Papers by Vincenzo BRANCALEONE
硫化水素の抗炎症と抗ウイルスの役割:COVID-19療法におけるH_2Sドナーを考慮する理由【JST・京大機械翻訳】
British Journal of Pharmacology, 2020
Defective Bile Acid Signaling Promotes Vascular Dysfunction, Supporting a Role for G‐Protein Bile Acid Receptor 1/Farnesoid X Receptor Agonism and Statins in the Treatment of Nonalcoholic Fatty Liver Disease
Journal of the American Heart Association
Background Patients with nonalcoholic fatty liver disease are at increased risk to develop athero... more Background Patients with nonalcoholic fatty liver disease are at increased risk to develop atherosclerotic cardiovascular diseases. FXR and GPBAR1 are 2 bile acid–activated receptors exploited in the treatment of nonalcoholic fatty liver disease: whether dual GPBAR1/FXR agonists synergize with statins in the treatment of the liver and cardiovascular components of nonalcoholic fatty liver disease is unknown. Methods and Results Investigations of human aortic samples obtained from patients who underwent surgery for aortic aneurysms and Gpbar1 −/− , Fxr −/− , and dual Gpbar1 −/‐ Fxr −/− mice demonstrated that GPBAR1 and FXR are expressed in the aortic wall and regulate endothelial cell/macrophage interactions. The expression of GPBAR1 in the human endothelium correlated with the expression of inflammatory biomarkers. Mice lacking Fxr and Gpbar1 −/− / Fxr −/− display hypotension and aortic inflammation, along with altered intestinal permeability that deteriorates with age, and severe dy...
International Journal of Molecular Sciences, May 31, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
International Journal of Inflammation, 2015
Frontiers in Pharmacology, Nov 7, 2022
<scp>H</scp> <sub>2</sub> <scp>S</scp> and Hypertension
Activity Methods For Animal Pharmacokinetic and Pharmacodynamic Studies
BENTHAM SCIENCE PUBLISHERS eBooks, Jun 25, 2023
Analysis of rheumatoid- vs psoriatic arthritis synovial fluid reveals differential macrophage (CCR2) and T helper subsets (STAT3/4 and FOXP3) activation
Autoimmunity Reviews, Dec 1, 2022
Frontiers in Pharmacology, Apr 4, 2022
The coronavirus disease 2019 (COVID-19) pandemic has brought great uncertainty to global economic... more The coronavirus disease 2019 (COVID-19) pandemic has brought great uncertainty to global economic development and social stability and posed a great threat to human life and health. The most effective response to the pandemic remains a combination of "vaccines plus drugs." The success of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has reduced the morbidity, severe illness and mortality caused by COVID-19 and, to a certain extent, has curbed the global spread of SARS-CoV-2. However, the emergence of iterations of SARS-CoV-2 variants has led to a reduction in the protection afforded by the marketed vaccines and even frequent breaches in the immune barrier. Although the Food and Drug Administration (FDA) has urgently authorized the use of several antibodies as drugs for COVID-19 treatment, these molecules still show significant limitations. First, they can be used only to treat patients with mild-to-moderate disease and be only administered intravenously, which is costly and limits their widespread use. Second, the mechanisms of action of antibody drugs predictably cause drug resistance problems, and none of the approved antibodies are effective against the currently prevalent omicron variant. In combating COVID-19, orally available small-molecule drugs are indispensable and may be the centerpiece in the prevention and control of the pandemic. Small-molecule drugs have shown excellent clinical effects in pre-and postexposure prophylaxis as well as in the early treatment of severe disease. Thus, the availability of these anti-SARS-CoV-2 drugs will turn COVID-19 into a preventable and treatable disease and provide an extremely important assurance for us to win the fight against SARS-CoV-2, therefore leading to elimination of the requirement for masks and a return to normal daily life in the near future. Small-molecule anti-SARS-CoV-2 drugs can be taken orally, mass produced, and supplied in large quantities with good accessibility and affordability. Especially since a large number of COVID-19 patients are currently mild-to-moderately ill, these patients can be treated at home with small-molecule drugs, which can greatly reduce the pressure on health care resources and the risk of cross-contamination. More importantly, these small-molecule drugs are targeted at relatively conserved sites of the virus to overcome drug resistance, and they maintain activity against SARS-CoV-2 variants of concern. All these advantages make small-molecule drugs unparalleled in COVID-19 treatment and the prevention and control of the pandemic. Drug repurposing is the most efficient drug discovery strategy in response to an unexpected emerging infectious disease in the early stage of the outbreak. Global efforts in small-molecule drug discovery have mainly focused on screening of drugs approved by the FDA or in the clinical stage, such as favipiravir, remdesivir, ebselen, and masitinib, to accelerate the evaluation of such drugs for COVID-19 by considering both their human pharmacokinetic properties and toxicity. Since the
Endogenous and exogenous hydrogen sulfide modulates urothelial bladder carcinoma development in human cell lines
Biomedicine & Pharmacotherapy, Jul 1, 2022
International Journal of Molecular Sciences, Apr 5, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Hydrogen sulfide regulates the redox state of soluble guanylate cyclase in CSE-/- mice corpus cavernosum microcirculation
Pharmacological Research
International Journal of Molecular Sciences
Vascular inflammation (VI) represents a pathological condition that progressively affects the int... more Vascular inflammation (VI) represents a pathological condition that progressively affects the integrity and functionality of the vascular wall, thus leading to endothelial dysfunction and the onset of several cardiovascular diseases. Therefore, the research of novel compounds able to prevent VI represents a compelling need. In this study, we tested erucin, the natural isothiocyanate H2S-donor derived from Eruca sativa Mill. (Brassicaceae), in an in vivo mouse model of lipopolysaccharide (LPS)-induced peritonitis, where it significantly reduced the amount of emigrated CD11b positive neutrophils. We then evaluated the anti-inflammatory effects of erucin in LPS-challenged human umbilical vein endothelial cells (HUVECs). The pre-incubation of erucin, before LPS treatment (1, 6, 24 h), significantly preserved cell viability and prevented the increase of reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-α) levels. Moreover, erucin downregulated endothelial hyperpermeabili...
Frontiers in Pharmacology
Activity Methods for Cardiovascular System Diseases
BENTHAM SCIENCE PUBLISHERS eBooks, Jun 25, 2023
Persulfidation of mitoKv7.4 channels contributes to the cardioprotective effects of the H2S-donor Erucin against ischemia/reperfusion injury
Biochemical Pharmacology, Sep 1, 2023
Hydrogen sulfide donor AP123 restores endothelial nitric oxide-dependent vascular function in hyperglycemia via a CREB-dependent pathway
Redox Biology
Scientific Reports, Jul 20, 2021
Clodronate is a bisphosphonate agent commonly used as anti-osteoporotic drug. Throughout its use,... more Clodronate is a bisphosphonate agent commonly used as anti-osteoporotic drug. Throughout its use, additional anti-inflammatory and analgesic properties have been reported, although the benefits described in the literature could not solely relate to their inhibition of bone resorption. Thus, the purpose of our in vitro study is to investigate whether there are underlying mechanisms explaining the anti-inflammatory effect of clodronate and possibly involving hydrogen sulphide (H 2 S). Immortalised fibroblast-like synoviocyte cells (K4IM) were cultured and treated with clodronate in presence of TNF-α. Clodronate significantly modulated iNOS expression elicited by TNF-α. Inflammatory markers induced by TNF-α, including IL-1, IL-6, MCP-1 and RANTES, were also suppressed following administration of clodronate. Furthermore, the reduction in enzymatic biosynthesis of CSE-derived H 2 S, together with the reduction in CSE expression associated with TNF-α treatment, was reverted by clodronate, thus rescuing endogenous H 2 S pathway activity. Clodronate displays antinflammatory properties through the modulation of H 2 S pathway and cytokines levels, thus assuring the control of the inflammatory state. Although further investigation is needed to stress out how clodronate exerts its control on H 2 S pathway, here we showed for the first the involvement of H 2 S in the additive beneficial effects observed following clodronate therapy. Bisphosphonates (BPs) are synthetic, non-hydrolysable pyrophosphate analogues containing a P-C-P core and R1 and R2 chains, bound to the central carbon 1,2. Currently, BPs represent the most widely used treatment for common skeletal disorders mediated by osteoclastic action such as osteoporosis, metastatic bone and Paget's disease, although their exact molecular mechanisms of action has only been clarified in the last decade 1,3. In particular, BPs mainly inhibit bone resorption, which underlies osteoporosis, together with other pathological conditions such as hypercalcemic malignancies, metastatic osteolytic bone or hyperparathyroidism 4,5. BPs can be divided in two main groups, non-nitrogen BPs (NN-BP) such as etidronate, clodronate and tildronate or nitrogen BPs (N-BP) such as pamidronate, alendronate, incadronate, and ibandronate 1,6,7. Generally, the anti-resorptive potency exhibited by N-BPs is greater than that shown by NN-BPs. This effect has been ascribed to the different mechanism of action 2. Clodronate (Clo) is one of the most known NN-BP, in which the two lateral chains are made up of two chlorine atoms 2,7,8. It has been widely used since the 60 s and today is still effective in the treatment of several osteometabolic disorders featured by excessive bone resorption 8,9. Although Clo is commonly used as anti-osteoporotic drug, recently many evidences have shown that Clo has also been successfully tested in erosive osteoarthritis (OA) upon intra-articular and parenteral administration 8,10,11. In this setting, Clo has been demonstrated to regulate the biosynthesis and the release of NO, expression of cycloxygenase 2 (COX 2) and pro-inflammatory cytokines such as TNF-α, IL-1β that are known to promote cartilage erosion, subchondral bone alterations and to inhibit progenitors maturation into chondrocytes in OA early stages 7,12-15. Furthermore, given its additional anti-inflammatory and analgesic properties, Clo is used to treat several musculoskeletal pathologic onsets ranging from complex regional pain syndrome (CRPS)
Involvement of proteinase activated receptor-2in the vascular response to sphingosine 1-phosphate
Clinical Science, 2014
S1P exerts a diverse set of vascular responses, and PAR-2 has been shown to be involved in vascul... more S1P exerts a diverse set of vascular responses, and PAR-2 has been shown to be involved in vascular inflammation as well as in other inflammatory-based diseases. In the present study, we demonstrate that S1P-mediated vascular effect involves PAR-2 activation.
N ‐Acylethanolamine acid amidase (NAAA) is dysregulated in colorectal cancer patients and its inhibition reduces experimental cancer growth
British Journal of Pharmacology, 2021
BACKGROUND AND PURPOSE N-acylethanolamine acid amidase (NAAA) is a lysosomal enzyme accountable f... more BACKGROUND AND PURPOSE N-acylethanolamine acid amidase (NAAA) is a lysosomal enzyme accountable for the breakdown of N-acylethanolamides (NAEs) and its pharmacological inhibition determines beneficial effects in inflammatory conditions. The knowledge of NAAA in cancer is fragmentary with an unclarified mechanism whereas its contribution to colorectal cancer (CRC) is unknown to date. EXPERIMENTAL APPROACH CRC xenograft and azoxymethane models assessed the in vivo pharmacological effect of NAAA inhibition; tumor secretome was evaluated by an oncogenic array; CRC cell lines were used for in vitro studies; cell cycle was analyzed by cytofluorimetry; NAAA was knocked down with siRNA; human biopsies were obtained from surgically resected CRC patients; gene expression was revealed by RT-PCR; NAEs were measured by LC-MS. KEY RESULTS The NAAA inhibitor AM9053 reduced CRC xenograft tumor growth and counteracted tumor development in the azoxymethane model. NAAA inhibition impacted the composition of the tumor secretome that negatively affected the expression of epidermal growth factor family members. In CRC cells, AM9053 reduced proliferation with a mechanism mediated by PPAR-α and TRPV1 and induced cell cycle arrest in the S phase with cyclin A2/CDK2 downregulation. NAAA knock-down mirrored the effects of NAAA pharmacological inhibition. NAAA expression was downregulated in human CRC tissues, with a consequential augmentation of NAEs levels and dysregulation of some of their targets. CONCLUSIONS AND IMPLICATIONS Our results provide unprecedented data on the functional importance of NAAA in CRC progression and its mechanism. We propose this enzyme as a valid drug target for the treatment of CRC growth and development.
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Papers by Vincenzo BRANCALEONE