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排序方式: 共有405条查询结果,搜索用时 15 毫秒
31.
Raed Salim Gali Garmi Zohar Nachum Eliezer Shalev 《Reproductive biology and endocrinology : RB&E》2010,8(1):81
Background
Variable decelerations are the most frequent fetal heart rate changes that are related to labor. The objective of the study was to estimate the impact of non-significant variable decelerations (NSV) appearing during the latent phase of labor on delivery mode and neonatal outcome. 相似文献32.
Immunotherapy with Bacillus Calmette–Guérin (BCG)—an attenuated strain of Mycobacterium bovis (M. bovis) used for anti tuberculosis immunization—is a clinically established procedure for the treatment of superficial bladder cancer.
However, the mode of action has not yet been fully elucidated, despite much extensive biological experience. The purpose of
this paper is to develop a first mathematical model that describes tumor-immune interactions in the bladder as a result of
BCG therapy. A mathematical analysis of the ODE model identifies multiple equilibrium points, their stability properties,
and bifurcation points. Intriguing regimes of bistability are identified in which treatment has potential to result in a tumor-free
equilibrium or a full-blown tumor depending only on initial conditions. Attention is given to estimating parameters and validating
the model using published data taken from in vitro, mouse and human studies. The model makes clear that intensity of immunotherapy
must be kept in limited bounds. While small treatment levels may fail to clear the tumor, a treatment that is too large can
lead to an over-stimulated immune system having dangerous side effects for the patient. 相似文献
33.
Goldin N Heyfets A Reischer D Flescher E 《Journal of bioenergetics and biomembranes》2007,39(1):51-57
Jasmonates are plant stress hormones that induce suppression of proliferation and death in cancer cells, while being selectively
inactive towards non-transformed cells. Jasmonates can overcome apoptotic blocks and exert cytotoxic effects on drug-resistant
cells expressing p53 mutations. Jasmonates induce a rapid depletion of ATP in cancer cells. Indeed, this steep drop occurs
when no signs of cell death are detectable yet. Experiments using modulators of ATP synthesis via glycolysis or oxidative
phosphorylation suggest that the latter is the pathway suppressed by jasmonates. Consequently, the direct effects of jasmonates
on mitochondria were evaluated. Jasmonates induced cytochrome c release and swelling in mitochondria isolated from cancer
cells but not from normal ones. Thus, the selectivity of jasmonates against cancer cells is rooted at the mitochondrial level,
and probably exploits differences between mitochondria from normal versus cancer cells. These findings position jasmonates
as promising anti-cancer drugs acting via energetic depletion in neoplastic cells. 相似文献
34.
Duarte CD Tributino JL Lacerda DI Martins MV Alexandre-Moreira MS Dutra F Bechara EJ De-Paula FS Goulart MO Ferreira J Calixto JB Nunes MP Bertho AL Miranda AL Barreiro EJ Fraga CA 《Bioorganic & medicinal chemistry》2007,15(6):2421-2433
We describe herein the discovery of LASSBio-881 (3c) as a novel in vivo antinociceptive, anti-inflammatory, and in vitro antiproliferative and antioxidant compound, with a cannabinoid ligand profile. We observed that LASSBio-881 (3c) was able to bind to CB1 receptors (71% at 100microM) and also to inhibit T-cell proliferation (66% at 10microM) probably by binding to CB2 receptors, in a non-proapoptotic manner, different from anandamide (1). It was also demonstrated that LASSBio-881 (3c) had an important antioxidant profile toward free radicals (DPPH and hydroxyl), probably due to its particular redox behavior, which reflects the presence of both nitro and 3,5-di-tert-butyl-4-hydroxyphenyl sub-units, as demonstrated by cyclic voltammetry studies. In addition, we showed that these structural sub-units are essential for the observed pharmacological activity. 相似文献
35.
Chlorophyllase is a rate-limiting enzyme in chlorophyll catabolism and is posttranslationally regulated 总被引:2,自引:0,他引:2
Harpaz-Saad S Azoulay T Arazi T Ben-Yaakov E Mett A Shiboleth YM Hörtensteiner S Gidoni D Gal-On A Goldschmidt EE Eyal Y 《The Plant cell》2007,19(3):1007-1022
Chlorophyll is a central player in harvesting light energy for photosynthesis, yet the rate-limiting steps of chlorophyll catabolism and the regulation of the catabolic enzymes remain unresolved. To study the role and regulation of chlorophyllase (Chlase), the first enzyme of the chlorophyll catabolic pathway, we expressed precursor and mature versions of citrus (Citrus sinensis) Chlase in two heterologous plant systems: (1) squash (Cucurbita pepo) plants using a viral vector expression system; and (2) transiently transformed tobacco (Nicotiana tabacum) protoplasts. Expression of full-length citrus Chlase resulted in limited chlorophyll breakdown in protoplasts and no visible leaf phenotype in whole plants, whereas expression of a Chlase version lacking the N-terminal 21 amino acids (ChlaseDeltaN), which corresponds to the mature protein, led to extensive chlorophyll breakdown in both tobacco protoplasts and squash leaves. ChlaseDeltaN-expressing squash leaves displayed a dramatic chlorotic phenotype in plants grown under low-intensity light, whereas under natural light a lesion-mimic phenotype occurred, which was demonstrated to follow the accumulation of chlorophyllide, a photodynamic chlorophyll breakdown product. Full-length and mature citrus Chlase versions were localized to the chloroplast membrane fraction in expressing tobacco protoplasts, where processing of the N-terminal 21 amino acids appears to occur. Results obtained in both plant systems suggest that Chlase functions as a rate-limiting enzyme in chlorophyll catabolism controlled via posttranslational regulation. 相似文献
36.
Cancer is a result of complex changes that occur in normal cells as they transform to become malignant and further when they become metastatic. These changes are not a consequence of a single protein but rather involve multiple proteins that function in pathways and networks. Thus, profiling cancer-associated changes requires simultaneous measurement of many proteins in a single sample. Identifying these changes may lead to the discovery of cancer-associated biomarkers that may assist in diagnosis, prognosis, patient monitoring and possibly for therapeutic purposes. Antibody arrays are a relatively new technology that enables one to perform multiplex high-throughput protein expression profiling. This review describes current technologies in antibody array and assay design, and presents a survey of the current literature on the use of these arrays in cancer research. 相似文献
37.
Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging
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Assaf Ben‐Meir Eliezer Burstein Aluet Borrego‐Alvarez Jasmine Chong Ellen Wong Tetyana Yavorska Taline Naranian Maggie Chi Ying Wang Yaakov Bentov Jennifer Alexis James Meriano Hoon‐Ki Sung David L. Gasser Kelle H. Moley Siegfried Hekimi Robert F. Casper Andrea Jurisicova 《Aging cell》2015,14(5):887-895
Female reproductive capacity declines dramatically in the fourth decade of life as a result of an age‐related decrease in oocyte quality and quantity. The primary causes of reproductive aging and the molecular factors responsible for decreased oocyte quality remain elusive. Here, we show that aging of the female germ line is accompanied by mitochondrial dysfunction associated with decreased oxidative phosphorylation and reduced Adenosine tri‐phosphate (ATP) level. Diminished expression of the enzymes responsible for CoQ production, Pdss2 and Coq6, was observed in oocytes of older females in both mouse and human. The age‐related decline in oocyte quality and quantity could be reversed by the administration of CoQ10. Oocyte‐specific disruption of Pdss2 recapitulated many of the mitochondrial and reproductive phenotypes observed in the old females including reduced ATP production and increased meiotic spindle abnormalities, resulting in infertility. Ovarian reserve in the oocyte‐specific Pdss2‐deficient animals was diminished, leading to premature ovarian failure which could be prevented by maternal dietary administration of CoQ10. We conclude that impaired mitochondrial performance created by suboptimal CoQ10 availability can drive age‐associated oocyte deficits causing infertility. 相似文献
38.
Spencer B Marr RA Gindi R Potkar R Michael S Adame A Rockenstein E Verma IM Masliah E 《PloS one》2011,6(1):e16575
Alzheimer's disease (AD), an incurable, progressive neurodegenerative disorder, is the most common form of dementia. Therapeutic options have been elusive due to the inability to deliver proteins across the blood-brain barrier (BBB). In order to improve the therapeutic potential for AD, we utilized a promising new approach for delivery of proteins across the BBB. We generated a lentivirus vector expressing the amyloid β-degrading enzyme, neprilysin, fused to the ApoB transport domain and delivered this by intra-peritoneal injection to amyloid protein precursor (APP) transgenic model of AD. Treated mice had reduced levels of Aβ, reduced plaques and increased synaptic density in the CNS. Furthermore, mice treated with the neprilysin targeting the CNS had a reversal of memory deficits. Thus, the addition of the ApoB transport domain to the secreted neprilysin generated a non-invasive therapeutic approach that may be a potential treatment in patients with AD. 相似文献
39.
Masliah E Rockenstein E Adame A Alford M Crews L Hashimoto M Seubert P Lee M Goldstein J Chilcote T Games D Schenk D 《Neuron》2005,46(6):857-868
Abnormal folding of alpha-synuclein (alpha-syn) is thought to lead to neurodegeneration and the characteristic symptoms of Lewy body disease (LBD). Since previous studies suggest that immunization might be a potential therapy for Alzheimer's disease, we hypothesized that immunization with human (h)alpha-syn might have therapeutic effects in LBD. For this purpose, halpha-syn transgenic (tg) mice were vaccinated with halpha-syn. In mice that produced high relative affinity antibodies, there was decreased accumulation of aggregated halpha-syn in neuronal cell bodies and synapses that was associated with reduced neurodegeneration. Furthermore, antibodies produced by immunized mice recognized abnormal halpha-syn associated with the neuronal membrane and promoted the degradation of halpha-syn aggregates, probably via lysosomal pathways. Similar effects were observed with an exogenously applied FITC-tagged halpha-syn antibody. These results suggest that vaccination is effective in reducing neuronal accumulation of halpha-syn aggregates and that further development of this approach might have a potential role in the treatment of LBD. 相似文献
40.
Hashimoto M Bar-On P Ho G Takenouchi T Rockenstein E Crews L Masliah E 《The Journal of biological chemistry》2004,279(22):23622-23629
Recent studies have shown that the neurodegenerative process in disorders with Lewy body formation, such as Parkinson's disease and dementia with Lewy bodies, is associated with alpha-synuclein accumulation and that beta-synuclein might protect the central nervous system from the neurotoxic effects of alpha-synuclein. However, the mechanisms are unclear. The main objective of the present study was to investigate the potential involvement of the serine threonine kinase Akt (also known as protein kinase B) signaling pathway in the mechanisms of beta-synuclein neuroprotection. For this purpose, Akt activity and cell survival were analyzed in synuclein-transfected B103 neuroblastoma cells and primary cortical neurons. Beta-synuclein transfection resulted in increased Akt activity and conferred protection from the neurotoxic effects of rotenone. Down-regulation of Akt expression resulted in an increased susceptibility to rotenone toxicity, whereas transfection with a lentiviral vector encoding for beta-synuclein was protective. The effects of beta-synuclein on the Akt pathway appear to be by direct interaction between these molecules and were independent of upstream signaling molecules. Taken together, these results indicate that the mechanisms of beta-synuclein neuroprotection might involve direct interactions between beta-synuclein and Akt and suggest that this signaling pathway could be a potential therapeutic target for neurological conditions associated with parkinsonism and alpha-synuclein aggregation. 相似文献