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71.
Tiziana Genovese Daniela Impellizzeri Ramona DAmico Marika Cordaro Alessio Filippo Peritore Rosalia Crupi Enrico Gugliandolo Salvatore Cuzzocrea Roberta Fusco Rosalba Siracusa Rosanna Di Paola 《International journal of molecular sciences》2022,23(8)
Low back pain (LBP) management is an important clinical issue. Inadequate LBP control has consequences on the mental and physical health of patients. Thus, acquiring new information on LBP mechanism would increase the available therapeutic tools. Resveratrol is a natural compound with many beneficial effects. In this study, we investigated the role of resveratrol on behavioral changes, inflammation and oxidative stress induced by LBP. Ten microliters of Complete Freund’s adjuvant (CFA) was injected in the lumbar intervertebral disk of Sprague Dawley rats to induce degeneration, and resveratrol was administered daily. Behavioral analyses were performed on day zero, three, five and seven, and the animals were sacrificed to evaluate the molecular pathways involved. Resveratrol administration alleviated hyperalgesia, motor disfunction and allodynia. Resveratrol administration significantly reduced the loss of notochordal cells and degenerative changes in the intervertebral disk. From the molecular point of view, resveratrol reduced the 5th/6th lumbar (L5–6) spinal activation of the WNT pathway, reducing the expression of WNT3a and cysteine-rich domain frizzled (FZ)8 and the accumulation of cytosolic and nuclear β-catenin. Moreover, resveratrol reduced the levels of TNF-α and IL-18 that are target genes strictly downstream of the WNT/β-catenin pathway. It also showed important anti-inflammatory activities by reducing the activation of the NFkB pathway, the expression of iNOS and COX-2, and the levels of PGE2 in the lumbar spinal cord. Moreover, resveratrol reduced the oxidative stress associated with inflammation and pain, as shown by the observed reduced lipid peroxidation and increased GSH, SOD, and CAT activities. Therefore, resveratrol administration controlled the WNT/β-catenin pathway and the related inflammatory and oxidative alterations, thus alleviating the behavioral changes induced by LBP. 相似文献
72.
Luca Rosalia Caglar Ozturk Sophie X. Wang Diego Quevedo-Moreno Mossab Y. Saeed Adam Mauskapf Ellen T. Roche 《Advanced functional materials》2024,34(8):2310085
Heart failure with preserved ejection fraction (HFpEF) is a major challenge in cardiovascular medicine, accounting for ≈50% of all cases of heart failure. Despite the ongoing efforts, no medical device has yet received FDA approval. This is largely due to the lack of an in vivo model of the HFpEF hemodynamics, resulting in the inability to evaluate device effectiveness in vivo prior to clinical trials. Here, the development of a highly tunable porcine model of HFpEF hemodynamics is described using implantable soft robotic sleeves, where controlled actuation of a left ventricular and an aortic sleeve can recapitulate changes in ventricular compliance and afterload associated with a broad spectrum of HFpEF hemodynamic phenotypes. The feasibility of the proposed model in preclinical testing is demonstrated by evaluating the hemodynamic response of the model post-implantation of an interatrial shunt device, which is found to be consistent with findings from in silico studies and clinical trials. This work overcomes limitations of prior HFpEF models, such as low hemodynamic accuracy, high costs, and long development phases. The versatile and adjustable platform introduced can transform HFpEF device development, aiming to enhance the lives of the 32 million people affected globally. 相似文献
73.
Rosalba Siracusa Ramona DAmico Daniela Impellizzeri Marika Cordaro Alessio Filippo Peritore Enrico Gugliandolo Rosalia Crupi Angela Trovato Salinaro Emanuela Raffone Tiziana Genovese Salvatore Cuzzocrea Roberta Fusco Rosanna Di Paola 《International journal of molecular sciences》2021,22(10)
Endometriosis is a gynecological condition affecting patients in reproductive age. The aim of this paper was to assess the effects of the autophagy and mitophagy induction in a rat model of endometriosis. Endometriosis was induced by the injection of uterine fragments, and rapamycin (0. 5 mg/kg) was administered once per week. One week from the induction, rats were sacrificed, and laparotomy was performed to collect the endometriotic implants and to further process them for molecular analysis. Western blot analysis was conducted on explanted lesions to evaluate the autophagy pathway during the pathology. Elevated phospho-serine/threonine kinase (p-AKT) and mammalian target of rapamycin (mTOR) expressions were detected in vehicle-treated rats, while Beclin and microtubule-associated protein 1A/1B-light chain 3 II (LC3II) expressions were low. Additionally, samples collected from vehicle groups indicated low Bnip3, Ambra1, and Parkin expressions, demonstrating impaired autophagy and mitophagy. Rapamycin administration reduced p-AKT and mTOR expressions and increased Beclin and LC3II, Bnip3, Ambra1, and Parkin expressions, activating both mechanisms. We also evaluated the impact of the impaired autophagy and mitophagy pathways on apoptosis and angiogenesis. Rapamycin was administered by activating autophagy and mitophagy, which increased apoptosis (assessed by Western blot analysis of Bcl-2, Bax, and Cleaved-caspase 3) and reduced angiogenesis (assessed by immunohistochemical analysis of vascular endothelial grow factor (VEGF) and CD34) in the lesions. All of these mechanisms activated by the induction of the autophagy and mitophagy pathways led to the reduction in the lesions’ volume, area and diameter. 相似文献
74.
Rosalia Bus Monica Miele Maria Concetta Sorrentino Giandomenico Amico Francesca Timoneri Vitale Miceli Mariangela Di Bella Giovanna Russelli Alessia Gallo Giovanni Zito Gioacchin Iannolo Pier Giulio Conaldi Matteo Bulati 《International journal of molecular sciences》2022,23(23)
At present, there is a lack of clinical evidence about the impact and long-term durability of the immune response induced by the third dose of mRNA vaccines. In this study, we followed up the B cell compartment behavior in a cohort of immunocompetent individuals three and six months after the third dose of vaccine. During this period, some subjects contracted the virus. In uninfected vaccinated subjects, we did not report any changes in serum spike-specific IgG levels, with a significant reduction in IgA. Instead, subjects recovered from natural infection showed a significant increase in both specific IgG and IgA. Moreover, we showed a time-related decrease in IgG neutralizing potential to all SARS-CoV-2 variants of concern (VOC) in uninfected compared to recovered subjects, who displayed an increased neutralizing ability, particularly against the omicron variant. Finally, we underlined the presence of a pool of SARS-CoV-2-specific B cells in both groups that are prone to respond to restimulation, as demonstrated by their ability to differentiate into plasma cells and to produce anti-SARS-CoV-2-specific immunoglobulins. These data lead us to assert the long-term effectiveness of the BNT162b2 vaccine in contrasting the severe form of the pathology and prevent COVID-19-associated hospitalization. 相似文献
75.
Tiziana Genovese Marika Cordaro Rosalba Siracusa Daniela Impellizzeri Sebastiano Caudullo Emanuela Raffone Francesco Macrí Livia Interdonato Enrico Gugliandolo Claudia Interlandi Rosalia Crupi Ramona DAmico Roberta Fusco Salvatore Cuzzocrea Rosanna Di Paola 《International journal of molecular sciences》2022,23(10)
Endometriosis is usually associated with inflammation and chronic pelvic pain. This paper focuses the attention on the anti-inflammatory, anti-oxidant and analgesic effects of cannabidiol (CBD) and on its potential role in endometriosis. We employed an in vivo model of endometriosis and administered CBD daily by gavage. CBD administration strongly reduced lesions diameter, volume and area. In particular, it was able to modify lesion morphology, reducing epithelial glands and stroma. CBD showed anti-oxidant effects reducing lipid peroxidation, the expression of Nox-1 and Nox-4 enzymes. CBD restored the oxidative equilibrium of the endogenous cellular defense as showed by the SOD activity and the GSH levels in the lesions. CBD also showed important antifibrotic effects as showed by the Masson trichrome staining and by downregulated expression of MMP-9, iNOS and TGF-β. CBD was able to reduce inflammation both in the harvested lesions, as showed by the increased Ikb-α and reduced COX2 cytosolic expressions and reduced NFkB nuclear localization, and in the peritoneal fluids as showed by the decreased TNF-α, PGE2 and IL-1α levels. CBD has important analgesic effects as showed by the reduced mast cells recruitment in the spinal cord and the reduced release of neuro-sensitizing and pro-inflammatory mediators. In conclusion, the collected data showed that CBD has an effective and coordinated effects in endometriosis suppression. 相似文献
76.
Joel Molina Jose Luis Sanchez-Salas Carlos Zuniga Eunice Mendoza Rosalia Cuahtecontzi Gabriela Garcia-Perez Edmundo Gutierrez Erick R. Bandala 《Journal of Materials Science》2014,49(2):786-793
Using a low-temperature, simple, and economic processing technique, TiO2 nanoparticles (rutile phase) are immobilized in an inorganic matrix and then deposited on glass for bacteria inactivation in water. Using this low thermal budget method (maximum processing temperature of 220 °C), thin films of immobilized TiO2 nanoparticles are obtained so that practical water decontamination after UV radiation is possible by avoiding the additional step of catalyst separation from treated water. In order to validate the photocatalytic activities of these TiO2 nanoparticles (prepared as thin films), they were tested for bacteria inactivation in water under UV–A radiation (λ > 365 nm), while extensive characterizations by dynamic light scattering, X-ray diffraction, ultra violet–visible absorption spectroscopy, fourier-transform infra red spectroscopy, and profilometry were also carried out. Despite previous reports on the low or lack of photocatalytic activity of rutile-phase TiO2, inactivation of Escherichia coli in water was observed when thin films of this material were used when compared with the application of UV radiation alone. Physical characterization of the films suggests that size and concentration-related effects may allow the existence of photocatalytic activity for rutile-TiO2 as long as they are exposed under UV–A radiation, whereas no effect on bacteria inactivation was observed for thin films in the absence of TiO2 or radiation. In brief, a low thermal budget process applied to thin films based on TiO2 nanoparticles has shown to be useful for bacteria inactivation, while possible application of these films on widely available substrates like polyethylene terephthalate materials is expected. 相似文献
77.
Cristina Perez-Ternero Rosalia Rodriguez-Rodriguez Juan Parrado Maria Alvarez de Sotomayor 《Journal of Functional Foods》2013,5(4):1673-1683
Grape pomace enzymatic extract (GP-EE) exhibits a potent antioxidant and vasodilator activity, although the mechanisms underlying this action are not completely understood. Our aim was to evaluate its vasoactive mechanisms, focusing on vascular NADPH oxidase and superoxide dismutase (SOD)-dependent pathways. GP-EE effectively restored vascular impairment induced by the NADPH oxidase activator endothelin-1 through downregulation of its Nox-1 and p47phox subunits. GP-EE partially prevented endothelial dysfunction elicited by the SOD inhibitor, DETCA, preserving EC-SOD and Mn-SOD isoenzymes protein expression. Although many of these vasoactive effects could be attributed to the presence of catechin, GP-EE was able to exert additional protection against the vascular deleterious effects evoked by NADPHox activation and SOD inhibition. This additional vasoprotection could be related to the enzymatic extraction process, providing polyphenols from winemaking residue with a potent activity against vascular dysfunction by preventing NADPHox activation and maintaining SOD defense, making GP-EE as an ideal nutritional supplement. 相似文献
78.
Ramona DAmico Francesco Monaco Rosalba Siracusa Marika Cordaro Roberta Fusco Alessio Filippo Peritore Enrico Gugliandolo Rosalia Crupi Salvatore Cuzzocrea Rosanna Di Paola Daniela Impellizzeri Tiziana Genovese 《International journal of molecular sciences》2021,22(21)
Disseminated intravascular coagulation (DIC) is a severe condition characterized by the systemic formation of microthrombi complicated with bleeding tendency and organ dysfunction. In the last years, it represents one of the most frequent consequences of coronavirus disease 2019 (COVID-19). The pathogenesis of DIC is complex, with cross-talk between the coagulant and inflammatory pathways. The objective of this study is to investigate the anti-inflammatory action of ultramicronized palmitoylethanolamide (um-PEA) in a lipopolysaccharide (LPS)-induced DIC model in rats. Experimental DIC was induced by continual infusion of LPS (30 mg/kg) for 4 h through the tail vein. Um-PEA (30 mg/kg) was given orally 30 min before and 1 h after the start of intravenous infusion of LPS. Results showed that um-PEA reduced alteration of coagulation markers, as well as proinflammatory cytokine release in plasma and lung samples, induced by LPS infusion. Furthermore, um-PEA also has the effect of preventing the formation of fibrin deposition and lung damage. Moreover, um-PEA was able to reduce the number of mast cells (MCs) and the release of its serine proteases, which are also necessary for SARS-CoV-2 infection. These results suggest that um-PEA could be considered as a potential therapeutic approach in the management of DIC and in clinical implications associated to coagulopathy and lung dysfunction, such as COVID-19. 相似文献
79.
Alessio Filippo Peritore Ramona DAmico Rosalba Siracusa Marika Cordaro Roberta Fusco Enrico Gugliandolo Tiziana Genovese Rosalia Crupi Rosanna Di Paola Salvatore Cuzzocrea Daniela Impellizzeri 《International journal of molecular sciences》2021,22(11)
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common and devastating clinical disorders with high mortality and no specific therapy. Lipopolysaccharide (LPS) is usually used intratracheally to induce ALI in mice. The aim of this study was to examine the effects of an ultramicronized preparation of palmitoylethanolamide (um-PEA) in mice subjected to LPS-induced ALI. Histopathological analysis reveals that um-PEA reduced alteration in lung after LPS intratracheal administration. Besides, um-PEA decreased wet/dry weight ratio and myeloperoxidase, a marker of neutrophils infiltration, macrophages and total immune cells number and mast cells degranulation in lung. Moreover, um-PEA could also decrease cytokines release of interleukin (IL)-6, interleukin (IL)-1β, tumor necrosis factor (TNF)-α and interleukin (IL)-18. Furthermore, um-PEA significantly inhibited the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation in ALI, and at the same time decreased extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38/MAPK) expression, that was increased after LPS administration. Our study suggested that um-PEA contrasted LPS-induced ALI, exerting its potential role as an adjuvant anti-inflammatory therapeutic for treating lung injury, maybe also by p38/NF-κB pathway. 相似文献
80.
Rosalba Siracusa Francesco Monaco Ramona DAmico Tiziana Genovese Marika Cordaro Livia Interdonato Enrico Gugliandolo Alessio Filippo Peritore Rosalia Crupi Salvatore Cuzzocrea Daniela Impellizzeri Roberta Fusco Rosanna Di Paola 《International journal of molecular sciences》2021,22(13)
Treating postoperative (PO) pain is a clinical challenge. Inadequate PO pain management can lead to worse outcomes, for example chronic post-surgical pain. Therefore, acquiring new information on the PO pain mechanism would increase the therapeutic options available. In this paper, we evaluated the role of a natural substance, epigallocatechin-3-gallate (EGCG), on pain and neuroinflammation induced by a surgical procedure in an animal model of PO pain. We performed an incision of the hind paw and EGCG was administered for five days. Mechanical allodynia, thermal hyperalgesia, and motor dysfunction were assessed 24 h, and three and five days after surgery. At the same time points, animals were sacrificed, and sera and lumbar spinal cord tissues were harvested for molecular analysis. EGCG administration significantly alleviated hyperalgesia and allodynia, and reduced motor disfunction. From the molecular point of view, EGCG reduced the activation of the WNT pathway, reducing WNT3a, cysteine-rich domain frizzled (FZ)1 and FZ8 expressions, and both cytosolic and nuclear β-catenin expression, and the noncanonical β-catenin–independent signaling pathways, reducing the activation of the NMDA receptor subtype NR2B (pNR2B), pPKC and cAMP response element-binding protein (pCREB) expressions at all time points. Additionally, EGCG reduced spinal astrocytes and microglia activation, cytokines overexpression and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) pathway, downregulating inducible nitric oxide synthase (iNOS) activation, cyclooxygenase 2 (COX-2) expression, and prostaglandin E2 (PGE2) levels. Thus, EGCG administration managing the WNT/β-catenin signaling pathways modulates PO pain related neurochemical and inflammatory alterations. 相似文献