The efficacy of salivary Histatin-1 protein in wound closure of nicotine treated human periodontal ligament fibroblast cells - In vitro study.

OBJECTIVES: The aims of this study were to investigate the efficacy of Histatin-1 in wound closure as well as effects on gene expression of nicotine-treated human Periodontal Ligament Fibroblast cells (HPDL) in vitro. DESIGN: HPDL grown in 2.5% culture medium treated with 10 ng/ml Histatin - 1 in the presence/absence of 0.5 µM nicotine were subjected to wound assay and migration was studied at 0 h, 6 h, 12 h and 24 h. Cells grown in 2.5% medium served as control. Cell migration was studied by wound gap and transwell migration assays. The effect of Histatin-1 on expression of matrix metalloproteinase 8 (MMP-8), insulin-like growth factor 1 (IGF-1), transforming growth factor beta (TGF-ß), collagen type I (COL1) and plasminogen activator inhibitor 1 (PAI-1) were studied. RESULTS: Histatin-1 treatment significantly decreased percentage wound gap at 12 h (62.96 ± 3.22 vs 79.23 ± 1.73; p < 0.05) and at 24 h (38.78 ± 7.59 vs 75.21 ± 4.94; p < 0.001) compared with controls. In nicotine+Histatin-1 treated cells, wound gap decreased to 70.2 ± 2.9% (p < 0.01) at 24 h compared to nicotine alone in which 82 ± 1.64% of wound gap was retained. Transwell migration assays showed significant migration of HPDL with Histatin-1 (p < 0.05). Gene expression demonstrated significant upregulation for IGF-1, TGF ß, COL1 and PAI-1 with Histatin-1. CONCLUSION: Histatin-1 significantly mitigated the effect of nicotine in wound healing assay involving HPDL fibroblast cells at 24 h. Histatin-1 aided wound closure is attributed to the upregulation of IGF-1, TGF ß, COL1, and PAI-1 genes.

Cancer immunotherapy resistance: The impact of microbiome-derived short-chain fatty acids and other emerging metabolites.

The landscape of cancer therapy has undergone dramatic changes over the past decade. Immune checkpoint inhibitors (ICIs) among various cancer immunotherapies have transformed the treatment paradigm for cancer therapy and improved the survival of patients. Nevertheless, oncologists are faced with key challenges that need to be overcome, such as the unpredictability of patient response to these therapies and the many immune-related adverse effects (irAEs). One major factor contributing to patient response to treatment is the composition of their gut microbiota. Many studies reported the role of gut microbiota in modulating immunotherapy. In particular, microbiota-derived metabolites, mainly short-chain fatty acids (SCFAs), have been the highlights of many studies exploring the association between the gut microbiome and patient sensitivity to cancer immunotherapy. This review discusses the role of gut microbiota-derived metabolites on patient response to ICIs and their potential use as predictive biomarkers and therapeutic targets to fine-tune, regulate, and enhance cancer immunotherapy.