Developmental and Tumor Angiogenesis Requires the Mitochondria-Shaping Protein Opa1

While endothelial cell (EC) function is influenced by mitochondrial metabolism, the role of mitochondrial dynamics in angiogenesis, the formation of new blood vessels from existing vasculature, is unknown. Here we show that the inner mitochondrial membrane mitochondrial fusion protein optic atrophy 1 (OPA1) is required for angiogenesis. In response to angiogenic stimuli, OPA1 levels rapidly increase to limit nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) signaling, ultimately allowing angiogenic genes expression and angiogenesis. Endothelial Opa1 is indeed required in an NFκB-dependent pathway essential for developmental and tumor angiogenesis, impacting tumor growth and metastatization. A first-in-class small molecule-specific OPA1 inhibitor confirms that EC Opa1 can be pharmacologically targeted to curtail tumor growth. Our data identify Opa1 as a crucial component of physiological and tumor angiogenesis

Hypnotic Focused Analgesia Obtained Through Body Dysmorphism Prevents Both Pain and Its Cardiovascular Effects

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Inhibition of the mitochondrial protein Opa1 curtails breast cancer growth.

peer reviewed[en] BACKGROUND: Mitochondrial fusion and fission proteins have been nominated as druggable targets in cancer. Whether their inhibition is efficacious in triple negative breast cancer (TNBC) that almost invariably develops chemoresistance is unknown. METHODS: We used a combination of bioinformatics analyses of cancer genomic databases, genetic and pharmacological Optic Atrophy 1 (OPA1) inhibition, mitochondrial function and morphology measurements, micro-RNA (miRNA) profiling and formal epistatic analyses to address the role of OPA1 in TNBC proliferation, migration, and invasion in vitro and in vivo. RESULTS: We identified a signature of OPA1 upregulation in breast cancer that correlates with worse prognosis. Accordingly, OPA1 inhibition could reduce breast cancer cells proliferation, migration, and invasion in vitro and in vivo. Mechanistically, while OPA1 silencing did not reduce mitochondrial respiration, it increased levels of miRNAs of the 148/152 family known to inhibit tumor growth and invasiveness. Indeed, these miRNAs were epistatic to OPA1 in the regulation of TNBC cells growth and invasiveness. CONCLUSIONS: Our data show that targeted inhibition of the mitochondrial fusion protein OPA1 curtails TNBC growth and nominate OPA1 as a druggable target in TNBC

The Mysterious Hypnotic Analgesia: Experimental Evidences

In the last years, the Laboratory of Experimental Hypnosis of the University of Padova and of the Institute Franco Granone of Torino, also in collaboration with the Foundation Hospital San Camillo in Venice, studied the effectiveness and the mechanisms of hypnotic analgesia in non-trigeminal an trigeminal pain. In this paper, the results of our work are summarized, starting from what was already known on the topic and exploring experimentally many different aspects of hypnotic analgesia. All the studies described in the present paper were conducted following scientific protocols and using the methods and means of Galilean science, employing in particular many instruments pertaining to human physiology and belonging to cardiology and neurology. This leads to the demonstration that hypnotic analgesia is an objective, real and measurable phenomenon