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11.
Vasilios Devetzis Arezoo Daryadel Stefanos Roumeliotis Marios Theodoridis Carsten A. Wagner Stefan Hettwer Uyen Huynh-Do Passadakis Ploumis Spyridon Arampatzis 《PloS one》2015,10(12)
Background
Diabetes is the leading cause of CKD in the developed world. C-terminal fragment of agrin (CAF) is a novel kidney function and injury biomarker. We investigated whether serum CAF predicts progression of kidney disease in type 2 diabetics.Methods
Serum CAF levels were measured in 71 elderly patients with diabetic nephropathy using a newly developed commercial ELISA kit (Neurotune®). Estimated glomerular filtration rate (eGFR) and proteinuria in spot urine were assessed at baseline and after 12 months follow up. The presence of end stage renal disease (ESRD) was evaluated after 24 months follow-up. Correlation and logistic regression analyses were carried out to explore the associations of serum CAF levels with GFR, proteinuria, GFR loss and incident ESRD. Renal handling of CAF was tested in neurotrypsin-deficient mice injected with recombinant CAF.Results
We found a strong association of serum CAF levels with eGFR and a direct association with proteinuria both at baseline (r = 0.698, p<0.001 and r = 0. 287, p = 0.02) as well as after 12 months follow-up (r = 0.677, p<0.001 and r = 0.449, p<0.001), respectively. Furthermore, in multivariate analysis, serum CAF levels predicted eGFR decline at 12 months follow-up after adjusting for known risk factors (eGFR, baseline proteinuria) [OR (95%CI) = 4.2 (1.2–14.5), p = 0.024]. In mice, injected CAF was detected in endocytic vesicles of the proximal tubule.Conclusion
Serum CAF levels reflect renal function and are highly associated with eGFR and proteinuria at several time points. Serum CAF was able to predict subsequent loss of renal function irrespective of baseline proteinuria in diabetic nephropathy. CAF is likely removed from circulation by glomerular filtration and subsequent endocytosis in the proximal tubule. These findings may open new possibilities for clinical trial design, since serum CAF levels may be used as a selection tool to monitor kidney function in high-risk patients with diabetic nephropathy. 相似文献12.
Davoud Nouri Inanlou Bagher Yakhchali Hossein Khanahmad Mossa Gardaneh Hesam Movassagh Reza Ahangari Cohan Mehdi Shafiee Ardestani Reza Mahdian Sirous Zeinali 《Biotechnology letters》2010,32(11):1615-1621
We have developed an integrase-defective lentiviral (LV) vector in combination with a gene-targeting approach for gene therapy
of β-thalassemia. The β-globin gene-targeting construct has two homologous stems including sequence upstream and downstream
of the β-globin gene, a β-globin gene positioned between hygromycin and neomycin resistant genes and a herpes simplex virus
type 1 thymidine kinase (HSVtk) suicide gene. Utilization of integrase-defective LV as a vector for the β-globin gene increased the number of selected clones
relative to non-viral methods. This method represents an important step toward the ultimate goal of a clinical gene therapy
for β-thalassemia. 相似文献
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Hemayatkar M Mahboudi F Majidzadeh-A K Davami F Vaziri B Barkhordari F Adeli A Mahdian R Davoudi N 《Biotechnology journal》2010,5(11):1198-1206
Recombinant tissue plasminogen activator (rt-PA) is one of the most important thrombolytic agents for treating cardiovascular obstructions such as stroke. Glycoprotein rt-PA is a serine protease, consisting of 527 amino acids of which 35 are cysteine residues. A variety of recombinant protein expression systems have been developed for heterologous gene expression in prokaryotic and eukaryotic hosts. In recent years, Leishmania tarentolae has been considered because of its safety aspects and special attributes in expression of complex proteins. In this study, two expression cassettes, each one including two copies of t-PA cDNA, were used for integration into the L. tarentolae genome by electroporation. Transformed clones were selected in the presence of appropriate antibiotics. Expression of active rt-PA was confirmed by Western blot and Zymography tests. Real-time PCR analysis was applied to investigate the presence of multiple t-PA gene copies in the parasite genome. Correlation of t-PA gene dosage and production rate was confirmed with real-time PCR. It was shown that the expression level of rt-PA in L. tarentolae is at least 480 IU/mL of culture media. This concentration of rt-PA is seven times higher than what was reported in previous studies in L. tarentolae and some other eukaryotic systems. 相似文献
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Norizadeh Abbariki Tannaz Shokrgozar Mohammad Ali Haghighipour Nooshin Aghdami Nasser Mahdian Rezak Amanzadeh Amir Jazayeri Maryam 《Molecular & cellular biomechanics : MCB》2014,11(1):19-37
Background: Environmental factors affect stem cell differentiation. In addition to chemical factors, mechanical signals have been suggested to enhance myogenic differentiation of stem cells. Therefore, this study was undertaken to illustrate and compare the effect of chemical and mechanical stimuli on Myogenin (MyoG) and Myosin heavy chani 2 (Myh2) expression of mouse bone marrowderived mesenchymal stem cells (BMSCs) and embryonic stem cells (ESCs). Methods: After isolation and expansion of BMSCs and generation of embryoid bodies and spontaneous differentiation of ESCs, cells were examined in 4 groups: (1) control group: untreated cells; (2) chemical group: cells incubated in myogenic medium (5-azacythidine and horse serum for BMSCs, dimethyl sulfoxide (DMSO) and horse serum for ESCs) for 5 days; (3) mechanical group: cells exposed to uniaxial cyclic strain (8%, 1 Hz, 24 h) and (4) chemical + mechanical group: cells incubated in myogenic medium for 4 days and then exposed to uniaxial cyclic strain. Real-time PCR was used to examine the expression of MyoG and Myh2 as specific myogenic markers. Results: suggested that mechanical loading, as a single factor, could elevate MyoG and Myh2 expression. Combining chemical with mechanical factor increases expression and there was no significant difference in MyoG expression of ESCs- and MSCs-chemical + mechanical groups; however, Myh2 expression was significantly higher in ESCs-mechanical group than that in the same group of MSCs. 相似文献
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Roghaye Arezumand Reza Mahdian Mahdi Behdani Hossein Khanahmad Jahangir Langari Nabiollah Namvarasl Reza Hassanzadeh-Ghasabeh Sirous Zeinali 《Saudi Journal of Biological Sciences》2014,21(1):35-39
Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family. Unlike VEGF, PlGF is dispensable for normal cell development as well as playing various roles in pathological angiogenesis which occurs in tissue ischemia, inflammation, and malignancy. The PlGF-1 has been considered as a potential candidate for the diagnosis and targeting of pathological angiogenesis. Camelidae serum contains an important fraction of functional antibodies, called heavy-chain antibodies (HcAbs) that are naturally devoid of light chains. Camelid HcAbs recognize their cognate antigens by a single variable-domain, referred to as VHH or Nanobody.Here, we describe the expression and purification of recombinant human PlGF-1 (rhPlGF-1). This protein was subsequently used for the preparation of camel heavy chain polyclonal antibody against rhPlGF-1.The recombinant expression plasmid pET-26b-hPlGF-1 was introduced into Escherichia coli BL21 cells to express the rhPlGF-1 protein. Purified rhPlGF-1 was used to immunize camel, the specific reactivity of HcAb was determined with ELISA and western blot. Western blot analysis indicated that the antiserum specifically reacted to the recombinant protein. The rhPlGF-1 protein and its antibody may be used for the development of detection assays needed for clinical research. 相似文献
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Saeed Babaee Gholamabbas Chehardoli Tahmineh Akbarzadeh Mohammad Ali Zolfigol Mohammad Mahdavi Arezoo Rastegari Farshad Homayouni Moghadam Zahra Najafi 《化学与生物多样性》2021,18(6):e2000924
A novel series of tacrine based cyclopentapyranopyridine- and tetrahydropyranoquinoline-kojic acid derivatives were designed, synthesized, and evaluated as anti-cholinesterase agents. The chemical structures of all target compounds were characterized by 1H-NMR, 13C-NMR, and elemental analyses. The synthesized compounds mostly inhibited acetylcholinesterase enzyme (AChE) with IC50 values of 4.18–48.71 μM rather than butyrylcholinesterase enzyme (BChE) with IC50 values of >100 μM. Among them, cyclopentapyranopyridine-kojic acid derivatives showed slightly better AChE inhibitory activity compared to tetrahydropyranoquinoline-kojic acid. The compound 10-amino-2-(hydroxymethyl)-11-(4-isopropylphenyl)-7,8,9,11-tetrahydro-4H-cyclopenta[b]pyrano[2′,3′ : 5,6]pyrano[3,2-e]pyridin-4-one ( 6f ) bearing 4-isopropylphenyl moiety and cyclopentane ring exhibited the highest anti-AChE activity with IC50 value of 4.18 μM. The kinetic study indicated that the compound 6f acts as a mixed inhibitor and the molecular docking studies also illustrated that the compound 6f binds to both the catalytic site (CS) and peripheral anionic site (PAS) of AChE. The compound 6f showed moderate neuroprotective properties against H2O2-induced cytotoxicity in PC12 cells. The theoretical ADME study also predicted good drug-likeness for the compound 6f . Based on these results, the compound 6f seems to be a very promising AChE inhibitor for the treatment of Alzheimer's disease. 相似文献
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Sharif Moradi Parisa Torabi Saeed Mohebbi Sara Amjadian Piter Bosma Farnoush Faridbod Vahid Khoddami Morteza Hosseini Sadegh Babashah Maryam Ghotbaddini Arezoo Rasti Faezeh Shekari Hamid Sadeghi-Abandansari Jafar Kiani Mehdi Shamsara Mohammad Kazemi-Ashtiani Samira Gholami 《BioEssays : news and reviews in molecular, cellular and developmental biology》2020,42(6):2000042