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排序方式: 共有228条查询结果,搜索用时 312 毫秒
31.
32.
Mohammad Hossein Hedayati Dariush Norouzian Mahdi Aminian Shahram Teimourian Reza Ahangari Cohan Soroush Sardari M. Reza Khorramizadeh 《The protein journal》2017,36(1):36-48
Erythropoietin (EPO) is the principal hormone which, has somewhat short half-life involved in the differentiation and regulation of circulating red blood cells. The present study was carried out to evaluate the capability of a polyethylene glycol mimetic technology as a biological alternative to improve pharmaceutical properties of human recombinant EPO. In silico models of EPO fused to 200 amino acids of proline, alanine, and serine (PAS) were initially generated and assessed by molecular dynamic (MD) simulation. The fluctuations of the modeled structure reached a plateau after 6000 ps of MD simulation. The Phi and psi analysis showed >99.2% of residues were located in the allowed regions. An expression vector consisting of EPO cDNA tagged to PAS coding sequences was synthesized and expressed in CHO-K1 Cells. The produced PASylated molecule was purified and characterized by standard analytical methods. The molecular weight of fusion protein was expanded to 70 kDa using sodium dodecyl sulfate polyacrylamide gel electrophoresis method. Analytical size exclusion chromatography revealed an approximately sevenfold increase in apparent size of produced protein. Although the in vitro potency of the fusion protein was significantly reduced (1.26?±?0.05 vs. 0.24?±?0.03 ng/ml) but, the in vivo activity was considerably increased up to 1.58?×?105 IU/ml in normocythemic mice assay. Pharmacokinetic animal studies revealed strongly 15.6-fold plasma half-life extension for the PASylated EPO (83.16?±?13.28 h) in comparison to epoetin α (8.5?±?2.4 h) and darbepoetin α (25.3?±?2.2h). 相似文献
33.
H. Dariush Fahimi 《Histochemistry and cell biology》2009,131(4):437-440
The historical circumstances that led to the discovery of the 3,3′-diamino-benzidine (DAB) method for staining of peroxisomes
40 years ago are reviewed. In the course of studies on the uptake and absorption of horse radish peroxidase in mammalian liver,
in sections incubated for detection of peroxidase activity in DAB, it was noted that peroxisomes also stained positively for
peroxidase activity. Subsequently, it was revealed that the peroxidatic activity of catalase, which is abundantly present
in peroxisomes, is responsible for that staining. This notion was confirmed in quantitative biochemical studies with crystalline
beef liver catalase and in tracer studies using catalase as an ultrastructural tracer. The application of the DAB method led
to the discovery of peroxisomes as a ubiquitous eukaryotic cell organelle, attracting great interest in their investigation
in biomedical research. 相似文献
34.
Kheirandish Maryam Siadat Seyed Davar Norouzian Dariush Razavi Mohamad Reza Aghasadeghi Mohammad Reza Rezaei Nima Farazmand Ali Izadi Mobarakeh Jalal Zangeneh Mehrangiz Moshiri Arfa Sadat Seyed Mehdi Salmani Ali Sharifat 《Annals of microbiology》2009,59(4):801-806
Neisseria meningitidis is efficiently phagocytosed by polymorphonuclear leukocytes (PMNS) following opsonization with opsonic antibodies; opsonophagocytosis is the primary mechanism for clearance of meningococci from the host. Thus, in testing meningococcal vaccines, the level of opsonophagocytic antibodies appears to correlate with vaccine-induced protection. Our previous studies demonstrated that the conjugation ofN. meningitidis serogroup A capsular polysaccharide (CPSA) to serogroup B outer membrane vesicle (OMV) could induce a high level of bactericidal antibody response against serogroup A meningococci in animals. The purpose of this study was to evaluate opsonophagocytic activity of the conjugate of CPSA to OMV (CPSA-OMV). In order to evaluate the potential efficacy of CPSA-OMV a flow cytometric opsonophagocytic assay was used. The conjugate and controls were injected intramuscularly into four groups of rabbits with boosters on days 14, 28 and 42 following primary immunization. The rabbits were bled prior to injection and two weeks after each injection. Opsonophagocytic activity of antibodies in hyperimmune sera through rabbit PMNS were measured with flow cytometer, using dihydrorhodamine-123 as a probe. The results indicated that our conjugate could induce a highly significant level of opsonophagocytic activity against serogroup A meningococci after 56 days compared to the control groups (P<0.05). We conclude that this conjugate represents a vaccine candidate against serogroups A and B meningococci after further investigation. 相似文献
35.
Zahra Razaghi Moghadam Kashani Hayedeh Ahrabian Elahe Elahi Abbas Nowzari-Dalini Elnaz Saberi Ansari Sahar Asadi Shahin Mohammadi Falk Schreiber Ali Masoudi-Nejad 《BMC bioinformatics》2009,10(1):318
Background
Complex networks are studied across many fields of science and are particularly important to understand biological processes. Motifs in networks are small connected sub-graphs that occur significantly in higher frequencies than in random networks. They have recently gathered much attention as a useful concept to uncover structural design principles of complex networks. Existing algorithms for finding network motifs are extremely costly in CPU time and memory consumption and have practically restrictions on the size of motifs. 相似文献36.
Etemadmoghadam D George J Cowin PA Cullinane C Kansara M;Australian Ovarian Cancer Study Group Gorringe KL Smyth GK Bowtell DD 《PloS one》2010,5(11):e15498
Genomic amplification of 19q12 occurs in several cancer types including ovarian cancer where it is associated with primary treatment failure. We systematically attenuated expression of genes within the minimally defined 19q12 region in ovarian cell lines using short-interfering RNAs (siRNA) to identify driver oncogene(s) within the amplicon. Knockdown of CCNE1 resulted in G1/S phase arrest, reduced cell viability and apoptosis only in amplification-carrying cells. Although CCNE1 knockdown increased cisplatin resistance in short-term assays, clonogenic survival was inhibited after treatment. Gain of 20q11 was highly correlated with 19q12 amplification and spanned a 2.5 Mb region including TPX2, a centromeric protein required for mitotic spindle function. Expression of TPX2 was highly correlated with gene amplification and with CCNE1 expression in primary tumors. siRNA inhibition of TPX2 reduced cell viability but this effect was not amplicon-dependent. These findings demonstrate that CCNE1 is a key driver in the 19q12 amplicon required for survival and clonogenicity in cells with locus amplification. Co-amplification at 19q12 and 20q11 implies the presence of a cooperative mutational network. These observations have implications for the application of targeted therapies in CCNE1 dependent ovarian cancers. 相似文献
37.
Previously we have demonstrated that maternal high fat diet (HF) during pregnancy increase cardiovascular risk in the offspring, and pharmacological intervention using statins in late pregnancy reduced these risk factors. However the effects of maternal HF-feeding and statin treatment during pregnancy on development of heart remain unknown. Hence we measured expression of genes involved in cell cycle progression (cyclin G1), ventricular remodelling brain natriuretic peptide (BNP), and environmental stress response small proline-rich protein 1A (SPRR 1A) in the offspring left ventricle (LV) from dams on HF with or without statin treatment. Female C57 mice were fed a HF diet (45 % kcal fat) 4 weeks prior to conception, during pregnancy and lactation. From the second half of the pregnancy and throughout lactation, half of the pregnant females on HF diet were given a water-soluble statin (Pravastatin) in their drinking water (HF + S). At weaning offspring were fed HF diet to adulthood (generating dam/offspring dietary groups HF/HF and HF + S/HF). These groups were compared with offspring from dams fed standard chow (C 21 % kcal fat) and fed C diet from weaning (C/C). LV mRNA levels for cyclin G1, BNP and SPRR 1A were measured by RT-PCR. Heart weights and BP in HF/HF offspring were higher versus C/C group. Maternal Pravastatin treatment reduced BP and heart weights in HF + S/HF female offspring to levels found in C/C group. LV cyclin G1 mRNA levels were lower in HF/HF versus both C/C and HF + S/HF offspring. BNP mRNA levels were elevated in HF/HF females but lower in males versus C/C. BNP gene expression in HF + S/HF offspring was similar to HF/HF. SPRR 1A mRNA levels were similar in all treatment groups. Statins given to HF-fed pregnant dams reduced cardiovascular risk in adult offspring, and this is accompanied by changes in expression of genes involved in adaptive remodelling in the offspring LV and that there is a gender difference. 相似文献
38.
Shokrollah Elahi Jill Van Kessel Tedele G. Kiros Stacy Strom Yoshihiro Hayakawa Mamoru Hyodo Lorne A. Babiuk Volker Gerdts 《PloS one》2014,9(10)
Innate immunity represents the first line of defense against invading pathogens in the respiratory tract. Innate immune cells such as monocytes, macrophages, dendritic cells, NK cells, and granulocytes contain specific pathogen-recognition molecules which induce the production of cytokines and subsequently activate the adaptive immune response. c-di-GMP is a ubiquitous second messenger that stimulates innate immunity and regulates biofilm formation, motility and virulence in a diverse range of bacterial species with potent immunomodulatory properties. In the present study, c-di-GMP was used to enhance the innate immune response against pertussis, a respiratory infection mainly caused by Bordetella pertussis. Intranasal treatment with c-di-GMP resulted in the induction of robust innate immune responses to infection with B. pertussis characterized by enhanced recruitment of neutrophils, macrophages, natural killer cells and dendritic cells. The immune responses were associated with an earlier and more vigorous expression of Th1-type cytokines, as well as an increase in the induction of nitric oxide in the lungs of treated animals, resulting in significant reduction of bacterial numbers in the lungs of infected mice. These results demonstrate that c-di-GMP is a potent innate immune stimulatory molecule that can be used to enhance protection against bacterial respiratory infections. In addition, our data suggest that priming of the innate immune system by c-di-GMP could further skew the immune response towards a Th1 type phenotype during subsequent infection. Thus, our data suggest that c-di-GMP might be useful as an adjuvant for the next generation of acellular pertussis vaccine to mount a more protective Th1 phenotype immune response, and also in other systems where a Th1 type immune response is required. 相似文献
39.
Markus Grabenbauer Kurt Sätzler Eveline Baumgart H. Dariush Fahimi 《Cell biochemistry and biophysics》2000,32(1-3):37-49
Peroxisomes in the human hepatoblastoma cell line, HepG2, exhibit distinct alterations of shape, size, and distribution, dependent
on culture conditions (cell density, duration in culture, and presence of specific growth factors). Although many cells with
elongated tubular peroxisomes are present in thinly seeded cultures, spherical particles forming large focal clusters are
found in confluent cultures. The authors have analyzed the ultrastructure and the spatial relationship of peroxisomes of HepG2
cells at different stages of differentiation, using three-dimensional (3D)-reconstruction of ultrathin serial sections, and
electronic image processing. Cells were prepared for immunofluorescence using different antibodies against peroxisomal matrix
and membrane proteins, as well as for electron microscopy after the alkaline 3,3′-diaminobenzidine staining for catalase.
The results indicate that the tubular peroxisomes, which can reach a length of several microns, are consistently isolated,
and never form an interconnected peroxisomal reticulum. At the time of disappearance of tubular peroxisomes, rows of spherical
peroxisomes, arranged like beads on a string, are observed, suggesting fission of tubular ones. In differentiated confluent
cultures, clusters of several peroxisomes are seen, which, by immunofluorescence, appear as large aggregates, but after 3D
reconstruction consist of single spherical and angular peroxisomes without interconnections. The majority of such mature spherical
peroxisomes (but not the tubular ones) exhibit tail-like, small tubular and vesicular attachments to their surface, suggesting
a close functional interaction with neighboring organelles, particularly the endoplasmic reticulum, which is often observed
in close vicinity of such peroxisomes. 相似文献
40.
The peroxisome: an update on mysteries 总被引:1,自引:0,他引:1
Peroxisomes contribute to several crucial metabolic processes such as β-oxidation of fatty acids, biosynthesis of ether phospholipids and metabolism of reactive oxygen species, which render them indispensable to human health and development. Peroxisomes are highly dynamic organelles that rapidly assemble, multiply and degrade in response to metabolic needs. In recent years, the interest in peroxisomes and their physiological functions has significantly increased. This review intends to highlight recent discoveries and trends in peroxisome research, and represents an update as well as a continuation of a former review article. Novel exciting findings on the biological functions, biogenesis, formation and degradation of peroxisomes, on peroxisomal dynamics and division, as well as on the interaction and cross-talk of peroxisomes with other subcellular compartments are addressed. Furthermore, recent findings on the role of peroxisomes in the brain are discussed. 相似文献