Early hepatocellular carcinoma (HCC) diagnosis is challenging. Moreover, for patients with alpha-fetoprotein (AFP)-negative HCC, this challenge is augmented. MicroRNAs (miRs) profiles may serve as potential HCC molecular markers. We aimed to assess plasma homo sapiens—(hsa)-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p—expression levels as a panel of biomarkers for HCC in chronic hepatitis C virus (CHCV) patients with liver cirrhosis (LC), especially AFP-negative HCC cases, as a step toward non-protein coding (nc) RNA precision medicine. Subjects and methods: 79 patients enrolled with CHCV infection with LC, subclassified into an LC group without HCC (n = 40) and LC with HCC (n = 39). Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p. Results: Plasma hsa-miR-21-5p and hsa-miR-155-5p demonstrated significant upregulation, while hsa-miR-199a-5p demonstrated significant downregulation in the HCC group (n = 39) when compared to the LC group (n = 40). hsa-miR-21-5p expression was positively correlated with serum AFP, insulin, and insulin resistance (r = 0.5, p < 0.001, r = 0.334, p = 0.01, and r = 0.303, p = 0.02, respectively). According to the ROC curves, for differentiating HCC from LC, combining AFP with each of hsa-miR-21-5p, hsa-miR-155-5p, and miR199a-5p improved the diagnostic sensitivity to 87%, 82%, and 84%, respectively, vs. 69% for AFP alone, with acceptable specificities of 77.5%, 77.5%, and 80%, respectively, and AUC = 0.89, 0.85, and 0.90, respectively vs. 0.85 for AFP alone. hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios discriminated HCC from LC at AUC = 0.76 and 0.71, respectively, with sensitivities = 94% and 92% and specificities = 48% and 53%, respectively. Upregulation of plasma hsa-miR-21-5p was considered as an independent risk factor for HCC development [OR = 1.198(1.063–1.329), p = 0.002]. Conclusions: Combining each of hsa-miR-21-5p, hsa-miR-155-5p, and hsa-miR-199a-5p with AFP made it possible to identify HCC development in the LC patients’ cohort with higher sensitivity than using AFP alone. hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios are potential HCC molecular markers for AFP-negative HCC patients. hsa-miR-21-5p was linked, clinically and via in silico proof, to insulin metabolism, inflammation, dyslipidemia, and tumorigenesis in the HCC patients’ group as well as for an upregulated independent risk factor for the emergence of HCC from LC in the CHCV patients.

Background: Neonatal sepsis (NS) is an important cause of morbidity and mortality among newborns. Its diagnosis depends mainly on blood culture that takes at least 48 hours to give results. Therefore, searching for biomarkers for early diagnosis is of value. We aimed to assess presepsin, soluble triggering receptor expressed on myeloid cells (sTREM-1), and neutrophil CD64 (nCD64) as early diagnostic biomarkers in NS, and to compare them individually and in combination. Methods: This hospital-based case–control study has been conducted on 60 full-term neonates recruited from the neonatal intensive care unit, Al-Zahraa Hospital, Al-Azhar University, Cairo, Egypt. Thirty infants with sepsis were compared to 30 postnatal age- and sex-matched healthy controls. Studied neonates were evaluated using clinical and laboratory indicators for sepsis. nCD64 was measured by flow cytometry and, serum presepsin and sTREM-1 were measured by ELISA. Results: Presepsin, sTREM-1, and nCD64 levels were significantly elevated in septic neonates vs control group (P<0.05). The sensitivities of presepsin, sTREM, and nCD64 were 100%, 96.7%, and 86.7%, respectively. Presepsin had the best diagnostic performance in early diagnosis of NS followed by sTREM-1 and nCD64. Conclusion: Presepsin and sTREM-1 are promising biomarkers in screening for NS in comparison with nCD64. However, nCD64 is better used in combination with other biomarkers as CRP.

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.

Background: The link between immune system and type 2 diabetes mellitus (T2DM) pathogenesis attracted attention to demonstrate the role of immune cells and their secreted cytokines in T2DM development and its subsequent foot complications. Objective: To investigate the relation between T Natural killer cell (TNK) %, Interleukin 4 (IL4) and Interferon gamma (IFN-γ) and diabetic foot infection (DFI) development in patients with diabetic foot ulcer (DFU). Patients and Methods: Ninety patients with diabetes were included in this work, divided as T2DM group (n=30), DFU group (n=30), and DFI group (n=30). TNK% was detected using flow cytometry. Serum IL4 and IFN-γ were measured by ELISA. Diabetes biochemical parameters were also analyzed. Results: Significant decrease was detected in TNK% and IFN-γ in DFI group compared to other 2 groups (P< 0.001). Significant decrease was detected in serum levels of IL4 in DFI group compared to T2DM group (P=0.006). IFN-γ/IL4 was significantly decreased in DFI compared to DFU group (P=0.020). There was a significant correlation of TNK% with both IL4 and IFN-γ (r=0.385, P< 0.001; r=0.534, P< 0.001, respectively). Significant negative correlation of TNK% with HbA1c and LDL was revealed (r=− 0.631, P< 0.001; and r=− 0.261, P=0.013, respectively), while a positive correlation was seen with HDL (r=0.287, P=0.006). A significant negative correlation of IL4 with HbA1c was found (r=− 0.514, P< 0.001;. As for IFN-γ, a significant negative correlation with HbA1c and LDL was detected (r=− 0.369, P< 0.001; r=− 0.229, P=0.030). TNK % and IFN-γ level showed negative correlations with disease duration/year (r=− 0.546, P< 0.001; r=− 0.338, P=0.001,respectively). Conclusion: Decline in TNK frequency has essential role in T2DM pathogenesis and subsequent foot complications. Downregulation of TNK% and IFN-γ level have potential roles in predicting infection of diabetic ulcer and are correlated with disease duration.

Drug-resistant Tuberculosis (DR-TB) is a global health burden with high morbidity and mortality in developing countries including Egypt. The susceptibility to infection with DR-TB strains may be genetically determined. Several interleukin gene polymorphisms were investigated as risk factors for tuberculosis infection but focusing on their association with DR-TB was limited. Therefore, the objective of this study is to assess the association of IL 17 − 197 G > A (rs2275913) single nucleotide polymorphism (SNP) with susceptibility to DR-TB strains in comparison to drug-sensitive tuberculosis (DS-TB) strains in Egyptian patients with pulmonary TB. This cross-sectional study was conducted on 80 patients with DR-TB strains and 80 with DS-TB strains as a control group. Both age and sex were comparable among the study’s groups. IL-17 − 197 G > A (rs2275913) SNP was genotyped by real-time PCR, and IL-17 serum concentration was measured by enzyme-linked immunosorbent assay (ELISA). The GA and AA genotype frequencies of IL 17 − 197 G > A (rs2275913) SNP were significantly higher in patients with DR-TB strains than those with DS-TB strains (p < 0.001). The frequency of the A allele was significantly (p < 0.001) higher in patients with DR-TB group (32.5%) compared to the control group (13.8%). Substantial higher serum levels of IL-17 were detected in the DR-TB group with significant association with AA and AG genotypes. Polymorphism in IL-17 -197 G > A (rs2275913) resulted in higher serum levels of IL-17 and Egyptian patients with such polymorphism are three times at risk of infection with DR-TB strains than patients with wild type.

Although primary open-angle glaucoma (POAG) is a major cause of blindness worldwide, patients’ immune response and its relation to the disease course have not been fully unraveled in terms of analyses of circulating B-cell subsets, as well as the association of these subsets with the severity of POAG clinical features. Subjects and Methods: Flow cytometry was used to determine B-cell subset frequencies from 30 POAG patients grouped by hierarchical cluster analysis or the mean deviation (MD) of the visual field (VF) and correlated with the patients’ clinical and pathological data, as well as with BSF-2(IL-6) and CSIF:TGIF(IL-10), which were quantified in peripheral blood samples of patients and controls by ELISA. Results: The total B-cell frequency was increased in the POAG group in comparison to the control group (n = 30). Frequencies of specific B-cell subsets, such as double-negative (DN) and naïve B-cell subsets, were increased in relation to the severity of the POAG disease. However, the unswitched memory B compartment subset decreased in the POAG group. Other non-typical B-cell subsets such as DN B cells also showed significant changes according to the POAG disease severity course. These differences allow us to identify POAG severity-associated inflammatory clusters in patients with specifically altered B-cell subsets. Finally, ocular parameters, biomarkers of inflammation, and other glaucoma-related or non-clinical scores exhibited correlations with some of these B-cell subpopulations. Conclusion: The severity of the POAG disease course is accompanied by changes in the B-cell subpopulation, namely, DN B cells. Furthermore, the existing relationship of the B-cell subset frequencies with the clinical and the inflammatory parameters BSF-2(IL-6), CSIF:TGIF(IL-10), and the BSF-2(IL-6) to CSIF:TGIF(IL-10) ratio suggests that these B lymphocyte cells could serve as potential molecular bio-markers for assessing POAG disease severity and/or progression.