NMAAP1 Expressed in BCG-Activated Macrophage Promotes M1 Macrophage Polarization

Qihui Liu,Xun Zhu,Yuan Tian,Xiangfeng Zhao,Haifeng Jing,Qi Xie,Peng Li,Dong Li,Dongmei Yan 한국분자세포생물학회 2015 Molecules and cells Vol.38 No.10

Macrophages are divided into two subpopulations: classically activated macrophages (M1) and alternatively activated macrophages (M2). BCG (Bacilli Calmette-Guérin) activates disabled naïve macrophages to M1 macrophages, which act as inflammatory, microbicidal and tumoricidal cells through cell-cell contact and/or the release of soluble factors. Various transcription factors and signaling pathways are involved in the regulation of macrophage activation and polarization. We discovered that BCG-activated macrophages (BAM) expressed a new molecule, and we named it Novel Macrophage Activated Associated Protein 1 (NMAAP1). 1 The current study found that the overexpression of NMAAP1 in macrophages results in M1 polarization with increased expression levels of M1 genes, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), Interleukin 6 (IL-6), Interleukin 12 (IL-12), Monocyte chemoattractant protein-1 (MCP-1) and Interleukin-1 beta (IL-1β), and decreased expression of some M2 genes, such as Kruppel-like factor 4 (KLF4) and suppressor of cytokine signaling 1 (SOCS1), but not other M2 genes, including arginase-1 (Arg-1), Interleukin (IL-10), transforming growth factor beta (TGF-β) and found in inflammatory zone 1 (Fizz1). Moreover, NMAAP1 overexpression in the RAW264.7 cell line increased cytotoxicity against MCA207 tumor cells, which depends on increased inflammatory cytokines rather than cell-cell contact. NMAAP1 also substantially enhanced the phagocytic ability of macrophages, which implies that NMAAP1 promoted macrophage adhesive and clearance activities. Our results indicate that NMAAP1 is an essential molecule that modulates macrophages phenotype and plays an important role in macrophage tumoricidal functions.

STABILITY OF RICCI FLOWS BASED ON KILLING CONDITIONS

Zhao, Peibiao,Cai, Qihui Korean Mathematical Society 2009 대한수학회지 Vol.46 No.6

C. Guenther studied the stability of DeTurck flows by using maximal regularity theory and center manifolds, but these arguments can not solve the stability of Ricci flows because the Ricci flow equation is not strictly parabolic. Recognizing this deficiency, the present paper considers and obtains the stability of Ricci flows, and of quasi-Ricci flows in view of some Killing conditions.

A Novel Accessory Molecule Trim59 Involved in Cytotoxicity of BCG-Activated Macrophages

Xiangfeng Zhao,Dongmei Yan,Qihui Liu,Baiqiu Du,Peng Li,Qu Cui,Xiao Han,Bairong Du,Xun Zhu 한국분자세포생물학회 2012 Molecules and cells Vol.34 No.3

BCG-activated macrophages (BAM) could kill the tumor cells through cell-cell contact. In this process membrane proteins play an important role. However, up to date, few membrane proteins were revealed. In this study, we se-lected a surface molecule named Trim59, which was spe-cifically expressed on BAM membrane (compared with the negative control). We cloned and prokaryoticly expressed the extracellular domain of Trim59, purified the recombinant protein and generated polyclonal antibodies. Immunohistochemistry showed that Trim59 abundantly expressed in spleen, stomach and ovary; intermediately expressed in brain, lung, kidney, muscle and intestine; but not in thymus, liver, heart, uterus. Using the antibodies to block Trim59 on BAM significantly reduced BAM cyto-toxicity against MCA207 cells. This demonstrated that Trim59 serves as an indispensable molecule in maintaining BAM activity. Overexpression of Trim59 in Raw264.7 cell line failed to lyse target MCA207 cells, which potentiated Trim59 per se could not enhance macrophage cytotoxicity; on another hand, overexpression of Trim59 enhance the pinocytosis and Phagocytosis activity of Raw-264.7, which imply Trim59 might mediate the cell-molecule interaction. Our results indicate Trim59 might be an essential accessory molecule in mediating BAM tumoricidal functions; and Trim59 is a phagocytosis-correlated molecule.

Stability of Ricci flows based on Killing conditions

Peibiao Zhao,Qihui Cai 대한수학회 2009 대한수학회지 Vol.46 No.6

C. Guenther studied the stability of DeTurck flows by using maximal regularity theory and center manifolds, but these arguments can not solve the stability of Ricci flows because the Ricci flow equation is not strictly parabolic. Recognizing this deficiency, the present paper considers and obtains the stability of Ricci flows, and of quasi-Ricci flows in view of some Killing conditions. C. Guenther studied the stability of DeTurck flows by using maximal regularity theory and center manifolds, but these arguments can not solve the stability of Ricci flows because the Ricci flow equation is not strictly parabolic. Recognizing this deficiency, the present paper considers and obtains the stability of Ricci flows, and of quasi-Ricci flows in view of some Killing conditions.

NMAAP1 Expressed in BCG-Activated Macrophage Promotes M1 Macrophage Polarization

Liu, Qihui,Tian, Yuan,Zhao, Xiangfeng,Jing, Haifeng,Xie, Qi,Li, Peng,Li, Dong,Yan, Dongmei,Zhu, Xun Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.10

Macrophages are divided into two subpopulations: classically activated macrophages (M1) and alternatively activated macrophages (M2). BCG (Bacilli Calmette-$Gu{\acute{e}}rin$) activates disabled $na{\ddot{i}}ve$ macrophages to M1 macrophages, which act as inflammatory, microbicidal and tumoricidal cells through cell-cell contact and/or the release of soluble factors. Various transcription factors and signaling pathways are involved in the regulation of macrophage activation and polarization. We discovered that BCG-activated macrophages (BAM) expressed a new molecule, and we named it Novel Macrophage Activated Associated Protein 1 (NMAAP1). 1 The current study found that the overexpression of NMAAP1 in macrophages results in M1 polarization with increased expression levels of M1 genes, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-${\alpha}$), Interleukin 6 (IL-6), Interleukin 12 (IL-12), Monocyte chemoattractant protein-1 (MCP-1) and Interleukin-1 beta (IL-$1{\beta}$), and decreased expression of some M2 genes, such as Kruppel-like factor 4 (KLF4) and suppressor of cytokine signaling 1 (SOCS1), but not other M2 genes, including arginase-1 (Arg-1), Interleukin (IL-10), transforming growth factor beta (TGF-${\beta}$) and found in inflammatory zone 1 (Fizz1). Moreover, NMAAP1 overexpression in the RAW264.7 cell line increased cytotoxicity against MCA207 tumor cells, which depends on increased inflammatory cytokines rather than cell-cell contact. NMAAP1 also substantially enhanced the phagocytic ability of macrophages, which implies that NMAAP1 promoted macrophage adhesive and clearance activities. Our results indicate that NMAAP1 is an essential molecule that modulates macrophages phenotype and plays an important role in macrophage tumoricidal functions.

Irreversible phase transition characteristic of 0.91Pb(Zn1/3Nb2/3) O3-0.09PbTiO3 single crystals by domain observation

Rongfeng Zhu,Qihui Zhang,Bijun Fang,Jianning Ding,Xiangyong Zhao,Haosu Luo 한국물리학회 2016 Current Applied Physics Vol.16 No.12

In situ temperature dependent ferroelectric domains dynamic evolution of the (001)pc oriented 0.91Pb(Zn1/3Nb2/3)O3-0.09PbTiO3 (PZNT91/9) single crystals was observed by polarized light microscopy (PLM) and real time synchrotron-radiation (SR) X-ray white-beam topography. Intricate domain structures including monoclinic phase are distinguished by PLM at room temperature, and irreversible domain configuration dynamic evolution upon thermal cycling is observed by both methods. Such irreversible domain evolution combined with coexistence of multi-phases and polarization rotation may be related to the extraordinary piezoelectric performance in the ferroelectric single crystals with the morphotropic phase boundary (MPB) compositions.

Silencing MR-1 attenuates atherosclerosis in ApoE^-/- mice induced by angiotensin II through FAK-Akt -mTOR-NF-kappaB signaling pathway

Chen, Yixi,Cao, Jianping,Zhao, Qihui,Luo, Haiyong,Wang, Yiguang,Dai, Wenjian The Korean Society of Pharmacology 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.2

Myofibrillogenesis regulator-1 (MR-1) is a novel protein involved in cellular proliferation, migration, inflammatory reaction and signal transduction. However, little information is available on the relationship between MR-1 expression and the progression of atherosclerosis. Here we report atheroprotective effects of silencing MR-1 in a model of Ang II-accelerated atherosclerosis, characterized by suppression focal adhesion kinase (FAK) and nuclear factor kappaB ($NF-{\kappa}B$) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the siRNA-MR-1 substantially attenuated Ang II-accelerated atherosclerosis with stabilization of atherosclerotic plaques and inhibited FAK, Akt, mammalian target of rapamycin (mTOR) and NF-kB activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in Ang II-treated vascular smooth muscle cells (VSMCs) and macrophages: siRNA-MR-1 inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of Ang II and highlight actions of silencing MR-1 to inhibit Ang II signaling, which is atheroprotective.

Silencing MR-1 attenuates atherosclerosis in ApoE–/– mice induced by angiotensin II through FAK-Akt –mTOR-NF-kappaB signaling pathway

Yixi Chen,Jianping Cao,Qihui Zhao,Haiyong Luo,Yiguang Wang,Wenjian Dai 대한생리학회-대한약리학회 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.2

Myofibrillogenesis regulator-1 (MR-1) is a novel protein involved in cellular proliferation, migration, inflammatory reaction and signal transduction. However,little information is available on the relationship between MR-1 expression and the progression of atherosclerosis. Here we report atheroprotective effects of silencing MR-1 in a model of Ang II-accelerated atherosclerosis, characterized by suppression focal adhesion kinase (FAK) and nuclear factor kappaB (NF-κB) signaling pathway,and atherosclerotic lesion macrophage content. In this model, administration of the siRNA-MR-1 substantially attenuated Ang II-accelerated atherosclerosis with stabilization of atherosclerotic plaques and inhibited FAK, Akt, mammalian target of rapamycin (mTOR) and NF-kB activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in Ang II-treated vascular smooth muscle cells (VSMCs) and macrophages: siRNA-MR-1 inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of Ang II and highlight actions of silencing MR-1 to inhibit Ang II signaling, which is atheroprotective.

The roles of interleukin-17A in risk stratification and prognosis of patients with sepsis-associated acute kidney injury

Heng Jin,Wei Wei,Yibo Zhao,Ai Ma,Keke Sun,Xiaoxi Lin,Qihui Liu,Songtao Shou,Yan Zhang 대한신장학회 2023 Kidney Research and Clinical Practice Vol.42 No.6

Background: The aim of this study was to evaluate the roles of interleukin (IL)-17A in risk stratification and prognosis of patients with sepsis-associated acute kidney injury (SAKI). Methods: We enrolled 146 sepsis patients (84 non-SAKI and 62 SAKI patients) admitted to the emergency department from November 2020 to November 2021. Patients with SAKI were differentiated based on the severity of acute kidney injury. All clinical parameters were evaluated upon admission before administering antibiotic treatment. Inflammatory cytokines were assessed using flow cytometry and the Pylon 3D automated immunoassay system (ET Healthcare). In addition, a receiver operating characteristic (ROC) curve was utilized to determine the prognostic values of IL-17A in SAKI. Results: The levels of creatinine, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor alpha, C-reactive protein, and procalcitonin (PCT) were significantly higher in the SAKI group than in the non-SAKI group (p < 0.05). The level of IL-17A revealed significant differences among stages 1, 2, and 3 in SAKI patients (p < 0.05). The mean levels of PCT, IL-4, and IL-17A were significantly higher in the non-survival group than in the survival group in SAKI patients (p < 0.05). In addition, the area under the ROC curve of IL-17A was 0.811. Moreover, the IL-17A cutoff for differentiating survivors from non-survivors was 4.7 pg/mL, of which the sensitivity and specificity were 77.4% and 71.0%, respectively. Conclusion: Elevated levels of IL-17A could predict that SAKI patients are significantly prone to worsening kidney injury with higher mortality. The usefulness of IL-17A in treating SAKI requires further research.

A Hydrogel-based First-Aid Tissue Adhesive with Effective Hemostasis and Anti-bacteria for Trauma Emergency Management

Dongjie Zhang,Li Mei,Yuanping Hao,Bingcheng Yi,Jilin Hu,Danyang Wang,Yaodong Zhao,Zhe Wang,Hailin Huang,Yongzhi Xu,Xuyang Deng,Cong Li,Xuewei Li,Qihui Zhou,Yun Lu 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background Clinical tissue adhesives remain some critical drawbacks for managing emergency injuries, such as inadequate adhesive strength and insufficient anti-infection ability. Herein, a novel, self-healing, and antibacterial carboxymethyl chitosan/polyaldehyde dextran (CMCS/PD) hydrogel is designed as the first-aid tissue adhesive for effective trauma emergency management. Methods We examined the gel-forming time, porosity, self-healing, antibacterial properties, cytotoxicity, adhesive strength, and hemocompatibility. Liver hemorrhage, tail severance, and skin wound infection models of rats are constructed in vivo, respectively. Results Results demonstrate that the CMCS/PD hydrogel has the rapid gel-forming (~ 5 s), good self-healing, and effective antibacterial abilities, and could adhere to tissue firmly (adhesive strength of ~ 10 kPa and burst pressure of 327.5 mmHg) with excellent hemocompatibility and cytocompatibility. This suggests the great prospect of CMCS/ PD hydrogel in acting as a first-aid tissue adhesive for trauma emergency management. The CMCS/PD hydrogel is observed to not only achieve rapid hemostasis for curing liver hemorrhage and tail severance in comparison to commercial hemostatic gel (Surgiflo ®) but also exhibit superior anti-infection for treating acute skin trauma compared with clinical disinfectant gel (Prontosan ®). Conclusions Overall, the CMCS/PD hydrogel offers a promising candidate for first-aid tissue adhesives to manage the trauma emergency. Because of the rapid gel-forming time, it could also be applied as a liquid first-aid bandage for mini-invasive surgical treatment.