出随应力刺激增加先升高又降低的趋势,差异均有统计学意义（P<0.05）。给予1000 μ强度应力刺激后,Col Ⅱ和Aggrecan均有不同程度的表达增加,分别增加了2.1倍和2.3倍,与对照组比较,差异有统计学意义（P<0.05）。随着牵张应力强度的增加,Col Ⅱ和Aggrecan基因表达逐渐降低,在4000 μ强度牵张应力刺激时,二者基因表达最低,差异具有统计学意义（P<0.05）。 结论 不同强度的牵张应力对人退变髓核细胞的增殖凋亡以及细胞外基质的表达作用不同。     

Hepatocellular carcinoma,hepatitis C virus infection and miRNA involvement: Perspectives for new therapeutic approaches

Chronic hepatitis C virus (HCV) infection is the principal etiology of cirrhosis and, ultimately, hepatocellular carcinoma (HCC). At present, approximately 71 million people are chronically infected with HCV, and 10%–20% of these are expected to develop severe liver complications throughout their lifetime. Scientific evidence has clearly shown the causal association between miRNAs, HCV infection and HCC. Although it is not completely clear whether miRNA dysregulation in HCC is the cause or the consequence of its development, variations in miRNA patterns have been described in different liver diseases, including HCC. Many studies have analyzed the importance of circulating miRNAs and their effect on cell proliferation and apoptosis. In this Review, we aim to summarize current knowledge on the association between miRNA, HCV and HCC from a diagnostic point of view, and also the potential implications for therapeutic approaches.