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排序方式: 共有1211条查询结果,搜索用时 15 毫秒
71.
Silvia Carra Germano Gaudenzi Alessandra Dicitore Davide Saronni Maria Celeste Cantone Alice Plebani Anna Ghilardi Maria Orietta Borghi Leo J. Hofland Luca Persani Giovanni Vitale 《International journal of molecular sciences》2021,22(6)
Medullary thyroid carcinoma (MTC) is a tumor deriving from the thyroid C cells. Vandetanib (VAN) and cabozantinib (CAB) are two tyrosine kinase inhibitors targeting REarranged during Transfection (RET) and other kinase receptors and are approved for the treatment of advanced MTC. We aim to compare the in vitro and in vivo anti-tumor activity of VAN and CAB in MTC. The effects of VAN and CAB on viability, cell cycle, and apoptosis of TT and MZ-CRC-1 cells are evaluated in vitro using an MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. In vivo, the anti-angiogenic potential of VAN and CAB is evaluated in Tg(fli1a:EGFP)y1 transgenic fluorescent zebrafish embryos by analyzing the effects on the physiological development of the sub-intestinal vein plexus and the tumor-induced angiogenesis after TT and MZ-CRC-1 xenotransplantation. VAN and CAB exert comparable effects on TT and MZ-CRC-1 viability inhibition and cell cycle perturbation, and stimulated apoptosis with a prominent effect by VAN in MZ-CRC-1 and CAB in TT cells. Regarding zebrafish, both drugs inhibit angiogenesis in a dose-dependent manner, in particular CAB shows a more potent anti-angiogenic activity than VAN. To conclude, although VAN and CAB show comparable antiproliferative effects in MTC, the anti-angiogenic activity of CAB appears to be more relevant. 相似文献
72.
Joana Silva Celso Alves Alice Martins Patrícia Susano Marco Simes Miguel Guedes Stephanie Rehfeldt Susete Pinteus Helena Gaspar Amrico Rodrigues Mrcia Ines Goettert Amparo Alfonso Rui Pedrosa 《International journal of molecular sciences》2021,22(4)
Parkinsons Disease (PD) is the second most common neurodegenerative disease worldwide, and is characterized by a progressive degeneration of dopaminergic neurons. Without an effective treatment, it is crucial to find new therapeutic options to fight the neurodegenerative process, which may arise from marine resources. Accordingly, the goal of the present work was to evaluate the ability of the monoterpenoid lactone Loliolide, isolated from the green seaweed Codium tomentosum, to prevent neurological cell death mediated by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y cells and their anti-inflammatory effects in RAW 264.7 macrophages. Loliolide was obtained from the diethyl ether extract, purified through column chromatography and identified by NMR spectroscopy. The neuroprotective effects were evaluated by the MTT method. Cells’ exposure to 6-OHDA in the presence of Loliolide led to an increase of cells’ viability in 40%, and this effect was mediated by mitochondrial protection, reduction of oxidative stress condition and apoptosis, and inhibition of the NF-kB pathway. Additionally, Loliolide also suppressed nitric oxide production and inhibited the production of TNF-α and IL-6 pro-inflammatory cytokines. The results suggest that Loliolide can inspire the development of new neuroprotective therapeutic agents and thus, more detailed studies should be considered to validate its pharmacological potential. 相似文献
73.
Cement and silica suspension rheological behaviour is modelled by supposing that particle aggregation occurs. With two independent parameters, the variation of the shear viscosity as a function of the shear rate for cement or silica suspensions having different solid volume fractions can be predicted. The model is in good agreement with experimental data. Cement suspensions are initially very similar to unreactive silica suspensions. The values of adhesion forces obtained seem to show that the effective interaction areas are very small. It reflects the fact that in the dormant period the particles are contacting at points, which become progressively higher in surface as C-S-H precipitates at these contacts. The model used is consistent with the observed power law variation of static and dynamic yield stresses with solid volume fraction. The aggregates formed under shear seem to be very compact, which is presumably related to the large solid volume fractions of the studied suspensions. 相似文献
74.
Marzia Pucci Stefania Raimondo Ornella Urzì Marta Moschetti Maria Antonietta Di Bella Alice Conigliaro Nadia Caccamo Marco Pio La Manna Simona Fontana Riccardo Alessandro 《International journal of molecular sciences》2021,22(22)
Tumor-associated macrophages play a key role in promoting tumor progression by exerting an immunosuppressive phenotype associated with the expression of programmed cell death ligand 1 (PD-L1). It is well known that tumor-derived small extracellular vesicles (SEVs) affect the tumor microenvironment, influencing TAM behavior. The present study aimed to examine the effect of SEVs derived from colon cancer and multiple myeloma cells on macrophage functions. Non-polarized macrophages (M0) differentiated from THP-1 cells were co-cultured with SEVs derived from a colorectal cancer (CRC) cell line, SW480, and a multiple myeloma (MM) cell line, MM1.S. The expression of PD-L1, interleukin-6 (IL-6), and other inflammatory cytokines as well as of the underlying molecular mechanisms were evaluated. Our results indicate that SEVs can significantly upregulate the expressions of PD-L1 and IL-6 at both the mRNA and protein levels and can activate the STAT3 signaling pathway. Furthermore, we identified the TLR4/NF-kB pathway as a convergent mechanism for SEV-mediated PD-L1 expression. Overall, these preliminary data suggest that SEVs contribute to the formation of an immunosuppressive microenvironment. 相似文献
75.
Manuel Gentiluomo Alice Luddi Annapaola Cingolani Marco Fornili Laura Governini Ersilia Lucenteforte Laura Baglietto Paola Piomboni Daniele Campa 《International journal of molecular sciences》2021,22(8)
Over the past decade, telomeres have attracted increasing attention due to the role they play in human fertility. However, conflicting results have been reported on the possible association between sperm telomere length (STL) and leukocyte telomere length (LTL) and the quality of the sperm parameters. The aim of this study was to run a comprehensive study to investigate the role of STL and LTL in male spermatogenesis and infertility. Moreover, the association between the sperm parameters and 11 candidate single nucleotide polymorphisms (SNPs), identified in the literature for their association with telomere length (TL), was investigated. We observed no associations between sperm parameters and STL nor LTL. For the individual SNPs, we observed five statistically significant associations with sperm parameters: considering a p < 0.05. Namely, ACYP2˗rs11125529 and decreased sperm motility (p = 0.03); PXK˗rs6772228 with a lower sperm count (p = 0.02); NAF1˗rs7675998 with increased probability of having abnormal acrosomes (p = 0.03) and abnormal flagellum (p = 0.04); ZNF208˗rs8105767 and reduction of sperms with normal heads (p = 0.009). This study suggests a moderate involvement of telomere length in male fertility; however, in our analyses four SNPs were weakly associated with sperm variables, suggesting the SNPs to be pleiotropic and involved in other regulatory mechanisms independent of telomere homeostasis, but involved in the spermatogenic process. 相似文献
76.
HER2 targeted therapies have significantly improved prognosis of HER2-positive breast and gastric cancer. HER2 overexpression and mutation is the pathogenic driver in non-small cell lung cancer (NSCLC) and colorectal cancer, however, to date, there are no approved HER2-targeted therapies with these indications. Trastuzumab deruxtecan (T-DXd) is a novel HER2-directed antibody drug conjugate showing significant anti-tumor activity in heavily pre-treated HER2-positive breast and gastric cancer patients. Preliminary data have shown promising objective response rates in patients with HER2-positive NSCLC and colorectal cancer. T-DXd has an acceptable safety profile, however with concerns regarding potentially serious treatment-emergent adverse events. In this review we focus on the pharmacologic characteristics and toxicity profile of T-Dxd, and provide an update on the most recent results of clinical trials of T-DXd in solid tumors. The referenced papers were selected through a PubMed search performed on 16 March 2021 with the following searching terms: T-DXd and breast cancer, or gastric cancer, or non-small cell lung cancer (NSCLC), or colorectal cancer. Oral presentation, abstracts, and posters presented at the American Society of Clinical Oncology (ASCO, Alexandria, VA, USA) 2020 and the European Society for Medical Oncology (ESMO, Lugano, Switzerland) 2020 annual meetings were retrieved for data on T-DXd. We also overview ongoing research and data of combination therapies currently under investigation, which will impact on future therapeutic strategies. Clinicaltrials.gov was searched to identify ongoing clinical trials of T-DXd alone or in combination in solid tumors. 相似文献
77.
Vanessa Kohl Oliver Drews Victor Costina Miriam Bierbaum Ahmed Jawhar Henning Roehl Christel Weiss Susanne Brendel Helga Kleiner Johanna Flach Birgit Spiess Wolfgang Seifarth Daniel Nowak Wolf-Karsten Hofmann Alice Fabarius Henning D. Popp 《International journal of molecular sciences》2021,22(11)
Non-targeted effects (NTE) of ionizing radiation may initiate myeloid neoplasms (MN). Here, protein mediators (I) in irradiated human mesenchymal stromal cells (MSC) as the NTE source, (II) in MSC conditioned supernatant and (III) in human bone marrow CD34+ cells undergoing genotoxic NTE were investigated. Healthy sublethal irradiated MSC showed significantly increased levels of reactive oxygen species. These cells responded by increasing intracellular abundance of proteins involved in proteasomal degradation, protein translation, cytoskeleton dynamics, nucleocytoplasmic shuttling, and those with antioxidant activity. Among the increased proteins were THY1 and GNA11/14, which are signaling proteins with hitherto unknown functions in the radiation response and NTE. In the corresponding MSC conditioned medium, the three chaperones GRP78, CALR, and PDIA3 were increased. Together with GPI, these were the only four altered proteins, which were associated with the observed genotoxic NTE. Healthy CD34+ cells cultured in MSC conditioned medium suffered from more than a six-fold increase in γH2AX focal staining, indicative for DNA double-strand breaks, as well as numerical and structural chromosomal aberrations within three days. At this stage, five proteins were altered, among them IQGAP1, HMGB1, and PA2G4, which are involved in malign development. In summary, our data provide novel insights into three sequential steps of genotoxic signaling from irradiated MSC to CD34+ cells, implicating that induced NTE might initiate the development of MN. 相似文献
78.
Enrico Capuzzi Alice Caldiroli Martina Capellazzi Ilaria Tagliabue Matteo Marcatili Fabrizia Colmegna Massimo Clerici Massimiliano Buoli Antonios Dakanalis 《International journal of molecular sciences》2021,22(17)
Esketamine (ESK) has been approved as a rapid-acting intranasal treatment for treatment-resistant depression (TRD). Although existing studies have investigated the efficacy of ESK in the 4-week induction phase, our knowledge about long-term ESK efficacy remains poor. The aim of this systematic review was to summarize the available data on long-term ESK efficacy for TRD. A systematic search was performed including articles in English, up to 31 March 2021. The search found 7 relevant studies, involving 1024 adult TRD patients. Continuing treatment with ESK after the 4-week induction phase may be associated with stable efficacy in relapse prevention among TRD patients. Conversely, the long-term antidepressant effectiveness upon discontinuation of ESK might be limited, although data from three studies had a moderate to high risk of bias. Overall, the results on the effectiveness of this compound in the long term are mixed. According to our findings, ESK treatment should be continued following the induction phase to reach a stable efficacy in relapse prevention, while the long-term antidepressant and anti-suicidal effects of ESK after discontinuation are inconsistent. Currently, the level of proof of ESK efficacy in long-term TRD treatment remains low and more RCTs with larger sample sizes and active comparators are needed. 相似文献
79.
Alice Perrin Monica Sorescu Mari-Therese Burton David E. Laughlin Michael McHenry 《JOM Journal of the Minerals, Metals and Materials Society》2017,69(11):2125-2129
This paper explores the FeCoNiCuMn high-entropy alloy system, where small departures from equiatomic composition have yielded technologically interesting 300-K Curie temperatures (\(T_{\mathrm{c}}\)), making them promising for magnetocaloric applications. We also demonstrate that the small deviations from equiatomic compositions do not affect the structural stability of our single-phase fcc-based solid solutions. Room-temperature Mössbauer spectroscopy measurements provide evidence for the distributed exchange interactions (\(J_{\mathrm{ex}}\)) occurring between the magnetic elements, which contribute to a broadened magnetocaloric effect observed for these alloys. The average hyperfine field observed in the Mössbauer spectra decreases as the \(T_{\mathrm{c}}\) of the alloys decrease, confirming direct current magnetic measurements. Multiple peaks in the hyperfine field distribution are interpreted considering pairwise ferromagnetic or antiferromagnetic \(J_{\mathrm{ex}}\) between all elements except the Cu diluent as contributing to overall magnetic exchange in the alloy. 相似文献
80.