المؤلفون: Pagano C., Coppola L., Navarra G., Avilia G., Savarese B., Torelli G., Bruzzaniti S., Piemonte E., Galgani M., Laezza C., Bifulco M.

المساهمون: Pagano, C., Coppola, L., Navarra, G., Avilia, G., Savarese, B., Torelli, G., Bruzzaniti, S., Piemonte, E., Galgani, M., Laezza, C., Bifulco, M.

مصطلحات موضوعية: cancer metabolism, glioblastoma, glycolysi, iPA, PKM2

الوصف: Glioblastoma (GBM) is a primary tumor in the central nervous system with poor prognosis. It exhibits elevated glucose uptake and lactate production. This metabolic state of aerobic glycolysis is known as the Warburg effect. N6-isopentenyladenosine (iPA), a natural cytokine modified with an isopentenyl moiety derived from the mevalonate pathway, has well-established anti-tumor activity. It inhibits cell proliferation in glioma cells, inducing cell death by apoptosis and/or necroptosis. In the present study, we found that iPA inhibits aerobic glycolysis in unmodified U87MG cells and in the same cell line engineered to over-express wild-type epidermal growth factor receptor (EGFR) or EGFR variant III (vIII), as well as in a primary GBM4 patient-derived cell line. The detection of glycolysis showed that iPA treatment suppressed ATP and lactate production. We also evaluated the response of iPA treatment in normal human astrocyte primary cells, healthy counterpart cells of the brain. Aerobic glycolysis in treated normal human astrocyte cells did not show significant changes compared to GBM cells. To determine the mechanism of iPA action on aerobic glycolysis, we investigated the expression of certain enzymes involved in this metabolic pathway. We observed that iPA reduced the expression of pyruvate kinase M2 (PKM2), which plays a key role in the regulation of aerobic glycolysis, promoting tumor cell proliferation. The reduction of PKM2 expression is a result of the inhibition of the inhibitor of nuclear factor kappa-B kinase subunit, beta/nuclear factor-kappa B pathway upon iPA treatment. In conclusion, these experimental results show that iPA may inhibit aerobic glycolysis of GBM in stabilized cell lines and primary GBM cells by targeting the expression and activity of PKM2.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:001188790900001; journal:FEBS OPENBIO; https://hdl.handle.net/11588/958636Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85188778868

الإتاحة: https://doi.org/10.1002/2211-5463.13766Test
https://hdl.handle.net/11588/958636Test

المؤلفون: Pagano C., Ciaglia E., Coppola L., Lopardo V., Raimondo A., Giuseppe M., Lembo S., Laezza C., Bifulco M.

المساهمون: Pagano, C., Ciaglia, E., Coppola, L., Lopardo, V., Raimondo, A., Giuseppe, M., Lembo, S., Laezza, C., Bifulco, M.

مصطلحات موضوعية: CBD, dendritic cell, macrophage, monocyte, natural killer, psoriasis

الوصف: Introduction: The involvement of endocannabinoid system (ECS) in the inflammatory cascade, and the ability of phytocannabinoids, endocannabinoids and their synthetic analogues to modulate it has become an interesting research area for new therapeutic approaches in inflammatory skin diseases. Cannabidiol (CBD) appears to be the most promising among phytocannabinoids, due to the lack of psychotropic effects and low toxicity profile. Its anti-inflammatory action has been highlighted in different preclinical models, ranging from experimental colitis to arthritis and neuroinflammation. Our aim was to evaluate CBD immune-modulatory effects in peripheral blood mononuclear cells (PBMC) of psoriasis individuals with particular attention to both innate and adaptative immune arms. Methods: We performed in vitro immune functional experiments to analyze CBD action on various immune cells active in psoriatic lesions. Results: The results showed that CBD produced a shift from Th1 to Th2 response, while boosting cytotoxic activity of Natural Killer (NK) cells. Furthermore, it also exerted a potent action on monocyte differentiation as, after CBD treatment, monocytes from psoriatic individuals were unable to migrate in response to inflammatory stimuli and to fully differentiate into mature dendritic cells. Finally, a M2 skewing of monocyte-derived macrophages by CBD also contributed to the fine tuning of the magnitude of immune responses. Conclusions: These data uncover new potential immunomodulatory properties of this cannabinoid suggesting a possible therapeutic action in the treatment of multiple inflammatory skin diseases.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:001198860000001; volume:15; journal:FRONTIERS IN IMMUNOLOGY; https://hdl.handle.net/11588/958641Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85189921227

الإتاحة: https://doi.org/10.3389/fimmu.2024.1373435Test
https://hdl.handle.net/11588/958641Test

المؤلفون: Bruzzaniti S., Piemonte E., Mozzillo E., Bruzzese D., Lepore M. T., Carbone F., de Candia P., Strollo R., Porcellini A., Marigliano M., Maffeis C., Bifulco M., Ludvigsson J., Franzese A., Matarese G., Galgani M.

المساهمون: Bruzzaniti, S., Piemonte, E., Mozzillo, E., Bruzzese, D., Lepore, M. T., Carbone, F., de Candia, P., Strollo, R., Porcellini, A., Marigliano, M., Maffeis, C., Bifulco, M., Ludvigsson, J., Franzese, A., Matarese, G., Galgani, M.

مصطلحات موضوعية: Autoimmune disease, Autoimmune thyroiditi, Biomarker, Coeliac disease, Soluble immune-checkpoint molecule, Type 1 diabetes

الوصف: Aims/hypothesis: We assessed the levels of blood circulating immune checkpoint molecules (ICMs) at diagnosis of type 1 diabetes, and determined their association with the risk of developing an additional autoimmune disorder over time. Methods: Children with new-onset type 1 diabetes (n = 143), without biological and/or clinical signs of additional autoimmune disorders, and healthy children (n = 75) were enrolled, and blood circulating levels of 14 ICMs were measured. The children with type 1 diabetes were divided into two groups on the basis of the development of an additional autoimmune disease in the 5 years after diabetes onset. Differences in soluble ICM levels between the groups were assessed, and a Cox regression analysis was used to evaluate their association with the risk of development of an additional autoimmune disease over time. To validate the data, circulating ICMs were measured in an independent cohort of 60 children with new-onset type 1 diabetes stratified into two groups. Results: We found that the levels of circulating ICMs were significantly higher in children with new-onset diabetes compared with healthy children. Further, we observed that children with type 1 diabetes who developed a second autoimmune disease over time (T1D-AAD+ children) had higher levels of soluble ICMs than children with type 1 diabetes who did not (T1D-AAD− children). Cox regression models revealed that high circulating levels of CD137/4-1BB and PD-1 molecules at diabetes diagnosis were associated with the risk of developing an additional autoimmune disease in both type 1 diabetes cohorts. Conclusions/interpretation: Our findings suggest that soluble CD137/4-1BB and PD-1 molecules may be used as prognostic biomarkers in children with type 1 diabetes, and may pave the way for novel immunological screening at diabetes onset, allowing early identification of children at higher risk of developing other autoimmune conditions over time. Graphical abstract: [Figure not available: see fulltext.]

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000799731900002; volume:65; firstpage:1390; lastpage:1397; numberofpages:8; journal:DIABETOLOGIA; https://hdl.handle.net/11588/888604Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85130721114

الإتاحة: https://doi.org/10.1007/s00125-022-05724-3Test
https://hdl.handle.net/11588/888604Test

المؤلفون: Pepe, G., Abate M., Marino, P., Randino, R., Pisanti, S., Basilicata, M. G., Verdiana, C., Bifulco, M., Cabri, W., D'Ursi, A. M., Rodriquez, M., Gómez-Monterrey, I. M., Manfra, M., Campiglia, P

المساهمون: Pepe, G., Abate, M., Marino, P., Randino, R., Pisanti, S., Basilicata, M. G., Verdiana, C., Bifulco, M., Cabri, W., D'Ursi, A. M., Rodriquez, M., Gómez-Monterrey, I. M., Manfra, M., Campiglia, P

الوصف: Ganoderma lucidum, is also known as “the fungus of immortality”. The pharmacological properties of G. lucidum, such as anti-inflammatory, antioxidant, antiaging, immunomodulatory and antitumour activities1, are due to its peculiar chemical composition in bioactive compounds such as polysaccharides, terpenoids, nucleotides, steroids, fatty acids, proteins and glycopeptides2. The present study reported the effect of G. lucidum on human keratinocytes as an in vitro skin model for evaluation of its dermatological applications.

العلاقة: ispartofbook:13th Young Medicinal Chemist's Symposium (13NPCF).; 13th Young Medicinal Chemist's Symposium (13NPCF).; https://hdl.handle.net/11563/165554Test

الإتاحة: https://hdl.handle.net/11563/165554Test

المؤلفون: Marzullo P., Bettini S., Menafra D., Aprano S., Muscogiuri G., Barrea L., Savastano S., Colao A., Magno S., Di Nisio A., Romano F., Poggiogalle E., Venneri M., Liccardi A., Tarsitano M. G., Di Renzo L., Tuccinardi D., Caprio M., Guzzardi M. A., Pelosini C., Pugliese G., Bottiglieri F., Gortan Cappellari G., Laudisio D., Pivari F., Brasacchio C., Lenzi A., Muratori F., Santini F., Busetto L., Sbraccia P., Soldati L., Salvatore D., Di Somma C., Giugliano D., Gnessi L., Capaldo B., Riccardi G., Barazzoni R., Guida B., Bifulco M., Esposito K., Vettor R., Macchia P. E., Casanueva F., Lubrano C., Beguinot F., Spera G., Belfiore A., Di Luigi L., Ritieni A., Napoli R., Vaccaro O., Sukkar S., Alviggi C., Pivonello R., Bellastella G., Scambia G., Bifulco G.

المساهمون: Marzullo, P., Bettini, S., Menafra, D., Aprano, S., Muscogiuri, G., Barrea, L., Savastano, S., Colao, A., Magno, S., Di Nisio, A., Romano, F., Poggiogalle, E., Venneri, M., Liccardi, A., Tarsitano, M. G., Di Renzo, L., Tuccinardi, D., Caprio, M., Guzzardi, M. A., Pelosini, C., Pugliese, G., Bottiglieri, F., Gortan Cappellari, G., Laudisio, D., Pivari, F., Brasacchio, C., Lenzi, A., Muratori, F., Santini, F., Busetto, L., Sbraccia, P., Soldati, L., Salvatore, D., Di Somma, C., Giugliano, D., Gnessi, L., Capaldo, B., Riccardi, G., Barazzoni, R., Guida, B., Bifulco, M., Esposito, K., Vettor, R., Macchia, P. E., Casanueva, F., Lubrano, C., Beguinot, F., Spera, G., Belfiore, A., Di Luigi, L., Ritieni, A., Napoli, R., Vaccaro, O., Sukkar, S., Alviggi, C., Pivonello, R., Bellastella, G., Scambia, G., Bifulco, G.

مصطلحات موضوعية: Gastrointestinal Microbiome, Gastrointestinal Tract, Human, Metabolic Disease, Neoplasm, Obesity

الوصف: Over the last few years, the complexity and diversity of gut microbiota within and across individuals has been detailed in relation to human health. Further, understanding of the bidirectional association between gut microbiota and metabolic disorders has highlighted a complimentary, yet crucial role for microbiota in the onset and progression of obesity-related cancers. While strategies for cancer prevention and cure are known to work efficiently when supported by healthy diet and lifestyle choices and physical activity, emerging evidence suggests that the complex interplay relating microbiota both to neoplastic and metabolic diseases could aid strategies for cancer treatment and outcomes. This review will explore the experimental and clinical grounds supporting the functional role of gut microbiota in the pathophysiology and progression of cancers in relation to obesity and its metabolic correlates. Therapeutic approaches aiding microbiota restoration in connection with cancer treatments will be discussed.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34363002; info:eu-repo/semantics/altIdentifier/wos/WOS:000683503200003; volume:45; issue:11; firstpage:2291; lastpage:2299; numberofpages:9; journal:INTERNATIONAL JOURNAL OF OBESITY; http://hdl.handle.net/11368/3029014Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85117894688; https://www.nature.com/articles/s41366-021-00866-7Test

الإتاحة: https://doi.org/10.1038/s41366-021-00866-7Test
http://hdl.handle.net/11368/3029014Test
https://www.nature.com/articles/s41366-021-00866-7Test

المؤلفون: Fiore D, Ramesh P, Proto MC, Piscopo C, Franceschelli S, ANZELMO, SABATO, Medema JP, Bifulco M, Gazzerro P.

المساهمون: Fiore, D, Ramesh, P, Proto, Mc, Piscopo, C, Franceschelli, S, Anzelmo, Sabato, Medema, Jp, Bifulco, M, Gazzerro, P.

مصطلحات موضوعية: 3D culture, Rimonabant, Wnt/β-Catenin, cannabinoid, colon cancer, colon cancer stem cells

الوصف: Colorectal cancer (CRC), like other tumor types, is a highly heterogeneous disease. Within the tumor bulk, intra-tumoral heterogeneity is also ascribable to Cancer Stem Cells (CSCs) subpopulation, characterized by high chemoresistance and the unique ability to retain tumorigenic potential, thus associated to tumor recurrence. High dynamic plasticity of CSCs, makes the development of winning therapeutic strategies even more complex to completely eradicate tumor fuel. Rimonabant, originally synthesized as antagonist/inverse agonist of Cannabinoid Receptor 1, is able to inactivate Wnt signaling, both in vitro and in vivo, in CRC models, through inhibition of p300-histone acetyltransferase activity. Since Wnt/β-Catenin pathway is the main player underlying CSCs dynamic, this finding candidates Rimonabant as potential modulator of cancer stemness, in CRC. In this work, using established 3D cultures of primary colon CSCs, taking into account the tumor heterogeneity through monitoring of Wnt activity, we demonstrated that Rimonabant was able to reduces both tumor differentiated cells and colon CSCs proliferation and to control their survival in long term cultures. Interestingly, in ex vivo model of wild type human organoids, retaining both architecture and heterogeneity of original tissue, Rimonabant showed no toxicity against cells from healthy colon epithelium, suggesting its potential selectivity toward cancer cells. Overall, results from this work provided new insights on anti-tumor efficacy of Rimonabant, strongly suggesting that it could be a novel lead compound for CRC treatment.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/29354056; info:eu-repo/semantics/altIdentifier/wos/WOS:000419349300002; volume:8; firstpage:949; lastpage:956; numberofpages:8; journal:FRONTIERS IN PHARMACOLOGY; http://hdl.handle.net/11386/4703894Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85040459727; http://dx.doi.org/10.3389/fphar.2017.00949Test

الإتاحة: https://doi.org/10.3389/fphar.2017.00949Test
http://hdl.handle.net/11386/4703894Test

المؤلفون: Ciaglia, E., Malfitano, A. M., Laezza, C., Fontana, A., Nuzzo, G., Cutignano, A., Abate, M., Bifulco, M., Gazzerro, P., PELIN, MARCO, SOSA, SILVIO

المساهمون: Ciaglia, E., Malfitano, A. M., Laezza, C., Fontana, A., Nuzzo, G., Cutignano, A., Abate, M., Pelin, Marco, Sosa, Silvio, Bifulco, M., Gazzerro, P.

مصطلحات موضوعية: Marine sponge, natural compound, inflammation, lymphocytes

الوصف: We assessed the immunomodulatory and anti-inflammatory effects of 9,11-dihydrogracilin A (DHG), a molecule derived from the Antarctic marine sponge Dendrilla membranosa. We used in vitro and in vivo approaches to establish DHG properties. Human peripheral blood mononuclear cells (PBMC) and human keratinocytes cell line (HaCaT cells) were used as in vitro system, whereas a model of murine cutaneous irritation was adopted for in vivo studies. We observed that DHG reduces dose dependently the proliferative response and viability of mitogen stimulated PBMC. In addition, DHG induces apoptosis as revealed by AnnexinV staining and downregulates the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B), signal transducer and activator of transcription (STAT) and extracellular signal–regulated kinase (ERK) at late time points. These effects were accompanied by down-regulation of interleukin 6 (IL-6) production, slight decrease of IL-10 and no inhibition of tumor necrosis factor-alpha (TNF-) secretion. To assess potential properties of DHG in epidermal inflammation we used HaCaT cells; this compound reduces cell growth, viability and migration. Finally, we adopted for the in vivo study the croton oil-induced ear dermatitis murine model of inflammation. Of note, topical use of DHG significantly decreased mouse ear edema. These results suggest that DHG exerts anti-inflammatory effects and its anti-edema activity in vivo strongly supports its potential therapeutic application in inflammatory cutaneous diseases.

وصف الملف: STAMPA

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/28788056; info:eu-repo/semantics/altIdentifier/wos/WOS:000408897400044; volume:18; issue:8; firstpage:1; lastpage:16; numberofpages:16; journal:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; http://hdl.handle.net/11368/2909410Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85026647995; http://www.mdpi.com/1422-0067/18/8/1643Test

الإتاحة: https://doi.org/10.3390/ijms18081643Test
http://hdl.handle.net/11368/2909410Test
http://www.mdpi.com/1422-0067/18/8/1643Test

المؤلفون: Martini M., Bifulco M., Orsini D.

المساهمون: Martini, M., Bifulco, M., Orsini, D.

مصطلحات موضوعية: History of hygiene, History of vaccination, Kingdom of the Two Sicilie, Public health, Vaccine hesitancy

الوقت: XIX century

الوصف: Objective: The current health emergency caused by COVID-19 disease shows several correspondences with well-known epidemics of the past. The knowledge of their management and overcoming could give us useful tools to face the present COVID-19 pandemic and future epidemics. Study design: On 1 March 1801, the first smallpox vaccinations were carried out in Palermo, and a few weeks later, the vaccine was also administered in Naples and the various provinces of the Kingdom. We aim to study the mass vaccination programme initiated by the Bourbon king Ferdinand IV that was the first large-scale campaign to be conducted in Italy and one of the first in Europe. Methods: The authors searched and examined historical testimony and different aspects linked to the public health issues on vaccination. It is a topical topic in the current period with the COVID pandemic. Results: Albeit with the due differences determined by the passage of time and by the scientific and cultural advances of modern society, this testimony from the past can provide us with food for thought regarding how to face the present COVID-19 pandemic and to prepare for the future. Indeed, it shows us how the terrible smallpox epidemic was handled and finally overcome, thanks to vaccination.

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36334583; volume:213; firstpage:47; lastpage:53; numberofpages:7; journal:PUBLIC HEALTH; https://hdl.handle.net/11365/1223198Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85142442467

الإتاحة: https://doi.org/10.1016/j.puhe.2022.09.012Test
https://hdl.handle.net/11365/1223198Test

المؤلفون: Bifulco, M, Di Zazzo, E, Pisanti, S, Martini, M, Orsini, D

المساهمون: Bifulco, M, Di Zazzo, E, Pisanti, S, Martini, M, Orsini, D

مصطلحات موضوعية: COVID-19 vaccine, Compulsory vaccination, History of vaccine, Prevention

الوصف: The current health emergency caused by COVID-19 disease shows several similarities with well-known epidemics of the past. The knowledge of their management and overcoming could give us useful tools to face the present COVID-19 pandemic. The Bourbon king Ferdinand I planned the first free large-scale mass vaccination programme conducted in Italy and one of the first in Europe to counteract smallpox. The vaccination campaign was characterized by many difficulties and the efforts made by the Southern Kingdoms governors were enormous. For example, the "ante litteram communication campaign ", aimed at convincing the so-called "hesitant " people and at confuting the arguments of vaccination opponents, was impressive. In 1821, the compulsory vaccination significantly reduced smallpox infections and death rates. Subsequently, several experiences followed this initiative, not without doubts and debates. Smallpox was finally eradicated worldwide only on the 9th December 1979. Despite to other countries, the "mandatory vaccination " is a topic often debated by Italian scientific and social communities. (C) 2022 Elsevier Ltd. All rights reserved.

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35534315; info:eu-repo/semantics/altIdentifier/wos/WOS:000809622500005; volume:40; issue:25; firstpage:3452; lastpage:3454; numberofpages:3; journal:VACCINE; https://hdl.handle.net/11365/1223197Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85129927070; https://www.sciencedirect.com/science/article/pii/S0264410X22004923Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9073592Test/

الإتاحة: https://doi.org/10.1016/j.vaccine.2022.04.052Test
https://hdl.handle.net/11365/1223197Test
https://www.sciencedirect.com/science/article/pii/S0264410X22004923Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9073592Test/

المؤلفون: Abate M., Pagano C., Masullo M., Citro M., Pisanti S., Piacente S., Bifulco M.

المساهمون: Abate, M., Pagano, C., Masullo, M., Citro, M., Pisanti, S., Piacente, S., Bifulco, M.

مصطلحات موضوعية: Apoptosi, Cosmeceutical, Garcinia mangostana, Mangostanin, Oxidative stress

الوصف: The fruit of Garcinia mangostana (mangosteen) is known in ancient traditional Asian medicine for its antioxidant, anti-inflammatory, immunomodulatory and anticancer activities. These effects are mainly due to the action of polyphenols known as xanthones, which are contained in the pericarp of the fruit. In recent years, there has been a growing interest from pharmaceutical companies in formulating new topicals based on mangosteen full extracts to prevent skin aging. However, the molecules responsible for these effects and the mechanisms involved have not been investigated so far. Here, the arils and shells of Garcinia mangostana were extracted with chloroform and methanol, and the extracts were further purified to yield 12 xanthone derivatives. Their effects were evaluated using in vitro cultures of human epidermal keratinocytes. After confirming the absence of cytotoxicity, we evaluated the antioxidant potential of these compounds, identifying mangostanin as capable of both protecting and restoring oxidative damage induced by H2O2 . We showed how mangostanin, by reducing the generation of intracellular reactive oxygen species (ROS), prevents the activation of AKT (protein kinase B), ERK (extracellular signal-regulated kinase), p53, and other cellular pathways underlying cell damage and apoptosis activation. In conclusion, our study is the first to demonstrate that mangostanin is effective in protecting the skin from the action of free radicals, thus preventing skin aging, confirming a potential toward its development in the nutraceutical and cosmeceutical fields.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000758548600001; volume:15; issue:1; journal:PHARMACEUTICALS; http://hdl.handle.net/11588/876264Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85123077629

الإتاحة: https://doi.org/10.3390/ph15010084Test
http://hdl.handle.net/11588/876264Test