Monocytes subsets altered distribution and dysregulated plasma hsa-miR-21-5p and hsa-miR-155-5p in HCV-linked liver cirrhosis progression to hepatocellular carcinoma.

PURPOSE: The authors aim to investigate the altered monocytes subsets distribution in liver cirrhosis (LC) and subsequent hepatocellular carcinoma (HCC) in association with the expression level of plasma Homo sapiens (has)-miR-21-5p and hsa-miR-155-5p. A step toward non-protein coding (nc) RNA precision medicine based on the immune perturbation manifested as altered monocytes distribution, on top of LC and HCC. METHODS: Seventy-nine patients diagnosed with chronic hepatitis C virus (CHCV) infection with LC were enrolled in the current study. Patients were sub-classified into LC group without HCC (n = 40), LC with HCC (n = 39), and 15 apparently healthy controls. Monocyte subsets frequencies were assessed by flow cytometry. Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p and hsa-miR-155-5p expression. RESULTS: Hsa-miR-21-5p correlated with intermediate monocytes (r = 0.30, p = 0.007), while hsa-miR-155-5p negatively correlated with non-classical monocytes (r = - 0.316, p = 0.005). ROC curve analysis revealed that combining intermediate monocytes frequency and hsa-miR-21 yielded sensitivity = 79.5%, specificity = 75%, and AUC = 0.84. In comparison, AFP yielded a lower sensitivity = 69% and 100% specificity with AUC = 0.85. Logistic regression analysis proved that up-regulation of intermediate monocytes frequency and hsa-miR-21-5p were independent risk factors for LC progression to HCC, after adjustment for co-founders. CONCLUSION: Monocyte subsets differentiation in HCC was linked to hsa-miR-21-5p and hsa-miR-155-5p. Combined up-regulation of intermediate monocytes frequency and hsa-miR-21-5p expression could be considered a sensitive indicator of LC progression to HCC. Circulating intermediate monocytes and hsa-miR-21-5p were independent risk factors for HCC evolution, clinically and in silico proved.

Utility of Monocyte Expression of HLA-DR versus T Lymphocyte Frequency in the Assessment of COVID-19 Outcome.

Background: Dysregulated immunity is a hallmark of SARS-CoV-2 infection. Immune suppression is indicated by low monocyte expression of human leukocyte antigen D-related (mHLA-DR). T cells are important antiviral cells. We aimed to assess the role of mHLA-DR and T lymphocyte frequency in predicting COVID-19 severity. Patients and Methods: This cross-sectional study enrolled 97 SARS-CoV-2 positive patients, including mild to moderate (n = 49) and severe cases admitted to intensive care unit (ICU) (n = 48). These ICU cases were further subdivided into survivors (n = 35) and non-survivors (n = 13). Results: Severe cases had a significant decrease in the mHLA-DR mean fluorescence intensity (MFI) and T lymphocyte percentage compared to mild to moderate cases (P<0.001). Non-survivors had a lower T lymphocyte percentage (P=0.004) than survivors. The mHLA-DR MFI and T lymphocyte percentage correlated with oxygen saturation (r=0.632, P<0.001) and (r=0.669, P<0.001), respectively. According to the ROC curves, mHLA-DR MFI, at a cutoff of 143 and an AUC of 0.9, is a reliable biomarker for distinguishing severe COVID-19 cases, with 89.6% sensitivity and 81.6% specificity, while T lymphocyte frequency had 81.3% sensitivity and 81.6% specificity at a cutoff of 54.4% and an AUC of 0.9. The T lymphocyte percentage as a predictor of ICU survival at a cutoff of 38.995% exhibited 100% sensitivity and 57.1% specificity. According to multivariate regression analysis, reduced mHLA-DR MFI and T lymphocyte percentage are independent predictors of COVID-19 severity (OR = 0.976, 95% CI: 0.955-0.997, P = 0.025) and (OR = 0.849, 95% CI: 0.741-0.972, P = 0.018), respectively. Conclusion: Reduced mHLA-DR expression and T-lymphocyte percentage are independent predictors of COVID-19 severity. Oxygen saturation percentage is correlated with mHLA-DR MFI and T lymphocyte frequency. The T lymphocyte frequency is a proposed predictor of COVID-19 survival in ICU admitted patients.

Copeptin: a neuroendocrine biomarker of COVID-19 severity.

Aim: To investigate the change in a serum level of copeptin, a neuroendocrine biomarker, in differentiating grades of COVID-19 severity on admission time and to find its diagnostic potential. Materials & Methods: 160 COVID-19 patients were classified according to disease severity into 80 mild to moderate and 80 severe patients. Serum copeptin level was assessed by ELISA on their admission time. Besides, serum CRP, ferritin and D-dimer were estimated. Results: Severe COVID-19 patients showed higher serum copeptin level in comparison to mild to moderate cases, with diagnostic potential to distinguish disease severity with 93.33% sensitivity and 100% specificity at cutoff value >18.5 Pmol/l. Conclusion: Serum copeptin was remarkably increased with COVID-19 severity with reasonable differentiation potential for recently admitted patients.

We conducted a biochemical study on the role of copeptin ­ a biomarker of acute stress due to COVID-19 infection ­ in classification of COVID-19 severity on admission over 160 adult patients. Copeptin was highly elevated in severe cases more than the mild to moderate ones. So, it may be an early marker in admission departments to ease early clinical decisions and medical intervention.

The expression of microRNA 146a in patients with ischemic stroke: an observational study.

AIM: We conducted the present prospective study to assess the level of microRNA (miRNA) 146a in patients with ischemic stroke and its correlation with patients' characteristics. METHODS: We conducted an observational study that included adult patients (≥18 years old) who presented within 24 hrs after the onset of the symptoms of acute ischemic stroke. In addition, age- and sex-matched healthy volunteers were included as control group. The primary outcome in the present study was the difference in miRNA 146a expression between patients with ischemic stroke and control group participants. The expression of miRNA 146a was measured using quantitative real-time PCR. Quantitative real-time PCR amplification and analysis were performed using Rotor-Gene Q thermal cycler. RESULTS: The present study included 44 patients with ischemic stroke and 22 matched controls. Regarding the primary outcome of the present study, the median expression of miRNA 146a in patients with ischemic stroke was -1.98 fold (IQR -27.1-3.9) compared to 1.75 fold (IQR -2.25-5.27) in control group (P<0.001). However, the subgroup analysis showed that the expression of miRNA 146a was significantly downregulated in comatosed patients only (P<0.001). The expression of miRNA 146a correlated negatively with Glasgow Coma Scale score in comatose patients (r=-0.352, P=0.022). CONCLUSION: In conclusion, the expression of miRNA 146a is significantly downregulated in ischemic stroke patients. Further studies are needed to assess its diagnostic utility and therapeutic potentials.

Frequency of Circulating B1a and B2 B-cell Subsets in Egyptian Patients with Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a growing health problem in Egypt. T2DM is recognized as chronic inflammatory disease with involvement of immune cells including B cells. We aimed to determine the frequency of antibody secreting B1a and B2 B cells in T2DM patients, their correlation with diabetes metabolic parameters and whether they play a role in diabetic foot infection (DFI) development. This study included 56 participants, recruited from Al-Zahraa hospital, Al-Azhar University, Egypt. Of these, 36 patients were diagnosed with T2DM, divided to two groups; (1) DM group (n=19) recently diagnosed, without foot complication; (2) DFI group (n=17); in addition to a Control group (n=20). The study assessed the frequency of circulating B1a (CD19+CD23-CD5+), and B2 (CD19+CD23+CD5-) cells by flow cytometry in diabetic patients. Comparison of the 3 studied groups revealed significant differences in frequency of studied total B cells (P=0.011), B1a (P < 0.001) and B2 subsets (P < 0.001). Comparison of B cell subsets between DFI, DM groups showed significant decrease in B1a in DFI group (P < 0.001). B1a cells % showed inverse correlation with HgA1c (r=-0.47, P < 0.001), LDL (r=-0.64, P < 0.001), and TG (r=-0.67, P < 0.001) but showed positive correlation with HDL (r=0.61, P < 0.001), while B2 cells showed opposite correlations. We concluded that imbalance of B cell subsets is seen in T2DM subjects. Beneficial role of B1a cells was spotted as they correlated inversely with glycemia and lipidemia in contrary to B2 cells. Decrease in B1a cells may predispose to DFI development.