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101.
Sohel M. Julovi Aiqun Xue Thao N. Thanh LE Anthony J. Gill Jerikho C. Bulanadi Mili Patel Lynne J. Waddington Kerry-Anne Rye Minoo J. Moghaddam Ross C. Smith 《PloS one》2016,11(3)
Background
Apolipoprotein A-II (ApoA-II) is down regulated in the sera of pancreatic ductal adenocarcinoma (PDAC) patients, which may be due to increase utilization of high density lipoprotein (HDL) lipid by pancreatic cancer tissue. This study examined the influence of exogenous ApoA-II on lipid uptake and cell growth in pancreatic cancer (PC) both in vitro and in vivo.Methods
Cryo transmission electron microscopy (TEM) examined ApoA-II’s influence on morphology of SMOFLipid emulsion. The influence of ApoA-II on proliferation of cancer cell lines was determined by incubating them with lipid+/-ApoA-II and anti-SR-B1 antibody. Lipid was labeled with the fluorophore, DiD, to trace lipid uptake by cancer cells in vitro by confocal microscopy and in vivo in PDAC patient derived xenograft tumours (PDXT) by fluorescence imaging. Scavenger receptor class B type-1(SR-B1) expression in PDAC cell lines and in PDAC PDXT was measured by western blotting and immunohistochemistry, respectively.Results
ApoA-II spontaneously converted lipid emulsion into very small unilamellar rHDL like vesicles (rHDL/A-II) and enhanced lipid uptake in PANC-1, CFPAC-1 and primary tumour cells as shown by confocal microscopy. SR-B1 expression was 13.2, 10.6, 3.1 and 2.3 fold higher in PANC-1, MIAPaCa-2, CFPAC-1 and BxPC3 cell lines than the normal pancreatic cell line (HPDE6) and 3.7 fold greater in PDAC tissue than in normal pancreas. ApoA-II plus lipid significantly increased the uptake of labeled lipid and promoted cell growth in PANC-1, MIAPaCa-2, CFPAC-1 and BxPC3 cells which was inhibited by anti SR-B1 antibody. Further, ApoA-II increased the uptake of lipid in xenografts by 3.4 fold.Conclusion
Our data suggest that ApoA-II enhance targeting potential of lipid in pancreatic cancer which may have imaging and drug delivery potentialities. 相似文献102.
Temporal relationship between neurotransmitter release and ion flux during spreading depression and anoxia 总被引:2,自引:0,他引:2
B Moghaddam J O Schenk W B Stewart A J Hansen 《Canadian journal of physiology and pharmacology》1987,65(5):1105-1110
Brain ion homeostasis is severely perturbed during spreading depression of Leao and during anoxia. The ionic composition of the extracellular space changes abruptly and approaches the intracellular concentrations owing to an increase in cell permeability. In spreading depression, synchronous transmitter efflux caused by a depolarization of the presynaptic terminals has been implicated as a possible mechanism that would explain the concomitant movement of ions. Anoxia, having many features in common with spreading depression, may follow the same mechanism. We have measured the concentrations of extracellular potassium with ion-selective microelectrodes and dopamine by in vivo voltammetry with carbon fiber microelectrodes during spreading depression and anoxia to compare the temporal relationship between the release of dopamine and ion movements in the striatum. There is a pronounced release of dopamine during both spreading depression and anoxia. In spreading depression, the sharp increase of potassium concentration that follows an initial smaller and slower increase of potassium is accompanied by the release of dopamine. In anoxia, the dopamine release clearly precedes the fast rise of extracellular potassium concentration. We conclude that in striatum, there is a pronounced dopamine release during spreading depression and anoxia, but that the relationships between ionic changes and transmitter release for these two phenomena are different and probably reflect different mechanisms. 相似文献
103.
Effects of alternate RNA splicing on glucokinase isoform activities in the pancreatic islet, liver, and pituitary 总被引:6,自引:0,他引:6
Y Liang T L Jetton E C Zimmerman H Najafi F M Matschinsky M A Magnuson 《The Journal of biological chemistry》1991,266(11):6999-7007
Different glucokinase isoforms are produced by tissue-specific alternative RNA splicing in the liver and pancreatic islet, the only tissues in which glucokinase activity has been detected. To determine whether differences in protein structure brought about by alternative RNA splicing have an effect on glucose phosphorylating activity, we expressed cDNAs encoding four different hepatic and islet glucokinase isoforms and determined the Km and Vmax of each. When the glucokinase B1 and L1 isoforms were expressed in eukaryotic cells, both high Km glucose phosphorylating activity and immunoreactive protein were detected. However, when the glucokinase B2 and L2 isoforms were expressed, both of which differ by deletion of 17 amino acids in a region between the putative glucose and ATP-binding domains, no high Km glucose phosphorylating activity and much less immunoreactive protein were detected. When the glucokinase B1 and B2 isoforms were expressed in Escherichia coli as fusion proteins with glutathione S-transferase, affinity-purified B1 fusion protein was able to phosphorylate glucose whereas the B2 fusion protein was not, thus indicating that the lack of glucose phosphorylating activity from both the B2 and L2 isoforms is due to lack of intrinsic activity in addition to accumulation of less protein. The Km values of the B1 and L1 isoforms, which differ from each other by 15 amino acids at the NH2 terminus, were similar, but the Vmax of the B1 isoform was 2.8-fold higher than that of the L1 isoform. Mutagenesis of the first two potential initiation codons in the glucokinase B1 cDNA from ATG to GTC (methionine to valine) indicated that the first ATG was crucial for activity and is, therefore, the likely translation initiation codon. Messenger RNAs encoding both the B2 and L2 isoforms of glucokinase were detected in islet and liver by polymerase chain reaction amplification of total cDNA, indicating that mRNAs utilizing this weak alternate splice acceptor site in the fourth exon are normally present in both the liver and islet but as minor components. A regulatory role for weak alternate splice acceptor and donor sites in the glucokinase gene was suggested by examining the expression of the gene in the pituitary and in AtT-20 cells. Interestingly, although glucokinase mRNAs of appropriate sizes were detected in both the AtT-20 cells and rat pituitaries, neither exhibited any detectable high Km glucose phosphorylating activity.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
104.
Mohammad Moghaddam Reza Omidbiagi Mohammad Reza Naghavi 《Biochemical Systematics and Ecology》2011,39(4-6):619-626
Amplified fragment length polymorphism (AFLP) markers were used to assess the genetic, diversity of 120 Ocimum accessions belonging to five species and varieties named: Ocimum ciliatum, Ocimum minimum, Ocimum basilicum var. purpurascens, O. basilicum var. dianatnejadii and O. basilicum var. alba. Eight AFLP primer combinations revealed 150 polymorphic bands (59.5%). The highest and the lowest PIC were 0.87 and 0.81 for E-CAA/M-ACC and E-CAA/M-AGA primer combinations, respectively, with average polymorphic information content (PIC) value of 0.84 over all primer combinations. Cluster analysis based on unweighted pair group method with arithmetic Average (UPGMA) and Jaccard’s coefficient grouped the five species and varieties into two main clusters. The first cluster contained the accessions belonging to O. ciliatum and the second comprised different botanical varieties of O. basilicum and O. minimum. The means of Shannon’s diversity index and Nei’s index of genetic diversity indicated that O. basilicum had the greatest variation, while O. ciliatum showed the least variation. Nei’s genetic identity measured in five Ocimum species and botanical varieties revealed the highest identity (0.939) between O. minimum and O. basilicum var. purpurascens and the lowest genetic identity (0.611) between O. basilicum var. purpurascens and O. ciliatum. In conclusion AFLP results indicated that O. minimum should be considered as a variety of O. basilicum. 相似文献
105.
106.
Bagher Farhood Keywan Mortezaee Nasser Hashemi Goradel Neda Khanlarkhani Ensieh Salehi Maryam Shabani Nashtaei Masoud Najafi Amirhossein Sahebkar 《Journal of cellular physiology》2019,234(5):5728-5740
Cancer is the second cause of death worldwide. Chemotherapy and radiotherapy are the most common modalities for the treatment of cancer. Experimental studies have shown that inflammation plays a central role in tumor resistance and the incidence of several side effects following both chemotherapy and radiotherapy. Inflammation resulting from radiotherapy and chemotherapy is responsible for adverse events such as dermatitis, mucositis, pneumonitis, fibrosis, and bone marrow toxicity. Chronic inflammation may also lead to the development of second cancer during years after treatment. A number of anti-inflammatory drugs such as nonsteroidal anti-inflammatory agents have been proposed to alleviate chronic inflammatory reactions after radiotherapy or chemotherapy. Curcumin is a well-documented herbal anti-inflammatory agents. Studies have proposed that curcumin can help management of inflammation during and after radiotherapy and chemotherapy. Curcumin targets various inflammatory mediators such as cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor κB (NF-κB), thereby attenuating the release of proinflammatory and profibrotic cytokines, and suppressing chronic production of free radicals, which culminates in the amelioration of tissue toxicity. Through modulation of NF-κB and its downstream signaling cascade, curcumin can also reduce angiogenesis, tumor growth, and metastasis. Low toxicity of curcumin is linked to its cytoprotective effects in normal tissues. This protective action along with the capacity of this phytochemical to sensitize tumor cells to radiotherapy and chemotherapy makes it a potential candidate for use as an adjuvant in cancer therapy. There is also evidence from clinical trials suggesting the potential utility of curcumin for acute inflammatory reactions during radiotherapy such as dermatitis and mucositis. 相似文献
107.
Nasser Hashemi Goradel Masoud Najafi Eniseh Salehi Bagher Farhood Keywan Mortezaee 《Journal of cellular physiology》2019,234(5):5683-5699
Cyclooxygenase-2 (COX-2) is frequently expressed in many types of cancers exerting a pleiotropic and multifaceted role in genesis or promotion of carcinogenesis and cancer cell resistance to chemo- and radiotherapy. COX-2 is released by cancer-associated fibroblasts (CAFs), macrophage type 2 (M2) cells, and cancer cells to the tumor microenvironment (TME). COX-2 induces cancer stem cell (CSC)-like activity, and promotes apoptotic resistance, proliferation, angiogenesis, inflammation, invasion, and metastasis of cancer cells. COX-2 mediated hypoxia within the TME along with its positive interactions with YAP1 and antiapoptotic mediators are all in favor of cancer cell resistance to chemotherapeutic drugs. COX-2 exerts most of the functions through its metabolite prostaglandin E2. In some and limited situations, COX-2 may act as an antitumor enzyme. Multiple signals are contributed to the functions of COX-2 on cancer cells or its regulation. Members of mitogen-activated protein kinase (MAPK) family, epidermal growth factor receptor (EGFR), and nuclear factor-κβ are main upstream modulators for COX-2 in cancer cells. COX-2 also has interactions with a number of hormones within the body. Inhibition of COX-2 provides a high possibility to exert therapeutic outcomes in cancer. Administration of COX-2 inhibitors in a preoperative setting could reduce the risk of metastasis in cancer patients. COX-2 inhibition also sensitizes cancer cells to treatments like radio- and chemotherapy. Chemotherapeutic agents adversely induce COX-2 activity. Therefore, choosing an appropriate chemotherapy drugs along with adjustment of the type and does for COX-2 inhibitors based on the type of cancer would be an effective adjuvant strategy for targeting cancer. 相似文献
108.
Nasser Hashemi Goradel Nasir Mohajel Ziba Veisi Malekshahi Samira Jahangiri Masoud Najafi Bagher Farhood Keywan Mortezaee Babak Negahdari Arash Arashkia 《Journal of cellular physiology》2019,234(6):8636-8646
Cancer therapy using oncolytic viruses is an emerging area, in which viruses are engineered to selectively propagate in tumor tissues without affecting healthy cells. Because of the advantages that adenoviruses (Ads) have over other viruses, they are more considered. To achieve tumor selectivity, two main modifications on Ads genome have been applied: small deletions and insertion of tissue- or tumor-specific promoters. Despite oncolytic adenoviruses ability in tumor cell lysis and immune responses stimulation, to further increase their antitumor effects, genomic modifications have been carried out including insertion of checkpoint inhibitors and antigenic or immunostimulatory molecules into the adenovirus genome and combination with dendritic cells and chemotherapeutic agents. This study reviews oncolytic adenoviruses structures, their antitumor efficacy in combination with other therapeutic strategies, and finally challenges around this treatment approach. 相似文献
109.
Hosseini Nashmin Fayazi Dalirfardouei Razieh Aliramaei Mohammad Reza Najafi Rezvan 《Biotechnology letters》2022,44(2):159-177
Biotechnology Letters - It only took 8 months for the pneumonia caused by a previously unknown coronavirus to turn into a global pandemic of unprecedentedly far-reaching implications. Failure of... 相似文献
110.
Hamid Tanzadehpanah Hanie Mahaki Neda Hosseinpour Moghadam Sadegh Salehzadeh Omid Rajabi Rezvan Najafi 《Journal of biomolecular structure & dynamics》2019,37(4):823-836
This study was carried out to evaluate the binding interaction of gefitinib (GEF) with human serum albumin (HSA) and calf thymus DNA (ct-DNA) using fluorescence, UV–Visible, zeta potential measurements and molecular docking methods in order to understand its pharmacokinetic mechanism. By increasing the temperature, a steady decrease in Stern–Volmer quenching constants was observed for HSA binding properties; this indicates a static type of fluorescence quenching. Negative values were calculated for Gibbs free energy (ΔG), enthalpy (ΔH), and entropy (ΔS) changes, indicating that the reaction is spontaneous and enthalpy-driven. Probe competitive experimental results showed that GEF contains the same binding site as warfarin and are consistent with modeling results. The zeta potential of the HSA increased with increasing GEF, which represents the presence of electrostatic interactions in the system. DNA binding properties were investigated in the presence of three probes. The experimental results showed that by increasing GEF to DNA-AO (acridine-orange) and DNA-MB (methylene-blue) system, the fluorescence intensity and absorbance spectra had no considerable change. Furthermore, with the addition of GEF to DNA, the zeta potential decreased gradually, indicating that the hydrophobic interaction between the GEF and the bases of DNA is the major factor. Thus, GEF can bind to DNA via a groove binding mode. It was also found that GEF entered into the minor groove in the A–T rich region of DNA fragment and bind via van der-Waals forces and three H-bond with double strands of DNA. This is in good agreement with experimental results. 相似文献