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171.
Identification of a novel RPGRIP1 mutation in an Iranian family with leber congenital amaurosis by exome sequencing 下载免费PDF全文
Saber Imani Jingliang Cheng Abdolkarim Mobasher‐Jannat Chunli Wei Shangyi Fu Lisha Yang Khosrow Jadidi Mohammad Hossein Khosravi Saman Mohazzab‐Torabi Marzieh Dehghan Shasaltaneh Yumei Li Rui Chen Junjiang Fu 《Journal of cellular and molecular medicine》2018,22(3):1733-1742
Leber congenital amaurosis (LCA) is a heterogeneous, early‐onset inherited retinal dystrophy, which is associated with severe visual impairment. We aimed to determine the disease‐causing variants in Iranian LCA and evaluate the clinical implications. Clinically, a possible LCA disease was found through diagnostic imaging, such as fundus photography, autofluorescence and optical coherence tomography. All affected patients showed typical eye symptoms associated with LCA including narrow arterioles, blindness, pigmentary changes and nystagmus. Target exome sequencing was performed to analyse the proband DNA. A homozygous novel c. 2889delT (p.P963 fs) mutation in the RPGRIP1 gene was identified, which was likely the deleterious and pathogenic mutation in the proband. Structurally, this mutation lost a retinitis pigmentosa GTPase regulator (RPGR)‐interacting domain at the C‐terminus which most likely impaired stability in the RPGRIP1 with the distribution of polarised proteins in the cilium connecting process. Sanger sequencing showed complete co‐segregation in this pedigree. This study provides compelling evidence that the c. 2889delT (p.P963 fs) mutation in the RPGRIP1 gene works as a pathogenic mutation that contributes to the progression of LCA. 相似文献
172.
Hassan Mansouri-Torshizi Fatemeh Khosravi Khatereh Abdi Sareh Zareian-Jahromi 《Journal of biomolecular structure & dynamics》2013,31(17):4419-4432
AbstractIn this study, four Co(III)-, Cu(II)-, Zn(II)- and Pd(II)-based potent antibacterial complexes of formula K3[Co(ox)3]·3H2O (I), [Cu(phen)2Cl]Cl·6.5H2O (II), [Zn(phen)3]Cl2 (III) and [Pd(phen)2](NO3)2 (IV) (where ox is oxalato and phen is 1,10-phenanthroline) were synthesized. They were characterized by elemental analysis, molar conductivity measurements, UV–vis, Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance (1H-NMR) techniques. These metal complexes were ordered in three combination series of I+II, I+II+III and I+II+III+IV. Antibacterial screening for each metal complex and their combinations against Gram-positive and Gram-negative bacteria revealed that all compounds were more potent antibacterial agents against the Gram-negative than those of the Gram-positive bacteria. The four metal complexes showed antibacterial activity in the order I > II > III > IV, and the activity of their combinations followed the order of I+II+III+IV > I+II+III > I+II. The DNA-binding properties of complex (I) and its three combinations were studied using electronic absorption and fluorescence (ethidium bromide displacement assay) spectroscopy. The results obtained indicated that all series interact effectively with calf thymus DNA (CT-DNA). The binding constant (Kb), the number of binding sites (n) and the Stern–Volmer constant (Ksv) were obtained based on the results of fluorescence measurements. The calculated thermodynamic parameters supported that hydrogen bonding and van der Waals forces play a major role in the association of each series of metal complexes with CT-DNA and follow the above-binding affinity order for the series.Communicated by Ramaswamy H. Sarma 相似文献
173.
Joodi G Ansari N Khodagholi F 《International journal of biological macromolecules》2011,48(5):726-735
There is mounting evidence implicating the role of oxidative stress induced by reactive oxygen species (ROS) in neurodegenerative disease, including Alzheimer's disease. In this study we aimed to investigate the possible protective effect of chitooligosaccharide (COS), an antioxidant oligosaccharide, on hydrogen peroxide induced apoptosis in NGF-differentitated rat pheochromocytoma (PC12) cells. COS treatment reversed the decrease of cell viability induced by H(2)O(2) and this was associated with diminished intracellular ROS and decreased level of cytosolic Ca(2+). Additionally, COS contributed to up-regulation of Bcl-2, down regulation of Bax protein and reduction of cleaved Caspase-3 protein. COS treatment stabilized Nrf2 in nucleus and increased the Hsp70 level within cell while down-regulated Hsp90 expression. Moreover, COS could inhibit the phosphorylation of different mitogen activated protein kinases (MAPKs), whose aberrant phosphorylation has been implicated in AD. Our findings suggest that heat shock response and MAPK cascades are both involved in cell survival, and by concomitantly regulating both pathways, COS can be a promising agent in treating neurodegenerative diseases. 相似文献
174.
Maryam Abolghasemi Sadra Samavarchi Tehrani Tooba Yousefi Ansar Karimian Ata Mahmoodpoor Aliakbar Ghamari Farhad Jadidi-Niaragh Mehdi Yousefi Hossein Samadi Kafil Milad Bastami Mahdi Edalati Shirin Eyvazi Mohsen Naghizadeh Niloufar Targhazeh Bahman Yousefi Amin Safa Maryam Majidinia Vahid Rameshknia 《Journal of cellular physiology》2020,235(6):5008-5029
Breast cancer is one of the most lethal malignancies in women in the world. Various factors are involved in the development and promotion of the malignancy; most of them involve changes in the expression of certain genes, such as microRNAs (miRNAs). MiRNAs can regulate signaling pathways negatively or positively, thereby affecting tumorigenesis and various aspects of cancer progression, particularly breast cancer. Besides, accumulating data demonstrated that miRNAs are a novel tool for prognosis and diagnosis of breast cancer patients. Herein, we will review the roles of these RNA molecules in several important signaling pathways, such as transforming growth factor, Wnt, Notch, nuclear factor-κ B, phosphoinositide-3-kinase/Akt, and extracellular-signal-regulated kinase/mitogen activated protein kinase signaling pathways in breast cancer. 相似文献
175.
Ran is a small GTPase that cycles between a guanosine diphosphate (GDP)-bound form (RanGDP) and a guanosine triphosphate (GTP)-bound form (RanGTP) and plays important roles in nuclear transport and mitosis. For studies of Ran function and its interactions with partner proteins, pure RanGDP and RanGTP complexes are critical. Ran complexed with the nonhydrolyzable GTP analog, GMPPNP (RanGMPPNP), is used instead of RanGTP when inhibition of hydrolysis is required. In this study, we demonstrate that the binding of Ran to a UNO Q ion exchange column is remarkably sensitive to small shifts in MgCl(2) concentration, and we use this property to purify recombinant RanGTP, RanGMPPNP, and RanGDP complexes. At 10 mM MgCl(2), Ran was found predominantly in the flow-through and, thus, was separated from the vast majority of bacterial proteins. After reducing the concentration of MgCl(2) to 5 mM, further purification of RanGTP, RanGMPPNP, and RanGDP was achieved by loading onto ion exchange columns and elution with an NaCl gradient. Purity of the resulting preparations was confirmed by releasing the bound nucleotide and checking it against a known nucleotide by high-performance liquid chromatography (HPLC). To further confirm the purity and function of the Ran preparations, appropriate protein-binding, enzymatic, and nuclear import assays were carried out. These methods should facilitate studies of cellular processes involving Ran by providing pure functional Ran-nucleotide complexes. 相似文献
176.
IDO‐Expressing Fibroblasts Protect Islet Beta Cells From Immunological Attack and Reverse Hyperglycemia in Non‐Obese Diabetic Mice 下载免费PDF全文
177.
Susan E. McNulty Niloufar B. Tohidian Frank L. Meyskens 《Pigment cell & melanoma research》2001,14(6):456-465
Metastatic melanomas are typically resistant to radiation and chemotherapy. The underlying basis for this phenomenon may result in part from defects in apoptotic pathways. Nuclear factor kappa B (NFκB) has been shown to control apoptosis in many cell types and normally functions as an immediate stress response mechanism that is rigorously controlled by multiple inhibitory complexes. We have previously shown that NFκB binding is elevated in metastatic melanoma cells relative to normal melanocytes. In the current study, Western blot analysis showed that, compared with normal melanocytes, melanoma cell lines have higher nuclear levels of the NFκB subunits p50 (7‐fold) and RelA (5–10‐fold). In response to tumor necrosis factor‐alpha (TNFα), both melanocytes and melanoma cells showed increased nuclear p50 and RelA levels, but levels in melanoma cells remained higher than in melanocytes. We also found that melanoma cells expressed higher cytoplasmic levels of RelA, p105/p50 and the inhibitory protein, inhibitor of kappa B alpha (IκBα) than melanocytes. To directly test whether RelA expression has an impact on melanoma cell survival, we used antisense RelA phosphorothioate oligonucleotides and found that melanoma cell viability was significantly decreased compared with untreated or control cultures. The constitutive activation of NFκB in metastatic melanoma cell cultures may, therefore, support an inappropriate cell survival pathway that can be therapeutically manipulated. 相似文献
178.
We have previously found an inverse relationship between certain cell growth parameters and plasmid size for a series of recombinant Escherichia coli strains containing pUC8 or one of a series of pUC8 recombinant derivatives. To extend these results we investigated whether there was a similar variation among our strains in oxygen requirement, which might be related to the differences in growth. During logarithmic growth in shake flasks, oxygen uptake by E. coli strain JM103 containing an 8.7-kb pUC8 derivative (pBS5) was 2.5 times that of JM103 harboring pUC8 (2.7 kb) and 7.5 times that of plasmid-free JM103. Supplementing the medium with acetate eliminated both the growth disadvantage of and the increased oxygen uptake by the strain harboring pBS5 compared with that containing pUC8. In all cases oxygen consumption decreased drastically as cells began and then continued into stationary phase, and no significant difference was seen among the three strains at these times. When the three strains were grown in a fermentor with continuous monitoring of oxygen levels, plasmid-free JM103 outgrew JM103 containing pUC8 or pBS5 at three levels of aeration. The latter two strains grew identically when aeration was high; their growth curves diverged, however, when aeration was low. In the fermentor experiments the point at which the growth of the three strains diverged was coincident with the point of oxygen depletion in the cultures. 相似文献