Low density lipoprotein receptor-related protein is a calreticulin coreceptor that signals focal adhesion disassembly

Thrombospondin (TSP) signals focal adhesion disassembly (the intermediate adhesive state) through interactions with cell surface calreticulin (CRT). TSP or a peptide (hep I) of the active site induces focal adhesion disassembly through binding to CRT, which activates phosphoinositide 3-kinase (PI3K) and extracellular signal-related kinase (ERK) through Galphai2 proteins. Because CRT is not a transmembrane protein, it is likely that CRT signals as part of a coreceptor complex. We now show that low density lipoprotein receptor-related protein (LRP) mediates focal adhesion disassembly initiated by TSP binding to CRT. LRP antagonists (antibodies, receptor-associated protein) block hep I/TSP-induced focal adhesion disassembly. LRP is necessary for TSP/hep I signaling because TSP/hep I is unable to stimulate focal adhesion disassembly or ERK or PI3K signaling in fibroblasts deficient in LRP. LRP is important in TSP-CRT signaling, as shown by the ability of hep I to stimulate association of Galphai2 with LRP. The isolated proteins LRP and CRT interact, and LRP and CRT are associated with hep I in molecular complexes extracted from cells. These data establish a mechanism of cell surface CRT signaling through its coreceptor, LRP, and suggest a novel function for LRP in regulating cell adhesion.     

Disruption of the Talin Gene Compromises Focal Adhesion Assembly in Undifferentiated but Not Differentiated Embryonic Stem Cells

We have used gene disruption to isolate two talin (−/−) ES cell mutants that contain no intact talin. The undifferentiated cells (a) were unable to spread on gelatin or laminin and grew as rounded colonies, although they were able to spread on fibronectin (b) showed reduced adhesion to laminin, but not fibronectin (c) expressed much reduced levels of β1 integrin, although levels of α5 and αV were wild-type (d) were less polarized with increased membrane protrusions compared with a vinculin (−/−) ES cell mutant (e) were unable to assemble vinculin or paxillin-containing focal adhesions or actin stress fibers on fibronectin, whereas vinculin (−/−) ES cells were able to assemble talin-containing focal adhesions. Both talin (−/−) ES cell mutants formed embryoid bodies, but differentiation was restricted to two morphologically distinct cell types. Interestingly, these differentiated talin (−/−) ES cells were able to spread and form focal adhesion-like structures containing vinculin and paxillin on fibronectin. Moreover, the levels of the β1 integrin subunit were comparable to those in wild-type ES cells. We conclude that talin is essential for β1 integrin expression and focal adhesion assembly in undifferentiated ES cells, but that a subset of differentiated cells are talin independent for both characteristics.     

Methodological challenges in the study of fetal growth

Several conceptual and methodological challenges must be solved in order to create knowledge that can be useful to pregnant women, their families, and any clinicians who serve them: (1) going beyond nominal and ordinal hypotheses and presenting estimates of conditional probabilities; (2) focusing on clearly defined outcomes; (3) modeling the relationship of fetal growth and length of gestation; (4) understanding the process of fetal growth even though most of our data is cross-sectional; (5) estimating the independent effects of genetics, race, ethnicity, maternal risk behaviors, medical prenatal care, and socioeconomic status on fetal growth and length of gestation; and (6) estimating the independent effects of maternal pre-pregnancy weight, weight gain during pregnancy, and nutrition on fetal growth and length of gestation. The analysis and writing of this study was funded, in part, by a grant from the National Institute of Child Health and Human Development (NICHD RO1 HD 20511). Troy D. Abell, Ph.D., M.P.H., is associate professor of anthropology and adjunct associate professor of family medicine at the University of Oklahoma. His major interests are in the biocultural determinants of fetal growth and the epistemologic issues inherent in statistical reasoning, scientific inference, and decision analysis.     

Crossroads of integrins and cadherins in epithelia and stroma remodeling

Adhesion events mediated by cadherin and integrin adhesion receptors have fundamental roles in the maintenance of the physiological balance of epithelial tissues, and it is well established that perturbations in their normal functional activity and/or changes in their expression are associated with tumorigenesis. Over the last decades, increasing evidence of a dynamic collaborative interaction between these complexes through their shared interactions with cytoskeletal proteins and common signaling pathways has emerged not only as an important regulator of several aspects of epithelial cell behavior, but also as a coordinated adhesion module that senses and transmits signals from and to the epithelia surrounding microenvironment. The tight regulation of their crosstalk is particularly important during epithelial remodeling events that normally take place during morphogenesis and tissue repair, and when defective it leads to cell transformation and aggravated responses of the tumor microenvironment that contribute to tumorigenesis. In this review we highlight some of the interactions that regulate their crosstalk and how this could be implicated in regulating signals across epithelial tissues to sustain homeostasis.     

Laparoscopic evaluation of the reproductive organs and abdominal cavity content of the lowland gorilla

Laparoscopy was used to examine the abdominal cavity and evaluate reproductive competence in six adult female gorillas which had not demonstrated copulatory activity within 12 months of examination. Blood samples were obtained on the day of laparoscopy and analyzed for serum estradiol-17β and progesterone. The uterus and oviducts of each gorilla appeared morphologically normal and free of lesions. The ovaries of three animals contained anatomical evidence of activity as indicated by the presence of luteal scars and a prominent corpus hemorrhagicum, corpus luteum, or developing follicles. No visible luteal or follicular tissue was observed on the ovaries of three gorillas. In the eldest female (age, 22 years) the ovaries were flaccid in texture and demonstrated irregularities in ovarian surface integrity, similar to that observed in women during reproductive senescence. Serum concentrations of estradiol-17β and progesterone on the day of laparoscopy corresponded with observed ovarian activity. All six females had extensive adhesions in the abdominal cavity exclusive of the reproductive organs. Numerous gut, omentum, and liver to peritoneum adhesions were observed. The results indicated that laparoscopy was a safe and effective method for evaluating anatomical competence in the gorilla. Uterine and ovarian integrity appeared morphologically normal, but only three of the six gorillas showed evidence of ongoing ovarian activity.     

宫血宁治疗宫内节育器后异常出血的疗效观察

目的：探讨宫血宁胶囊用于治疗宫内放置节育器后异常子宫出血的临床疗效。方法：350例宫内置器后异常出血患者随机分为观察组（175例）与对照组（175例）,其中观察组给予宫血宁胶囊治疗,对照组给予抗菌止血常规西药治疗,比较两组患者治疗前后月经异常变化情况及治疗效果。结果：①观察组治愈率、总有效率分别为56.00%和92.57%,对照组治愈率、总有效率为25.71%和75.43%,组间差异有统计学意义（P〈0.01）。②经过治疗,观察组与对照组患者月经异常症状均得到明显缓解,与治疗前比较差异有显著性（P〈0.01）,其中观察组患者经量增多、经期延长和经间点滴出血等症状例数分别减少至9例、7例和1例,对照组减少至34例、30例和15例,组间差异有统计学意义（P〈0.05）。③经过治疗,观察组患者平均月经持续时间从11.74±4.69d减少至6.92±2.34d,对照组从12.11±5.25d减少至9.28±3.14d,两组间差异有统计学意义（P〈0.05）。结论：宫血宁胶囊可有效治疗因宫内放置节育器所引起的子宫异常出血,且疗效优于抗菌止血西药治疗,值得进一步推广。     

Effect of IL-18 on intrauterine infection of HBV in mice on cell molecular level

ObjectiveThe objective of this study is to investigate the effect of IL-18 on intrauterine infection of HBV (Hepatitis B Virus) in mice based on cellular and molecular level, and to analyze its mechanism, as well as the relationship between IL-18 and intrauterine infection of HBV.MethodsPregnant rats are taken as the study subjects and divided into two groups according to infection and non-infection, namely the study group and the control group. Firstly, the peripheral blood of rats and the blood of newborn mice are collected for the determination of hepatitis B in two-and-a-half pairs. Then, the levels of interleukin-18 (IL-18), interferon-γ (IFN-γ) and interleukin-4 (IL-4) in peripheral serum are detected by ELISA (Enzyme Linked Immunosorbent Assay). Finally, the two groups of horizontal values are compared and analyzed. The effect of IL-18 on intrauterine infection of HBV in mice is investigated based on the level of cell and molecular.ResultsThe levels of IL-18, IFN-γ, IL-4 and IFN-γ/IL-4 in the two groups are compared and analyzed. The levels of IL-18, IFN-γ and IFN-γ/IL-4 in the study group are significantly lower than those in the control group, with statistical significance. However, the level of IL-4 in the study group is higher than that in the control group, with statistical significance.ConclusionIt is found that the decrease of HL-type specific response and the enhancement of Th2-type specific response in pregnant mice are closely related to HBV intrauterine infection. Moreover, the decrease of IL-18 secretion in peripheral blood may cause intrauterine infection of HBV. This study can make people better realize the mechanism of HBV intrauterine infection, and effectively help clinical prevention and treatment of intrauterine infection.     

Annexin A6 contributes to the invasiveness of breast carcinoma cells by influencing the organization and localization of functional focal adhesions

The interaction of annexin A6 (AnxA6) with membrane phospholipids and either specific extracellular matrix (ECM) components or F-actin suggests that it may influence cellular processes associated with rapid plasma membrane reorganization such as cell adhesion and motility. Here, we examined the putative roles of AnxA6 in adhesion-related cellular processes that contribute to breast cancer progression. We show that breast cancer cells secrete annexins via the exosomal pathway and that the secreted annexins are predominantly cell surface-associated. Depletion of AnxA6 in the invasive BT-549 breast cancer cells is accompanied by enhanced anchorage-independent cell growth but cell–cell cohesion, cell adhesion/spreading onto collagen type IV or fetuin-A, cell motility and invasiveness were strongly inhibited. To explain the loss in adhesion/motility, we show that vinculin-based focal adhesions in the AnxA6-depleted BT-549 cells are elongated and randomly distributed. These focal contacts are also functionally defective because the activation of focal adhesion kinase and the phosphoinositide-3 kinase/Akt pathway were strongly inhibited while the MAP kinase pathway remained constitutively active. Compared with normal human breast tissues, reduced AnxA6 expression in breast carcinoma tissues correlates with enhanced cell proliferation. Together this suggests that reduced AnxA6 expression contributes to breast cancer progression by promoting the loss of functional cell–cell and/or cell–ECM contacts and anchorage-independent cell proliferation.     

血乳酸和心肌酶变化在胎儿宫内窘迫新生儿中的临床意义

目的:探讨血乳酸和心肌酶变化在胎儿宫内窘迫新生儿中的临床意义。方法:选取2017年3月到2018年8月期间在我院出生的胎儿宫内窘迫新生儿120例,其中有55例出生后未出现窒息,将其纳入观察1组,另外65例新生儿出生后出现窒息则纳入观察2组,同时选取同期在我院出生的健康、足月新生儿60例作为对照组。比较三组新生儿的血乳酸、乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酸激酶同工酶MB(CKMB)、血氧分压(PaO_2)、二氧化碳分压(PaCO_2)的水平,并分析血乳酸与心肌酶、PaO_2、PaCO_2的相关性。结果:出生时、出生后5d,观察2组的血乳酸、LDH、CK、CKMB水平均高于观察1组和对照组,且观察1组的血乳酸、LDH、CK、CKMB水平均高于对照组,差异均有统计学意义(P0.05)。出生时,观察2组的PaO_2水平低于观察1组和对照组,PaCO_2水平高于观察1组和对照组,差异均有统计学意义(P0.05),观察1组的PaO_2水平低于对照组,PaCO_2水平高于对照组,差异均有统计学意义(P0.05)。Pearson相关性分析结果显示,胎儿宫内窘迫新生儿血乳酸水平与CK、CKMB、PaCO_2呈正相关,与PaO_2呈负相关(P0.05),与LDH无明显的相关性(P0.05);LDH、CK、CKMB与PaCO_2呈正相关,与PaO_2呈负相关(P0.05)。结论:胎儿宫内窘迫新生儿血乳酸和心肌酶水平明显升高,且出生后存在窒息的新生儿中更为明显,胎儿宫内窘迫新生儿血乳酸、心肌酶水平与缺氧程度密切相关。     

流产术后并发宫腔粘连的危险因素分析及宫腔镜联合雌孕激素的干预效果研究

目的:分析流产术后并发宫腔粘连的危险因素,并探讨宫腔镜联合雌孕激素对宫腔粘连的干预效果,以期为宫腔粘连的防治提供依据。方法:选取2016年1月至2017年2月于我院接受流产术后并发宫腔粘连的患者100例作为粘连组,另选取同期于我院接受流产术后未发生宫腔粘连的患者100例作为未粘连组。比较粘连组和未粘连组患者基本资料、既往史情况、手术指标,并采用多因素Logistic回归分析流产术后并发宫腔粘连的危险因素。进一步将粘连组按照随机数字表法分成对照组(n=50)和观察组(n=50),对照组患者进行雌孕激素治疗,观察组患者进行宫腔镜联合雌孕激素治疗。比较观察组与对照组患者治疗3个周期后首次月经情况以及临床疗效。结果:粘连组孕次、产次、吸宫时负压、吸宫时间以及合并盆腔炎时间均高于未粘连组,差异均有统计学意义(P0.05)。经多因素Logistic回归分析可得,吸宫时负压≧500 mm Hg、吸宫时间≧15 min为流产术后并发宫腔粘连的危险因素(P0.05)。观察组治疗3个周期后首次月经量减少发生率、首次月经中期子宫内膜厚度≤8 mm发生率低于对照组,治疗有效率高于对照组(P0.05)。结论:吸宫时负压≧500 mm Hg、吸宫时间≧15 min均属于流产术后并发宫腔粘连的独立危险因素,临床应根据以上危险因素采取相应预防措施,以减少宫腔粘连的发生。而对于已发生宫腔粘连的患者,采用宫腔镜联合雌孕激素治疗具有较好的干预效果,值得在临床上推广应用。