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101.
Biagio Barone Luigi Napolitano Marco Abate Luigi Cirillo Pasquale Reccia Francesco Passaro Carmine Turco Simone Morra Francesco Mastrangelo Antonio Scarpato Ugo Amicuzi Vincenzo Morgera Lorenzo Romano Francesco Paolo Calace Savio Domenico Pandolfo Luigi De Luca Achille Aveta Enrico Sicignano Massimiliano Trivellato Gianluca Spena Carlo DAlterio Giovanni Maria Fusco Raffaele Vitale Davide Arcaniolo Felice Crocetto 《International journal of molecular sciences》2022,23(7)
Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains. 相似文献
102.
Erica Costantini Lisa Aielli Federica Serra Lorenzo De Dominicis Katia Falasca Pamela Di Giovanni Marcella Reale 《International journal of molecular sciences》2022,23(4)
Wound healing (WH) proceeds through four distinct phases: hemostasis, inflammation, proliferation, and remodeling. Impaired WH may be the consequence of the alteration of one of these phases and represents a significant health and economic burden to millions of individuals. Thus, new therapeutic strategies are the topics of intense research worldwide. Although radiofrequency electromagnetic field (RF-EMF) has many medical applications in rehabilitation, pain associated with musculoskeletal disorders, and degenerative joint disorders, its impact on WH is not fully understood. The process of WH begins just after injury and continues during the inflammatory and proliferative phases. A thorough understanding of the mechanisms by which RF-EMF can improve WH is required before it can be used as a non-invasive, inexpensive, and easily self-applicable therapeutic strategy. Thus, the aim of this study is to explore the therapeutic potential of different exposure setups of RF-EMF to drive faster healing, evaluating the keratinocytes migration, cytokines, and matrix metalloproteinases (MMPs) expression. The results showed that RF-EMF treatment promotes keratinocytes’ migration and regulates the expression of genes involved in healing, such as MMPs, tissue inhibitors of metalloproteinases, and pro/anti-inflammatory cytokines, to improve WH. 相似文献
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Eicosapentaenoic Acid,Arachidonic Acid and Eicosanoid Metabolism in Juvenile Barramundi Lates calcarifer
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Michael J. Salini Nicholas M. Wade Bruno C. Araújo Giovanni M. Turchini Brett D. Glencross 《Lipids》2016,51(8):973-988
A two part experiment was conducted to assess the response of barramundi (Lates calcarifer; initial weight = 10.3 ± 0.03 g; mean ± S.D.) fed one of five diets with varying eicosapentaenoic acid (diets 1, 5, 10, 15 and 20 g/kg) or one of four diets with varying arachidonic acid (1, 6, 12, 18 g/kg) against a fish oil control diet. After 6 weeks of feeding, the addition of EPA or ARA did not impact on growth performance or feed utilisation. Analysis of the whole body fatty acids showed that these reflected those of the diets. The ARA retention demonstrated an inversely related curvilinear response to either EPA or ARA. The calculated marginal utilisation efficiencies of EPA and ARA were high (62.1 and 91.9 % respectively) and a dietary ARA requirement was defined (0.012 g/kg0.796/day). The partial cDNA sequences of genes regulating eicosanoid biosynthesis were identified in barramundi tissues, namely cyclooxygenase 1 (Lc COX1a, Lc COX1b), cyclooxygenase 2 (Lc COX2) and lipoxygenase (Lc ALOX‐5). Both Lc COX2 and Lc ALOX‐5 expression in the liver tissue were elevated in response to increasing dietary ARA, meanwhile expression levels of Lc COX2 and the mitochondrial fatty acid oxidation gene carnitine palmitoyltransferase 1 (Lc CPT1a) were elevated in the kidney. A low level of EPA increased the expression of Lc COX1b in the liver. Consideration should be given to the EPA to ARA balance for juvenile barramundi in light of nutritionally inducible nature of the cyclooxygenase and lipoxygenase enzymes. 相似文献
106.
Synthesis,Pharmacological Evaluation,and Docking Studies of Novel Pyridazinone‐Based Cannabinoid Receptor Type 2 Ligands
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Dr. Giulio Ragusa Dr. Serena Bencivenni Dr. Paula Morales Dr. Tyra Callaway Dr. Dow P. Hurst Dr. Battistina Asproni Dr. Stefania Merighi Dr. Giovanni Loriga Prof. Gerard A. Pinna Prof. Patricia H. Reggio Prof. Stefania Gessi Prof. Gabriele Murineddu 《ChemMedChem》2018,13(11):1102-1114
In recent years, cannabinoid type 2 receptors (CB2R) have emerged as promising therapeutic targets in a wide variety of diseases. Selective ligands of CB2R are devoid of the psychoactive effects typically observed for CB1R ligands. Based on our recent studies on a class of pyridazinone 4‐carboxamides, further structural modifications of the pyridazinone core were made to better investigate the structure–activity relationships for this promising scaffold with the aim to develop potent CB2R ligands. In binding assays, two of the new synthesized compounds [6‐(3,4‐dichlorophenyl)‐2‐(4‐fluorobenzyl)‐cis‐N‐(4‐methylcyclohexyl)‐3‐oxo‐2,3‐dihydropyridazine‐4‐carboxamide ( 2 ) and 6‐(4‐chloro‐3‐methylphenyl)‐cis‐N‐(4‐methylcyclohexyl)‐3‐oxo‐2‐pentyl‐2,3‐dihydropyridazine‐4‐carboxamide ( 22 )] showed high CB2R affinity, with Ki values of 2.1 and 1.6 nm , respectively. In addition, functional assays of these compounds and other new active related derivatives revealed their pharmacological profiles as CB2R inverse agonists. Compound 22 displayed the highest CB2R selectivity and potency, presenting a favorable in silico pharmacokinetic profile. Furthermore, a molecular modeling study revealed how 22 produces inverse agonism through blocking the movement of the toggle‐switch residue, W6.48. 相似文献
107.
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
108.
Potent,Metabolically Stable 2‐Alkyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐adenines as Adenosine A2A Receptor Ligands
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Dr. Silvia Pace Dr. Giandomenico Brogin Dr. Maria Antonietta Stasi Dr. Teresa Riccioni Franco Borsini Dr. Francesca Capocasa Dr. Francesco Manera Carlo Tallarico Dr. Pietro Grossi Dr. Federica Vacondio Dr. Michele Bassi Dr. Francesca Bartoccini Dr. Simone Lucarini Dr. Giovanni Piersanti Prof. Giorgio Tarzia Walter Cabri Dr. Patrizia Minetti 《ChemMedChem》2015,10(7):1149-1152
Inhibition of adenosine A2A receptors has been shown to elicit a therapeutic response in preclinical animal models of Parkinson’s disease (PD). We previously identified the triazolo‐9H‐purine, ST1535, as a potent A2AR antagonist. Studies revealed that ST1535 is extensively hydroxylated at the ω‐1 position of the butyl side chain. Here, we describe the synthesis and evaluation of derivatives in which the ω‐1 position has been substituted (F, Me, OH) in order to block metabolism. The stability of the compounds was evaluated in human liver microsomes (HLM), and the affinity for A2AR was determined. Two compounds, (2‐(3,3‐dimethylbutyl)‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐6‐amine ( 3 b ) and 4‐(6‐amino‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐2‐yl)‐2‐methylbutan‐2‐ol ( 3 c ), exhibited good affinity against A2AR (Ki=0.4 nM and 2 nM , respectively) and high in vitro metabolic stability (89.5 % and 95.3 % recovery, respectively, after incubation with HLM for two hours). 相似文献
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110.
Cold groundwater temperatures and conductive heat flow in the Mt. Amiata geothermal area, Tuscany, Italy 总被引:1,自引:0,他引:1
Giovanni Chiodini Paola Comodi Stefano Giaquinto Bruno Mattioli Anna Rosa Zanzari 《Geothermics》1988,17(4)
The hydrogeochemical study of the cold springs present in the Mt. Amiata geothermal area, where the Bagnore and Piancastagnaio geothermal fields are situated, has defined the different shallow groundwater systems.The cold groundwater temperature of the volcanic phreatic aquifer is largely correlated with the geothermal heat flow. Through the analysis of the temperature of cold groundwaters, a possible method for geothermal prospection has been developed, supported by the results obtained in the studied area. Through the enthalpic balance of the aquifer and in agreement with available data, a geothermal flow of about 200 mW m-2 has been calculated. 相似文献