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Polychlorinated biphenyls(PCBs) are persistent environmental endocrine disruptor. This study aim to investigate the changes of the ectopic endometrium invasive ability and the possible mechanism after exposure to PCBs during pregnancy. In total, 12 female Sprague Dawley rats were intraperitoneally injected with Aroclor 1221 (1 mg/kg) or dimethyl sulfoxide (1 mg/kg) at 16 and 18 days of gestation. The endometriosis model was established by autogenous uterine abdominal wall implantation 2 months after birth. The degree of adhesion between the endometriosis and the greater omentum, as well as cell morphology and Transwell invasion patterns were used to evaluate the invasive ability of progeny ectopic endometrial stromal cells (ESCs). Moreover, the effect of the enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2)/ trimethylation of Histone 3 lysine 27 (H3K27me3) axis was examined using a highly selective EZH2 inhibitor, GSK126. After gestational PCBs exposure, the adhesion between the endometrium and the greater omentum was enhanced (P

The developmental origins of health and disease concept illustrates that exposure in early life to various factors may affect the offspring's long-term susceptibility to disease. During development, the nervous system is sensitive and vulnerable to the environmental insults. Polychlorinated biphenyls (PCBs), which are divided into dioxin-like (DL-PCBs) and non-dioxin-like PCBs (NDL-PCBs), are synthetic persistent environmental endocrine-disrupting chemicals. The toxicological mechanisms of DL-PCBs have been associated with the activation of the aryl hydrocarbon receptor and NDL-PCBs have been associated with ryanodine receptor-mediated calcium ion channels, which affect neuronal migration, promote dendritic growth and alter neuronal connectivity. In addition, PCB accumulation in the placenta destroys the fetal placental unit and affects endocrine function, particularly thyroid hormones and the dopaminergic system, leading to neuroendocrine disorders. However, epidemiological investigations have not achieved a consistent result in different study cohorts. The present review summarizes the epidemiological differences and possible mechanisms of the effects of intrauterine PCB exposure on neurological development.

Objective This study was performed to assess the predictive value of the anti-Müllerian hormone (AMH) serum level for spontaneous pregnancy in women after endometriosis surgery. Methods In total, 124 patients with suspected ovarian endometrioma planning to undergo laparoscopic ovarian cystectomy were divided into a high AMH group (AMH > 2 ng/mL) and low AMH group (AMH ≤ 2 ng/mL) according to their preoperative AMH levels. The postoperative AMH levels were also measured, and pregnancy outcomes were followed up. Results Twenty-one patients were excluded, and 52 pregnancies were registered in the remaining 103 patients diagnosed with endometriosis. The pregnancy rate was significantly greater in the high than low AMH group. Receiver operator characteristics analysis of preoperative AMH, postoperative AMH, and the AMH decline rate showed that preoperative AMH was associated with the greatest area under the curve. Kaplan–Meier curves showed that women in the high AMH group had a significantly higher cumulative pregnancy rate than those in the low AMH group. Conclusion The preoperative AMH level might be a useful marker to predict the occurrence of natural pregnancy and could be offered as part of the fertility strategy to women who desire pregnancy after endometriosis surgery.

BACKGROUND Studies have shown that the concentration of interleukin (IL)-6 in peritoneal fluid is increased in patients with endometriosis; however, whether the disorders involving IL-6 contribute to the development of endometriosis is still unclear. In the present study, we evaluated the potential role of IL-6 and IL-6 receptor (IL-6R) in the pathogenesis of endometriosis. MATERIAL AND METHODS We examined activated macrophages and the expression of membrane-binding receptor (mIL-6R) in peritoneal fluid using flow cytometry. The levels of IL-6 and the IL-6 soluble receptor (sIL-6R) in peritoneal fluid and plasma in patients with endometriosis was measured by an enzyme-linked immunosorbent assay. RESULTS Activated macrophages and mIL-6R in peritoneal fluid were increased in patients with endometriosis. IL-6 and sIL-6R in peritoneal fluid were also increased in patients with endometriosis; however, there was an increase in plasma IL-6 and a decrease in plasma sIL-6R. The endometriosis group was categorized into 2 groups according to the retrospective American Fertility Society Score (r-AFS): group A and group B. Peritoneal fluid sIL-6R in endometriosis group B was significantly higher than in endometriosis group A and the control group. CONCLUSIONS Disorders involving IL-6 and IL-6R are correlated with the etiology of endometriosis. An increase in sIL-6R in peritoneal fluid promotes the development of endometriosis by enhancing the bioactivity of IL-6.

Endometriosis is associated with inflammatory reaction, and reactive oxidative species (ROS) are highly pro-inflammatory factors. Mitochondria are responsible for the production of ROS and energy. However, little is known about how mitochondria regulate ROS generation and energy metabolism in endometriosis. In our study, we investigated mitochondrial structure and function of ectopic endometrial stromal cells (ESCs) in ovarian endometriosis. We found mitochondria in ectopic ESCs generated more ROS and energy than controlled groups. Mitochondrial superoxide dismutase (SOD2), as an antioxidant enzyme, was found highly expressed in ectopic endometrium compared with normal endometrium. Due to its antioxidant role, SOD2 promoted the development of endometriosis by maintaining functional mitochondria to support high energetic metabolism of ectopic ESCs. We also showed that SOD2 promoted cell proliferation and migration in ovarian endometriosis. Inhibiting SOD2 expression reduced proliferation and migration of ectopic ESCS, and increased cell apoptosis. Therefore, understanding the role of mitochondrial dysfunction and SOD2 in ovarian endometriosis may provide new strategies to treat this disease.

Objective This study was performed to assess whether prophylactic uterine artery embolization (UAE) is beneficial for second-trimester abortion with complete placenta previa (CPP). Methods Patients with CPP who underwent second-trimester pregnancy termination by labor induction with or without UAE from January 2010 to January 2018 were retrospectively reviewed. In total, 25 patients were eligible for analysis. The primary outcomes were the abortion success rate and bleeding volume, and the secondary outcomes were the induction-to-abortion time, length of hospital stay, and complications. Results CPP occurred in all 25 patients. Fifteen patients underwent prophylactic UAE (UAE group) and 10 did not (control group). Abortion was successful in 13 of 15 (86.7%) women in the UAE group and in 9 of 10 (90.0%) women in the control group. There was no significant difference in the bleeding volume or induction-to-abortion time between the two groups. The hospital stay was longer and pyrexia was more common in the UAE than control group. Conclusion Prophylactic UAE did not markedly improve the outcomes of second-trimester abortion in patients with CPP. Conversely, it may increase the risk of complications and prolong the hospital stay.

A population of cartilage stem/progenitor cells can be derived from fully differentiated chondrocytes that have the potential to reassume their chondrocytic phenotype for efficient cartilage regeneration. This novel concept supports the possibility of using in vitro amplified chondrocyte-derived progenitor cells for joint repair., Articular cartilage is not a physiologically self-renewing tissue. Injury of cartilage often progresses from the articular surface to the subchondral bone, leading to pathogenesis of tissue degenerative diseases, such as osteoarthritis. Therapies to treat cartilage defects using autologous chondrocyte-based tissue engineering have been developed and used for more than 20 years; however, the challenge of chondrocyte expansion in vitro remains. A promising cell source, cartilage stem/progenitor cells (CSPCs), has attracted recent attention. Because their origin and identity are still unclear, the application potential of CSPCs is under active investigation. Here we have captured the emergence of a group of stem/progenitor cells derived from adult human chondrocytes, highlighted by dynamic changes in expression of the mature chondrocyte marker, COL2, and mesenchymal stromal/stem cell (MSC) marker, CD146. These cells are termed chondrocyte-derived progenitor cells (CDPCs). The stem cell-like potency and differentiation status of CDPCs were determined by physical and biochemical cues during culture. A low-density, low-glucose 2-dimensional culture condition (2DLL) was critical for the emergence and proliferation enhancement of CDPCs. CDPCs showed similar phenotype as bone marrow mesenchymal stromal/stem cells but exhibited greater chondrogenic potential. Moreover, the 2DLL-cultured CDPCs proved efficient in cartilage formation both in vitro and in vivo and in repairing large knee cartilage defects (6–13 cm2) in 15 patients. These findings suggest a phenotype conversion between chondrocytes and CDPCs and provide conditions that promote the conversion. These insights expand our understanding of cartilage biology and may enhance the success of chondrocyte-based therapies. Significance Injury of cartilage, a non-self-repairing tissue, often progresses to pathogenesis of degenerative joint diseases, such as osteoarthritis. Although tissue-derived stem cells have been shown to contribute to tissue renewal and homeostasis, the derivation, biological function, and application potential of stem/progenitor cells found in adult human articular cartilage are incompletely understood. This study reports the derivation of a population of cartilage stem/progenitor cells from fully differentiated chondrocytes under specific culture conditions, which have the potential to reassume their chondrocytic phenotype for efficient cartilage regeneration. These findings support the possibility of using in vitro amplified chondrocyte-derived progenitor cells for joint cartilage repair.

With the progress of global industrialization and environmental deterioration, the relationship between human health and the living environment has become an increasing focus of attention. Polychlorinated biphenyls (PCBs, including dioxin-like polychlorinated biphenyls and non-dioxin-like polychlorinated biphenyls), as part of the organic chlorine contaminants, have been suspected as playing a role in the etiopathogenesis of endometriosis. Several population-based studies have proposed that exposure to PCBs may increase the risk of developing endometriosis, while some epidemiological studies have failed to find any association between PCBs and endometriosis. The purpose of this review is to discuss the potential pathophysiological relationship between endometriosis and PCBs with a focus on both dioxin-like polychlorinated biphenyls and non-dioxin-like polychlorinated biphenyls.

The repair of osteochondral defects can be enhanced with scaffolds but is often accompanied with undesirable terminal differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Parathyroid hormone-related protein (PTHrP) has been shown to inhibit aberrant differentiation, but administration at inappropriate time points would have adverse effects on chondrogenesis. This study aims to develop an effective tissue engineering strategy by combining PTHrP and collagen-silk scaffold for osteochondral defect repair. The underlying mechanisms of the synergistic effect of combining PTHrP administration with collagen-silk scaffold implantation for rabbit knee joint osteochondral defect repair were investigated. In vitro studies showed that PTHrP treatment significantly reduced Alizarin Red staining and expression of terminal differentiation-related markers. This is achieved in part through blocking activation of the canonical Wnt/β-catenin signaling pathway. For the in vivo repair study, intra-articular injection of PTHrP was carried out at three different time windows (4-6, 7-9 and 10-12 weeks) together with implantation of a bi-layer collagen-silk scaffold. Defects treated with PTHrP at the 4-6 weeks time window exhibited better regeneration (reconstitution of cartilage and subchondral bone) with minimal terminal differentiation (hypertrophy, ossification and matrix degradation), as well as enhanced chondrogenesis (cell shape, Col2 and GAG accumulation) compared with treatment at other time windows. Furthermore, the timing of PTHrP administration also influenced PTHrP receptor expression, thus affecting the treatment outcome. Our results demonstrated that intra-articular injection of PTHrP at 4-6 weeks post-injury together with collagen-silk scaffold implantation is an effective strategy for inhibiting terminal differentiation and enhancing chondrogenesis, thus improving cartilage repair and regeneration in a rabbit model.

Despite the presence of cartilage-derived mesenchymal stem cells (C-MSCs) and synovial membrane-derived mesenchymal stem cells (SM-MSCs) populations, partial-thickness cartilage defects, in contrast to the full-thickness defects, are devoid of spontaneous repair capacity. This study aims to create an in situ matrix environment conducive to C-MSCs and SM-MSCs to promote cartilage self-repair. Spontaneous repair with MSCs migration into the defect area was observed in full-thickness defects, but not in partial-thickness defects in rabbit model. Ex vivo and in vitro studies showed that subchondral bone or type 1 collagen (col1) scaffold was more permissive for MSCs adhesion than cartilage or type 2 collagen (col2) scaffold and induced robust stromal cell-derived factors-1 (SDF-1) dependent migration of MSCs. Furthermore, creating a matrix environment with col1 scaffold containing SDF-1 enhanced in situ self-repair of partial-thickness defects in rabbit 6 weeks post-injury. Hence, the inferior self-repair capacity in partial-thickness defects is partially owing to the non-permissive matrix environment. Creating an in situ matrix environment conducive to C-MSCs and SM-MSCs migration and adhesion with col1 scaffold containing SDF-1 can be exploited to improve self-repair capacity of cartilage.

Osteonecrosis of the femoral head (ONFH) is a common but intractable disease. In this study, we investigated the mechanisms regulating alterations in mesenchymal stem cell (MSC) differentiation in ONFH. Five patients who were diagnosed with ONFH were enrolled in this study. Bone MSCs (BMSCs) were isolated from the osteonecrotic zone in the femoral head (FH-pMSCs) and from the normal zone in the pelvis (hMSCs) of the same patient. Morphology, cell proliferation and expression of mediators of the Wnt signalling pathway were evaluated. There were significant differences in cell proliferation and expression of surface markers between the two populations of cells. FH-pMSCs exhibited significantly lower osteogenic differentiation compared with hMSCs (P < 0.0001). Dissection of the Wnt pathway showed that FH-pMSCs had significantly higher GSK3β expression compared with hMSCs (P < 0.001). Addition of LiCl, a GSK3β inhibitor, significantly increased osteogenic differentiation in FH-pMSCs, suggesting a relationship between the microenvironment and regulation of stem cell behaviour in ONFH. FH-pMSCs also exhibited significant downregulation of other mediators of the Wnt signalling pathway, including runx2 and β-catenin. Our data suggested that mediators of the Wnt signalling pathway, such as GSK3β could be important therapeutic targets for early-stage ONFH.

Introduction Interleukin-1β (IL-1β) and nerve growth factor (NGF) are key regulators in the pathogenesis of inflammatory arthritis; specifically, IL-1β is involved in tissue degeneration and NGF is involved in joint pain. However, the cellular and molecular interactions between IL-1β and NGF in articular cartilage are not known. Cartilage stem/progenitor cells (CSPCs) have recently been identified in osteoarthritic (OA) cartilage on the basis of their migratory properties. Here we hypothesize that IL-1β/NGF signaling is involved in OA cartilage degeneration by targeting CSPCs. Method NGF and NGF receptor (NGFR: TrkA and p75NTR) expression in healthy and OA human articular cartilage and isolated chondrocytes was determined by immunostaining, qRT-PCR, flow cytometry and western blot. Articular cartilage derived stem/progenitor cells were collected and identified by stem/progenitor cell characteristics. 3D-cultured CSPC pellets and cartilage explants were treated with NGF and NGF neutralizing antibody, and extracellular matrix changes were examined by sulfated glycosaminoglycan (GAG) release and MMP expression and activity. Results Expression of NGF, TrkA and p75NTR was found to be elevated in human OA cartilage. Cellular changes upon IL-1β and/or NGF treatment were then examined. NGF mRNA and NGFR proteins levels were upregulated in cultured chondrocytes exposed to IL-1β. NGF was chemotactic for cells isolated from OA cartilage. Cells isolated on the basis of their chemotactic migration towards NGF demonstrated stem/progenitor cell characteristics, including colony-forming ability, multi-lineage differentiation potential, and stem cell surface markers. The effects of NGF perturbation in cartilage explants and 3D-cultured CSPCs were next analyzed. NGF treatment resulted in extracellular matrix catabolism indicated by increased sGAG release and MMP expression and activity; conversely, treatment with NGF neutralizing antibody inhibited increased MMP levels, and enhanced tissue inhibitor of matrix metalloprotease-1 (TIMP1) expression in OA cartilage explants. NGF blockade with neutralizing antibody also affected cartilage matrix remodeling in 3D-CSPC pellet cultures. Conclusion Our results strongly suggest that NGF signaling is a contributing factor in articular cartilage degeneration in OA, which likely targets a specific subpopulation of progenitor cells, the CSPCs, affecting their migratory and matrix remodeling activities. These findings provide novel cellular/signaling therapeutic targets in osteoarthritic cartilage. Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0840-x) contains supplementary material, which is available to authorized users.

In order to ensure the imaging resolution of aerial camera and compensating defocusing caused by the changing of atmospheric temperature, pressure, oblique photographing distance and other environmental factor [1,2], and to meeting the overall design requirements of the camera for the lower mass and smaller size , the linear focusing mechanism is designed. Through the target surface support, the target surface component is connected with focusing driving mechanism. Make use of precision ball screws, focusing mechanism transforms the input rotary motion of motor into linear motion of the focal plane assembly. Then combined with the form of linear guide restraint movement, the magnetic encoder is adopted to detect the response of displacement. And the closed loop control is adopted to realize accurate focusing. This paper illustrated the design scheme for a focusing mechanism and analyzed its error sources. It has the advantages of light friction and simple transmission chain and reducing the transmission error effectively. And this paper also analyses the target surface by finite element analysis and lightweight design. Proving that the precision of focusing mechanism can achieve higher than 3um, and the focusing range is ±2mm.

Aerial cameras exist the image motion on the flight. The image motion has seriously affected the image quality, making the image edge blurred and gray scale loss. According to the actual application situation, when high quality and high precision are required, the image motion compensation (IMC) should be adopted. This paper designs galvanometer control system of IMC. The voice coil motor as the actuator has a simple structure, fast dynamic response and high positioning accuracy. Double-loop feedback is also used. PI arithmetic and Hall sensors are used at the current feedback. Fuzzy-PID arithmetic and optical encoder are used at the speed feedback. Compared to conventional PID control arithmetic, the simulation results show that the control system has fast response and high control accuracy.

Figure S1 showing immunodetection of CD271/p75NTR in normal rabbit cartilage, Figure S2 showing characterization of the cell surface epitope profile of migratory cells isolated from human OA articular cartilage, Figure S3 showing the gene expression profile of human OA cartilage explants after NGF (10 ng/ml) treatment for 14 days, and Table S1 presenting primer sequences for real-time RT-PCR. (DOCX 1277 kb)

Terminal differentiation often occurs in the repair progress of osteochondral defects. It is reported that parathyroid hormone-related protein (PTHrP) could inhibit terminal differentiation but may elicit adverse effects on chondrogenesis when administrated at improper time. Here we apply PTHrP by optimal intra-articular injection together with implantation of a collagen-silk scaffold to treat osteochondral defect. The injection schedule was set at three different time windows: 4-6, 7-9 and 10-12 weeks post-operatively. Samples were obtained and evaluated macroscopically, histologically and immunohistochemically at 16 weeks post-injury. In vivo delivery of PTHrP at 4-6 weeks exhibited better repairing effects and less terminal differentiation compared with other time windows. These results showed that PTHrP would invoke best repair effects for osteochondral defects when intraarticularly injected at 4-6 weeks post-injury, which not only prevented terminal differentiation but also promoted cartilage regeneration in rabbit model. The findings offer insight into understanding the mechanisms involved and pave the way for clinical application of PTHrP for osteochondral defects repair.

Collaborative design is the most important task of all activities at the lifecycle of product development under Networked Manufacturing (NM) environment. Application Service Provider (ASP) is a practical service style of informationization and ASP-based system is a effective approach to NM platforms. In this paper, combined industrial requirements with our efforts in some research projects funded by Hi-Tech R&D Program of China and Beijing Municipal Sci-Tech Program, an ASP-based distributed collaborative design system namely Co-Design is proposed to support remote collaboration among enterprises. Architecture of the system is presented and some key techniques of collaborative design are researched. Now the proposed Co-Design system has been implemented and used as ASP tools to help several small and medium enterprises to accelerate their product development and typical application examples shows that substantial benefits can be achieved by reducing of collaboration expenditure, development cost and shortening time to market.