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21.
Qing-shan Liang Jian-Gang Xie ChaoPing Yu ZhuSheng Feng JingChang Ma Yuan Zhang Dong Wang JianGuo Lu Ran Zhuang Jikai Yin 《Experimental & molecular medicine》2021,53(3):393
Splenectomy has been reported to improve liver fibrosis in patients with cirrhosis and hypersplenism. However, the mechanisms remain unclear. Tumor necrosis factor superfamily 14 (TNFSF14; also known as LIGHT) is highly expressed in the context of fibrosis and promotes disease progression in patients with fibrotic diseases such as pulmonary and skin fibrosis. Here, we determined whether splenectomy controls the production of LIGHT to improve liver fibrosis. Splenectomy reduced serum LIGHT levels in cirrhotic patients with hypersplenism and a ConA-induced liver fibrosis mouse model. Blocking LIGHT resulted in the downregulation of TGF-β1 in RAW264.7 cells. LIGHT treatment of RAW264.7 and JS1 cells in coculture regulated transforming growth factor-β1 (TGF-β1) expression through the activation of JNK signaling. Small interfering RNA-mediated silencing of lymphotoxin β receptor (LTβR) in macrophages resulted in pronounced decreases in the levels of fibrosis and αSMA in JS1 cells. These results indicated that LIGHT bound to LTβR and drove liver fibrosis in vitro. Blocking TGF-β1 abolished the effect of LIGHT in vitro. Furthermore, the administration of recombinant murine LIGHT protein-induced liver fibrosis with splenectomy, while blocking LIGHT without splenectomy improved liver fibrosis in vivo, revealing that the decrease in fibrosis following splenectomy was directly related to reduced levels of LIGHT. Thus, high levels of LIGHT derived from the spleen and hepatic macrophages activate JNK signaling and lead to increased TGF-β1 production in hepatic macrophages. Splenectomy attenuates liver fibrosis by decreasing the expression of LIGHT.Subject terms: Tumour-necrosis factors, Liver fibrosis, Hepatic stellate cells, Liver cirrhosis, Experimental models of disease 相似文献
22.
Photodissociation dynamics of the CH3 radical at 212.5 nm has been investigated using the H atom Rydberg tagging time-of-flight method with a pure CH3 radical source generated by the photolysis of CH3I at 266 nm. Time-of-flight spectra of the H atom products from the photolysis of both cold and hot methyl radicals have been measured at different photolysis polarizations. Experimental results indicate that the photodissociation of the methyl radical in its ground vibrational state at 212.5 nm excitation occurs on a very fast time scale in comparison with its rotational period, indicating the CH3 dissociation at 212.5 nm occurs on the excited 3s Rydberg state surface. Experimental evidence also shows that the photodissociation of the methyl radical in the nu2 = 1 state of the umbrella mode at 212.5 nm excitation is characteristically different from that in the ground vibrational state. 相似文献
23.
The Turán number of a k-uniform hypergraph H,denoted by exk(n;H),is the maximum number of edges in any k-uniform hypergraph F on n vertices which does not contain H as a subgraph.Let Cl~((k)) denote the family of all k-uniform minimal cycles of length l;S(?1,…,?r) denote the family of hypergraphs consisting of unions of r vertex disjoint minimal cycles of length ?1,…?r,respectively,and Cl~((k))denote a k-uniform linear ... 相似文献
24.
This paper is considering the problem of traveling wave solutions (TWS) for a susceptible-exposed-infectious-recovered (SEIR) epidemic model with discrete diffusion. The threshold condition for the existence and nonexistence of TWS is obtained. More specifically, such kind of solutions are governed by the threshold number ?0. We can find a critical wave speed c? if ?0 > 1, by employing the Schauder's fixed point theorem, limiting argument and two-sided Laplace transform, we confirm that there exists TWS for c > c?, while there exists no TWS for c < c?. We also obtain the nonexistence of TWS for ?0 ≤ 1. At last, we give some biological explanations from the epidemiological perspective. 相似文献
25.
Jin Yi Xu Qian Ran Wei Yi Hua Xiao Ming Wu Qiu Juan Wang Jing Zhang 《中国化学快报》2007,18(3):251-254
A series of 2-alkylbenzimidazole derivatives 9a-n have been designed and synthesized as a novel class of non-peptide angiotensin Ⅱ AT1 receptor antagonists. The synthesized compounds were evaluated for their antagonism of angiotensin Ⅱ, induced contraction in the rabbit thoracic aortic ring and the results showed that compounds 9a, 9g and 9j exhibited potent antagonistic activity of AT1 receptor. 相似文献
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29.
WeiHuaHAN HaoRanLI 《中国化学快报》2005,16(1):15-16
(-)-cis-1, 3-Dibenzyl-hexahydrofuro[3, 4-d]imidazole-2, 4-dione was prepared by a new synthesis method from meso dicarboxylic acid and dehydroabietylamine by asymmetric reduction in good yield with up to 91.6% e.e. value. 相似文献
30.
Mezer A Friedman R Noivirt O Nachliel E Gutman M 《The journal of physical chemistry. B》2005,109(22):11379-11388
The surface of a protein, or a membrane, is spotted with a multitude of proton-binding sites, some of which are only a few angstroms apart. When a proton is released from one site, it propagates through the water by a random walk under the bias of the local electrostatic potential determined by the distribution of the charges on the protein. Some of the released protons disperse into the bulk, but during the first few nanoseconds, the released protons can be trapped by encounter with nearby acceptor sites. This process resembles a scenario which corresponds with the time-dependent Debye-Smoluchowski equation. In the present study, we investigated the mechanism of proton transfer between sites that are only a few angstroms apart, using as a model the proton exchange between sites on a small molecule, fluorescein, having two, spectrally distinguishable, proton-binding sites. The first site is the oxyanion on the chromophore ring structure. The second site is the carboxylate moiety on the benzene ring of the molecule. Through our experiments, we were able to reconstruct the state of protonation at each site and the velocity of proton transfer between them. The fluorescein was protonated by a few nanosecond long proton pulse under specific conditions that ensured that the dye molecules would be protonated only by a single proton. The dynamics of the protonation of the chromophore were measured under varying initial conditions (temperature, ionic strength, and different solvents (H(2)O or D(2)O)), and the velocity of the proton transfer between the two sites was extracted from the overall global analysis of the signals. The dynamics of the proton transfer between the two proton-binding sites of the fluorescein indicated that the efficiency of the site-to-site proton transfer is very sensitive to the presence of the screening electrolyte and has a very high kinetic isotope effect (KIE = 55). These two parameters clearly distinguish the mechanism from proton diffusion in bulk water. The activation energy of the reaction (E(a) = 11 kcal mol(-1)) is also significantly higher than the activation energy for proton dissociation in bulk water (E(a) approximately 2.5 kcal mol(-1)). These observations are discussed with respect to the effect of the solute on the water molecules located within the solvation layer. 相似文献