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• Spinal glia attribute to the development and maintenance of burn-induced pain. • Microglia p38-TNF signaling is crucial in the early-phase of burn-induced pain. • Astrocyte JNK-CXCL1 signaling attributes to the late-phase of burn-induced pain. • Spinal microglia-derived TNF is a critical mediator in burn-induced astrogliosis. Burn injury-induced pain (BIP) is an extremely complicated condition usually resistant to analgesic drugs, while its pathogenesis remains unknown. Considerable attention has been attracted to elucidate the glial mechanisms in chronic pain. In this study, we initiatively used a mouse model of second‐degree BIP to investigate the underlying non-neuronal mechanisms at the spinal cord level. Our behavioral results showed that hind-paw burn injury caused persistent allodynia and hyperalgesia for 2 weeks in mice. Further studies revealed that both microglia and astrocytes activated in a spatially- and temporally-dependent manner in spinal cord after burn injury. In addition, the phosphorylated p38 mitogen-activated protein kinase (MAPK)-mediated tumor necrosis factor (TNF) release in spinal microglia is essentially attributed to the early stage of BIP, while the c-Jun N-terminal kinase (JNK) MAPK-dependent chemokine CXCL1 expression is mainly involved in the maintenance of pain hypersensitivity. Most strikingly, burn injury-induced pain symptoms and the activation of astrocytes were significantly suppressed by TNF inhibitor Thalidomide. On the contrary, intrathecal injection of TNF caused apparent pain hypersensitivity, accompanied by the activation of astrocytes and the upregulation of CXCL1 via the JNK MAPK signaling pathway, indicating that TNF is the key cytokine in the interaction between microglia and astrocytes at the spinal level. Moreover, treatment with the CXCR2 receptor antagonist SB225002 to block the biological activities of CXCL1 significantly attenuated the mechanical allodynia and thermal hyperalgesia in this BIP model. Taken together, this study indicates that intervention of glial pathways provides a new perspective in the management of BIP. [ABSTRACT FROM AUTHOR]

Clinical evidence has shown an elevated myocardial infarction (MI) risk after PM2.5 (particulate matter < 2.5 μm) exposure. Incident MI may result from rupture of vulnerable plaques. To test whether PM2.5 could promote plaque vulnerability, we exposed PM2.5 to apoe-/- mice by intranasal instillation. We detected the lipid, collagen, macrophage and smooth muscle cells (SMCs) content, and fibrous cap thickness to evaluate the plaque vulnerability. Plaques in HFD-fed mice with PM2.5 treatment for 24 weeks had increased lipid content and macrophage recruitment, and reduced collagen content, fibrous cap thickness and SMCs infiltration. Besides, 4-week exposure to PM2.5 could reduce the fibrous cap thickness, collagen content, but increase the macrophage infiltration and SMCs loss in a rapid atherosclerosis model. In existing plaques, PM2.5 could also decrease the fibrous cap thickness, collagen content. In RAW264.7, PM2.5 could promote the transformation of macrophage into foam cells. The expression of TLR4/MyD88/NFκB and CD36 were upregulated by PM2.5 treatment. Besides, the expression of CD36 promoted by PM2.5 was downregulated by the TLR4 inhibitor or MyD88/NFκB SiRNA. In conclusion, our data indicated that short- and long-term PM2.5 exposure increased plaque vulnerability. The underlying mechanism might be the PM2.5-enhanced formation of foam cells via TLR4/MyD88/NFκB pathway. • Exposure to PM2.5 promotes development of atherosclerosis. • Both short- and long-term exposure to PM2.5 could increase plaque vulnerability in mice. • In existing plaques, PM2.5 could also increase plaque vulnerability regardless of diet. • PM2.5 promotes the formation of foam cells via TLR4/MyD88/NFκB pathway. [ABSTRACT FROM AUTHOR]

Abstract: A hybrid organic–inorganic material based on vermiculite was prepared to remove diethyl phthalate (DEP) from aqueous solution. Natural vermiculite was activated with HCl to improve the specific surface area and was then modified by silanization using trimethylchlorosilane. Organovermiculite prepared by ion exchange with hexadecyl trimethylammonium bromide (HDTMAB) was also tested for comparison. The leaching of 2molL−1 HCl at 80°C increased the specific surface area of vermiculite from 14.4 to 500.0m2 g−1, and the average pore-diameter was decreased from 7.90nm to 2.75nm. Fourier transform infrared spectroscopy (FTIR) spectra indicated that trimethysilyl groups were grafted covalently on the surface of acid vermiculites. The specific surface area of trimethylchlorosilane-modified acid vermiculites (TMAVs) (355.4m2 g−1) was much larger than that of organovermiculite (6.0m2 g−1). The isotherm adsorption experiments of DEP showed that TMAVs exhibited linear isotherms, suggesting that the uptake of DEP was controlled by partitioning mechanism. The maximal partition coefficient (Kd ) of TMAVs was 3.1 times higher than that of organovermiculite, implying that TMAVs had stronger organic affinity than organovermiculite. The results demonstrate that the adsorption capacity and mechanism of organoclays were controlled by the specific surface area and organic loading, whereas the length of alkyl chain of organic modifier was not the key factor. [Copyright &y& Elsevier]

Abstract: The symmetry operator Q = Y 2 is introduced to re-describe the Heisenberg spin triangles in the {V6} molecule, where Y stands for the Yangian operator which can be viewed as special form of Dzyaloshinsky–Moriya (DM) interaction for spin 1/2 systems. Suppose a parallelogram Heisenberg model that is comprised of four -spins commutes with Q, which mean that it possesses Yangian symmetry, we show that the ground state of the Hamiltonian H 4 for the model allows to take the total spin S =1 by choosing some suitable exchange constants in H 4. In analogy to the molecule {V6} where the two triangles interact through Yangian operator we then give the magnetization for the theoretical molecule “{V8}” model which is comprised of two parallelograms. Following the example of molecule {V15}, we give another theoretical molecule model regarding the four -spins system with total spin S =1 and predict the local moments to be , respectively. [Copyright &y& Elsevier]

Background: Elucidating the underlying mechanisms and developing protective strategies for the pathophysiological consequences of cardiopulmonary bypass (CPB) have been hampered due to the absence of a satisfactory long-term recovery animal model. The objective of this study was to establish a survival experimental model of CPB in rats to meet the requirement of these studies. Materials and methods: Male SD rats (450–550 g) were randomly divided into CPB (n = 10) group and Sham group (n = 10). All rats were anaesthetized and mechanically ventilated. The femoral artery and vein were cannulated for continuous blood pressure recordings and fluid replacement, respectively. The CPB circuit comprised a venous reservoir, a membrane oxygenator, and a roller pump. Blood was drained from the right atrium via a jugular vein catheter and returned to the right carotid artery. Priming consisted of 8 ml of homologous blood and 8 ml of colloid. CPB was conducted for 60 min at a flow rate of 100–150 ml/kg/min in the CPB group. Haemodynamic investigations, blood gas analysis, and survival studies were performed subsequently. Results: Our data show that the rat model principally simulated the clinical setting of CPB in terms of its construction, configuration, performance, material surface area, and priming volume to blood volume ratio. All CPB rats survived and the 2-week follow-up period remained uneventful. Conclusions: The rat model of CPB was easy to establish and was associated with excellent survival. This model should facilitate the investigation of the pathophysiological processes concerning CPB-related multiple organ dysfunction and possible protective interventions. [Copyright &y& Elsevier]

• Blocking JAK2/STAT3 signaling attenuates IL-6-inhibited neurogenesis of NSCs. • JAK2/STAT3 pathway regulates IL-6-induced TET3 and DNMT1 expression in NSCs. • NeuroD1 was regulated by TET3 and DNMT1 in JAK2/STAT3-dependent manner. • JAK2/STAT3 pathway mediates the expressions of TET3 and DNMT1 in APP/PS1 mice. • JAK2/STAT3 inhibition alleviates memory deficits in APP/PS1 mice. Neuroinflammation, considered as a pathological hallmark of Alzheimer's disease (AD), has been demonstrated to affect hippocampal neurogenesis and cognitive function. Interleukin-6 (IL-6) is a proinflammatory cytokine known to modulate neurogenesis. However, the mechanisms are still largely unknown. Here, we reported that IL-6 suppressed neurogenesis via a JAK2/STAT3 signaling in neural stem cells (NSCs). Importantly, we found that NeuroD1 (Neurogenic differentiation 1) gene expression, which drives NSCs neurodifferentiation, was regulated by TET3 and DNMT1 in a JAK2/STAT3-dependent manner. We further found that JAK2/STAT3 inhibition enhanced demethylation of NeuroD1 regulatory elements in IL-6-treated cells, which is related to the significant upregulation of TET3 expression as well as the decreased expression of DNMT1. Furthermore, Inhibiting JAK2/STAT3 significantly rescued the memory deficits and hippocampal neurogenesis dysfunction in APP/PS1 mice. Our data suggest that JAK2/STAT3 signaling plays a vital role in suppressing neurogenesis of NSCs exposed to IL-6 at the epigenetic level, by regulating DNA methylation/demethylation. [ABSTRACT FROM AUTHOR]

During mouse development, part of the cells derived from the second heart field (SHF) progenitors contributes to the elongation and enlargement of the outflow tract (OFT) that subsequently septates into the trunks of aorta (Ao) and pulmonary artery (PA). Thus, the cardiac progenitor-originated cells are distributed to both Ao and PA. Here, we investigated that how these cells are assigned to the two great arteries during OFT septation through lineage tracing technology. By use of the inducible Mef2c-AHF-CreERT2; Rosa2 6-mTmG reporter system, two waves of SHF progenitors and their derivatives were identified, and they made differential contribution to the Ao and PA, respectively. While the early wave of cells (at E7.5) was preferentially destined to the Ao, the second wave of cells (from E8.5 till E11.5) made its favorite path to the PA. In addition, we unveiled PDK1 as a critical regulator of the second wave of cells as deletion of Pdk1 resulted in poorly developed PA leading to pulmonary stenosis. Thus, this study provides insights into the understanding of the pre-determined cell fate of the cardiac progenitor-derived cells with preferential contribution to the Ao and PA, as well as of the pathogenesis of pulmonary stenosis. • Two waves of second heart field progenitors and their derivatives were identified. • They made differential contribution to the aorta and pulmonary artery. • The early wave preferentially destined to aorta, the second to pulmonary artery. • PDK1 is a critical regulator of the second wave of cells. • Deletion of Pdk1 caused poorly developed pulmonary artery and pulmonary stenosis. [ABSTRACT FROM AUTHOR]

Abstract Mesenchymal stem cells (MSCs) have been shown to be efficacy to attenuating cardiovascular inflammation; however, there are many limitations to stem cell treatment. Present study was to prove MSC-derived exosomes (MSC-Exos) could alleviating inflammatory cardiomyopathy by improving the inflammatory microenvironment of myocardium, especially by regulating the activity of macrophages. Mice were intraperitoneal injected of doxorubicin (DOX) to establish a dilated cardiomyopathy (DCM) model, and then received intravenous injection of either MSC-Exos or PBS as control. Mice receiving MSC-Exos showed improved cardiac function via echocardiography and attenuated cardiac dilation via HE staining, as well as reduced cardiomyocytes apoptosis. Expression levels of inflammatory factors were reduced. And there was a significant decrease of the inflammatory cells infiltration in the MSC-Exos treatment group comparing to the PBS group. Meanwhile, MSC-Exos could remarkably attenuate the pro-inflammatory macrophages amount in both blood and heart, which was proved that MSC-Exos relied on the JAK2-STAT6 pathway mediating macrophages activation. MSC-Exos improved the inflammatory microenvironment of dilated cardiomyopathy by regulating the polarization of the macrophage, which may hold promise for dilated cardiomyopathy clinical therapy. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by deposition of amyloid-β (Aβ) plaques, neurofibrillary tangles, and neuronal loss, accompanied by neuroinflammation. Neuroinflammatory processes are thought to contribute to AD pathophysiology. Metformin has been reported to have anti-inflammatory efficacy. However, whether metformin is responsible for the anti-neuroinflammation and neuroprotection on APPswe/PS1ΔE9 (APP/PS1) mice remains unclear. Here we showed that metformin attenuated spatial memory deficit, neuron loss in the hippocampus and enhanced neurogenesis in APP/PS1 mice. In addition, metformin administration decreased amyloid-β (Aβ) plaque load and chronic inflammation (activated microglia and astrocytes as well as pro-inflammatory mediators) in the hippocampus and cortex. Further study demonstrated that treatment with metformin enhanced cerebral AMPK activation. Meanwhile, metformin notably suppressed the activation of P65 NF-κB, mTOR and S6K, reduced Bace1 protein expression. Our data suggest that metformin can exert functional recovery of memory deficits and neuroprotective effect on APP/PS1 mice via triggering neurogenesis and anti-inflammation mediated by regulating AMPK/mTOR/S6K/Bace1 and AMPK/P65 NF-κB signaling pathways in the hippocampus, which may contribute to improvement in neurological deficits. [ABSTRACT FROM AUTHOR]

DEP domain containing 1 (DEPDC1) is recently reported to be overexpressed in several types of human cancer; however the role of DEPDC1 in prostate cancer remains to be investigated. Herein, we identified that the DEPDC1 mRNA and protein expression levels were dramatically increased in prostate cancer tissues and cell lines. Overexpression of DEPDC1 promoted, but depletion of DEPDC1 inhibited cell proliferation by regulating the G1-S phase cell cycle transition. Importantly, we found that DEPDC1 was essential for the tumor growth and formation of bone metastases of prostate cancer cells in vivo . Finally, we demonstrated that DEPDC1 interacted with E2F1 and increased its transcriptional activity, leading to hyper-activation of E2F signaling in prostate cancer cells. Our findings reveal an oncogenic role of DEPDC1 in prostate cancer progression via activation of E2F signaling, and suggest DEPDC1 might be a potential therapeutic target against the disease. [ABSTRACT FROM AUTHOR]

Clinical evidence has indicated an increased myocardial infarction (MI) morbidity and mortality after exposure to air pollution (particulate matter<2.5 μm, PM2.5). However, the mechanisms by which PM2.5 aggravates MI remain unknown. Present study was to explore the adverse effect of PM2.5 on myocardium after MI and the potential mechanisms. Male mice with MI surgery were treated with PM2.5 by intranasal instillation. Neonatal mice ventricular myocytes (NMVMs) subjected to hypoxia were also incubated with PM2.5 to determine the role of PM2.5 in vitro . Exposure to PM2.5 significantly impaired the cardiac function and increased the infarct size in MI mice. TUNEL assay, flow cytometry and western blotting of Caspase 3, Bax and BCl-2 indicated that PM2.5 exposure could cause cellular apoptosis in vivo and in vitro . Besides, PM2.5 activated NFκB pathway and increased gene expression of IL-1β and IL-6 in NMVMs with hypoxia, which could be effectively reversed by SN-50-induced blockade of NFκB translocation to the nucleus. In summary, air pollution induces myocardium apoptosis and then impairs cardiac function and aggravates MI via NFκB activation. [ABSTRACT FROM AUTHOR]

For the first time, a novel strategy is developed to couple photocatalytic oxidation with photocatalytic reduction to achieve one-pot conversion of rhodamine (RhB) to methanol and ethanol by using rGO/SrTi 0.95 Fe 0.05 O 3− δ photocatalyst. In the approach, RhB was photocatalytically degraded to CO 2 and water, and then the as-obtained CO 2 was converted into CH 3 OH and C 2 H 5 OH by means of photocatalytic reduction under simulated sunlight irradiation. Photocatalytic experimental results show the 1%rGO/SrTi 0.95 Fe 0.05 O 3− δ has the best photocatalytic activity among the as-prepared catalysts and the corresponding product rate of CH 3 OH and C 2 H 5 OH is 10.76 and 6.14 μmol g −1 h −1 , respectively, with a 1.53% apparent quantum efficiency. Furthermore, a photocatalytic mechanism was proposed to explain the detailed process of one-pot conversion of RhB into hydrocarbons. The present work gives a good example to combine the photodegradation of RhB with photoreduction of CO 2 and proposes a new method to simultaneously tackle the problems of environmental pollution and energy crisis. [ABSTRACT FROM AUTHOR]

Here we found that low-concentration of perifosine, an Akt inhibitor, surprisingly protected cardiomyocytes from oxygen glucose deprivation (OGD)/re-oxygenation. In H9c2 cardiomyocytes, non-cytotoxic perifosine (0.1–0.5 μM) suppressed OGD/re-oxygenation-induced reactive oxygen species (ROS) production, p53 mitochondrial translocation and cyclophilin D complexation, as well as mitochondrial membrane potential (MMP) reduction. Molecularly, perifosine activated AMP-activated kinase (AMPK) signaling to increase intracellular NADPH (nicotinamide adenine dinucleotide phosphate) content in H9c2 cells. On the other hand, AMPK inhibition by AMPKα1 shRNA-knockdown in H9c2 cells significantly reduced perifosine-induced NADPH production, and alleviated perifosine-mediated anti-oxidant and cytoprotective activities against OGD/re-oxygenation. In primary murine cardiomyocytes, perifosine similarly activated AMPK signaling, and offered significant protection against OGD/re-oxygenation, which was largely attenuated with siRNA knockdown of AMPKα1. We demonstrate an unexpected function of perifosine (low-concentration) in protecting cardiomyocytes from OGD/re-oxygenation. [ABSTRACT FROM AUTHOR]

In this study, strain-level visualized analysis of cold-stressed Vibrio parahaemolyticus based on matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass fingerprinting was investigated. All the peptide mass fingerprinting profiles obtained were analyzed by self-organized map (SOM) and cluster analysis. Our results showed that the peptide mass fingerprinting profiles of V. parahaemolyticus substantially changed under cold stress at strain level. The cold-stressed V. parahaemolyticus strains were distributed to 14 neurons by SOM classification, almost totally different from the controls. This is the first time that so many strains had been chosen to study bacterial cold stress responses, which can help promote an overall understanding to stress responses of cold-stressed strains. [ABSTRACT FROM AUTHOR]

Abstract: Syndecan-4 (synd4) is a heparan sulfate proteoglycan, involved in repair following tissue damage, through modulating neovascularization and inflammation. In acute myocardial infarction its myocardial expression is up-regulated in a time-dependent manner, and in synd4-deficient mice severe cardiac dysfunction and abnormal remodeling are observed following induction of myocardial infarction. Here we explored the therapeutic potential of sustained synd4 over-expression in the context of myocardial infarction. Adenovirus containing the synd4 gene (Ad-synd4), or corresponding control adenovirus (Ad-null), was administered intramyocardially in rats immediately after induction of myocardial infarction. Cardiac function was ascertained by echocardiography, hemodynamic assessment and brain natriuretic peptide level 28days post-intervention. Hearts were excised for molecular and histological analyses at predetermined time points. We observed reduced mortality and improved cardiac function post-myocardial infarction in the Ad-synd4 as compared to the Ad-null group, with associated attenuation of cardiac remodeling, less myocyte loss and reduced fibrosis. Additionally, the Ad-synd4 group exhibited endothelial cell activation and increased angiogenesis and arteriogenesis in the myocardium. The Ad-synd4 group also showed evidence of reduced myocardial inflammation as compared with the Ad-null group, with reduced inflammatory cell (CD45+) and myofibroblast (α-SMA+) infiltration as well as suppressed collagen III deposition and iNOS expression. Our results suggest that sustained synd4 over-expression in the myocardium is of therapeutic benefit following experimental myocardial infarction, through inducing neovascularization, suppressing tissue inflammation and fibrosis, with resultant improvements in cardiac function and remodeling. [Copyright &y& Elsevier]

Abstract: Decreased levels of circulating endothelial progenitor cells (EPCs) predict increased risk of cardiovascular events in diabetic patients. Insulin treatment exerts important cardiovascular protection. Whether and how insulin participates in the EPC regulation of postnatal neovascularization are currently unclear. We employed a mouse hindlimb ischemia model to study EPC mobilization in non-diabetic and streptozotocin-induced diabetic mice. Insulin was administered to diabetic animals postoperatively. To determine the role of EPCs contributing to postnatal vasculogenesis, we used bone marrow-transplanted mice whose bone marrow cells selectively expressed enhanced green fluorescent protein (EGFP). Insulin treatment improved EPC mobilization into peripheral blood, accelerated transcutaneous oxygen pressure restoration and increased capillary density in the ischemic limb associated with partial incorporation of EGFP-positive cells into the capillaries. Insulin treatment restored ischemia-induced release of stromal-derived growth factor 1α and vascular endothelial growth factor (VEGF), and consequently enhanced the activity of Akt and endothelial nitric oxide synthase (eNOS) as well as matrix metalloproteinase-9 in bone marrow. Insulin also augmented tissue-level activation of VEGF/Akt/eNOS pathway. However, all such effects of insulin were completely blocked by combined treatment with a NOS inhibitor. Our data suggested that insulin treatment improved ischemia-induced EPC mobilization and contributed to compensatory neovascularization in diabetic mice through a VEGF/eNOS-related pathway. [Copyright &y& Elsevier]

Abstract: Endothelial progenitor cells (EPCs) exhibit impaired function in the context of diabetes, and advanced glycation end products (AGEs), which accumulate in diabetes, may contribute to this. In the present study, we investigated the mechanism by which AGEs impair late EPC function. EPCs from human umbilical cord blood were isolated, and incubated with AGE-modified albumin (AGE-albumin) at different concentrations found physiologically in plasma. Apoptosis, migration, and tube formation assays were used to evaluate EPC function including capacity for vasculogenesis, and expression of the receptor for AGEs (RAGE), Akt, endothelial nitric oxide synthase (eNOS), and cycloxygenase-2 (COX-2) were determined. Anti-RAGE antibody was used to block RAGE function. AGE-albumin concentration-dependently enhanced apoptosis and depressed migration and tube formation, but did not affect proliferation, of late EPCs. High AGE-albumin increased RAGE mRNA and protein expression, and decreased Akt and COX-2 protein expression, whilst having no effect on eNOS mRNA or protein in these cells. These effects were inhibited by co-incubation with anti-RAGE antibody. These results suggest that RAGE mediates the AGE-induced impairment of late EPC function, through down-regulation of Akt and COX-2 in these cells. [Copyright &y& Elsevier]

Background: The relationship between elastolytic matrix metalloproteinases (MMPs) (such as MMP-2, MMP-9) and thoracic aortic dissection (TAD) has been described, but little is known regarding the role of collagenolytic MMPs in thoracic aortic dissection. The aim of this study was to determine the role of MMP-8 in acute thoracic aortic dissection. Materials and Methods: Forty-five patients affected by TAD and 40 with acute myocardial infarction (AMI) were recruited into this study. Blood samples within 72 h of the onset of symptoms were available for all the 85 patients. Healthy individuals were selected from the out-patients who complained of chest pain but in whom no cardiovascular diseases were found. Plasma levels of MMP-1, -8, -13 were measured by enzyme-linked immunosorbent assay (ELISA) technique in all subjects. Aortic tissue samples obtained during surgery were evaluated by Western blot for MMP-8 and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression. Results: Plasma MMP-8 levels in patients affected by TAD and AMI were both higher than that in healthy subjects (284.35 ± 96.32 ng/mL and 88.57 ± 26.71 ng/mL versus 75.39 ± 23.36 ng/mL). The difference of the MMP-8 level between TAD patients and healthy subjects was significant (P = 0.000). No significant differences were found in MMP-1 and MMP-13 plasma levels among the three groups. Conclusions: The acute phase of TAD is characterized by a prominent increase of MMP-8 plasma level, which may play a key role in the occurrence of TAD. MMP-8 could be involved in the acute inflammatory reaction and may be a useful marker for the diagnosis of acute TAD. [ABSTRACT FROM AUTHOR]