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排序方式: 共有223条查询结果,搜索用时 15 毫秒
81.
Cong Y Pawlisz E Bryant P Balan S Laurine E Tommasi R Singh R Dubey S Peciak K Bird M Sivasankar A Swierkosz J Muroni M Heidelberger S Farys M Khayrzad F Edwards J Badescu G Hodgson I Heise C Somavarapu S Liddell J Powell K Zloh M Choi JW Godwin A Brocchini S 《Bioconjugate chemistry》2012,23(2):248-263
The efficacy of protein-based medicines can be compromised by their rapid clearance from the blood circulatory system. Achieving optimal pharmacokinetics is a key requirement for the successful development of safe protein-based medicines. Protein PEGylation is a clinically proven strategy to increase the circulation half-life of protein-based medicines. One limitation of PEGylation is that there are few strategies that achieve site-specific conjugation of PEG to the protein. Here, we describe the covalent conjugation of PEG site-specifically to a polyhistidine tag (His-tag) on a protein. His-tag site-specific PEGylation was achieved with a domain antibody (dAb) that had a 6-histidine His-tag on the C-terminus (dAb-His(6)) and interferon α-2a (IFN) that had an 8-histidine His-tag on the N-terminus (His(8)-IFN). The site of PEGylation at the His-tag for both dAb-His(6)-PEG and PEG-His(8)-IFN was confirmed by digestion, chromatographic, and mass-spectral studies. A methionine was also inserted directly after the N-terminal His-tag in IFN to give His(8)Met-IFN. Cyanogen bromide digestion studies of PEG-His(8)Met-IFN were also consistent with PEGylation at the His-tag. By using increased stoichiometries of the PEGylation reagent, it was possible to conjugate two separate PEG molecules to the His-tag of both the dAb and IFN proteins. Stability studies followed by in vitro evaluation confirmed that these PEGylated proteins retained their biological activity. In vivo PK studies showed that all of the His-tag PEGylated samples displayed extended circulation half-lives. Together, our results indicate that site-specific, covalent PEG conjugation at a His-tag can be achieved and biological activity maintained with therapeutically relevant proteins. 相似文献
82.
Roya Kolahdouz-Mohammadi Farzad Shidfar Sepideh Khodaverdi Tahereh Arablou Sahel Heidari Nesa Rashidi Ali-Akbar Delbandi 《Journal of cellular and molecular medicine》2021,25(2):1116-1127
Endometriosis is an inflammatory disease affecting reproductive-aged women. Immunologic disturbance, as well as inflammation, have crucial roles in the pathogenesis of endometriosis. In this study, we evaluated the effects of resveratrol treatment on expression of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), IL-8, and regulated upon activation, normal T cell expressed and secreted (RANTES) in endometrial stromal cells from patients with endometriosis compared with non-endometriotic controls. Thirteen eutopic (EuESCs) and nine ectopic (EESCs) endometrial stromal cells from endometriotic patients as well as eleven endometrial stromal cells from non-endometriotic controls (CESCs) were treated with resveratrol (100 μmol/L) or ethanol, and gene and/or protein expression of MCP-1, IL-6, IL-8 and RANTES was examined at 6, 24 and 48 hours following treatment in the cells from all origins. Resveratrol treatment significantly reduced gene and protein expression of MCP-1, IL-6, and IL-8 in EuESCs and EESCs compared with CESCs (P < .05-.001, P < .05-.001 and P < .05-<.01, respectively), and this reduction was more noticeable in EESCs than EuESCs (P < .05-<.001). Besides, resveratrol treatment significantly reduced RANTES protein expression in EESCs in all time intervals (P < .05). Resveratrol treatment significantly reduced the expression of MCP-1, IL-6, IL-8 and RANTES in EESCs. 相似文献
83.
84.
Atena Soleimani Fereshteh Asgharzadeh Farzad Rahmani Amir Avan Saeedeh Mehraban Maryam Fakhraei Mohammad Hassan Arjmand Maryam Moradi Binabaj Mohammad Reza Parizadeh Gordon A. Ferns Mikhail Ryzhikov Amir Reza Afshari Jalal Naghinezhad Sayyed Hadi Sayyed-Hosseinian Majid Khazaei Seyed Mahdi Hassanian 《Journal of cellular physiology》2020,235(2):1349-1357
Here, we have investigated the therapeutic potency of EW-7197, a transforming growth factor-β type I receptor kinase inhibitor, against postsurgical adhesion band formation. Our results showed that this pharmacological inhibitor prevented the frequency and the stability of adhesion bands in mice model. We have also shown that downregulation of proinflammatory cytokines, reduce submucosal edema, attenuation of proinflammatory cell infiltration, inhibition of oxidative stress, decrease in excessive collagen deposition, and suppression of profibrotic genes at the site of surgery are some of the mechanisms by which EW-7197 elicits its protective responses against adhesion band formation. These results clearly suggest that EW-7197 has novel therapeutic properties against postsurgical adhesion band formation with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in postsurgery patients. 相似文献
85.
86.
Khalighi Sikaroudi Masoumeh Sedaghat Meghdad Shidfar Farzad Talebi Sepide Hosseini-Baharanchi Fatemeh Sadat Masoodi Mohsen Farahani Safoura Vasheghani 《Amino acids》2023,55(2):193-202
Amino Acids - The hypertonicity of internal anal sphincter resting pressure is one of the main causes of chronic anal fissure. Therefore, the aim of this study was to assess the effect of oral... 相似文献
87.
Rabie TS Crooijmans RP Bovenhuis H Vereijken AL Veenendaal T van der Poel JJ Van Arendonk JA Pakdel A Groenen MA 《Animal genetics》2005,36(6):468-476
Pulmonary hypertension syndrome (PHS), also referred to as ascites syndrome, is a growth-related disorder of chickens frequently observed in fast-growing broilers with insufficient pulmonary vascular capacity at low temperature and/or at high altitude. A cross between two genetically different broiler dam lines that originated from the White Plymouth Rock breed was used to produce a three-generation population. This population was used for the detection and localization of quantitative trait loci (QTL) affecting PHS-related traits. Ten full-sib families consisting of 456 G2 birds were typed with 420 microsatellite markers covering 24 autosomal chromosomes. Phenotypic observations were collected on 4202 G3 birds and a full-sib across family regression interval mapping approach was used to identify QTL. There was statistical evidence for QTL on chicken chromosome 2 (GGA2), GGA4 and GGA6. Suggestive QTL were found on chromosomes 5, 8, 10, 27 and 28. The most significant QTL were located on GGA2 for right and total ventricular weight as percentage of body weight (%RV and %TV respectively). A related trait, the ratio of right ventricular weight as percentage to total ventricular weight (RATIO), reached the suggestive threshold on this chromosome. All three QTL effects identified on GGA2 had their maximum test statistic in the region flanked by markers MCW0185 and MCW0245 (335-421 cM). 相似文献
88.
Corbett MC Hu Y Naderi F Ribbe MW Hedman B Hodgson KO 《The Journal of biological chemistry》2004,279(27):28276-28282
Nitrogenase, the enzyme system responsible for biological nitrogen fixation, is believed to utilize two unique metalloclusters in catalysis. There is considerable interest in understanding how these metalloclusters are assembled in vivo. It has been presumed that immature iron-molybdenum cofactor-deficient nitrogenase MoFe proteins contain the P-cluster, although no biosynthetic pathway for the assembly of this complex cluster has been identified as yet. Through the comparison by iron K-edge x-ray absorption edge and extended fine structure analyses of cofactor-deficient MoFe proteins resulting from nifH and nifB deletion strains of Azotobacter vinelandii, a novel [Fe-S] cluster is identified in the DeltanifH MoFe protein. The iron-iron scattering displayed by the DeltanifH MoFe protein is more similar to that of a standard [Fe(4)S(4)]-containing protein than that of the DeltanifB MoFe protein, which is shown to contain a "normal" P-cluster. The iron-sulfur scattering of the DeltanifH MoFe protein, however, indicates differences in its cluster from an [Fe(4)S(4)](Cys)(4) site that may be consistent with the presence of either oxygenic or nitrogenic ligation. Based on these results, models for the [Fe-S] center in the DeltanifH MoFe protein are constructed, the most likely of which consist of two separate [Fe(4)S(4)] sites, each with some non-cysteinyl coordination. This type of model suggests that the P-cluster is formed by the condensation of two [Fe(4)S(4)] fragments, possibly concomitant with Fe protein (NifH)-induced conformational change. 相似文献
89.
Phytosomal‐curcumin antagonizes cell growth and migration,induced by thrombin through AMP‐Kinase in breast cancer 下载免费PDF全文
Milad Hashemzehi Reihane Behnam‐Rassouli Seyed Mahdi Hassanian Maryam Moradi‐Binabaj Reyhaneh Moradi‐Marjaneh Farzad Rahmani Hamid Fiuji Mahdi Jamili Mahdi Mirahmadi Nadia Boromand Mehran Piran Mohieddin Jafari Amirhossein Sahebkar Amir Avan Majid Khazaei 《Journal of cellular biochemistry》2018,119(7):5996-6007