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991.
    
S1P is the final product of sphingolipid metabolism, which interacts with five widely expressed GPCRs (S1P1-5). Increasing numbers of studies have indicated the importance of S1P3 in various pathophysiological processes. Recently, we have identified a pepducin (compound KRX-725-II) acting as an S1P3 receptor antagonist. Here, aiming to optimize the activity and selectivity profile of the described compound, we have synthesized a series of derivatives in which Tyr, in position 4, has been substituted with several natural aromatic and unnatural aromatic and non-aromatic amino acids. All the compounds were evaluated for their ability to inhibit vascular relaxation induced by KRX-725 (as S1P3 selective pepducin agonist) and KRX-722 (an S1P1-selective pepducin agonist). Those selective towards S1P3 (compounds V and VII) were also evaluated for their ability to inhibit skeletal muscle fibrosis. Finally, molecular dynamics simulations were performed to derive information on the preferred conformations of selective and unselective antagonists.  相似文献   
992.
    
Osteoarthritis (OA) is a degenerative bone disease that involved micro and macro-environment of joints. To date, there are no radical curative treatments for OA and novel therapies are mandatory. Recent evidence suggests the role of miRNAs in OA progression. In our previous studies, we demonstrated the role of miR-31-5p and miR-33a families in different bone regeneration signaling. Here, we investigated the role of miR-31-5p and miR-33a-5p in OA progression. A different expression of miR-31-5p and miR-33a-5p into osteoblasts and chondrocytes isolated from joint tissues of OA patients classified in based on different Kellgren and Lawrence (KL) grading was highlighted; and through a bioinformatic approach the common miRNAs target Specificity proteins (Sp1) were identified. Sp1 regulates the expression of gap junction protein Connexin43 (Cx43), which in OA drives the modification of (i) osteoblasts and chondrocytes genes expression, (ii) joint inflammation cytokines releases and (iii) cell functions. Concerning this, thanks to gain and loss of function studies, the possible role of Sp1 as a modulator of CX43 expression through miR-31-5p and miR-33a-5p action was also evaluated. Finally, we hypothesize that both miRNAs cooperate to modulate the expression of SP1 in osteoblasts and chondrocytes and interfering, consequently, with CX43 expression, and they might be further investigated as new possible biomarkers for OA.  相似文献   
993.
994.
    
Despite the recurring outbreak of resistance mechanisms and adverse reactions, doxorubicin (Doxo) still remains the standard-of-care for several cancers, including osteosarcoma (OS). As an appealing source of phytochemical compounds, naturally occurring molecules have extensively been reported to overcome Doxo limitations in preclinical models. Unlike other dietary polyphenols, only few studies recognize chlorogenic acid (CGA) as a potential partner in combination therapy, while, conversely, its anticancer evidence is steadily growing, ultimately in OS. On this basis, herein we examine the cooperating effects between CGA and Doxo in U2OS and MG-63 human OS cells. With respect to Doxo alone, the concomitant administration of CGA further decreased cell viability and growth, promoting cell death potentially via apoptosis induction. Furthermore, a longer-lasting reduction in clonogenic potential deeply supported the CGA ability to improve Doxo efficacy in those cells. Remarkably, CGA treatment ameliorated Doxo-induced cytotoxicity in H9c2 rat cardiomyocyte cells instead. Although inactivation of p44/42 MAPK was detected in response to CGA plus Doxo, PD98059-mediated p44/42 MAPK impairment enhanced the combination outcome in OS cells. These findings firstly propose CGA as a promising chemosensitizer and cardioprotective agent in OS therapy, suggesting the p44/42 MAPK pathway as relevantly involved in CGA-mediated Doxo susceptibility.  相似文献   
995.
    
The nutraceutical and organoleptic quality of the extra virgin olive oil (EVOO) depends on a process that begins with the olive ripening and ends with the packaging and storage. As the EVOO quality decay is mainly induced by the oxidation process, the gaseous composition of the atmosphere during both malaxation and storage can play a key role. Because of that, the aim of this research work is to determine the influence of the gaseous composition of the atmosphere used during malaxation and storage on an unfiltered EVOO shelf life, and to individuate the best “malaxation atmosphere × storage atmosphere” combination to adopt to more effectively slow down the oil quality decay rate during storage. The combined experimental conditions used during malaxation and storage significantly affect the quality decay rate of the EVOO over one year of storage for all the evaluated parameters. In conclusion, the gaseous composition of the atmosphere used during both malaxation and storage deeply affects the shelf life of the unfiltered EVOO as regards its chemical and sensory features, especially when air is used. On the contrary, the best results are obtained when an inert gas (nitrogen or argon) is used during both phases. Practical Applications : The regular consumption of EVOO represents one of the main cornerstones of the Mediterranean diet. According to the FDA (Food and Drug Administration), this product can be considered as a healthy food because of its extraordinary nutraceutical and organoleptic properties, so that if consumers consume half a tablespoon of olive oil per day—without increasing their daily calorie intake—they can significantly reduce the incidence of several degenerative diseases as well as the risks associated with them. The knowledge of the impact of different “malaxation atmosphere × storage atmosphere” combinations on the quality decay rate during storage of an unfiltered EVOO can allow to identify the best operating conditions to be used during its production and storage, in order to preserve the nutraceutical and organoleptic properties of this product over time, thus extending its commercial life in terms of both quality parameters and healthy properties.  相似文献   
996.
    
The rise of antimicrobial resistance has necessitated novel strategies to efficiently combat pathogenic bacteria. Metal-based compounds have been proven as a possible alternative to classical organic drugs. Here, we have assessed the antibacterial activity of seven gold complexes of different families. One compound, a cyclometalated Au(III) C^N complex, showed activity against Gram-positive bacteria, including multi-drug resistant clinical strains. The mechanism of action of this compound was studied in Bacillus subtilis. Overall, the studies point towards a complex mode of antibacterial action, which does not include induction of oxidative stress or cell membrane damage. A number of genes related to metal transport and homeostasis were upregulated upon short treatment of the cells with gold compound. Toxicity tests conducted on precision-cut mouse tissue slices ex vivo revealed that the organogold compound is poorly toxic to mouse liver and kidney tissues, and may thus, be treated as an antibacterial drug candidate.  相似文献   
997.
Reticular oxygen of Al2O3 or CeOx supported on Al2O3 was used for the epoxidation of propene without any double bond cleavage. In batch reaction, Al2O3 alone was able to convert propene into propene oxide (PO) with 100% selectivity and 2% conversion of propene with a close to 3:1 ratio with respect to the number of Al(III) reduced to elemental Al. When Ce2O3/Al2O3 or CeO2/Al2O3 was used, Al remained in its +3 oxidation state, while the Ce oxide was the oxidant as demonstrated by XPS analyses. CeOx/Al2O3 was more active (propene conversion yield of 4–5%) but the selectivity was lower (70%) as PO was isomerized into acetone and propionaldehyde.

Interestingly the use of reticular oxygen very much improves the selectivity with respect to the use of pure O2. In fact, while propene was more efficiently oxidized (10%) with O2 in presence of Al2O3 or CeOx/Al2O3, the selectivity was as low as 40% because C1 and C2 products were formed. However, the use of reticular oxygen represents a selective two-step technique for the use of molecular oxygen as oxidant of propene. The used oxides can be re-oxidized and the whole process can be further improved towards higher yields.

PO is quantitatively converted into propene carbonate by reaction with CO2 in presence of Nb2O5.  相似文献   

998.
Three-dimensional morphology of polyethylene single crystals grown from dilute solutions and from the melt has been examined by atomic force microscopy. The observation of single crystals clarifies the morphology of chair-type as well as hollow pyramidal type for solution crystallization. From the melt, only chair-type was obtained. It has been confirmed that the screw dislocations in the chair-type follow a selection rule of the handedness in a manner to relieve the distortion in the chair-type. The meaning of the selection is discussed in connection with the twisting correlation in the banded spherulites grown from the melt of non-chiral polymers, such as polyethylene.  相似文献   
999.
  总被引:4,自引:0,他引:4  
The inactivation kinetics of Bacillus subtilis spores with ozone and monochloramine was characterized by a lag phase followed by a pseudo-first-order rate of inactivation. The lag phase decreased and the post-lag phase rate constant increased with increasing temperature within the range investigated (1-30 degrees C for ozone, 1-20 degrees C for monochloramine). The corresponding activation energies were 46820 J/mol for ozone and 79640 J/mol for monochloramine. The CT concept was found to be valid within the concentration range investigated of 0.44-4.8 mg/l for ozone, and 3.8-7.7 mg/l as Cl(2) for monochloramine. The inactivation kinetics of B. subtilis spores with both ozone and monochloramine varied with pH within the range of pH 6-10 investigated. The fastest ozone and monochloramine inactivation rates were observed at pH 10 and 6, respectively. Different stocks of the same strain of B. subtilis spores had different resistance to ozone and monochloramine mainly because of discrepancies in the extent of the lag phase. B. subtilis spores might not be conservative surrogates for C. parvum oocysts for ozone disinfection at relatively low temperature mainly due to the spores having a lower activation energy compared to that for the oocysts. In contrast, the activation energy for monochloramine was comparable for both microorganisms but differences in the extent of the lag phase might result in the spores being overly conservative surrogates for the oocysts at relatively low temperature.  相似文献   
1000.
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