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1.
Jingwei Shi Xujun Song Benno Traub Michael Luxenhofer Marko Kornmann 《International journal of molecular sciences》2021,22(6)
Interleukin (IL)-4 and IL-13 are known as pleiotropic Th2 cytokines with a wide range of biological properties and functions especially in immune responses. In addition, increasing activities have also been determined in oncogenesis and tumor progression of several malignancies. It is now generally accepted that IL-4 and IL-13 can exert effects on epithelial tumor cells through corresponding receptors. Type II IL-4 receptor (IL-4Rα/IL-13Rα1), predominantly expressed in non-hematopoietic cells, is identified to be the main target for both IL-4 and IL-13 in tumors. Moreover, IL-13 can also signal by binding to the IL-13Rα2 receptor. Structural similarity due to the use of the same receptor complex generated in response to IL-4/IL-13 results in overlapping but also distinct signaling pathways and functions. The aim of this review was to summarize knowledge about IL-4 and IL-13 and their receptors in pancreatic cancer in order understand the implication of IL-4 and IL-13 and their receptors for pancreatic tumorigenesis and progression and for developing possible new diagnostic and therapeutic targets. 相似文献
2.
Dr. Elena Petit Dr. Lluís Bosch Prof. Anna M. Costa Ignacio Rodríguez-Izquierdo Dr. Daniel Sepúlveda-Crespo Prof. M. Angeles Muñoz-Fernández Prof. Jaume Vilarrasa 《ChemMedChem》2021,16(14):2217-2222
Amides from indole-3-glyoxylic acid and 4-benzoyl-2-methylpiperazine, which are related to entry inhibitors developed by Bristol-Myers Squibb (BMS), have been synthesized with aliphatic chains located at the C7 position of the indole ring. These spacers contain an azido group suitable for the well-known Cu(I)-catalyzed (3+2)-cycloaddition or an activated triple bond for the nucleophilic addition of thiols under physiological conditions. Reaction with polyols (β-cyclodextrin and hyperbranched polyglycerol) decorated with complementary click partners has afforded polyol-BMS-like conjugates that are not cytotoxic (TZM.bl cells) and retain the activity against R5-HIV-1NLAD8 isolates. Thus, potential vaginal microbicides based on entry inhibitors, which can be called of 4th generation, are reported here for the first time. 相似文献
3.
Reliable joints of Ti3SiC2 ceramic and TC11 alloy were diffusion bonded with a 50 μm thick Cu interlayer. The typical interfacial structure of the diffusion boned joint, which was dependent on the interdiffusion and chemical reactions between Al, Si and Ti atoms from the base materials and Cu interlayer, was TC11/α-Ti + β-Ti + Ti2Cu + TiCu/Ti5Si4 + TiSiCu/Cu(s, s)/Ti3SiC2. The influence of bonding temperature and time on the interfacial structure and mechanical properties of Ti3SiC2/Cu/TC11 joint was analyzed. With the increase of bonding temperature and time, the joint shear strength was gradually increased due to enhanced atomic diffusion. However, the thickness of Ti5Si4 and TiSiCu layers with high microhardness increased for a long holding time, resulting in the reduction of bonding strength. The maximum shear strength of 251 ± 6 MPa was obtained for the joint diffusion bonded at 850 °C for 60 min, and fracture primarily occurred at the diffusion layer adjacent to the Ti3SiC2 substrate. This work provided an economical and convenient solution for broadening the engineering application of Ti3SiC2 ceramic. 相似文献
4.
Yuria Jang Hong Moon Sohn Young Jong Ko Hoon Hyun Wonbong Lim 《International journal of molecular sciences》2021,22(1)
Background: Recently, it was reported that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL and was shown to compete with RANK to bind RANKL and suppress canonical RANK signaling during osteoclast differentiation. The critical role of the protein triad RANK–RANKL in osteoclastogenesis has made their binding an important target for the development of drugs against osteoporosis. In this study, point-mutations were introduced in the RANKL protein based on the crystal structure of the RANKL complex and its counterpart receptor RANK, and we investigated whether LGR4 signaling in the absence of the RANK signal could lead to the inhibition of osteoclastogenesis.; Methods: The effects of point-mutated RANKL (mRANKL-MT) on osteoclastogenesis were assessed by tartrate-resistant acid phosphatase (TRAP), resorption pit formation, quantitative real-time polymerase chain reaction (qPCR), western blot, NFATc1 nuclear translocation, micro-CT and histomorphological assay in wild type RANKL (mRANKL-WT)-induced in vitro and in vivo experimental mice model. Results: As a proof of concept, treatment with the mutant RANKL led to the stimulation of GSK-3β phosphorylation, as well as the inhibition of NFATc1 translocation, mRNA expression of TRAP and OSCAR, TRAP activity, and bone resorption, in RANKL-induced mouse models; and Conclusions: The results of our study demonstrate that the mutant RANKL can be used as a therapeutic agent for osteoporosis by inhibiting RANKL-induced osteoclastogenesis via comparative inhibition of RANKL. Moreover, the mutant RANKL was found to lack the toxic side effects of most osteoporosis treatments. 相似文献
5.
Cheng-Chin Huang Ching-Yao Yang Chin-Chuan Su Kai-Min Fang Cheng-Chieh Yen Ching-Ting Lin Jui-Min Liu Kuan-I Lee Ya-Wen Chen Shing-Hwa Liu Chun-Fa Huang 《International journal of molecular sciences》2021,22(9)
4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a major active metabolite of bisphenol A (BPA), is generated in the mammalian liver. Some studies have suggested that MBP exerts greater toxicity than BPA. However, the mechanism underlying MBP-induced pancreatic β-cell cytotoxicity remains largely unclear. This study demonstrated the cytotoxicity of MBP in pancreatic β-cells and elucidated the cellular mechanism involved in MBP-induced β-cell death. Our results showed that MBP exposure significantly reduced cell viability, caused insulin secretion dysfunction, and induced apoptotic events including increased caspase-3 activity and the expression of active forms of caspase-3/-7/-9 and PARP protein. In addition, MBP triggered endoplasmic reticulum (ER) stress, as indicated by the upregulation of GRP 78, CHOP, and cleaved caspase-12 proteins. Pretreatment with 4-phenylbutyric acid (4-PBA; a pharmacological inhibitor of ER stress) markedly reversed MBP-induced ER stress and apoptosis-related signals. Furthermore, exposure to MBP significantly induced the protein phosphorylation of JNK and AMP-activated protein kinase (AMPK)α. Pretreatment of β-cells with pharmacological inhibitors for JNK (SP600125) and AMPK (compound C), respectively, effectively abrogated the MBP-induced apoptosis-related signals. Both JNK and AMPK inhibitors also suppressed the MBP-induced activation of JNK and AMPKα and of each other. In conclusion, these findings suggest that MBP exposure exerts cytotoxicity on β-cells via the interdependent activation of JNK and AMPKα, which regulates the downstream apoptotic signaling pathway. 相似文献
6.
为探究某加氢装置高压换热器管束腐蚀泄漏原因,利用Aspen Plus工艺模拟软件计算了冷低压分离器油相(简称冷低分油)中水质量分数分别为1%,2%,3%时,冷低分油系统的露点温度、氯化铵结晶温度、氯化铵潮解点温度和相对湿度。结果表明:相较于经验的露点温度预测方法,通过引入潮解点、划分系统“湿环境”温度范围判断氯化铵垢下腐蚀风险区域的方法与实际腐蚀案例更为切合;在3种油相含水条件下,换热器管束存在氯化铵垢下腐蚀的“湿环境”温度范围分别为:50~103 ℃,50~161 ℃,50~176 ℃;随着油相中含水量的提高,“湿环境”腐蚀区域逐渐向高温部位迁移,预计铵盐导致的垢下腐蚀将会愈加严重。 相似文献
7.
Yuguang Chao Peng Zhou Jianping Lai Weiyu Zhang Huawei Yang Shiyu Lu Hui Chen Kun Yin Menggang Li Lu Tao Changshuai Shang Meiping Tong Shaojun Guo 《Advanced functional materials》2021,31(24):2100923
Designing a semiconductor-based heterostructure photocatalyst for achieving the efficient separation of photogenerated electron-hole pairs is highly important for enhancing H2 releasing photocatalysis. Here, a new class of Ni1−xCoxSe2–C/ZnIn2S4 hierarchical nanocages with abundant and compact ZnIn2S4 nanosheets/Ni1−xCoxSe2 C nanosheets 2D/2D hetero–interfaces, is designed and synthesized. The constructed heterostructure photocatalyst exposes rich hetero-junctions, supplying the broad and short transfer paths for charge carriers. The close contacts of these two kinds of nanosheets induce a strong interaction between ZnIn2S4 and Ni1−xCoxSe2 C, improving the separation and transfer of photo-generated electron-hole pairs. As a consequence, the distinctive Ni1−xCoxSe2 C/ZnIn2S4 hierarchical nanocages without using additional noble-metal cocatalysts, display remarkable H2-relaesing photocatalytic activity with a rate of 5.10 mmol g−1 h−1 under visible light irradiation, which is 6.2 and 30 times higher than those of fresh ZnIn2S4 nanosheets and bare Ni1−xCoxSe2 C nanocages, respectively. Spectroscopic characterizations and theory calculations reveal that the strong interaction between ZnIn2S4 and Ni1−xCoxSe2 C 2D/2D hetero-interfaces can powerfully promote the separation of photo-generated charge carriers and the electrons transfer from ZnIn2S4 to Ni1−xCoxSe2 C. 相似文献
8.
Asami Nishikori Yoshito Nishimura Rei Shibata Koh-ichi Ohshima Yuka Gion Tomoka Ikeda Midori Filiz Nishimura Tadashi Yoshino Yasuharu Sato 《International journal of molecular sciences》2021,22(8)
Immunoglobulin G4-related disease (IgG4-RD) is a systemic disorder characterized by tissue fibrosis and intense lymphoplasmacytic infiltration, causing progressive organ dysfunction. Activation-induced cytidine deaminase (AID), a deaminase normally expressed in activated B-cells in germinal centers, edits ribonucleotides to induce somatic hypermutation and class switching of immunoglobulin. While AID expression is strictly controlled under physiological conditions, chronic inflammation has been noted to induce its upregulation to propel oncogenesis. We examined AID expression in IgG4-related ophthalmic disease (IgG4-ROD; n = 16), marginal zone lymphoma with IgG4-positive cells (IgG4+ MZL; n = 11), and marginal zone lymphoma without IgG4-positive cells (IgG4- MZL; n = 12) of ocular adnexa using immunohistochemical staining. Immunohistochemistry revealed significantly higher AID-intensity index in IgG4-ROD and IgG4+ MZL than IgG4- MZL (p < 0.001 and = 0.001, respectively). The present results suggest that IgG4-RD has several specific causes of AID up-regulation in addition to inflammation, and AID may be a driver of oncogenesis in IgG4-ROD to IgG4+ MZL. 相似文献
9.
Qi Xiao Xinyao Dong Xiumei Yin Hong Wang Hua Zhong Mingming Xing Ying Tian Yao Fu Bin Dong Xixian Luo 《Journal of the American Ceramic Society》2021,104(3):1415-1423
Multicolor upconversion luminescence materials show significantly applications in materials science. In this paper, the novel Yb3+-sensitized Na3La(VO4)2 upconversion luminescence crystals are synthesized by the solid-state reaction method. Three primary colors upconversion luminescence are successfully achieved in Na3La(VO4)2:Yb3+,Tm3+, Na3La(VO4)2:Yb3+,Er3+, and Na3La(VO4)2:Yb3+,Ho3+ crystals excited by the single 980 nm LD. Multicolor upconversion luminescence can be obtained by simply adjusting the combination ratios of these three samples. Luminescence mechanisms of the Yb3+-sensitized system are discussed in detail. In the Na3La(VO4)2 host material, the Yb3+/Ho3+ codoped system exhibits unusual red upconversion luminescence based on the short decay time of Ho3+ ion 5I6 level, which provides the possibility of three primary color luminescence under 980 nm excitation. 相似文献
10.
《International Journal of Hydrogen Energy》2022,47(38):17056-17068
The study of steels which guarantee safety and reliability throughout their service life in hydrogen-rich environments has increased considerably in recent years. Their mechanical behavior in terms of hydrogen embrittlement is of utmost importance. This work aims to assess the effects of hydrogen on the tensile properties of quenched and tempered 42CrMo4 steels. Tensile tests were performed on smooth and notched specimens under different conditions: pre-charged in high pressure hydrogen gas, electrochemically pre-charged, and in-situ hydrogen charged in an acid aqueous medium. The influence of the charging methodology on the corresponding embrittlement indexes was assessed. The role of other test variables, such as the applied current density, the electrolyte composition, and the displacement rate was also studied. An important reduction of the strength was detected when notched specimens were subjected to in-situ charging. When the same tests were performed on smooth tensile specimens, the deformation results were reduced. This behavior is related to significant changes in the operative failure micromechanisms, from ductile (microvoids coalescence) in absence of hydrogen or under low hydrogen contents, to brittle (decohesion of martensite lath interfaces) under the most stringent conditions. 相似文献