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排序方式: 共有3423条查询结果,搜索用时 12 毫秒
21.
22.
Roberto Lande Immacolata Pietraforte Anna Mennella Raffaella Palazzo Francesca Romana Spinelli Konstantinos Giannakakis Francesca Spadaro Mario Falchi Valeria Riccieri Katia Stefanantoni Curdin Conrad Cristiano Alessandri Fabrizio Conti Loredana Frasca 《International journal of molecular sciences》2021,22(4)
LL37 acts as T-cell/B-cell autoantigen in Systemic lupus erythematosus (SLE) and psoriatic disease. Moreover, when bound to “self” nucleic acids, LL37 acts as “danger signal,” leading to type I interferon (IFN-I)/pro-inflammatory factors production. T-cell epitopes derived from citrullinated-LL37 act as better antigens than unmodified LL37 epitopes in SLE, at least in selected HLA-backgrounds, included the SLE-associated HLA-DRB1*1501/HLA-DRB5*0101 backgrounds. Remarkably, while “fully-citrullinated” LL37 acts as better T-cell-stimulator, it loses DNA-binding ability and the associated “adjuvant-like” properties. Since LL37 undergoes a further irreversible post-translational modification, carbamylation and antibodies to carbamylated self-proteins other than LL37 are present in SLE, here we addressed the involvement of carbamylated-LL37 in autoimmunity and inflammation in SLE. We detected carbamylated-LL37 in SLE-affected tissues. Most importantly, carbamylated-LL37-specific antibodies and CD4 T-cells circulate in SLE and both correlate with disease activity. In contrast to “fully citrullinated-LL37,” “fully carbamylated-LL37” maintains both innate and adaptive immune-cells’ stimulatory abilities: in complex with DNA, carbamylated-LL37 stimulates plasmacytoid dendritic cell IFN-α production and B-cell maturation into plasma cells. Thus, we report a further example of how different post-translational modifications of a self-antigen exert complementary effects that sustain autoimmunity and inflammation, respectively. These data also show that T/B-cell responses to carbamylated-LL37 represent novel SLE disease biomarkers. 相似文献
23.
Neuroprotective Effects of Testosterone in the Hypothalamus of an Animal Model of Metabolic Syndrome
Erica Sarchielli Paolo Comeglio Sandra Filippi Ilaria Cellai Giulia Guarnieri Alessandra Marzoppi Sarah Cipriani Linda Vignozzi Annamaria Morelli Mario Maggi 《International journal of molecular sciences》2021,22(4)
Metabolic syndrome (MetS) is known to be associated to inflammation and alteration in the hypothalamus, a brain region implicated in the control of several physiological functions, including energy homeostasis and reproduction. Previous studies demonstrated the beneficial effects of testosterone treatment (TTh) in counteracting some MetS symptoms in both animal models and clinical studies. This study investigated the effect of TTh (30 mg/kg/week for 12 weeks) on the hypothalamus in a high-fat diet (HFD)-induced animal model of MetS, utilizing quantitative RT-PCR and immunohistochemical analyses. The animal model recapitulates the human MetS features, including low testosterone/gonadotropin plasma levels. TTh significantly improved MetS-induced hypertension, visceral adipose tissue accumulation, and glucose homeostasis derangements. Within hypothalamus, TTh significantly counteracted HFD-induced inflammation, as detected in terms of expression of inflammatory markers and microglial activation. Moreover, TTh remarkably reverted the HFD-associated alterations in the expression of important regulators of energy status and reproduction, such as the melanocortin and the GnRH-controlling network. Our results suggest that TTh may exert neuroprotective effects on the HFD-related hypothalamic alterations, with positive outcomes on the circuits implicated in the control of energy metabolism and reproductive tasks, thus supporting a possible role of TTh in the clinical management of MetS. 相似文献
24.
Margaret Ottaviano Emilio Francesco Giunta Marianna Tortora Marcello Curvietto Laura Attademo Davide Bosso Cinzia Cardalesi Mario Rosanova Pietro De Placido Erica Pietroluongo Vittorio Riccio Brigitta Mucci Sara Parola Maria Grazia Vitale Giovannella Palmieri Bruno Daniele Ester Simeone 《International journal of molecular sciences》2021,22(7)
As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients. 相似文献
25.
Luis O. Soto-Rojas B. Berenice Campa-Crdoba Charles R. Harrington Andrs Salas-Casas Mario Hernandes-Alejandro Ignacio Villanueva-Fierro Marely Bravo-Muoz Linda Garcs-Ramírez Fidel De La Cruz-Lpez Miguel ngel Ontiveros-Torres Goar Gevorkian Mar Pacheco-Herrero Jos Luna-Muoz 《International journal of molecular sciences》2021,22(7)
Alzheimer’s disease (AD) is a neurodegenerative disease, characterized histopathologically by intra-neuronal tau-related lesions and by the accumulation of amyloid β-peptide (Aβ) in the brain parenchyma and around cerebral blood vessels. According to the vascular hypothesis of AD, an alteration in the neurovascular unit (NVU) could lead to Aβ vascular accumulation and promote neuronal dysfunction, accelerating neurodegeneration and dementia. To date, the effects of insoluble vascular Aβ deposits on the NVU and the blood–brain barrier (BBB) are unknown. In this study, we analyze different Aβ species and their association with the cells that make up the NVU. We evaluated post-mortem AD brain tissue. Multiple immunofluorescence assays were performed against different species of Aβ and the main elements that constitute the NVU. Our results showed that there are insoluble vascular deposits of both full-length and truncated Aβ species. Besides, insoluble aggregates are associated with a decrease in the phenotype of the cellular components that constitute the NVU and with BBB disruption. This approach could help identify new therapeutic targets against key molecules and receptors in the NVU that can prevent the accumulation of vascular fibrillar Aβ in AD. 相似文献
26.
27.
Summary The catalytic performance (activity and polymer properties) of metallocenes with different symmetries in combination with methylaluminoxane (MAO) in the polymerization of propylene has been investigated at different temperatures, under standardized reaction conditions. The zirconocene rac-ethylene (5-1-indenyl) zirconium (IV) dichloride, with C2 symmetry, produces isotatic polypropylene and isopropylidene(5-cyclopentadienyl (5-9-fluorenyl) zirconium (IV) dichloride, with C
S
symmetry, syndiotactic polypropylene. The degree of the tacticity of these polymers increases with decreasing polymerization temperature. Only atactic polypropylene was formed with the unbridged zirconocenes bis(5-cyclopentadienyl) zirconium (IV) dichloride and bis(5-indenyl zirconium (IV) dichloride at any temperature investigated (10–60°C). 相似文献
28.
The report presents an innovative solar barometric distillation technology for seawater desalting (SW-SBD) which has several attractive features such as: (1) efficient vacuum solar collectors of simple construction; (2) a barometric layout for quasi-steady operation at subatmospheric pressure; (3) a demister system of simple mechanical construction; and (4) an electronic control system regulating plant productivity parameters on available solar radiation flux. The proposed seawater desalting technology consists of single-effect distillation with water vapor produced and heated at subatmospheric pressure in a solar collector loop; the basic layout, operational features, and energy efficiency are presented and analysed in detail. Subsequent reports will provide technico-economical data from prototype desalting plants in view of industrial implementation. A promising specific electric energy consumption,∼2 kWm3 offresh water produced, was found by estimating pumping power requirements of major SW-SBD plant pumps. A sizable reduction in produced water cost with respect to an existing solar seawater desalting plant in Abu Dhabi is expected on the basis of a preliminary economic evaluation for a ∼100 m3/d plant prototype. 相似文献
29.
Anibal Mario Nervi Raul Omar Peluffo Rodolfo R. Brenner Alicia Isabel Leikin 《Lipids》1980,15(4):263-268
The effect of ethanol on the fatty acid desaturation by rat liver has been studied using liquid diets of different composition.
Acute ethanol administration increased triacylglycerols of total liver lipids, but did not modify significantly the lipidic
composition of microsomes. The Δ6 and Δ5 desaturases were inhibited by ethanol whereas the Δ9 desaturase and fatty acid synthetase
were apparently modified only by diet composition. NADH-cytochrome (cyt.) c reductase was partially inhibited, whereas NADH-cyt.
b5 reductase remained practically unaltered and NADPH-cyt. c reductase activity was enhanced. Decreased electrons supplied by
the microsomal cyt. b5 electron transport chain would not be the reason for the inhibition of Δ6 and Δ5 desaturases by ethanol. 相似文献
30.
Fiber Coating Concepts for Brittle-Matrix Composites 总被引:4,自引:0,他引:4
Janet B. Davis Jan P. A. Löfvander Anthony G. Evans Ewald Bischoff Mario L. Emiliani 《Journal of the American Ceramic Society》1993,76(5):1249-1257
The current interest in tough, high-temperature materials has motivated fiber coating development for brittle-matrix composites with brittle reinforcements. Such coatings are needed for controlled interface debonding and frictional sliding. The system investigated in this study was sapphire fiber-reinforced alumina. This system is thermochemically stable for severe use conditions, exhibits little thermal expansion mismatch, and utilizes the excellent strength and creep resistance of sapphire reinforcements. Porous oxide and refractory metal coatings which satisfy requirements for toughness improvement in these composites were identified by employing a variety of newly developed mechanical testing techniques for determining the interfacial fracture energies and sliding resistances. 相似文献