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A better deepening of the mechanisms underlying the disease is needed to define effective and mechanism\u2010targeted treatments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To understand whether the sebocyte differentiation process could be involved in the pathogenesis of the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Protein expressions were evaluated by Western blot analysis and\n                      <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>\n                      ;\n                      <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n                      levels by real\u2010time\n                      <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>\n                      , lipid analysis and lipid peroxidation were performed by gas chromatography, mass spectrometry and spectrophotometric assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro,<\/jats:italic>\n                      low differentiated\n                      <jats:styled-content style=\"fixed-case\">SZ<\/jats:styled-content>\n                      95 sebocyte expressed an up\u2010modulation of genes involved in sebogenesis and a higher level of insulin receptor respect to differentiated cells, resulting in an increased response to insulin and in the production of acne\u2010like sebum. The induction of\n                      <jats:styled-content style=\"fixed-case\">SZ<\/jats:styled-content>\n                      95 sebocyte differentiation by the peroxisome proliferator\u2010activated receptor \u03b3 (\n                      <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\n                      \u03b3) modulator\n                      <jats:styled-content style=\"fixed-case\">NAC<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">GED<\/jats:styled-content>\n                      0507 reduced the response to insulin normalizing the sebum production and decreasing the release of proinflammatory mediators.\n                      <jats:italic>In vivo<\/jats:italic>\n                      treatment of acne patients with\n                      <jats:styled-content style=\"fixed-case\">NAC<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">GED<\/jats:styled-content>\n                      0507 1% gel ameliorated clinical manifestations and induced in sebum the expression of\n                      <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\n                      \u03b3, associated with the decrease in mammalian target of rapamycin activation and levels of inflammatory molecules, confirming the results obtained\n                      <jats:italic>in\u00a0vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The study provides relevant insight into acne pathogenesis, identifying an alteration of sebocyte differentiation as pathogenetic basis of the disease and the induction of the differentiation process as a therapeutic target in acne therapy interfering with all pathogenic mechanisms.<\/jats:p>\n         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