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941.
PGE2 plays an important role in a broad spectrum of physiological and pathological processes mediated through a membrane-bound G protein-coupled receptor (GPCR) called EP receptor. In mammals, four subtypes of EP receptor (EP 1-4) are identified and each of them functions through different signal transduction pathways. Orthologous EP receptors have also been identified in other non-mammalian species, such as chicken and zebrafish. EP4 is the only identified PGE2 receptor to date in Atlantic salmon but its tissue distribution and function have not been studied in any detail. In this study, we first sequenced EP4 receptor in different tissues and found that the presence of the 3nt deletion in the 5’ untranslated region was accompanied by silent mutation at nt 668. While attempting to amplify the same sequence in TO cells (an Atlantic salmon macrophage-like cell line), we failed to obtain the full-length product. Further investigation revealed different isoform of EP4 receptor in TO cells and we subsequently documented its presence in different Atlantic salmon tissues. These two isoforms of EP4 receptor share high homology in their first half of sequence but differ in the second half part with several deletion segments though the final length of coding sequence is the same for two isoforms. We further studied the immunomodulation effect of PGE2 in TO cells and found that PGE2 inhibited the induction of CXCL-10, CCL-4, IL-8 and IL-1β genes expression in a time dependent manner and without cAMP upregulation. 相似文献
942.
Background
Long-term hypoxia (LTH) is an important stressor related to health and disease during development. At different time points from fetus to adult, we are exposed to hypoxic stress because of placental insufficiency, high-altitude residence, smoking, chronic anemia, pulmonary, and heart disorders, as well as cancers. Intrauterine hypoxia can lead to fetal growth restriction and long-term sequelae such as cognitive impairments, hypertension, cardiovascular disorders, diabetes, and schizophrenia. Similarly, prolonged hypoxic exposure during adult life can lead to acute mountain sickness, chronic fatigue, chronic headache, cognitive impairment, acute cerebral and/or pulmonary edema, and death.Aim
LTH also can lead to alteration in metabolites such as fumarate, 2-oxoglutarate, malate, and lactate, which are linked to epigenetic regulation of gene expression. Importantly, during the intrauterine life, a fetus is under a relative hypoxic environment, as compared to newborn or adult. Thus, the changes in gene expression with development from fetus to newborn to adult may be as a consequence of underlying changes in the metabolic profile because of the hypoxic environment along with developmental maturation. To examine this possibility, we examined the metabolic profile in carotid arteries from near-term fetus, newborn, and adult sheep in both normoxic and long-term hypoxic acclimatized groups.Results
Our results demonstrate that LTH differentially regulated glucose metabolism, mitochondrial metabolism, nicotinamide cofactor metabolism, oxidative stress and antioxidants, membrane lipid hydrolysis, and free fatty acid metabolism, each of which may play a role in genetic-epigenetic regulation. 相似文献943.
Han Gil Seo Nam-Jong Paik Shi-Uk Lee Byung-Mo Oh Min Ho Chun Bum Sun Kwon Moon Suk Bang 《PloS one》2015,10(6)
Background
Botulinum toxin type A is widely used for treating spasticity. Neuronox (Neu-BoNT/A), a newly manufactured botulinum toxin a, has not yet been investigated for its efficacy and safety in the treatment of post-stroke upper limb spasticity.Objective
We evaluated the efficacy and safety of Neuronox (Neu-BoNT/A) compared with BOTOX (onabotulinum toxin A) for treating post-stroke upper limb spasticity.Methods
In total, 196 stroke patients with moderate to severe upper limb spasticity were randomly assigned to either Neuronox or BOTOX intervention. The wrist flexors were mandatory and elbow, finger, and thumb flexors were optional muscles to be injected. Assessments were performed at baseline and 4, 8, and 12 weeks after the intervention. The primary outcome measure was the change from baseline of the Modified Ashworth Scale (MAS) at the wrist flexors at week 4. Secondary outcome measures included the change of MAS at each visit, response rate, Disability Assessment Scale (DAS), Carer Burden Scale, and Global Assessment of treatment benefit.Results
Primary outcome measures were -1.39±0.79 and -1.56±0.81 in the Neuronox and BOTOX groups, respectively. The difference was within the noninferiority margin of 0.45 (95% upper limit=0.40). There were no significant differences between the groups in the secondary outcome and safety measures, except the change of the MAS at the elbow flexors at week 12 (-0.88±0.75 in the Neuronox group, -0.65±0.74 in the BOTOX group; P=0.0429). Both groups showed significant improvements in the MAS, DAS, and Carer Burden Scale at weeks 4, 8, and 12.Conclusion
Neuronox showed equivalent efficacy and safety compared with BOTOX for treating post-stroke upper limb spasticity.Trial Registration
ClinicalTrials.gov NCT01313767 相似文献944.
Sean Michael Carroll Ming‐Chun Lee Christopher J. Marx 《Evolution; international journal of organic evolution》2014,68(3):760-771
Adaptation of one set of traits is often accompanied by attenuation of traits important in other selective environments, leading to fitness trade‐offs. The mechanisms that either promote or prevent the emergence of trade‐offs remain largely unknown, and are difficult to discern in most systems. Here, we investigate the basis of trade‐offs that emerged during experimental evolution of Methylobacterium extorquens AM1 to distinct growth substrates. After 1500 generations of adaptation to a multi‐carbon substrate, succinate (S), many lineages had lost the ability to use one‐carbon compounds such as methanol (M), generating a mixture of M+ and M? evolved phenotypes. We show that trade‐offs in M? strains consistently arise via antagonistic pleiotropy through recurrent selection for loss‐of‐function mutations to ftfL (formate‐tetrahydrofolate ligase), which improved growth on S while simultaneously eliminating growth on M. But if loss of FtfL was beneficial, why were M trade‐offs not found in all populations? We discovered that eliminating FtfL was not universally beneficial on S, as it was neutral or even deleterious in certain evolved lineages that remained M+. This suggests that sign epistasis with earlier arising mutations prevented the emergence of mutations that drove trade‐offs through antagonistic pleiotropy, limiting the evolution of metabolic specialists in some populations. 相似文献
945.
946.
Chun Liu Beihai Ge Chao He Yi Zhang Xiaowen Liu Kejian Liu Cuiping Qian Yu Zhang Wenzhong Peng Xiaomei Guo 《Biochemical and biophysical research communications》2014
Mitofusin 2 (Mfn2) inhibits atherosclerotic plaque formation, but the underlying mechanism remains elusive. This study aims to reveal how Mfn2 functions in the atherosclerosis. Mfn2 expression was found to be significantly reduced in arterial atherosclerotic lesions of both mice and human compared with healthy counterparts. Here, we observed that Mfn2 increased cellular cholesterol transporter expression in macrophages by upregulating peroxisome proliferator-activated receptor-γ, an effect achieved at least partially by inhibiting extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) pathway. These findings provide insights into potential mechanisms of Mfn2-mediated alterations in cholesterol transporter expression, which may have significant implications for the treatment of atherosclerotic heart disease. 相似文献
947.
948.
Chun Tang Yun Li Xiaojun Lin Jinghua Ye Weinian Li Zhixiang He Fangfei Li Xiaoyan Cai 《Cellular immunology》2014
Tumor necrosis factor (TNF)-α is one of the major proinflammatory mediators of rheumatic arthritis (RA); the regulatory factors for TNF-α release is not fully understood. This study aims to investigate the role of prolactin receptor (PRLR) activation in regulating the expression and release of TNF-α from CD14+ monocytes. The results showed that the expression of PRLR was detectable in CD14+ monocytes of healthy subjects, which was markedly increased in RA patients. Exposure to PRL in the culture increased the expression and release of TNF-α from CD14+ monocytes, which was abolished by the PRLR gene silencing or blocking the mitogen activated protein (MAPK) pathway. We conclude that exposure to PRL increases TNF-α release from CD14+ monocytes of RA patients, which can be abolished by PRLR gene silencing or treating with MAPK inhibitor. 相似文献
949.
Lawrence J. Berliner 《European biophysics journal : EBJ》2010,39(4):579-588
This is a historical overview of the advent of applications of spin labeling to biological systems and the subsequent developments
from the perspective of a scientist who was working as a Ph.D. student when the technique was conceived and was fortunate
enough to participate in its development. In addition, the historical development of in vivo applications of EPR on animals
and other living systems is described from a personal perspective. 相似文献
950.
Boje Müller Gundula A. Noll Antonia M. Ernst Boris Rüping Sira Groscurth Richard M. Twyman Lawrence M. Kawchuk Dirk Prüfer 《Applied microbiology and biotechnology》2010,88(3):689-698
Forisomes are mechanoproteins that undergo ATP-independent contraction–expansion cycles triggered by divalent cations, pH
changes, and electrical stimuli. Although native forisomes from Medicago truncatula comprise a number of subunits encoded by separate genes, here we show that at least two of those subunits (MtSEO1 and MtSEO4)
can assemble into homomeric forisome bodies that are functionally similar to their native, multimeric counterparts. We expressed
these subunits in plants and yeast, resulting in the purification of large quantities of artificial forisomes with unique
characteristics depending on the expression platform. These artificial forisomes were able to contract and expand in vitro
like native forisomes and could respond to electrical stimulation when immobilized between interdigital transducer electrodes.
These results indicate that recombinant artificial forisomes with specific characteristics can be prepared in large amounts
and used as components of microscale and nanoscale devices. 相似文献