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61.
62.
Ignacio Hernandez Laura Tesoro Rafael Ramirez-Carracedo Javier Diez-Mata Sandra Sanchez Marta Saura Jose Luis Zamorano Carlos Zaragoza Laura Botana 《International journal of molecular sciences》2021,22(6)
In response to cardiac ischemia/reperfusion, proteolysis mediated by extracellular matrix metalloproteinase inducer (EMMPRIN) and its secreted ligand cyclophilin-A (CyPA) significantly contributes to cardiac injury and necrosis. Here, we aimed to investigate if, in addition to the effect on the funny current (I(f)), Ivabradine may also play a role against cardiac necrosis by reducing EMMPRIN/CyPA-mediated cardiac inflammation. In a porcine model of cardiac ischemia/reperfusion (IR), we found that administration of 0.3 mg/kg Ivabradine significantly improved cardiac function and reduced cardiac necrosis by day 7 after IR, detecting a significant increase in cardiac CyPA in the necrotic compared to the risk areas, which was inversely correlated with the levels of circulating CyPA detected in plasma samples from the same subjects. In testing whether Ivabradine may regulate the levels of CyPA, no changes in tissue CyPA were found in healthy pigs treated with 0.3 mg/kg Ivabradine, but interestingly, when analyzing the complex EMMPRIN/CyPA, rather high glycosylated EMMPRIN, which is required for EMMPRIN-mediated matrix metalloproteinase (MMP) activation and increased CyPA bonding to low-glycosylated forms of EMMPRIN were detected by day 7 after IR in pigs treated with Ivabradine. To study the mechanism by which Ivabradine may prevent secretion of CyPA, we first found that Ivabradine was time-dependent in inhibiting co-localization of CyPA with the granule exocytosis marker vesicle-associated membrane protein 1 (VAMP1). However, Ivabradine had no effect on mRNA expression nor in the proteasome and lysosome degradation of CyPA. In conclusion, our results point toward CyPA, its ligand EMMPRIN, and the complex CyPA/EMMPRIN as important targets of Ivabradine in cardiac protection against IR. 相似文献
63.
Roberta Squecco Alessia Tani Flaminia Chellini Rachele Garella Eglantina Idrizaj Irene Rosa Sandra Zecchi-Orlandini Mirko Manetti Chiara Sassoli 《International journal of molecular sciences》2021,22(7)
Bone marrow-mesenchymal stem/stromal cells (MSCs) may offer promise for skeletal muscle repair/regeneration. Growing evidence suggests that the mechanisms underpinning the beneficial effects of such cells in muscle tissue reside in their ability to secrete bioactive molecules (secretome) with multiple actions. Hence, we examined the effects of MSC secretome as conditioned medium (MSC-CM) on ex vivo murine extensor digitorum longus muscle injured by forced eccentric contraction (EC). By combining morphological (light and confocal laser scanning microscopies) and electrophysiological analyses we demonstrated the capability of MSC-CM to attenuate EC-induced tissue structural damages and sarcolemnic functional properties’ modifications. MSC-CM was effective in protecting myofibers from apoptosis, as suggested by a reduced expression of pro-apoptotic markers, cytochrome c and activated caspase-3, along with an increase in the expression of pro-survival AKT factor. Notably, MSC-CM also reduced the EC-induced tissue redistribution and extension of telocytes/CD34+ stromal cells, distinctive cells proposed to play a “nursing” role for the muscle resident myogenic satellite cells (SCs), regarded as the main players of regeneration. Moreover, it affected SC functionality likely contributing to replenishment of the SC reservoir. This study provides the necessary groundwork for further investigation of the effects of MSC secretome in the setting of skeletal muscle injury and regenerative medicine. 相似文献
64.
Kvin Nay William J. Smiles Jacqueline Kaiser Luke M. McAloon Kim Loh Sandra Galic Jonathan S. Oakhill Andrew L. Gundlach John W. Scott 《International journal of molecular sciences》2021,22(8)
As life expectancy has increased, particularly in developed countries, due to medical advances and increased prosperity, age-related neurological diseases and mental health disorders have become more prevalent health issues, reducing the well-being and quality of life of sufferers and their families. In recent decades, due to reduced work-related levels of physical activity, and key research insights, prescribing adequate exercise has become an innovative strategy to prevent or delay the onset of these pathologies and has been demonstrated to have therapeutic benefits when used as a sole or combination treatment. Recent evidence suggests that the beneficial effects of exercise on the brain are related to several underlying mechanisms related to muscle–brain, liver–brain and gut–brain crosstalk. Therefore, this review aims to summarize the most relevant current knowledge of the impact of exercise on mood disorders and neurodegenerative diseases, and to highlight the established and potential underlying mechanisms involved in exercise–brain communication and their benefits for physiology and brain function. 相似文献
65.
Maria Buuales Maria Cristina Ballesteros-Briones Manuela Gonzalez-Aparicio Sandra Hervas-Stubbs Eva Martisova Uxua Mancheo Ana Ricobaraza Sara Lumbreras Cristian Smerdou Ruben Hernandez-Alcoceba 《International journal of molecular sciences》2021,22(8)
Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local or regional expression of monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In this work, we describe a high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped with a mifepristone-inducible system for the controlled expression of an anti-programmed death ligand 1 (PD-L1) blocking antibody. The vector was tested in an immune-competent mouse model of colorectal cancer based on implantation of MC38 cells. A single local administration of HCA-EFZP-aPDL1 in subcutaneous lesions led to a significant reduction in tumor growth with minimal release of the antibody in the circulation. When the vector was tested in a more stringent setting (rapidly progressing peritoneal carcinomatosis), the antitumor effect was marginal even in combination with other immune-stimulatory agents such as polyinosinic-polycytidylic acid (pI:C), blocking mAbs for T cell immunoglobulin, mucin-domain containing-3 (TIM-3) or agonistic mAbs for 4-1BB (CD137). In contrast, macrophage depletion by clodronate liposomes enhanced the efficacy of HCA-EFZP-aPDL1. These results highlight the importance of addressing macrophage-associated immunoregulatory mechanisms to overcome resistance to ICIs in the context of colorectal cancer. 相似文献
66.
67.
The integration of reaction and separation in catalytic membrane reactors has received increasing attention during the past 30 years. The combination promises to deliver more compact and less capital-intensive processes with substantial savings in energy consumption. With the advent of new inorganic materials and processing techniques, there has been renewed interest in exploiting the benefits of membranes in many industrial applications. Zeolite membranes, however, have only recently been considered for catalytic membrane reactor applications. Despite the significant recent interest in these types of membranes there are relatively few reports of the application of such membranes in high-temperature catalytic membrane reactor applications. This can be attributed to a number of limitations that still need to be addressed such as the relatively high price of membrane units, the difficulty of controlling the membrane thickness, permeance, high-temperature sealing, reproducibility and the dilemma of upscaling. A number of research efforts, with some degree of success have been directed to finding solutions to the remaining challenges. This review makes a critical assessment of what has been achieved in the past few years in terms of hurdles that still stand in the way of the successful implementation of zeolite membrane reactors in industry. 相似文献
68.
Johannes C. Jansen Marialuigia Macchione Raniero Mendichi Enrico Drioli 《Polymer》2005,46(25):11366-11379
Asymmetric gas separation membranes were prepared by the dry-casting technique from PEEKWC, a modified amorphous glassy poly(ether ether ketone). The phase inversion process and membrane performance were correlated to the properties of the polymer and the casting solution (molar mass, polymer concentration, solution rheology and thermodynamics). It was found that a broad molar mass distribution of the polymer in the casting solution is most favourable for the formation of a highly selective membrane with a dense skin and a porous sub-layer. Thus, membranes with an effective skin thickness of less than 1 μm were obtained, exhibiting a maximum O2/N2 selectivity of 7.2 and a CO2/CH4 selectivity of 39, both significantly higher than in a corresponding thick dense PEEKWC membrane and also comparable to or higher than that of the most commonly used polymers for gas separation membranes. The CO2 and O2 permeance were up to 9.5×10−3 and 1.8×10−3 m3/(m2 h bar) (3.5 and 0.67 GPU), respectively. 相似文献
69.
Hydrogenation of double bonds was observed to occur during the isobutane chemical ionization mass spectrometry (MS) of unsaturated
fatty esters. Chemical ionization (CI) spectra of a series of methyl esters in the C16–C20 carbon range containing 0–4 double
bonds showed a variety of ionization characteristics in the molecular ion cluster, including hydride abstraction, charge exchange,
protonation and, for the unsaturated fatty acids (FA), hydrogenation of the double bond followed by protonation.
The mention of firm names or trade products does not imply that they are endorsed or recommended by the U.S. Department of
Agriculture over other firms or similar products not mentioned. 相似文献
70.
Acyl CoA:cholesterol acyltransferase (EC2.3.1.26, ACAT), responsible for intracellular esterification of cholesterol, may
play an important role in cholesterol trafficking within the cell, and thus, in maintenance of cellular cholesterol homeostasis.
Bile acids are potential regulators of cholesterol trafficking in the liver. Therefore, the effect of bile salts on hepatic
ACAT activity was studied in the perfused rat liver. ACAT activity was increased after liver perfusion with either taurocholate
or taurochenodeoxycholate. However, addition of these bile salts at physiological concentrationsin vitro had little effect on microsomal ACAT activity. The increase in hepatic ACAT activity due to perfusion with bile salts was
accompanied by reduced accumulation of very low density lipoprotein cholesterol in the perfusate, but there was no effect
on 3-hydroxy-3-methylglutaryl-CoA reductase activity. Hepatic ACAT activity was decreased after bile diversion for four hours
in the intact animal. This treatment had no statistically significant effect on 3-hydroxy-3-methylglutaryl-CoA reductase activity.
These data suggest that bile salts induce changes in hepatic compartmentation and traffic of cholesterol within the hepatocyte
accompanied by response of ACAT activity to maintain cellular cholesterol homeostasis. 相似文献