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排序方式: 共有1772条查询结果,搜索用时 125 毫秒
91.
Mariarosaria Conte Rosanna Palumbo Alessandra Monti Elisabetta Fontana Angela Nebbioso Menotti Ruvo Lucia Altucci Nunzianna Doti 《International journal of molecular sciences》2022,23(1)
The AIF/CypA complex exerts a lethal activity in several rodent models of acute brain injury. Upon formation, it translocates into the nucleus of cells receiving apoptotic stimuli, inducing chromatin condensation, DNA fragmentation, and cell death by a caspase-independent mechanism. Inhibition of this complex in a model of glutamate-induced cell death in HT-22 neuronal cells by an AIF peptide (AIF(370-394)) mimicking the binding site on CypA, restores cell survival and prevents brain injury in neonatal mice undergoing hypoxia-ischemia without apparent toxicity. Here, we explore the effects of the peptide on SH-SY5Y neuroblastoma cells stimulated with staurosporine (STS), a cellular model widely used to study Parkinson’s disease (PD). This will pave the way to understanding the role of the complex and the potential therapeutic efficacy of inhibitors in PD. We find that AIF(370-394) confers resistance to STS-induced apoptosis in SH-SY5Y cells similar to that observed with CypA silencing and that the peptide works on the AIF/CypA translocation pathway and not on caspases activation. These findings suggest that the AIF/CypA complex is a promising target for developing novel therapeutic strategies against PD. 相似文献
92.
Seigo Nagashima Anderson Azevedo Dutra Mayara Pezzini Arantes Rafaela Chiuco Zeni Carolline Konzen Klein Flvia Centenaro de Oliveira Giulia Werner Piper Isadora Drews Brenny Marcos Roberto Curcio Pereira Rebecca Benicio Stocco Ana Paula Camargo Martins Eduardo Morais de Castro Caroline Busatta Vaz de Paula Andra Novaes Moreno Amaral Cleber Machado-Souza Cristina Pellegrino Baena Lucia Noronha 《International journal of molecular sciences》2022,23(3)
Mast cells (MCs) have relevant participation in inflammatory and vascular hyperpermeability events, responsible for the action of the kallikrein–kinin system (KKS), that affect patients inflicted by the severe form of COVID-19. Given a higher number of activated MCs present in COVID-19 patients and their association with vascular hyperpermeability events, we investigated the factors that lead to the activation and degranulation of these cells and their harmful effects on the alveolar septum environment provided by the action of its mediators. Therefore, the pyroptotic processes throughout caspase-1 (CASP-1) and alarmin interleukin-33 (IL-33) secretion were investigated, along with the immunoexpression of angiotensin-converting enzyme 2 (ACE2), bradykinin receptor B1 (B1R) and bradykinin receptor B2 (B2R) on post-mortem lung samples from 24 patients affected by COVID-19. The results were compared to 10 patients affected by H1N1pdm09 and 11 control patients. As a result of the inflammatory processes induced by SARS-CoV-2, the activation by immunoglobulin E (IgE) and degranulation of tryptase, as well as Toluidine Blue metachromatic (TB)-stained MCs of the interstitial and perivascular regions of the same groups were also counted. An increased immunoexpression of the tissue biomarkers CASP-1, IL-33, ACE2, B1R and B2R was observed in the alveolar septum of the COVID-19 patients, associated with a higher density of IgE+ MCs, tryptase+ MCs and TB-stained MCs, in addition to the presence of intra-alveolar edema. These findings suggest the direct correlation of MCs with vascular hyperpermeability, edema and diffuse alveolar damage (DAD) events that affect patients with a severe form of this disease. The role of KKS activation in events involving the exacerbated increase in vascular permeability and its direct link with the conditions that precede intra-alveolar edema, and the consequent DAD, is evidenced. Therapy with drugs that inhibit the activation/degranulation of MCs can prevent the worsening of the prognosis and provide a better outcome for the patient. 相似文献
93.
Maria Lucia Iacovino Chiara Carmen Miceli Marco De Felice Biagio Barone Luca Pompella Francesco Chiancone Erika Di Zazzo Giuseppe Tirino Carminia Maria Della Corte Ciro Imbimbo Ferdinando De Vita Felice Crocetto 《International journal of molecular sciences》2022,23(3)
Muscle invasive bladder cancer (MIBC) is a widespread malignancy with a worse prognosis often related to a late diagnosis. For early-stage MIBC pts, a multidisciplinary approach is mandatory to evaluate the timing of neoadjuvant chemotherapy (NAC) and surgery. The current standard therapy is platinum-based NAC (MVAC-methotrexate, vinblastine, doxorubicin, and cisplatin or Platinum–Gemcitabine regimens) followed by radical cystectomy (RC) with lymphadenectomy. However, preliminary data from Vesper trial highlighted that dose-dense NAC MVAC is endowed with a good pathological response but shows low tolerability. In the last few years, translational-based research approaches have identified several candidate biomarkers of NAC esponsiveness, such as ERCC2, ERBB2, or DNA damage response (DDR) gene alterations. Moreover, the recent consensus MIBC molecular classification identified six molecular subtypes, characterized by different sensitivity to chemo- or targeted or immunotherapy, that could open a novel procedure for patient selection and also for neoadjuvant therapies. The Italian PURE-01 phase II Trial extended data on efficacy and resistance to Immune Checkpoint Inhibitors (ICIs) in this setting. In this review, we summarize the most relevant literature data supporting NAC use in MIBC, focusing on novel therapeutic strategies such as immunotherapy, considering the better patient stratification and selection emerging from novel molecular classification. 相似文献
94.
Marie Ebeyer-Masotta Tanja Eichhorn Ren Weiss Vladislav Semak Lucia Laukov Michael B. Fischer Viktoria Weber 《International journal of molecular sciences》2022,23(3)
Inflammation and thrombosis are closely intertwined in numerous disorders, including ischemic events and sepsis, as well as coronavirus disease 2019 (COVID-19). Thrombotic complications are markers of disease severity in both sepsis and COVID-19 and are associated with multiorgan failure and increased mortality. Immunothrombosis is driven by the complement/tissue factor/neutrophil axis, as well as by activated platelets, which can trigger the release of neutrophil extracellular traps (NETs) and release further effectors of immunothrombosis, including platelet factor 4 (PF4/CXCL4) and high-mobility box 1 protein (HMGB1). Many of the central effectors of deregulated immunothrombosis, including activated platelets and platelet-derived extracellular vesicles (pEVs) expressing PF4, soluble PF4, HMGB1, histones, as well as histone-decorated NETs, are positively charged and thus bind to heparin. Here, we provide evidence that adsorbents functionalized with endpoint-attached heparin efficiently deplete activated platelets, pEVs, PF4, HMGB1 and histones/nucleosomes. We propose that this elimination of central effectors of immunothrombosis, rather than direct binding of pathogens, could be of clinical relevance for mitigating thrombotic complications in sepsis or COVID-19 using heparin-functionalized adsorbents. 相似文献
95.
de Oliveira Amanda Gerhardt Moreno Janaina Fernandes de Sousa Ana Maria Furtado Esccio Viviane Alves de Oliveira Cavalcanti Guimares Maria Jos da Silva Ana Lucia Nazareth 《Polymer Bulletin》2020,77(6):2889-2904
Polymer Bulletin - Investigating the compatibility mechanism of hybrid composites based on two polymers and one mineral nanofiller is a challenge that needs to be better understood. This study... 相似文献
96.
It is shown that peroxidation of phosphatidylcholine (PC) is enhanced in liver of mice fed a hepatocarcinogenic choline-deficient
diet containing 0.1% w/w ethionine. Mice were divided into 4 groups and fed for 3 weeks one of the following diets: choline-supplemented;
choline-supplemented containing ethionine; choline-deficient; and choline-deficient containing ethionine. Phosphatidylcholine
hydroperoxide (PCOOH) of liver lipids was measured by high performance liquid chromatography using a chemiluminescence detector.
Mice fed a choline-deficient diet containing ethionine showed 6-fold higher PCOOH levels than the choline-supplemented control
mice: the PCOOH/PC molar ratios of liver lipids were 32.3×10−5 and 5.6×10−5, respectively. In addition to this remarkable degree of lipid peroxidation in liver of mice fed the choline-deficient diet
containing ethionine, we also observed a significant liver fatty infiltration, a decrease in plasma and liver α-tocopherol,
and an increase in liver injury-indicative enzyme activities. Also, marker enzymes for hepatocarcinogenesis, glucose-6-phosphatase
and γ-glutamyl transpeptidase were affected. These data suggest that enhanced hydroperoxidation of phosphatidylcholine may
participate in hepatocarcinogenesis provoked by choline deficiency in the presence of ethionine. 相似文献
97.
Dr. Patricia García‐Domínguez Mélanie Weiss Ilaria Lepore Prof. Dr. Rosana Álvarez Prof. Dr. Lucia Altucci Prof. Dr. Hinrich Gronemeyer Prof. Dr. Ángel R. de Lera 《ChemMedChem》2012,7(12):2101-2112
A novel epigenetic modulator that displays a DNMT1 inhibition and DNMT3A activation profile was characterized (compound 8 ). This compound is a derivative of palmitic acid that incorporates the putative reactive functional group (diynone) of the peyssonenyne natural products. Other analogues containing the diynone or an acetoxyenediyne did not show the same biological profile. In U937 human leukemia cells, diynone 8 induced cell differentiation and apoptosis, which correlated with the expression of Fas protein. Very surprisingly, diynone 8 was toxic to normal human fibroblasts (BJ) and mouse embryo fibroblasts (MEF), but not to immortalized human fibroblasts (BJEL); this unique effect was not observed with the classical DNMT inhibitor 5‐azacytidine. Therefore, compound 8 interferes in a very specific manner with signaling pathways, the activities of which differ between normal and immortalized cell types. This toxicity is reminiscent of the effects of Dnmt1 ablation on mouse fibroblasts. In fact, some of the genes deregulated by the loss of Dnmt1 are similarly deregulated by 8 , but not by the DNMT inhibitor SGI‐1027. 相似文献
98.
The multi-scale Gibbs–Helmholtz constrained (GHC) equation is a new predictive cubic equation of state that constrains the energy parameter in the SRK equation to satisfy the Gibbs–Helmholtz equation. It makes use of internal energies of departure calculated from NTP Monte Carlo simulations at the molecular length scale and a novel up-scaling expression to determine the energy parameter at the bulk phase length scale. 相似文献
99.
Advances in Bioapplications of Carbon Nanotubes 总被引:1,自引:0,他引:1
Fushen Lu Lingrong Gu Mohammed J. Meziani Xin Wang Pengju G. Luo Lucia Monica Veca Li Cao Ya‐Ping Sun 《Advanced materials (Deerfield Beach, Fla.)》2009,21(2):139-152
This progress report provides an overview on recent advances in bioapplications of carbon nanotubes including the chemical modification of carbon nanotubes, targeting specifically their covalent and noncovalent conjugations with a variety of biological and bioactive species (proteins and peptides, DNAs/RNAs, and carbohydrates). Furthermore, the significant recent development and progress in the use of carbon nanotubes for biosensors, drug and other delivery systems, bioimaging, etc. and in the understanding of in vivo biodistribution and toxicity of carbon nanotubes are reported. 相似文献
100.
Simon Barquera Fabricio Campirano Anabelle Bonvecchio Lucia Hernández-Barrera Juan A Rivera Barry M Popkin 《Nutrition journal》2010,9(1):47