Myeloid IL4R? in Cardiovascular Remodeling

Cardiovascular disease is the leading cause of death, and understanding the pathophysiological changes that occur in response to injury is important for identifying novel drug targets and developing improved therapeutics. The process of cardiovascular remodeling, which occurs after injury and includes structural and functional changes has been identified as a target for therapeutic intervention. Reprogramming macrophages towards a reparative phenotype in cardiovascular remodeling is a potential therapeutic approach. Interleukin-4 receptor (IL4R) signaling is an inducer of alternatively activated macrophages (AAM or M2), and M2 macrophages are critically involved in inflammation resolution, tissue repair and pathological development of fibrosis. IL-4 administration can be beneficial, but the important IL-4 responsive cell types mediating the protection have not been identified. We hypothesized that macrophages are the critical target cell type of IL-4, and macrophage IL4R signaling plays an important role in cardiovascular remodeling by controlling macrophage polarization. In order to test this hypothesis, we generated myeloid (macrophage/monocyte and neutrophil)-specific IL-4 receptor α knockout (MyIL4RαKO) mice. Bone marrow derived macrophages from MyIL4RαKO mice showed a significantly blunted response to the M2 macrophage stimulus IL-4 and a markedly augmented response to the M1 macrophage stimulus LPS, indicating the importance of IL4Rα signaling in macrophage polarization in vitro. In addition, significant decreases of M2 macrophage markers at basal levels were shown in the heart suggesting that endogenous IL4R is required for appropriate macrophage polarization of resident cardiac macrophages. In cardiac remodeling post myocardial infarction (MI), the infarct size of MyIL4RαKO mice at 1 week post-MI was significantly smaller than that of control mice and infarct thickness at 3 weeks was significantly increased, indicating the involvement of myeloid IL4Rα signaling in cardiac remodeling post-MI. No changes in collage deposition were detected within the infarct, but there was evidence of an important role for endogenous cytokine action at the myeloid IL-4R since there was greater cardiac dysfunction in MyIL4RαKO mice. Surprisingly, IL4Rα knockout in myeloid cells did not change the percentage or number of M2 macrophages in infarct tissues post-MI. This does not support the hypothesis that IL4Rα signaling mediates cardiac remodeling via its control of macrophage polarization, but rather that the effect on myeloid phenotype is considerably subtler. In angiotensin II and high salt-induced hypertensive cardiovascular injury, cardiac and vascular fibrosis was substantially decreased in MyIL4RαKO mice. This corresponded to significant changes in fibrosis-related signaling pathways including TGFβ, Gal3 and BMP9 signaling. MyIL4RαKO mice also showed significantly increased mRNA expression of reactive oxygen species (ROS) generation related genes. This suggests that myeloid IL4Rα signaling significantly alters cardiovascular remodeling post hypertensive injury by regulating collagen accumulation and ROS generation. Similar to what we found in the MI model, ablation of IL4Rα in myeloid cells did not induce changes in the polarization of M2 macrophages in the heart and aorta during hypertensive injury. This suggests that the changes in cardiovascular remodeling may not be attributed to a simple alteration in global macrophage polarization. In conclusion, results from both injury models suggest that myeloid cells are critical targets of endogenous IL4Rα signaling, and myeloid IL4Rα signaling is very important in modulating cardiovascular remodeling post injury. However, the mechanism by which myeloid IL4Rα signaling regulates cardiovascular remodeling is not simply through a global change in M2 macrophage polarization in vivo, and the exact mechanism needs to be determined further.PHDCell and Developmental BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/144197/1/jruisong_1.pd

Comparison of serum apolipoprotein A-I between Chinese multiple sclerosis and other related autoimmune disease

<p>Abstract</p> <p>Background</p> <p>Serum apolipoprotein (apo) A-I was considered to be an immune regulator and could suppress pro-inflammatory cytokines generated by activated T cell in some autoimmune diseases. However, the change of serum apoA-I levels in multiple sclerosis (MS) patients is unknown.</p> <p>Methods</p> <p>In the presentation we performed a study on serum apoA-I levels in the patients with MS. We enrolled some age and gender matched patients with MS, autoimmune demyelinating diseases (Guillain-Barre Syndrome and Clinically Isolated Syndrome), neuroinflammatory diseases (viral encephalitis), autoimmune connective diseases (rheumatoid arthritis and systemic lupus erythematosus) and healthy control groups, and tested their serum lipids levels: total cholesterol (TC), triglyceride (TG), high-density lipoproteins (HDL), apolipoproteinB100 (apoB100), apolipoproteinA-I (apoA-I).</p> <p>Results</p> <p>For all patients, age had no effect on serum apoA-I levels (<it>P </it>> 0.05). Meanwhile, we proved the highest serum apoA-I levels in MS patients and the lowest serum apoA-I levels in SLE patients. Serum apoA-I levels was significantly elevated in female MS patients (P = 0.033; P < 0.05).</p> <p>Conclusion</p> <p>In short we believed that patients with MS and other autoimmune demyelination had significantly decreased serum levels of apo A-I.</p

Increased p38-MAPK is responsible for chemotherapy resistance in human gastric cancer cells

<p>Abstract</p> <p>Background</p> <p>Chemoresistance is one of the main obstacles to successful cancer therapy and is frequently associated with Multidrug resistance (MDR). Many different mechanisms have been suggested to explain the development of an MDR phenotype in cancer cells. One of the most studied mechanisms is the overexpression of P-glycoprotein (P-gp), which is a product of the <it>MDR1 </it>gene. Tumor cells often acquire the drug-resistance phenotype due to upregulation of the <it>MDR1 </it>gene. Overexpression of <it>MDR1 </it>gene has often been reported in primary gastric adenocarcinoma.</p> <p>Methods</p> <p>This study investigated the role of p38-MAPK signal pathway in vincristine-resistant SGC7901/VCR cells. P-gp and MDR1 RNA were detected by Western blot analysis and RT-PCR amplification. Mitgen-activated protein kinases and function of P-gp were demonstrated by Western blot and FACS Aria cytometer analysis. Ap-1 activity and cell apoptosis were detected by Dual-Luciferase Reporter Assay and annexin V-PI dual staining.</p> <p>Results</p> <p>The vincristine-resistant SGC7901/VCR cells with increased expression of the multidrug-resistance 1 (<it>MDR1</it>) gene were resistant to P-gp-related drug and P-gp-unrelated drugs. Constitutive increases of phosphorylated p38-MAPK and AP-1 activities were also found in the drug-resistant cells. Inhibition of p38-MAPK by SB202190 reduced activator protein-1 (AP-1) activity and <it>MDR1 </it>expression levels and increased the sensitivity of SGC7901/VCR cells to chemotherapy.</p> <p>Conclusion</p> <p>Activation of the p38-MAPK pathway might be responsible for the modulation of P-glycoprotein-mediated and P-glycoprotein-unmediated multidrug resistance in the SGC7901/VCR cell line.</p

Is elevated SUA associated with a worse outcome in young Chinese patients with acute cerebral ischemic stroke?

<p>Abstract</p> <p>Background</p> <p>Elevated serum uric acid (SUA) levels can enhance its antioxidant prosperities and reduce the occurrence of cerebral infarction. Significantly elevated SUA levels have been associated with a better prognosis in patients with cerebral infarction; however, the results from some studies on the relationship between SUA and the prognosis of patients with cerebral infarction remain controversial.</p> <p>Methods</p> <p>We analyzed the relationship between SUA and clinical prognosis of 585 young Chinese adults with acute ischemic stroke as determined by the modified Rankin Scale at discharge. Using multivariate logistic regression modeling, we explore the relationship between SUA levels and patient's clinical prognosis.</p> <p>Results</p> <p>Lower SUA levels at time of admission were observed more frequently in the lowest quintile for patients with severe stroke (P = 0.02). Patients with cerebral infarction patients caused by small-vessel blockage had higher SUA concentrations (P = 0.01) and the lower mRS scores (P < 0.01) were observed in, while the lowest SUA concentrations and the highest mRS scores were seen in patients with cardiogenic cerebral infarction patients. Logistic regression analysis adjusted for confounders confirmed the following independent predictors for young cerebral infarction: uric acid (-0.003: 95%CI 0.994 to 0.999) and platelet (0.004, 95%CI 0.993 to 0.996).</p> <p>Conclusion</p> <p>Elevated SUA is an independent predictor for good clinical outcome of acute cerebral infarction among young adults.</p

Thermal analysis and effects study of evaporator exit vapor quality in a separate heat pipe

© 2020 Elsevier Ltd A separate heat pipe is a kind of wickless heat pipe in which flow boiling occurs in the evaporator and flow condensation occurs in condenser. The evaporator and condenser can be installed in different places. Working fluid circulates in the heat pipe due to static pressure difference between the evaporator and condenser. The separate heat pipe is a high efficiency heat transfer device which can transport heat for a long distance without considerable losses. It is becoming more and more widely used in various fields, such as heat recovery, solar energy collection, air conditioning, passive cooling and so on. In the present study, a numerical model for a separate heat pipe is established and verified with experimental results. Reasonable agreement with MAE of 3.94% between the model and experimental data is obtained. Further studies depict that vapor quality at evaporator exit varies from 0.1 to 1 and shows great self-adjustment ability under different working conditions. Due to the self-adjustment, the separate heat pipe can maintain its heat transfer performance in the charge range of 0.55 m–1.35 m. And this range is strongly affected by both vapor quality at evaporator exit and liquid column height in the downcomer

Type and Sources of Salt Efflorescence in Painted Stone Carvings from Pujiang Museum, Sichuan, China

Painted stone carvings from Pujiang Museum in Chengdu were excavated from the Ming tombs near to Chengdu Metro Line 7. The Ming burial sites were the eunuch graves of the Shu King, and their tomb was constructed mostly of stone and decorated with paintings and carvings on its surface, which are of great value. However, during their burial, these painted stone carvings suffered significant salt damage. In this research, we performed optical microscope (OM) analysis, Raman spectra (RAM), ion chromatography (IC) analysis, X-ray fluorescence spectroscopy (XRF), X-ray powder diffraction (XRD), and petrographic microscopy (PM) to clarify the salt composition and influence. According to the results, the majority of the salt on the painted layer is CaSO4·2H2O. Before excavation, interaction between acid rain, soil, and groundwater created salt efflorescence on the paint layer’s surface. The deterioration of the paint layer caused by gypsum was divided into two stages: before excavation and during in situ preservation. This research provides a foundation for the removal and prevention of salt efflorescence

Type and Sources of Salt Efflorescence in Painted Stone Carvings from Pujiang Museum, Sichuan, China

Painted stone carvings from Pujiang Museum in Chengdu were excavated from the Ming tombs near to Chengdu Metro Line 7. The Ming burial sites were the eunuch graves of the Shu King, and their tomb was constructed mostly of stone and decorated with paintings and carvings on its surface, which are of great value. However, during their burial, these painted stone carvings suffered significant salt damage. In this research, we performed optical microscope (OM) analysis, Raman spectra (RAM), ion chromatography (IC) analysis, X-ray fluorescence spectroscopy (XRF), X-ray powder diffraction (XRD), and petrographic microscopy (PM) to clarify the salt composition and influence. According to the results, the majority of the salt on the painted layer is CaSO4&middot;2H2O. Before excavation, interaction between acid rain, soil, and groundwater created salt efflorescence on the paint layer&rsquo;s surface. The deterioration of the paint layer caused by gypsum was divided into two stages: before excavation and during in situ preservation. This research provides a foundation for the removal and prevention of salt efflorescence