Non-classical monocytes frequency and serum vitamin D3 levels are linked to diabetic foot ulcer associated with peripheral artery disease.

AIMS/INTRODUCTION: Peripheral artery disease (PAD) serves as a risk factor for diabetic foot ulcers (DFUs). PAD pathology involves atherosclerosis and impaired immunity. Non-classical monocytes are believed to have an anti-inflammatory role. 1,25-Dihydroxy vitamin D (vitamin D3 ) is claimed to have immune-modulating and lipid-regulating roles. Vitamin D receptor is expressed on monocytes. We aimed to investigate if circulating non-classical monocytes and vitamin D3 were implicated in DFUs associated with PAD. MATERIALS AND METHODS: There were two groups of DFU patients: group 1 (n = 40) included patients with first-degree DFUs not associated with PAD, and group 2 (n = 50) included patients with DFU with PAD. The monocyte phenotypes were detected using flow cytometry. Vitamin D3 was assessed by enzyme-linked immunosorbent assay. RESULTS: DFU patients with PAD showed a significant reduction in the frequency of non-classical monocytes and vitamin D3 levels, when compared with DFU patients without PAD. The percentage of non-classical monocytes positively correlated with vitamin D3 level (r = 0.4, P < 0.01) and high-density lipoprotein (r = 0.5, P < 0.001), whereas it was negatively correlated with cholesterol (r = -0.5, P < 0.001). Vitamin D3 was negatively correlated with triglyceride/high-density lipoprotein (r = -0.4, P < 0.01). Regression analysis showed that a high vitamin D3 serum level was a protective factor against PAD occurrence. CONCLUSIONS: Non-classical monocytes frequency and vitamin D3 levels were significantly reduced in DFU patients with PAD. Non-classical monocytes frequency was associated with vitamin D3 in DFUs patients, and both parameters were linked to lipid profile. Vitamin D3 upregulation was a risk-reducing factor for PAD occurrence.

Cytotoxic T Cell Expression of Leukocyte-Associated Immunoglobulin-Like Receptor-1 (LAIR-1) in Viral Hepatitis C-Mediated Hepatocellular Carcinoma.

Virus-related hepatocellular carcinoma (HCC) pathogenesis involves liver inflammation, therefore, despite successful treatment, hepatitis C virus (HCV) may progress to HCC from initiated liver cirrhosis. Cytotoxic T cells (Tcs) are known to be involved in HCV-related cirrhotic complications and HCC pathogenesis. The inhibitory checkpoint leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is expressed on Tcs. Therefore, we aimed to determine whether the Tc expression level of LAIR-1 is associated with HCC progression and to evaluate LAIR-1 expression as a noninvasive biomarker for HCC progression in the context of liver cirrhosis related to HCV genotype 4 (G4) in Egyptian patients' peripheral venous blood liquid biopsy. A total of 64 patients with HCC and 37 patients with liver cirrhosis were enrolled in this case-controlled study, and their LAIR-1 expression on Tc related to the progression of liver cirrhosis was examined and compared to that of the apparently healthy control group (n = 20). LAIR-1 expression was analyzed using flow cytometry. Results: The HCC group had significantly higher LAIR-1 expression on Tc and percentage of Tc positive for LAIR-1 (LAIR-1+Tc%) than the HCV G4-related liver cirrhosis group. LAIR-1+Tc% was correlated with the HCC surrogate tumor marker AFP (r = 0.367, p = 0.001) and insulin resistance and inflammation prognostic ratios/indices. A receiver operating characteristic (ROC) curve revealed that adding LAIR-1+Tc% to AFP can distinguish HCC transformation in the Egyptian patients' cohort. Upregulated LAIR-1 expression on Tc could be a potential screening noninvasive molecular marker for chronic inflammatory HCV G4 related liver cirrhosis. Moreover, LAIR-1 expression on Tc may be one of the players involved in the progression of liver cirrhosis to HCC.