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31.
32.
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
33.
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
34.
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
35.
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
36.
M. F. Stroosnijder N. Zheng W. J. Quadakkers R. Hofman A. Gil F. Lanza 《Oxidation of Metals》1996,46(1-2):19-35
The effect of niobium implantation (2×1016 and 1017 ions/cm2) on the oxidation behavior of a -TiAl-based intermetallic alloy Ti–48Al–2Cr in air at 800°C has been examined. Isothermal studies with exposure times up to 200 hr and cyclic-oxidation tests up to 800 hr revealed a negligible effect for the low implantation dose. However, a remarkable decrease in oxidation rates was observed for the material implanted with 1017 Nb ions/cm2. The improvement in the oxidation resistance appeared to be similar to that obtained by alloying of the intermetallic with a few atomic percent niobium. Possible mechanisms for the effect of niobium on the oxidation resistance of TiAl-base intermetallics are discussed in view of the results obtained for the implanted material. 相似文献
37.
38.
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
39.
Seon Jeong Kim Seoung Gil Yoon Young Moo Lee Kay Hyeok An Sun I. Kim 《应用聚合物科学杂志》2003,90(5):1389-1392
Temperature‐responsive interpenetrating polymer network (IPN) hydrogels constructed with poly(vinyl alcohol) and poly(diallyldimethylammonium chloride) using the sequential IPN method were studied. The characteristics of IPN hydrogels were investigated using the dynamic vapor sorption system. IPN hydrogels exhibited a relatively high sorption ratio, 180–360% at room temperature. The sorption ratio of hydrogels depended on temperature. Diffusion coefficients were calculated according to the Fickian Law at several temperatures. The apparent activation energy was 5.43 kJ mol?1, which corresponds to typical diffusion processes. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1389–1392, 2003 相似文献
40.
Although carbon fiber epoxy composite materials have excellent properties for structures, the joint in composite materials often reduces the efficiency of the composite structure because the joint is often the weakest area in the composite structure.
In this paper, the effects of the adhesive thickness and the adherend surface roughness on the static and fatigue strengths of adhesively-bonded tubular polygonal lap joints have been investigated by experimental methods. The dependencies of the static and fatigue strengths on the stacking sequences of the composite adherends were observed.
From the experimental investigations, it was found that the fatigue strength of the circular adhesively-bounded joints was quite dependent on the surface roughness of the adherends and that polygonal adhesively-bonded joints had better fatigue strength characteristics than circular adhesively-bonded joints. 相似文献
In this paper, the effects of the adhesive thickness and the adherend surface roughness on the static and fatigue strengths of adhesively-bonded tubular polygonal lap joints have been investigated by experimental methods. The dependencies of the static and fatigue strengths on the stacking sequences of the composite adherends were observed.
From the experimental investigations, it was found that the fatigue strength of the circular adhesively-bounded joints was quite dependent on the surface roughness of the adherends and that polygonal adhesively-bonded joints had better fatigue strength characteristics than circular adhesively-bonded joints. 相似文献