Role of ursolic acid chalcone,a synthetic analogue of ursolic acid,in inhibiting the properties of CD133+ sphere-forming cells in liver stem cells

The expression of CD133 decreases with differentiation of tumor cell, indicating that CD133 is a specific marker for isolation and identification of CSCs. In the present study the effect of Ursolic acid chalcone (UAC) on CD133⁺ hepatocellular carcinoma cell (HCC CSCs) differentiation, their self-renewal, tumorigenic capacity and sensitivity to chemotherapeutic drugs was studied. The results demonstrated that UAC inhibits the expression of CD133⁺ in a dose and time-dependent manner in PLC/PRF/5 and Huh7 HCC cells. The inhibition was significant at 50 μM and on day 8. The percentage of CD133⁺ cells decreased from an initial 59.3% in PLC/PRF/5 to 37.1% and 78.2% in Huh7 to 59.2% on treatment with UAC. There was inhibition of Oct4, Tert, Bmi1, β-catenin, ABCG2, and tumor sphere-related gene Ep300. In addition it also decreased number of CK19-positive cells and increased number of CK8/18-positive cells. UAC treatment caused a decrease in self-renewal capability and increase in sensitivity to doxorubicin and vincristine drugs in CD133⁺ HCC CSCs. Therefore, UAC can be a potent therapeutic agent to target differentiation of CSC in HCC.     

CD147 and MMP-9 expressions in type II/III adenocarcinoma of esophagogastric junction and their clinicopathological significances

Objectives: To investigate CD147 and matrix metalloproteinase-9 (MMP-9) expressions in type II/III adenocarcinoma of esophagogastric junction (AEG), and their clinicopathological significances. Methods: Seventy-four patients clinically and pathologically diagnosed with type II/III AEG were analyzed, each undergoing radical total gastrectomy and Roux-en-Y esophagojejunostomy. The avidin streptavidin-perosidase immunohistochemistry technique was used to detect CD147 and MMP-9 in type II/III AEGs and 20 para-tumor controls, and their correlations with clinicopathological data and their reciprocal relationship were then analyzed. Kaplan-Meier survival analysis was conducted to reveal their prognostic significances. SPSS 20.0 was used for data analysis. A difference was statistically significant with P < 0.05, and very significant with P < 0.01. Results: In type II/III AEG CD147 and MMP-9 were mainly expressed on cellular membrane of in tumor cell cytoplasm. MMP-9 expression was significantly stronger at tumor-stroma junction and front edge of invasion. Their positive rates were significantly higher in malignant tissues than para-tumor tissues (P < 0.01 for both). There existed a significant positive correlation between both expressions (P < 0.05). They were significantly more highly expressed in cancers with lymphatic metastasis (P < 0.01 for both), at TNM III/IV stages (P < 0.01 for both), and with poor differentiation grade (P < 0.05 for both). Higher CD147 and MMP-9 expression rates were correlated with inferior postsurgical survivals (P < 0.05 for both). Conclusions: CD147 and MMP-9 could be novel biomarkers for type II/III AEG, and potentially predict tumor progression and prognosis. They are worth further investigation.     

TGF-β/TIMP-1/MMP-1信号通路在有氧运动改善心衰大鼠心脏重塑中的作用

摘要 目的：观察10周有氧运动对慢性心力衰竭大鼠心脏重塑的影响并探讨转化生长因子-β/金属蛋白酶组织抑制物-1/基质金属蛋白酶-1（transforming growth factor-β/tissue inhibitors of metalloproteinase-1/matrix metalloproteinase,TGF-β/TIMP-1/MMP-1）信号通路在心衰运动康复中的作用。 方法：38只Wistar大鼠随机分为假手术对照组（S组）、心衰对照组（H组）和心衰运动组（HE组）。HE组大鼠进行10周跑台运动,S组和H组保持安静状态。利用心脏超声检测心脏结构与功能;利用Masson染色法检测心肌胶原容积分数（CVF）;实时荧光定量PCR 检测Ⅰ型胶原（Col-Ⅰ）、Ⅲ型胶原（Col-Ⅲ）和心钠素（ANF）mRNA表达,Western blot检测TGF-β、TIMP-1和MMP-1蛋白表达水平。 结果：①与S组比较,H组左室重量（LVW）、左室质量指数（LVMI）、左室舒张期前壁厚度（LVAWDd）、左室收缩期前壁厚度（LVAWDs）、左室舒张期后壁厚度（LVPWDd）、左室收缩期后壁厚度（LVPWDs）,胶原容积分数（CVF）,Col-Ⅰ、Col-Ⅲ和心钠素（ANF） mRNA,TGF-β,MMP-1和TIMP-1蛋白表达升高（P<0.05）,BW、LVIDd、FS、LVEF,MMP-1/TIMP-1比值降低（P<0.05）。②与H组比较,HE组CVF,Col-Ⅰ、Col-Ⅲ和ANF mRNA,TGF-β、MMP-1和TIMP-1蛋白表达降低（P<0.05）,LVW、LVMI、LVIDd,FS、LVEF,MMP-1/TIMP-1比值升高（P<0.05）。 结论：长期运动改善心衰大鼠心脏重塑,其机制与部分恢复TGF-β/TIMP-1/MMP-1信号功能,减少胶原沉积并减轻心肌纤维化有关。     

脱细胞真皮基质植入预防Frey综合征的临床观察

目的：探讨脱细胞真皮基质植入对Frey综合征的预防作用。方法：89例腮腺良性肿瘤手术病例分为实验组和对照组,实验组42例腮腺切除术后植入脱细胞真皮基质,对照组腮腺切除术后不植入脱细胞真皮基质,分别于术后12个月及24个月时复查对比两组患者Frey综合征发生率。结果：实验组术后12个月及24个月复查,Frey综合症发生率均低于对照组,发生率差异有统计学意义;两组患者Frey综合症发生率与腮腺肿块大小无明显相关。结论：近期观察显示,异种脱细胞真皮基质植入是一种简便有效的降低Frey综合症发生率的方法。     

The neuropeptide vasoactive intestinal peptide: direct effects on immune cells and involvement in inflammatory and autoimmune diseases

Neuropeptides represent an important category of endogenous contributors to the establishment and maintenance of immune deviation in the immune‐privileged organs such as the CNS and in the control of acute inflammation in the peripheral immune organs. Vasoactive intestinal peptide (VIP) is a major immunoregulatory neuropeptide widely distributed in the central and peripheral nervous system. In addition to neurones, VIP is synthesized by immune cells which also express VIP receptors. Here, we review the current information on VIP production and VIP‐receptor‐mediated effects in the immune system, the role of endogenous and exogenous VIP in inflammatory and autoimmune disorders and the present and future VIP therapeutic approaches.     

An Immunohistochemical Study of Matrix Components in Early‐Stage Vascular Canals Within Mandibular Condylar Cartilage in Midterm Human Fetuses

Matrix components of vascular canals (VCs) in human fetal mandibular condylar cartilage (15–16 weeks of gestation) were analyzed by immunohistochemistry. Prevascular canals (PVCs), consisting of spindle‐shaped cells without capillary invasion, were observed within the cartilage. Intense immunoreactivity for collagen type I, weak immunoreactivity for aggrecan and tenascin‐C, weak hyaluronan (HA) staining, and abundant argyrophilic fibers in PVCs indicated that they contain noncartilaginous fibrous connective tissues that was different from those in the perichondrium/periosteum. These structural and immunohistochemical features of PVCs are different from those of previously reported cartilage canals of the long bone. Capillaries entered the VCs from the periosteum and ascended through VCs. Following capillary invasion, loose connective tissue had formed in the lower part of VCs, and immunoreactivity for collagen types I and III, tenascin‐C, and HA staining was evident in the matrix of loose connective tissue. No chondroclasts or osteogenic cells were seen at the front of capillary invasion, although small, mononuclear tartrate‐resistant acid phosphatase (TRAP)‐positive cells were present. Meanwhile, TRAP‐positive, multinucleated chondroclasts and flattened, osteoblast‐like cells were observed in the loose connective tissue at the lower part of VCs. These results may indicate slow progress of endochondral ossification in human fetal mandibular condyle. Further, unique matrix components in PVCs/VCs, which were different from those in cartilage canals in long bone, may reflect the difference of speed of endochondral ossification in cartilage canals and human fetal mandibular condyles. Anat Rec, 298:1560–1571, 2015. © 2015 Wiley Periodicals, Inc.     

The Basement Membrane and the Sex Establishment in the Juvenile Hermaphroditism During Gonadal Differentiation of the Gymnocorymbus ternetzi (Teleostei: Characiformes: Characidae)

Although there are several studies on morphogenesis in Teleostei, until now there is no research describing the role of the basement membrane in the establishment of the germinal epithelium during gonadal differentiation in Characiformes. In attempt to study these events that result in the formation of ovarian and testicular structures, gonads of Gymnocorymbus ternetzi were prepared for light microscopy. During gonadal development in G. ternetzi, all individuals first developed ovarian tissue. The undifferentiated gonad was formed by somatic cells (SC) and primordial germ cells (PGCs). After successive mitosis, the PGCs became oogonia, which entered into meiosis originating oocytes. An interstitial tissue developed. In half of the individuals, presumptive female, prefollicle cells synthesized a basement membrane around oocyte forming a follicle. Along the ventral region of the ovary, the tissue invaginated to form the ovigerous lamellae, bordered by the germinal epithelium. Stroma developed and the follicle complexes were formed. The gonadal aromatase was detected in interstitial cells in the early steps of the gonadal differentiation in both sexes. In another half of the individuals, presumptive male, there was no synthesis of basement membrane. The interstitium was invaded by numerous granulocytes. Pre‐Leydig cells proliferated. Apoptotic oocytes were observed and afterward degenerated. Spermatogonia appeared near the degenerating oocytes and associated to SCs, forming testicular tubules. Germinal epithelium developed and the basement membrane was synthesized. Concomitantly, there was decrease of the gonadal aromatase and increase in the 3β‐HSD enzyme expression. Thus, the testis was organized on an ovary previously developed, constituting an indirect gonochoristic differentiation. Anat Rec, 298:1984–2010, 2015. © 2015 Wiley Periodicals, Inc.     

Lithium enhanced cell proliferation and differentiation of mesenchymal stem cells to neural cells in rat spinal cord

Lithium has been shown to inhibit apoptosis of neural progenitor cells (NPCs) and promote differentiation of NPCs. However, there was rare data to discuss the effects of lithium on neural differentiation of mesenchymal stem cells (MSCs). Here, we investigated the potential promotion of lithium to MSC proliferation and neural differentiation in vitro and after transplanted into the ventral horn of rat spinal cord in vivo. We found that lithium possesses the ability to promote proliferation of GFP-MSCs in a dose dependent manner as verified by growth curve and bromodeoxyuridine (BrdU) incorporation assays; While in neural induction medium, lithium (0.1 mM) promotes neural differentiation of GFP-MSCs as verified by immunostaining and quantitative analysis. After transplantation of GFP-MSCs into the rat spinal cord, lithium treatment enhanced cell survival and neural differentiation after transplantation as verified by immunohistochemistry. These data suggested that lithium could be a potential drug to augment the therapeutic efficiency of MSCs transplantation therapy in central nervous system (CNS) disorders.     

Correlation between matrix metalloproteinase-9 and endometriosis

Endometrial implantation is the major cause of endometriosis (EMS). Matrix metalloproteinase (MMPs) can degrade multiple extracellular matrix and has been postulated to be related with EMC occurrence. This study thus investigated serum and ascites levels of MMP-9 in EMS patients, in an attempt to discuss the correlation between MMP-9 and EMS. A total of 100 EMS patients, including eutopic endometrium and ectopic endometrium, were recruited in this study along with hysteromyoma patients as the control group. Peripheral blood and ascites samples were collected and tested for MMP-9 levels using gelatin zymogram and enzyme-linked immunosorbent assay (ELISA). In EMS patients, MMP-9 levels in serum and ascites were 6.24±0.53 mM and 38.57±4.93 mM, respectively. Both of them were significantly higher than those in control group (P<0.05). Eutopic endometrium group had higher MMP-9 levels compared to those in ectopic endometrium ones (P<0.05). With advancement of disease stage, EMS patients had progressively elevated MMP-9 levels (P<0.05). Patients at proliferative stage had higher MMP-9 secretion (P<0.05). In summary, site of endometrium, clinical stage and proliferative cycle were independent risk factors for EMS. The elevation of serum and ascites MMP-9 existed in EMS patients, of which those had ectopic endometrium, advanced stage and at proliferative stage had higher MMP-9 expression.