Effect of sesame (Sesamum indicum L.) consumption on glycemic control in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.

Conflicting evidence exists on the effect of sesame consumption on glucose metabolism in patients with type 2 diabetes (T2D). Therefore, this meta-analysis focuses on the relationship between sesame (Sesamum indicum L.) intervention and glycemic control in patients with T2D. Published literature was retrieved and screened from PubMed, Scopus, ISI Web of Science, and the Cochrane Library up to December 2022. Outcome measures included fasting blood sugar (FBS) concentrations, fasting insulin levels, and hemoglobin A1c (HbA1c) percentage. Pooled effect sizes were reported as weighted mean differences (WMDs) and 95% confidence intervals (CIs). Eight clinical trials (395 participants) were eligible for meta-analyses. Overall, sesame consumption significantly reduced serum FBS (WMD: -28.61 mg/dL, 95% CI: -36.07 to -21.16, p˂0.001; I2 = 98.3%) and HbA1c percentage (WMD: -0.99%, 95% CI: -1.22 to -0.76, p ≤ 0.001; I2 = 65.1%) in patients with T2D. However, sesame consumption did not significantly influence fasting insulin levels (Hedges's: 2.29, 95% CI: -0.06 to 4.63, p = 0.06; I2 = 98.1%). In summary, the current meta-analysis showed a promising effect of sesame consumption on glycemic control through reducing FBS and HbA1c, yet additional prospective studies are recommended, using higher doses and longer intervention period, to confirm the impact of sesame consumption on insulin levels in T2D patients.

Dapsone- and nitroso dapsone-specific activation of T cells from hypersensitive patients expressing the risk allele HLA-B*13:01.

BACKGROUND: Research into drug hypersensitivity associated with the expression of specific HLA alleles has focussed on the interaction between parent drug and the HLA with no attention given to reactive metabolites. For this reason, we have studied HLA-B*13:01-linked dapsone hypersensitivity to (a) explore whether the parent drug and/or nitroso metabolite activate T cells and (b) determine whether HLA-B*13:01 is involved in the response. METHODS: Peripheral blood mononuclear cells (PBMC) from six patients were cultured with dapsone and nitroso dapsone, and proliferative responses and IFN-γ release were measured. Dapsone- and nitroso dapsone-specific T-cell clones were generated and phenotype, function, HLA allele restriction, and cross-reactivity assessed. Dapsone intermediates were characterized by mass spectrometry. RESULTS: Peripheral blood mononuclear cells from six patients and cloned T cells proliferated and secreted Th1/2/22 cytokines when stimulated with dapsone (clones: n = 395; 80% CD4+ CXCR3hi CCR4hi , 20% CD8+CXCR3hi CCR4hi CCR6hi CCR9hi CCR10hi ) and nitroso dapsone (clones: n = 399; 78% CD4+, 22% CD8+ with same chemokine receptor profile). CD4+ and CD8+ clones were HLA class II and class I restricted, respectively, and displayed three patterns of reactivity: compound specific, weakly cross-reactive, and strongly cross-reactive. Nitroso dapsone formed dimers in culture and was reduced to dapsone, providing a rationale for the cross-reactivity. T-cell responses to nitroso dapsone were dependent on the formation of a cysteine-modified protein adduct, while dapsone interacted in a labile manner with antigen-presenting cells. CD8+ clones displayed an HLA-B*13:01-restricted pattern of activation. CONCLUSION: These studies describe the phenotype and function of dapsone- and nitroso dapsone-responsive CD4+ and CD8+ T cells from hypersensitive patients. Discovery of HLA-B*13:01-restricted CD8+ T-cell responses indicates that drugs and their reactive metabolites participate in HLA allele-linked forms of hypersensitivity.

Characterization of Healthy Donor-Derived T-Cell Responses Specific to Telaprevir Diastereomers.

Telaprevir, a protease inhibitor, was used alongside PEGylated interferon-α and ribavirin to treat hepatitis C viral infections. The triple regimen proved successful; however, the appearance of severe skin reactions alongside competition from newer drugs restricted its use. Skin reactions presented with a delayed onset indicative of a T-cell mediated reaction. Thus, the aim of this study was to investigate whether telaprevir and/or its diastereomer, which is generated in humans, activates T-cells. Telaprevir in its S-configured therapeutic form and the R-diastereomer were cultured directly with peripheral blood mononuclear cells from healthy donors prior to the generation of T-cell clones by serial dilution. Drug-specific CD4+ and CD8+ T-cell clones responsive to telaprevir and the R-diastereomer were generated and characterized in terms of phenotype and function. The clones proliferated with telaprevir and diastereomer concentrations of 5-20 µM and secreted IFN-γ, IL-13, and granzyme B. In contrast, the telaprevir M11 metabolite did not stimulate T-cells. The CD8+ T-cell response was MHC I-restricted and dependent on the presence of soluble drug. Flow cytometric analysis showed that clones expressed chemokine receptors CCR4 (skin homing) and CXCR3 (migration to peripheral tissue) and 1 of 3 distinct TCR Vßs; TCR Vß 2, 5.1, or 22. These data show the propensity of both R- and S-forms of telaprevir to generate skin-homing cytotoxic T-cells that may induce the adverse reactions observed in human patients.