排序方式: 共有91条查询结果,搜索用时 156 毫秒
61.
The eye uses vitamin A as a cofactor to sense light and, during this process, some vitamin A molecules dimerize, forming vitamin A dimers. A striking chemical signature of retinas undergoing degeneration in major eye diseases such as age-related macular degeneration (AMD) and Stargardt disease is the accumulation of these dimers in the retinal pigment epithelium (RPE) and Bruch’s membrane (BM). However, it is not known whether dimers of vitamin A are secondary symptoms or primary insults that drive degeneration. Here, we present a chromatography-free method to prepare gram quantities of the vitamin A dimer, A2E, and show that intravenous administration of A2E to the rabbit results in retinal degeneration. A2E-damaged photoreceptors and RPE cells triggered inflammation, induced remolding of the choroidal vasculature and triggered a decline in the retina’s response to light. Data suggest that vitamin A dimers are not bystanders, but can be primary drivers of retinal degeneration. Thus, preventing dimer formation could be a preemptive strategy to address serious forms of blindness.KEY WORDS: Vitamin A, Neurodegeneration, Bisretinoids, A2E, RPE, Vitamin A dimer, Age-related macular degeneration, AMD, Stargardt 相似文献
62.
Vasoactive intestinal peptide (VIP), a 28-amino acid neuropeptide/neurotransmitter, is widely distributed in both the central and peripheral nervous system. VIP is released by both neurons and immune cells. Various cell types, including immune cells, express VIP receptors. VIP has pleiotropic effects as a neurotransmitter, immune regulator, vasodilator and secretagogue. This review is focused on VIP production and effects on immune cells, VIP receptor signaling as related to immune functions, and the involvement of VIP in inflammatory and autoimmune disorders. The review addresses present clinical use of VIP and future therapeutic directions. 相似文献
63.
Vernata V Grechko Doina G Ciobanu Ilya S Darevsky Sergey A Kosushkin Dmitri A Kramerov 《Génome》2006,49(10):1297-1307
Satellite DNA repeats were studied in Caucasian populations of 18 rock lizard species of the genus Darevskia. Four subfamilies (Caucasian Lacerta satellites (CLsat)I-IV) were identified, which shared 70%-75% sequence similarity. The distribution of CLsat subfamilies among the species was studied. All the species could be divided into at least 3 clades, depending on the content of CLsat subfamilies in each genome: "saxicola", "rudis", and "mixta" lizards. CLsatI was found in all studied species, but in very different quantities; the "saxicola" group contained this subfamily predominantly. The "rudis" group also contained CLsatIII, and the "mixta" group carried considerable amounts of CLsatII. The highest concentrations of CLsatI and CLsatII were detected in 2 ground lizards--D. derjugini and D. praticola, respectively. D. parvula predominantly carried CLsatIII. CLsatIV was found only in the Crimean species D. lindholmi. The distribution patterns of satellite subfamilies show possible postglacial speciation within the genus Darevskia. A hybrid origin of species that possess 2 or 3 CLsat subfamilies and important clarifications to the systematics of the genus are proposed. 相似文献
64.
Carasevici E Cozmei C Constantinescu D Sorete-Arbore A Grămadă D Mihăescu T 《Roumanian archives of microbiology and immunology》2006,65(1-2):46-52
Developing countries like Romania have a high incidence of tuberculosis. Literature data suggest that people in these countries have an important Th2-type immune background which prevents a protective Th1 response of the host against Mycobacterium tuberculosis. Our study is the first attempt in Romania to identify cytokine patterns in active tuberculosis. The study included 15 patients with active pulmonary tuberculosis and 11 healthy volunteers. Peripheral blood mononuclear cells (PBMC), stained with carboxyfluoresceine-diacetate-succinimidylester (CFSE), were incubated for 7 days with purified protein derivate (PPD) or with medium alone. Intracellular synthesis of IFNgamma and IL-4 in proliferated (CFSE(low)) T cells was detected by flowcytometry. The results showed that both Th1 (IFNgamma) and Th2 (IL-4) cytokines are produced in response to in vitro PPD-stimulation of PBMC from pulmonary tuberculosis patients and healthy controls. Moreover, the proportion between IFNgamma and IL-4 is tilted in favour of IL-4 in PPD-activated (CD3+ CFSE(low)) cells from healthy persons, who did not develop active tuberculosis during the two-year study time interval. This predominance of Th2 effectors points to the need to further investigate the role of IL-4 in the M. tuberculosis infection. 相似文献
65.
This review summarizes evidence on the effect of excess circulating glucose concentration and AGE-albumin on the aortic endothelial cells (ECs) phenotype, transport function, and expression of signalling molecules. The recent reports on the ECs dysfunction in diabetes are briefly reviewed, to provide a broader view on the link between ECs structural changes, functional alterations, and the underlying biochemical mechanisms. The original results emerging from streptozotocin-injected mice and human aortic endothelial cells grown in high (25 mM) glucose concentration are presented. Compared to physiological condition, in diabetes aortic ECs switch to a biosynthetic phenotype, present an increased number of caveolae, and enhance (by approximately 20%) transcytosis of AGE-albumin (AGE-Alb). In cultured ECs, 25 mM glucose induces approximately 2.6 fold increase in pSTAT-3 and pERK1 and approximately 1.8 fold increase in pERK2; further exposure to 5 microM AGE-Alb causes approximately 4.3 fold increase in pERK1/2 (vs. 5 mM glucose). Together, these data may explain the phenotypic change, enhanced permeability, and proliferation of aortic ECs in diabetic conditions. 相似文献
66.
Vassiliou E Sharma V Jing H Sheibanie F Ganea D 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(11):6955-6964
Since dendritic cells (DC) participate in both innate and adaptive immunity, their survival and expansion is tightly controlled. Little is known about the mechanisms of DC apoptosis. PGE(2), an arachidonic acid metabolite, plays an essential role in DC migration. We propose a novel function for PGE(2) as a DC survival factor. Our studies demonstrate that PGE(2) protects DC in vitro against apoptosis induced by withdrawal of growth factors or ceramide. DC matured in conditions that inhibit endogenous PGE(2) release are highly susceptible to apoptosis and exogenous PGE(2) re-establishes the more resistant phenotype. The antiapoptotic effect is mediated through EP-2/EP-4 receptors and involves the PI3K --> Akt pathway. PGE(2) leads to increased phosphorylation of Akt, protection against mitochondrial membrane compromise, and decreased caspase 3 activity. Macroarray data indicate that PGE(2) leads to the down-regulation of a number of proapoptotic molecules, i.e., BAD, several caspases, and granzyme B. In vivo, higher numbers of immature and Ag-loaded CFSE-labeled DC are present in the draining lymph nodes of mice inoculated with PGE(2) receptor agonists, compared with animals treated with ibuprofen or controls injected with PBS. This suggests that PGE(2) acts as an endogenous antiapoptotic factor for DC and raises the possibility of using PGE(2) agonists to increase the survival of Ag-loaded DC following in vivo administration. 相似文献
67.
Lewis TA Young MA Arrington MP Bayless L Cai X Collart P Eckman JB Ellis JL Ene DG Libertine L Nicolas JM Scannell RT Wels BF Wenberg K Wypij DM 《Bioorganic & medicinal chemistry letters》2004,14(22):5591-5594
A series of compounds possessing both H(1) histamine receptor antagonist and 5-lipoxygenase (5-LO) inhibitory activities was synthesized. The H(1)-binding scaffolds of cetirizine, efletirizine, and loratadine were linked to a lipophilic N-hydroxyurea, the 5-LO inhibiting moiety of zileuton. Both activities were observed in vivo, as was increased CYP3A4 inhibition compared to their respective single-function drugs. Selected analogs in the series were shown to be orally active in guinea pig models. 相似文献
68.
Radu DL Georgescu A Stavaru C Carale A Popov D 《Journal of cellular and molecular medicine》2004,8(3):349-358
The double transgenic mice (dTg) were obtained by mating: (i) transgenic mice expressing the hemagglutinin of influenza virus under the insulin promoter with (ii) transgenic mice expressing specific T lymphocytes with receptor for the immunodominant epitope of the same virus. In this study we show that dTg mice developed type 1 diabetes mellitus associated with hyperglycemia, low level of plasma insulin, glucosuria, weight loss and approximately 90% mortality (at 3 months biological age). The membrane of red blood cells was more sensitive to osmotic shock in diabetic mice, compared to non-diabetic mice, assessing systemic oxidative stress. Both vasoconstriction and vasorelaxation of the renal arteries decreased significantly in diabetic mice (compared to the control group of non-diabetic mice) related to the phenotypic change of endothelium and smooth muscle cells within the artery wall. This animal model, may be used in developing various strategies to study pancreatic beta-cell function, as well as for a better metabolic control conducting to a reduced risk of vascular complications. 相似文献
69.
Constantin A Constantinescu E Dumitrescu M Calin A Popov D 《Journal of cellular and molecular medicine》2005,9(3):683-691
In this study we investigated the effects of ageing on the carbonyl stress (protein carbonyls and 4-hydroxy-2-nonenal groups) and glutathione antioxidant defense in red blood cells (RBCs) of obese Type 2 diabetic patients with/without hypertensive complications. To this purpose the following methods were used: spectrophotometry (protein carbonyls, glutathione and glutathione peroxidase assays), immunofluorescence (4-hydroxy-2-nonenal localization), western blotting (immunodetection of carbonylated proteins). The results showed that compared to RBCs of healthy subjects, in obese Type 2 diabetics, ageing is associated with: (i) an increase in the concentration and expression of carbonylated proteins, a marker of oxidative stress; (ii) a decrease of both non-enzymatic and enzymatic endogenous glutathione defenses; (iii) a severely disturbed oxidant/antioxidant balance when obesity was associated with hypertension. The simultaneous insults of high blood pressure, obesity, and diabetes conducted to the highest carbonyl stress, exposure of 4-hydroxy-2-nonenal Michel adducts at the outer leaflet of RBCs plasmalemma, and the lowest glutathione antioxidant potential, particularly in elderly patients. These results can explain the gradual age-dependent diminishment of the detoxification potential of RBCs that at the old age can not overcome the deleterious effects of the high systemic oxidative stress. 相似文献
70.
Radu E Simionescu O Regalia T Dumitrescu D Popescu LM 《Journal of cellular and molecular medicine》2002,6(4):593-598
Epidermal stem cells (ESC) are responsible for maintaining skin cellular homeostasis, as they give rise to fast-dividing transit amplifying cells committed to terminal differentiation, while retaining their self-renewal capacity. However, no pure ESC cultures are available and no highly specific cytochemical marker was identified. We report here the experimental conditions allowing the selective enrichment in ESC, using cultured adult human keratinocytes. The main step was the selection of cells able to rapidly adhere to human collagen type IV in vitro . Thus, an increased proportion of putative ESC of about 65% was obtained, as demonstrated by p63 expression. 相似文献