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<p>We investigate the role of prokineticin, T-reg cells, and oxidative metabolism in the progression of obesity-related NASH to HCC. Our findings on a cohort of 250 patients, including Obese NAFLD and Non-Obese NAFLD, reveal significant insights. In Obese NAFLD, <i>PK-1</i> mRNA expression was reduced by 2.4-fold (<i>p</i> &lt; 0.01) compared to Non-Obese NAFLD, while <i>PK-2</i> was upregulated by 1.4-fold (<i>p</i> &lt; 0.005), and <i>FABP-5</i> increased by 1.4-fold (<i>p</i> &lt; 0.005) compared to T2DM. <i>IL-10</i> mRNA expression was 2.4-fold higher (<i>p</i> &lt; 0.005) in MetS verses to Non-Obese NAFLD. <i>Nrf-2</i> expression was elevated by 1.13-fold in Non-Obese NAFLD compared to Obese NAFLD (<i>p</i> &lt; 0.05). Flow cytometric analysis of T-reg cells was three times lower in Obese NAFLD compared to MetS (<i>p</i> &lt; 0.005), with a notable reduction in CD8<sup>+</sup> cells and an increase in CD4<sup>+</sup> cells. Correlation analysis in Obese NAFLD revealed strong positive correlations between IL-10 and T-reg (<i>r</i> = 1), CD4<sup>+</sup> (<i>r</i> = 0.99), and CD8<sup>+</sup> cells (<i>r</i> = 0.99). <i>PK-1</i> expression correlated with CD8<sup>+</sup> cells (<i>r</i> = 0.52), while <i>PK-2</i> negatively correlated with C-type lectin (<i>r</i>=-0.49). <i>FABP-5</i> exhibited significant positive correlations with <i>PK-1</i> (<i>r</i> = 0.54) and <i>IL-10</i> (<i>r</i> = 0.63). We highlight the interplay between prokineticins, immune modulation, and metabolic oxidative factors to offer potential therapeutic targets to prevent progression to HCC, instilling hope for the future of NASH treatment.</p>

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Role of prokineticins and T-reg cells in obesity-associated metabolic oxidative dysregulation in NAFLD

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月12日

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  • Shyam Prakash,
  • Priyatma,
  • Ram Aasarey,
  • Shahid Khan,
  • Naval K. Vikram,
  • Shalimar,
  • Medha,
  • Saumya Srivastava,
  • Shivam Pandey,
  • Akanksha Priya,
  • Sandeep Aggarwal

摘要

We investigate the role of prokineticin, T-reg cells, and oxidative metabolism in the progression of obesity-related NASH to HCC. Our findings on a cohort of 250 patients, including Obese NAFLD and Non-Obese NAFLD, reveal significant insights. In Obese NAFLD, PK-1 mRNA expression was reduced by 2.4-fold (p < 0.01) compared to Non-Obese NAFLD, while PK-2 was upregulated by 1.4-fold (p < 0.005), and FABP-5 increased by 1.4-fold (p < 0.005) compared to T2DM. IL-10 mRNA expression was 2.4-fold higher (p < 0.005) in MetS verses to Non-Obese NAFLD. Nrf-2 expression was elevated by 1.13-fold in Non-Obese NAFLD compared to Obese NAFLD (p < 0.05). Flow cytometric analysis of T-reg cells was three times lower in Obese NAFLD compared to MetS (p < 0.005), with a notable reduction in CD8+ cells and an increase in CD4+ cells. Correlation analysis in Obese NAFLD revealed strong positive correlations between IL-10 and T-reg (r = 1), CD4+ (r = 0.99), and CD8+ cells (r = 0.99). PK-1 expression correlated with CD8+ cells (r = 0.52), while PK-2 negatively correlated with C-type lectin (r=-0.49). FABP-5 exhibited significant positive correlations with PK-1 (r = 0.54) and IL-10 (r = 0.63). We highlight the interplay between prokineticins, immune modulation, and metabolic oxidative factors to offer potential therapeutic targets to prevent progression to HCC, instilling hope for the future of NASH treatment.