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911.
Xiaohe Li Xiaoyang Ma Yang Miao Jianwei Zhang Buri Xi Wenqi Li Qianyi Zhang Li Chen Yue Yang Hongli Li Luqing Wei Honggang Zhou Cheng Yang 《Journal of cellular and molecular medicine》2023,27(3):422-434
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that seriously threatens the health of patients. The pathogenesis of IPF is still unclear, and there is a lack of effective therapeutic drugs. Myofibroblasts are the main effector cells of IPF, leading to excessive deposition of extracellular matrix (ECM) and promoting the progression of fibrosis. Inhibiting the excessive activation and relieving autophagy blockage of myofibroblasts is the key to treat IPF. PI3K/Akt/mTOR pathway plays a key regulatory role in promoting fibroblast activation and autophagy inhibition in lung fibrosis. Duvelisib is a PI3K inhibitor that can simultaneously inhibit the activities of PI3K-δ and PI3K-γ, and is mainly used for the treatment of relapsed/refractory chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma tumour (SLL). In this study, we aimed to examine the effects of Duvelisib on pulmonary fibrosis. We used a mouse model of bleomycin-induced pulmonary fibrosis to evaluate the effects of Duvelisib on pulmonary fibrosis in vivo and further explored the potential pharmacological mechanisms of Duvelisib in lung fibroblasts in vitro. The in vivo experiments showed that Duvelisib significantly alleviated bleomycin-induced collagen deposition and improved pulmonary function. In vitro and in vivo pharmacological experiments showed that Duvelisib dose-dependently suppressed lung fibroblast activation and improved autophagy inhibition by inhibiting the phosphorylation of PI3K, Akt and mTOR. Our results indicate that Duvelisib can alleviate the severity of pulmonary fibrosis and provide potential drugs for the treatment of pulmonary fibrosis. 相似文献
912.
通过广泛收集和分离,获得根霉属(Rhizopus)、曲霉属(Aspergillus)及裂褶菌属(Schizophyllum)等属菌株897株。产酸指示平板上的变色圈测定结果表明,它们中间628株为产酸菌。通过纸层析对产酸菌发酵液酸谱的分析,获得129株L-苹果酸产生菌,经进一步测定发酵液中L-苹果酸的含量,筛选出以葡萄糖为原料,摇瓶发酵140小时,L-苹果酸产率48.37g/L,对糖转化率48.37×10-2 的菌株LMO2。经初步鉴定,这一菌株为曲霉(Asper-gillus sp.)以LM02作为出发株,采用亚硝基胍、自然污染细菌、甲基磺酸乙酯及紫外线进行诱变处理,选育出葡萄糖为原料,L-苹果酸产率较高的突变抹N1-14、N1-14、NE1412、NU1416及NU1419。其中N1-14 的L-苹果酸产量最高,比出发株提高46.2×10-2。N1-14 的菌丝生长速度快,产孢能力强,摇瓶发酵葡萄糖140小时,平均L-苹果酸产率为72.53g/L,对糖转化率53.74×10-2。全发酵液经薄层层析测定,不含黄曲霉毒素。发酵产物分离提纯后,得到白色粉末状结晶,经纸层析、质谱及红外光谱测定,证明为L-苹果酸。 相似文献
913.
Crystal structure analysis of amicyanin and apoamicyanin from Paracoccus denitrificans at 2.0 A and 1.8 A resolution. 下载免费PDF全文
R. Durley L. Chen L. W. Lim F. S. Mathews V. L. Davidson 《Protein science : a publication of the Protein Society》1993,2(5):739-752
The crystal structure of amicyanin, a cupredoxin isolated from Paracoccus denitrificans, has been determined by molecular replacement. The structure has been refined at 2.0 A resolution using energy-restrained least-squares procedures to a crystallographic residual of 15.7%. The copper-free protein, apoamicyanin, has also been refined to 1.8 A resolution with residual 15.5%. The protein is found to have a beta-sandwich topology with nine beta-strands forming two mixed beta-sheets. The secondary structure is very similar to that observed in the other classes of cupredoxins, such as plastocyanin and azurin. Amicyanin has approximately 20 residues at the N-terminus that have no equivalents in the other proteins; a portion of these residues forms the first beta-strand of the structure. The copper atom is located in a pocket between the beta-sheets and is found to have four coordinating ligands: two histidine nitrogens, one cysteine sulfur, and, at a longer distance, one methionine sulfur. The geometry of the copper coordination is very similar to that in the plant plastocyanins. Three of the four copper ligands are located in the loop between beta-strands eight and nine. This loop is shorter than that in the other cupredoxins, having only two residues each between the cysteine and histidine and the histidine and methionine ligands. The amicyanin and apoamicyanin structures are very similar; in particular, there is little difference in the positions of the coordinating ligands with or without copper. One of the copper ligands, a histidine, lies close to the protein surface and is surrounded on that surface by seven hydrophobic residues. This hydrophobic patch is thought to be important as an electron transfer site. 相似文献
914.
915.
Aldo Ferretti Vincent P. Flanagan Joseph T. Judd Padmanabhan P. Nair Philip R. Taylor 《The Journal of nutritional biochemistry》1993,4(12)
Dietary supplementation with a fish oil concentrate (FOC) reduced the endogenous synthesis of prostacyclin (PGI2), as measured by the excretion of its major urinary catabolite, 2,3-dinor-6-oxo-PGF1α (PGI2-M). Thirty-four healthy men (24–57 years old) were given controlled diets and supplements that provided 40% of the energy from fat and a minimum of 22 mg/d of α-tocopherol for two consecutive experimental periods of 10 weeks each. During the experimental periods, the men received capsules containing 15 g/d of a placebo oil (PO) (period 1) or 15 g/d of the FOC (period 2). In addition to the PO or FOC, capsules contained 1 mg of α-tocopherol per g of fat as an antioxidant. The average daily excretion of PGI2-M during the last week of FOC supplementation (period 2) was 22% less (P = 0.0001) than at the end of the first period. These results are at variance with those reported in comparable human studies conducted by other investigators during the middle and late 1980s. A 20% reduction (P = 0.003) in the 11-dehydrothromboxane B2 to 2,3-dinor-6-oxo-PGF1α excretion ratio at the end of period 2 in this study demonstrates that a shift of the n-6 to n-3 polyunsaturated fatty acid ratio from 12.5 to 2.3 brings about a substantial modulation of the eicosanoid system. 相似文献
916.
Carton W. Chen Tin-Wein Yu † Yi-Shing Lin Helen M. Kieser David A. Hopwood 《Molecular microbiology》1993,7(6):925-932
The SLP2 plasmid had previously been demonstrated genetically to exist In Streptomyces lividans by its ability to promote conjugation and to elicit‘pocks’on recipient (SLP2?) cultures, but it had not been physically detected. Using pulsed-field gel electrophoresis, a 50kb linear DNA was isolated from SLP2+ but not SLP2? strains of S. lividans, and from Streptomyces coelicolor and Streptomyces parvulus strains to which SLP2 had been transferred by conjugation or transformation. We conclude that this linear DNA is SLP2. The terminal fragments of SLP2 were cloned. The determined sequences revealed a 44 bp imperfect terminal inverted repeat. The terminal 12 bp sequence of SLP2 was identical to those of two other Streptomyces linear plasmids, pSLA2 and pSCL, and similar to the terminal sequences of another Streptomyces linear plasmid, SCP1. The termini of SLP2 DNA were resistant to digestion by λ exonuclease and ExoIII. A truncated (probably crippled) copy of Tn4811 is present on the plasmid. While the SLP2 plasmid exists as a tree form in the host, a 15.7 kb sequence corresponding to the segment of SLP2 from Tn4811 to the right terminus is also present (at a copy number similar to the free form) elsewhere in the genome of S. lividans. Furthermore, SLP2 is partially homologous to a newly discovered 650 kb linear plasmid in S. parvulus. 相似文献
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919.
920.