Search

Preeclampsia (PE) is considered as a disease of placental origin. However, the specific mechanism of placental abnormalities remains elusive. This study identified thrombospondin‐1 (THBS1) is downregulated in preeclamptic placentae and negatively correlated with blood pressure. Functional studies show that THBS1 knockdown inhibits proliferation, migration, and invasion and increases the cycle arrest and apoptosis rate of HTR8/SVneo cells. Importantly, THBS1 silencing induces necroptosis in HTR8/SVneo cells, accompanied by the release of damage‐associated molecular patterns (DAMPs). Necroptosis inhibitors necrostatin‐1 and GSK′872 restore the trophoblast survival while pan‐caspase inhibitor Z‐VAD‐FMK has no effect. Mechanistically, the results show that THBS1 interacts with transforming growth factor B‐activated kinase 1 (TAK1), which is a central modulator of necroptosis quiescence and affects its stability. Moreover, THBS1 silencing up‐regulates the expression of neuronal precursor cell‐expressed developmentally down‐regulated 4 (NEDD4), which acts as an E3 ligase of TAK1 and catalyzes K48‐linked ubiquitination of TAK1 in HTR8/SVneo cells. Besides, THBS1 attenuates PE phenotypes and improves the placental necroptosis in vivo. Taken together, the down‐regulation of THBS1 destabilizes TAK1 by activating NEDD4‐mediated, K48‐linked TAK1 ubiquitination and promotes necroptosis and DAMPs release in trophoblast cells, thus participating in the pathogenesis of PE. [ABSTRACT FROM AUTHOR]

The book "Current Issues in Syntactic Cartography: A crosslinguistic perspective" edited by Fuzhen Si and Luigi Rizzi provides a comprehensive study of syntactic cartography. The book is organized into 12 papers that focus on theoretical and descriptive issues of specific aspects of syntactic cartography. The chapters cover topics such as the left periphery, the Inflection Phrase (IP) zone, and the Verb Phrase (VP) zone. The book includes contributions from leading scholars and explores various languages, including Romance, Germanic, Semitic, Japanese, and Chinese. It is recommended for linguists interested in generative syntax and offers new theories and unfamiliar data for exploration. [Extracted from the article]

Neutrophil extracellular traps (NETs) released by activated neutrophils typically consist of DNA-histone complexes and granule proteins. NETs were originally identified as a host defense system against foreign pathogens and are strongly associated with autoimmune diseases. However, a novel and predominant role of NETs in cancer is emerging. Increasing evidence has confirmed that many stimuli can facilitate NET formation in an NADPH oxidase (NOX)-dependent/NOX-independent manner. In cancer, NETs have been linked to cancer progression, metastasis, and cancer-associated thrombosis. In this review, we aimed to summarize the current available knowledge regarding NET formation and focused on the role of NETs in cancer biological behaviors. The potential target for cancer therapy will be further discussed. [ABSTRACT FROM AUTHOR]

The process of laser welding is modelled using the meshless Lagrangian Smoothed Particle Hydrodynamics (SPH) method. Significant physical effects during the welding process like heat conduction, surface tension, and the occuring phase transitions melting, solidification, and evaporation are considered in the model. By coupling an SPH code with a ray tracer that tracks the propagation of independent light rays in the capillary and calculates the locally absorbed intensity by means of geometrical optics, the laser-material interaction is represented in detail, even for complex capillary geometries. Therefore, both heat conduction and deep penetration laser welding can be simulated using this co-simulation approach. The model is able to predict the temperature distribution during the welding process and the dimensions of the resulting weld seam. Furthermore, the vaporisation threshold and deep penetration threshold can be estimated. The numerical results are validated by comparing the obtained threshold values with experimental data and an analytical approximation during seam welding of aluminum. (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

We previously reported that cyclophilin A (CyPA) production is upregulated in preeclampsia (PE). Moreover, CyPA is known to induce PE-like features in pregnant mice and impair trophoblast invasiveness. In this study, we further illustrated the role of CyPA in PE. RNA-seq analysis, RT-qPCR, immunohistochemical (IHC) staining, and western blotting of mouse placentae revealed that CyPA increased the levels of extracellular matrix (ECM) proteins, such as collagen I and fibronectin, and activated the TGF-β/Smad3 signaling pathway. Additionally, CyPA inhibited the expression of genes involved in epithelial-mesenchymal transition (EMT) (e.g., E-cadherin, N-cadherin, and vimentin) in mouse placentae. We then constructed stable overexpressing and knock-down CyPA cell models (using HTR8/SVneo cells) to clarify the molecular mechanism. We found that CyPA regulated the levels of ECM-related proteins and the EMT process through the TGF-β/Smad3 pathway. We also identified SERPINH1 as a putative CyPA-binding protein, using liquid chromatography-electrospray mass spectrometry (LC-MS)/MS. SERPINH1 was found to be upregulated in the placentae of PE. Silencing SERPINH1 expression reversed the upregulation of ECM proteins and inhibition of the EMT process induced by the overexpression of CyPA. These findings revealed the functions of CyPA in the impaired invasiveness of trophoblasts in PE and indicated that CyPA and SERPINH1 may represent promising targets for the treatment of PE. [Display omitted] • CyPA induces ECM deposition and inhibits the expression of EMT-related genes in trophoblast. • CyPA regulates ECM and EMT related protein in trophoblast via TGF-β/Smad3 signaling pathway. • CyPA interacts with SERPINH1. • SERPINH1 is upregulated in preeclamptic placentae. • Silencing the expression of SERPINH1 reverses the effects induced by CyPA. [ABSTRACT FROM AUTHOR]

Age-associated decreases in follicle number and oocyte quality result in a decline in female fertility, which is associated with increased infertility. Granulosa cells play a major role in oocyte development and maturation both in vivo and in vitro. However, it is unclear whether a reduction in cryptochrome 1 (Cry1) expression contributes to granulosa cell senescence, and further exploration is needed to understand the underlying mechanisms. In this study, we investigated the role of Cry1, a core component of the molecular circadian clock, in the regulation of senescence in ovarian granulosa cells. Western blotting and qRT-PCR showed that Cry1 expression was downregulated in aged human ovarian granulosa cells and was correlated with age and anti-Müllerian hormone (AMH) levels. RNA-seq analysis suggested that ferritinophagy was increased after Cry1 knockdown in KGN cells. MDA, iron, and reactive oxygen species (ROS) assays were used to detect cellular ferritinophagy levels. Ferroptosis inhibitors, iron chelators, autophagy inhibitors, and nuclear receptor coactivator 4 (NCOA4) knockdown alleviated KGN cell senescence induced by Cry1 knockdown. Immunofluorescence, immunoprecipitation, and ubiquitination assays indicated that Cry1 affected NCOA4 ubiquitination and degradation through HERC2, thereby affecting NCOA4-mediated ferritinophagy and causing granulosa cell senescence. KL201, a Cry1 stabilizer, enhanced ovarian function in naturally aged mice by reducing ferritinophagy. Our study reveals the potential mechanisms of action of Cry1 during ovarian aging and provides new insights for the clinical treatment of age-related fertility decline. A proposed molecular model of Cry1 in regulating senescence of human granulosa cells. Cry1 depletion reduced the expression of the E3 ubiquitin ligase HERC2, which reduced the ubiquitination and degradation of NCOA4, thereby promoting ferritinophagy and inducing granulosa cell senescence. [Display omitted] • Cry1 expression is downregulated in aged human ovarian granulosa cells. • Cry1 induces KGN cell senescence through NCOA4-mediated ferritinophagy. • Cry1 affects NCOA4 ubiquitination and degradation through HERC2. • Cry1 stabilizer KL201 enhances ovarian function by reducing ferritinophagy in middle-aged mice. [ABSTRACT FROM AUTHOR]

Numerous studies suggest that excessive maternal inflammation and defective extravillous trophoblast (EVT) invasion could contribute to the development of preeclampsia (PE), but the underlying mechanism remains unclear. Some evidence suggests that CyPA is elevated in PE. This research aims to investigate the effect of recombinant human CyPA on trophoblast migration and invasion both in vitro and in vivo. We detected the expression and localization of CyPA in human placenta and explored the effects of CyPA on cell migration and invasion on HTR8/SVneo cell. Additionally, the expression levels of matrix metalloproteinase (MMP)-2/9 and molecules in the p38/ERK/JNK signaling pathway were detected. We established a mouse model by injecting pregnant mice with recombinant human CyPA and measured blood pressure, albumin/creatinine ratio, fetal and placenta weight of mice. Moreover, we examined the placental histology and MMP-2/9 and p38/ERK/JNK expression. Our results showed that CyPA inhibited the migration and invasion of HTR8/SVneo cells in a dose-dependent manner, decreasing the expression of matrix metalloproteinase (MMP)-2/9 and molecules in the p38/ERK/JNK signaling pathway. Silencing CyPA could reverse the above effects. Moreover, CyPA could induce PE-like features in pregnant mice and disrupt the structure of the mouse placenta by reducing the junctional zone area. CyPA attenuated the trophoblast invasiveness in mice placenta by downregulating MMP-2/9 expression and p38/ERK/JNK pathway activity. We proposed that CyPA could inhibit trophoblast migration and invasion both in vitro and in vivo , which was involved in PE development. [ABSTRACT FROM AUTHOR]

Background: The long-term survival after vascularized composite allotransplantation (VCA) is often limited by systemic rejection as well as the adverse effects of immunosuppressants. The stromal vascular fraction (SVF) can be expanded to produce adipose-derived stem cells (ADSC) which represents a combination of endothelial cells, preadipocytes, immune cells, and ADSC. It has been demonstrated that ADSC possess consistently reliable clinical results. However, literature is scarce regarding SVF in VCA. This study seeks to determine the impact of ex vivo allograft pretreatment in combination with SVF cells in the ability to promote composite tissue allotransplantation immunotolerance. Methods: A rat hind limb allotransplant model was used to investigate the influence of ex vivo pretreatment of SVF and ADSC on VCA survival. Intravascular cell-free saline, ADSC, or SVF was infused into the models with immunosuppressants. The histopathological examination and duration that the allografts went without displaying symptoms of rejection was documented. Peripheral T lymphocytes and Tregs were quantified with flow cytometry while allotissue expressions of CD31 were quantified with immunohistochemical staining (IHC). ELISA was used to detect vascular endothelial growth factor (VEGF)-A as well as anti- and pro-inflammatory cytokines. Results: We demonstrated that ex vivo treatment of allografts with SVF or ADSC prolonged allograft survival in contrast to medium control cohorts. There were also enhanced levels of immunomodulatory cytokines and increased VEGF-A and CD31 expression as well as reduced infiltration and proliferation of T lymphocytes along with raised Treg expressions. Conclusion: These studies demonstrated that adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model and have the potential to establish immunotolerance. [ABSTRACT FROM AUTHOR]

Background: Substantial studies have demonstrated that oxidative stress placenta and endothelial injury are considered to inextricably critical events in the pathogenesis of preeclampsia (PE). Systemic inflammatory response and endothelial dysfunction are induced by the circulating factors released from oxidative stress placentae. As a novel biomarker of oxidative stress, advanced oxidation protein products (AOPPs) levels are strongly correlated with PE characteristics. Nevertheless, the molecular mechanism underlying the effect of factors is still largely unknown. Methods: With the exponential knowledge on the importance of placenta-derived extracellular vesicles (pEVs), we carried out lncRNA transcriptome profiling on small EVs (sEVs) secreted from AOPPs-treated trophoblast cells and identified upregulated lncRNA TDRKH-AS1 as a potentially causative factor for PE. We isolated and characterized sEVs from plasma and trophoblast cells by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting. The expression and correlation of lncRNA TDRKH-AS1 were evaluated using qRT-PCR in plasmatic sEVs and placentae from patients. Pregnant mice injected with TDRKH-AS1-riched trophoblast sEVs was performed to detect the TDRKH-AS1 function in vivo. To investigate the potential effect of sEVs-derived TDRKH-AS1 on endothelial function in vitro, transcriptome sequencing, scanning electron Microscopy (SEM), immunofluorescence, ELISA and western blotting were conducted in HUVECs. RNA pulldown, mass spectrometry, RNA immunoprecipitation (RIP), chromatin isolation by RNA purification (ChIRP) and coimmunoprecipitation (Co-IP) were used to reveal the latent mechanism of TDRKH-AS1 on endothelial injury. Results: The expression level of TDRKH-AS1 was significantly increased in plasmatic sEVs and placentae from patients, and elevated TDRKH-AS1 in plasmatic sEVs was positively correlated with clinical severity of the patients. Moreover, pregnant mice injected with TDRKH-AS1-riched trophoblast sEVs exhibited a hallmark feature of PE with increased blood pressure and systemic inflammatory responses. Pyroptosis, an inflammatory form of programmed cell death, is involved in the development of PE. Indeed, our in vitro study indicated that sEVs-derived TDRKH-AS1 secreted from AOPPs-induced trophoblast elevated DDIT4 expression levels to trigger inflammatory response of pyroptosis in endothelial cells through interacting with PDIA4. Conclusions: Herein, results in the present study supported that TDRKH-AS1 in sEVs isolated from oxidative stress trophoblast may be implicated in the pathogenesis of PE via inducing pyroptosis and aggravating endothelial dysfunction. [ABSTRACT FROM AUTHOR]

• The effects of the electrical field and different liquid media on hydration products were studied. • The portlandite had been proved to be affected by the electrical field. • The pure water affected the stability of C S H gel under the electrical field. • The fractal model was used to analyze the pore structure and morphology of hydration products. Electrical fields accelerate the sulfate attack, which induces detrimental effects on the durability of cement-based materials. However, the role of the electrical field and aggressive liquid media in the degradation process is still unclear. Investigation of the role of the electrical field and aggressive liquid media during the degradation allows a better understanding of the mechanism of accelerated technique. Four different liquid media were used in this work to study the effect of the electrical field and liquid media in terms of the stability of hydration products. The evolution of hydration products was experimentally identified using multiple techniques, including X-ray diffraction (XRD), thermogravimetric analysis (TG), transmission electron microscopy (TEM), nitrogen adsorption/desorption (NAD), pH and CaO content measurements. The results indicated that the C S H structure was stable under the electrical field and saturated Ca(OH) 2 solution. The calcium loss under the electrical field was more likely to leach out from portlandite even though the mixed Ca(OH) 2 -Na 2 SO 4 solution was present. A severe degradation occurred under the electrical field and low-pH liquid media (pure water, Na 2 SO 4 -MgSO 4 solutions). The Ca/Si ratio significantly decreased from 1.34 to 0.82 under the coupling effect of the electrical field and Na 2 SO 4 -MgSO 4 solutions. Based on the fractal dimension results derived from NAD and TEM, the variations of pore structure and C S H gel morphology were quantitatively characterized. The coupled electrical field and low-pH liquid media dramatically altered the microstructure of hydration products, resulting in coarser pore networks and a shift to the disordered C S H gel. [ABSTRACT FROM AUTHOR]

IL-9 is a proinflammatory cytokine that plays a critical role in autoimmunity and inflammatory diseases. However, its role in tumorigenesis has not been well studied. In this study, we found that IL-9 expression was significantly increased and associated with poor progression in human non-small cell lung cancer (NSCLC). Ectopic expression of IL-9 in NSCLC cells did not affect cell proliferation and apoptosis in vitro , but markedly promoted tumor growth in vivo. Immune-profile analysis showed no significant changes in the frequencies of infiltrated immune cells in the tumor site, neither in nude mice nor in immune-competent mice. However, we found that VEGF and microvessel density (MVD) were significantly increased in xenografts. IL-9 could promote cell growth and tube formation of HUVEC cells in vitro. In addition, correlation analysis implied a significant positive relationship between the density of IL-9 and VEGF, as well as MVD in human NSCLC tissues. Finally, we found that IL-9 stimulated tumor angiogenesis via STAT3 signaling. Together, our findings demonstrate a promoting role of IL-9 in lung cancer development, probably through promoting tumor angiogenesis. IL-9 thus may represent a new prognostic marker and therapeutic target for NSCLC. • IL-9 expression was increased and associated with poor progression in human NSCLC. • Ectopic expression of IL-9 repressed in vivo tumor growth of NSCLC. • IL-9 promotes tumor angiogenesis via STAT3 signaling. [ABSTRACT FROM AUTHOR]