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521.
Kazem Mashayekhi Mojtaba Sankian Saeed Mohammadian Haftcheshmeh Ramezan Ali Taheri Kazem Hassanpour Gholamreza Farnoosh 《Biotechnology progress》2021,37(5):e3191
To increase the efficiency of aptamers to their targets, a simple and novel method has been developed based on aptamer oligomerization. To this purpose, previously anti-human TNF-α aptamer named T1–T4 was trimerized through a trimethyl aconitate core for neutralization of in vitro and in vivo of TNF-α. At first, 54 mer T1–T4 aptamers with 5′-NH2 groups were covalently coupled to three ester residues in the trimethyl aconitate. In vitro activity of novel anti-TNF-α aptamer and its dissociation constant (Kd) was done using the L929 cell cytotoxicity assay. In vivo anti-TNF-α activity of new oligomerized aptamer was assessed in a mouse model of cutaneous Shwartzman. Anchoring of three T1–T4 aptamers to trimethyl aconitate substituent results in formation of the 162 mer fragment, which was well revealed by gel electrophoresis. In vitro study indicated that the trimerization of T1–T4 aptamer significantly improved its anti-TNF-α activity compared to non-modified aptamers (P < 0.0001) from 40% to 60%. The determination of Kd showed that trimerization could effectively enhance Kd of aptamer from 67 nM to 36 nM. In vivo study showed that trimer aptamer markedly reduced mean scar size from 15.2 ± 1.2 mm to 1.6 ± 0.1 mm (P < 0.0001), which prevent the formation of skin lesions. In vitro and in vivo studies indicate that trimerization of anti-TNF-α aptamer with a novel approach could improve the anti-TNF-α activity and therapeutic efficacy. According to our findings, a new anti-TNF-α aptamer described here could be considered an appropriate therapeutic agent in treating several inflammatory diseases. 相似文献
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Sara Hosseini Samaneh Hosseini Mohammad Salehi 《Journal of cellular physiology》2020,235(12):9752-9762
Despite encouraging advances in fertility technology, the success rate of an ongoing pregnancy is relatively low and predominantly associated with implantation failure. Inflammatory responses are beneficial in the fetomaternal interface and supposedly accelerate the chances for successful implantation. The current study aims to determine the effect of Toll-like receptor 4 (TLR4) overexpression in mouse blastocysts via Let-7a downregulation using intracytoplasmic sperm injection-sperm-mediated gene transfer on embryo attachment rate. The pLenti-III-GFP-miR-Off-Let-7a vector was transmitted to oocytes derived via in vitro maturation (IVM) and in vivo oocytes by using NaOH-treated spermatozoa. Let-7a and TLR4 expression levels were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), immunocytochemistry, and western blot analysis in both oocytes and embryos. Blastocyst adhesion on the endometrial cells was monitored by microscopic analysis. qRT-PCR results showed that Let-7a expression decreased in the IVM (GV-MII) oocytes compared to the in vivo oocyte (MII) group (p < .05). TLR4 showed a higher expression in GV-MII oocytes at both the gene and protein levels (p < .05). Following anti-miR-Let-7a transmission, the TLR4 expression level was significantly upregulated in embryos compared with the control groups (p < .05). Attachment and migration of trophoblasts cells towards endometrial cells dramatically increased compared to the control group (p < .05). Based on our results, we concluded that Let-7a might mediate embryo attachment through regulation of TLR4 expression levels. 相似文献
524.
Zahra Jafarpour Gholamreza Pouladfar Seyed Ali Malek Hosseini Mohammad Firoozifar Peyman Jafari 《Microbiology and immunology》2020,64(6):407-415
Liver transplantation (LT) is a potentially curative treatment for terminal stage hepatic diseases. Bacterial infections are the main causes of mortality and morbidity in the early period after LT. Identifying the risk factors could help in minimizing their development. We prospectively investigated the incidence, characteristics, and risk factors of bacterial infections among the recipients during hospitalization after LT and assigned a predictive score. All 389 consecutive adults who underwent LT at the main referral hospital of LT in Iran during 1 year were enrolled prospectively in a cohort study. Infection group consisted of 143 recipients (36.8%). Urinary tract and surgical site infections were the most frequent ones. Gram-negative bacteria were more prevalent than Gram-positive ones. Independent risk factors were female sex (relative risks = 2.13), age ≤ 43.5 years (3.70), hospital stay ≥ 9.5 days (5.22), abdominal reoperation (3.03), vancomycin-resistant Enterococci colonization (5.52), hospitalization 3 months prior to LT (3.25), mechanical ventilation ≥48 hr (4.93), and renal replacement therapies (13.40). We developed a risk score for the prediction of bacterial infections with an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.81–0.89) with sensitivity of 88% and specificity of 64%. In the infection group, mortality was higher than in controls (18.9% vs. 2.0%) with longer hospitalization (16 vs. 10 days; P < 0.001). We detected a high rate of bacterial infections leading to longer hospital stay and higher mortality rate. The formulated risk score can help predict bacterial infections; however, it requires clinical validation in further studies. 相似文献
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