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991.
Aurora Eliana Merulla Michele Stella Cristina Barbagallo Rosalia Battaglia Angela Caponnetto Giuseppe Broggi Roberto Altieri Francesco Certo Rosario Caltabiano Marco Ragusa Giuseppe Maria Vincenzo Barbagallo Cinzia Di Pietro Michele Purrello Davide Barbagallo 《International journal of molecular sciences》2022,23(22)
The involvement of non-coding RNAs (ncRNAs) in glioblastoma multiforme (GBM) pathogenesis and progression has been ascertained but their cross-talk within GBM cells remains elusive. We previously demonstrated the role of circSMARCA5 as a tumor suppressor (TS) in GBM. In this paper, we explore the involvement of circSMARCA5 in the control of microRNA (miRNA) expression in GBM. By using TaqMan® low-density arrays, the expression of 748 miRNAs was assayed in U87MG overexpressing circSMARCA5. Differentially expressed (DE) miRNAs were validated through single TaqMan® assays in: (i) U87MG overexpressing circSMARCA5; (ii) four additional GBM cell lines (A172; CAS-1; SNB-19; U251MG); (iii) thirty-eight GBM biopsies; (iv) twenty biopsies of unaffected brain parenchyma (UC). Validated targets of DE miRNAs were selected from the databases TarBase and miRTarbase, and the literature; their expression was inferred from the GBM TCGA dataset. Expression was assayed in U87MG overexpressing circSMARCA5, GBM cell lines, and biopsies through real-time PCR. TS miRNAs 126-3p and 515-5p were upregulated following circSMARCA5 overexpression in U87MG and their expression was positively correlated with that of circSMARCA5 (r-values = 0.49 and 0.50, p-values = 9 × 10−5 and 7 × 10−5, respectively) in GBM biopsies. Among targets, IGFBP2 (target of miR-126-3p) and NRAS (target of miR-515-5p) mRNAs were positively correlated (r-value = 0.46, p-value = 0.00027), while their expression was negatively correlated with that of circSMARCA5 (r-values = −0.58 and −0.30, p-values = 0 and 0.019, respectively), miR-126-3p (r-value = −0.36, p-value = 0.0066), and miR-515-5p (r-value = −0.34, p-value = 0.010), respectively. Our data identified a new GBM subnetwork controlled by circSMARCA5, which regulates downstream miRNAs 126-3p and 515-5p, and their mRNA targets IGFBP2 and NRAS. 相似文献
992.
993.
Elena Spinetti Pietro Delre Michele Saviano Dritan Siliqi Gianluca Lattanzi Giuseppe Felice Mangiatordi 《International journal of molecular sciences》2022,23(14)
The Shwachman–Diamond Syndrome (SDS) is an autosomal recessive disease whose majority of patients display mutations in a ribosome assembly protein named Shwachman–Bodian–Diamond Syndrome protein (SBDS). A specific therapy for treating this rare disease is missing, due to the lack of knowledge of the molecular mechanisms responsible for its pathogenesis. Starting from the observation that SBDS single-point mutations, localized in different domains of the proteins, are responsible for an SDS phenotype, we carried out the first comparative Molecular Dynamics simulations on three SBDS mutants, namely R19Q, R126T and I212T. The obtained 450-ns long trajectories were compared with those returned by both the open and closed forms of wild type SBDS and strongly indicated that two distinct conformations (open and closed) are both necessary for the proper SBDS function, in full agreement with recent experimental observations. Our study supports the hypothesis that the SBDS function is governed by an allosteric mechanism involving domains I and III and provides new insights into SDS pathogenesis, thus offering a possible starting point for a specific therapeutic option. 相似文献
994.
Eleonora Binatti Alessio Gerussi Donatella Barisani Pietro Invernizzi 《International journal of molecular sciences》2022,23(12)
Chronic inflammation is the hallmark of fibrotic disorders and is characterized by the activation of immune cells in the damaged tissues. Macrophages have emerged as central players in the fibrotic process since they initiate, sustain and amplify the inflammatory reaction. As regards the liver, distinct populations of phagocytic cells, like Kupffer cells and monocyte-derived macrophages, are indisputably key cells implicated in the pathogenesis of several chronic liver diseases. In this review, we summarize the current knowledge on the origin, role and functions of macrophages in fibrotic conditions, with a specific focus on liver fibrosis; then, we discuss some innovative therapeutic strategies targeting macrophages in fibrotic liver diseases. 相似文献
995.
996.
Alessandro de Sire Nicola Marotta Martina Ferrillo Francesco Agostini Cristiano Sconza Lorenzo Lippi Stefano Respizzi Amerigo Giudice Marco Invernizzi Antonio Ammendolia 《International journal of molecular sciences》2022,23(5)
To date, the application of oxygen-ozone (O2O3) therapy has significantly increased in the common clinical practice in several pathological conditions. However, beyond the favorable clinical effects, the biochemical effects of O2O3 are still far from being understood. This comprehensive review aimed at investigating the state of the art about the effects of O2O3 therapy on pro-inflammatory cytokines serum levels as a modulator of oxidative stress in patients with musculoskeletal and temporomandibular disorders (TMD). The efficacy of O2O3 therapy could be related to the moderate oxidative stress modulation produced by the interaction of ozone with biological components. More in detail, O2O3 therapy is widely used as an adjuvant therapeutic option in several pathological conditions characterized by chronic inflammatory processes and immune overactivation. In this context, most musculoskeletal and temporomandibular disorders (TMD) share these two pathophysiological processes. Despite the paucity of in vivo studies, this comprehensive review suggests that O2O3 therapy might reduce serum levels of interleukin 6 in patients with TMD, low back pain, knee osteoarthritis and rheumatic diseases with a concrete and measurable interaction with the inflammatory pathway. However, to date, further studies are needed to clarify the effects of this promising therapy on inflammatory mediators and their clinical implications. 相似文献
997.
Alessandro Lazzaro Gabriella De Girolamo Valeria Filippi Giuseppe Pietro Innocenti Letizia Santinelli Giancarlo Ceccarelli Enrico Maria Trecarichi Carlo Torti Claudio Maria Mastroianni Gabriella d&#x;Ettorre Alessandro Russo 《International journal of molecular sciences》2022,23(2)
Sepsis is a life-threatening condition that arises when the body’s response to an infection injures its own tissues and organs. Despite significant morbidity and mortality throughout the world, its pathogenesis and mechanisms are not clearly understood. In this narrative review, we aimed to summarize the recent developments in our understanding of the hallmarks of sepsis pathogenesis (immune and adaptive immune response, the complement system, the endothelial disfunction, and autophagy) and highlight novel laboratory diagnostic approaches. Clinical management is also discussed with pivotal consideration for antimicrobic therapy management in particular settings, such as intensive care unit, altered renal function, obesity, and burn patients. 相似文献
998.
999.
Sara Salucci;Matteo Giordani;Michele Betti;Laura Valentini;Pietro Gobbi;Michele Mattioli; 《Microscopy research and technique》2024,87(4):685-694
Exposure to mineral fibers represents an occupational and environmental hazard since particulate inhalation leads to several health disorders. However, few data are available on the effect of fibers with high solubility like natural epsomite, a water-soluble fiber with an inhalable size that allows it to penetrate biological systems, with regard to the respiratory tract. This study evaluated the natural (fibrous epsomite) and synthetic (Epsom salt) magnesium sulfate pathogenicity. Investigations have been performed through morpho-functional and biochemical analyses, in an in vitro cell model that usually grows as monocytes, but that under appropriate conditions differentiates into macrophages. These latter, known as alveolar macrophages, if referred to lungs, represent the first line of defense against harmful inhaled stimuli. Morphological observations reveal that, if Epsom salt induces osmotic stress on cell culture, natural epsomite fibers lead to cellular alterations including thickening of the nuclear envelope and degenerated mitochondria. Moreover, the insoluble fraction (impurities) internalized by cells induces diffuse damage characterized at the highest dosage and exposure time by secondary necrosis or necrotic cell death features. Biochemical analyses confirm this mineral behavior that involves MAPK pathway activation, resulting in many different cellular responses ranging from proliferation control to cell death. Epsom salt leads to MAPK/ERK activation, a marker predictive of overall survival. Unlike, natural epsomite induces upregulation of MAPK/p38 protein involved in the phosphorylation of downstream targets driving necrotic cell death. These findings demonstrate natural epsomite toxicity on U937 cell culture, making the inhalation of these fibers potentially hazardous for human health. 相似文献
1000.
Francesco Mosca Osvaldo Zarivi Natalia Battista Mauro Maccarrone Pietro Giorgio Tiscar 《International journal of molecular sciences》2021,22(9)
Anandamide (AEA) is one of the best characterized members of the endocannabinoid family and its involvement in many pathophysiological processes has been well documented in vertebrates and invertebrates. Here, we report the biochemical and functional characterization of key elements of the endocannabinoid system in hemocytes isolated from the Mediterranean mussel Mytilus galloprovincialis. We also show the effects of exogenous AEA, as well as of capsaicin, on the cell ability to migrate and to activate the respiratory burst, upon in vitro stimulation of phagocytosis. Interestingly, our findings show that both AEA and capsaicin suppress the hemocyte response and that the use of selective antagonists of CB2 and TRPV1 receptors revert their inhibitory effects. Overall, present data support previous evidence on the presence of endocannabinoid signaling in mollusks and advance our knowledge about the evolutionary origins of this endogenous system and its role in the innate response of mollusks. 相似文献