ABSTRACT
[Objective] To investigate the effects of mitochondrial unfolded-protein response (UPRmt) on the aggregation toxicity of Aβ protein in Alzheimer's disease (AD).[Methods] By cloning the mitochondrial outer membrane tomm-22,inner membrane E04A4.5 and atfs-1 genes of Caenorhabditis elegans (C.elegans) and constructing the L4440 interference vectors,HT115 competent cells were transformed to prepare tomm-22,E04A4.5 and atfs-1 RNAi bacteria.The effects of tomm-22 and E04A4.5 RNAi on the process of paralysis were investigated through transgenic AD disease models CL4176 and CL2006.The life span of wild type N2 C.elegans was observed after RNAi of tomm-22 and E04A4.5.The regulatory role of ATFS-1 signaling by atfs-1 RNAi in inhibition of Aβ protein aggregation was detected.The dynamic changes of UPRmt in transgenic SJ4100 nematode and the autophagy level in transgenic DA2123 nematodes were analyzed by tomm-22 and E04A4.5 RNAi.[Results] We successfully established the UPRmt model by cloning mitochondrial tomm-22 and E04A4.5 of C.elegans and further constructing RNAi bacteria,and showed that they can suppress aggregation toxicity of Amyloid-β (Aβ) protein in AD model CL4176,and slow down paralysis process.The life span of wild type N2 was significantly shortened after feeding with the tomm-22 and E04A4.5 RNAi bacteria.At the same time,the progressive paralysis AD model CL2006 shows a delayed paralysis in the early stage of life cycle but get acceleration in the late.These results illustrate that the UPRmt can alleviate the mitochondrial stress and improve the function of mitochondria at least in the short term.The atfs-1 RNAi confirmed that delayed paralysis process of AD model CL4176 is not directly related to the ATFS-1 signal.However,tomm-22 and E04A4.5 RNAi can gradually increase the UPRmt response and induce the expression level of autophagy-related molecules LGG-1,suggesting that tomm-22 and E04A4.5 RNAi may play a role in delaying the AD disease process by enhancing the activity of autophagy in C.elegans.[Conclusions] The study found that the UPRmt can inhibit the accumulation of A β protein by coordinating the signal transduction between mitochondria and nucleus,and can help to restore mitochondria and even intracellular protein homeostasis for protecting the normal physiological function of cells,and also provides new targets for prevention and treatment of neurodegenerative diseases such as AD.
ABSTRACT
Endothelial leukocyte adhesion molecule -1 ( ELAM -1 ) is a member of the cell adhesion molecules,which plays a great role in the distant metastasis of tumor in ligand interactions between sLe (x)and sLe(a).Recently,it becomes a new research hotspot on applying ELAM -1 in targeted cancer therapy.Many studies results show that by regulation of ELAM -1 in biological effects ,such as ELAM-1 and ligand inhibitors , monoclonal antibody ,targeting gene ,and other mediates of the path of blocking therapy ,thereby inhibiting or bloc-king tumor distant metastasis ,so as to achieve the purpose of tumor therapy and improve the prognosis .Therefore , ELAM-1 is expected to exert a critical role in the tumor targeted therapy .In this paper ,the application value of ELAM-1 in tumor related targeted therapy is reviewed .
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the biotransformation of daphnetin by suspension transgenic hairy root of Polygonum multiflorum and provide a biotechnological method for large-scale production of the daphnetin-8-O-beta-D-glucoside using this new culture system.</p><p><b>METHOD</b>Daphnetin was added into the media of suspension to culture 36 h. The biotransformation product was detected with TLC and HPLC, and isolated by various chromatographic methods. The influence of co-cultured time on conversion ratio, content of degradation product and the reason for the degradation of product II were investigated using HPLC.</p><p><b>RESULT</b>One biotransformation product, daphnetin-8-O-beta-D-glucoside, was obtained, the optimal co-cultured time in suspension hairy root of P. multiflorum was 36 h with the highest biotransformation molar ratio of 32.11%, the sucrose medium (sucrose-only) can increase the biotransformation molar ratio to 72.44%. The result demonstrated that the degradation products of the product II was induced by the MS medium.</p><p><b>CONCLUSION</b>The potential application of suspension transgenic hairy root of P. multflorum in the sucrose-only medium on generating daphnetin-8-Obeta-D- glucoside could be prospective.</p>
Subject(s)
Biotransformation , Coculture Techniques , Glucosides , Metabolism , Plant Roots , Genetics , Metabolism , Plants, Genetically Modified , Polygonum , Genetics , Metabolism , Umbelliferones , MetabolismABSTRACT
Objective To explore the influence of nursing intervention on knowledge,attitude and behavior on patients with abnormal glucose metabolism during pregnancy.Methods 220 cases of abnormal glucose metabolism during pregnancy were randomly divided into the experimental group and the control group,110 patients in each group.The patients in the control group were given only the general health education.The patients in the experimental group were given a series of nursing interventions on this basis.Mter treatment patients were investigated with influence of nursing intervention on knowledge,auimde and behavior.Results The gestational diabetes knowledge and treatment compliance of awareness in the experimental group were better than the control group.Conclusions During the blood glucose control treat-ment for patients with abnormal glucose metabolism during pregnancy,taking some care interventions can improve the patients' knowledge awareness and treatment compliance,and thus effectively control blood sugar levels,reduce the incidence of complications,making pregnancy safer and healthier.