The aim of this clinical trial was to control the cytokine storm by administering mesenchymal stem cells (MSCs) to critically-ill COVID-19 patients, to evaluate the healing effect, and to systematically investigate how the treatment works. Patients with moderate and critical COVID-19 clinical manifestations were separated as Group 1 (moderate cases, n = 10, treated conventionally), Group 2 (critical cases, n = 10, treated conventionally), and Group 3 (critical cases, n = 10, treated conventionally plus MSCs transplantation therapy of three consecutive doses on treatment days 0, 3, and 6, (as 3 × 10⁶ cells/kg, intravenously). The treatment mechanism of action was investigated with evaluation markers of the cytokine storm, via biochemical parameters, levels of proinflammatory and anti-inflammatory cytokines, analyses of tissue regeneration via the levels of growth factors, apoptosis markers, chemokines, matrix metalloproteinases, and granzyme-B, and by the assessment of the immunomodulatory effects via total oxidant/antioxidant status markers and the levels of lymphocyte subsets. In the assessment of the overall mortality rates of all the cases, six patients in Group-2 and three patients in Group-3 died, and there was no loss in Group-1. Proinflammatory cytokines IFNγ, IL-6, IL-17A, IL-2, IL-12, anti-inflammatory cytokines IL-10, IL-13, IL-1ra, and growth factors TGF-β, VEGF, KGF, and NGF levels were found to be significant in Group-3. When Group-2 and Group-3 were compared, serum ferritin, fibrinogen and CRP levels in Group-3 had significantly decreased. CD45 +, CD3 +, CD4 +, CD8 +, CD19 +, HLA-DR +, and CD16 + / CD56 + levels were evaluated. In the statistical comparison of the groups, significance was only determined in respect of neutrophils. The results demonstrated the positive systematic and cellular effects of MSCs application on critically ill COVID-19 patients in a versatile way. This effect plays an important role in curing and reducing mortality in critically ill patients.

The epigenetic features contribute to variations in host susceptibility to SARS-CoV-2 infection and severity of symptoms. This study aimed to evaluate the relationship between the relative expression of microRNAs (miRNAs) and the severity of the disease in COVID-19 patients. The miRNA profiles were monitored during the different stages of the disease course using reverse transcription–quantitative polymerase chain reaction (RT-qPCR). The expression levels of the selected 11 miRNAs were measured in the blood samples collected from 73 patients (moderate, n = 37; severe, n = 25; critically ill, n = 11, a total of 219 longitudinal samples) on hospitalization day and days 7 and 21. Expression changes were expressed as “fold change” compared to healthy controls (n = 10). Our study found that several miRNAs differed according to disease severity, with the miR-155-5p the most strongly upregulated (p = 0.0001). A statistically significant negative correlation was observed between the expression of miR-155-5p and its target gene, the suppressor of cytokine signaling 1 (SOCS1). The relative expression of miR-155-5p was significantly increased and SOCS1 was significantly decreased with the disease progression (r = −0.805 p = 0.0001, r = −0.940 p = 0.0001, r = −0.933 p = 0.0001 for admission, day 7, and day 21, respectively). The overexpression of miR-155-5p has significantly increased inflammatory cytokine production and promoted COVID-19 progression. We speculated that microRNA-155 facilitates immune inflammation via targeting SOCS1, thus establishing its association with disease prognosis.

This study evaluated the short and long-term prognostic value of galectin-3 in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). Patients (n = 143) were admitted with STEMI and followed up for 2 years. The study population was divided into high and low galectin-3 groups based on the admission median value of serum galectin-3. Primary clinical outcomes consisted of cardiovascular (CV) mortality, non-fatal reinfarction, stroke, and target vessel revascularization (TVR). CV events were recorded in hospital and at 1 and 2 years. The primary clinical outcomes (in-hospital, 1 year and 2 year) were significantly higher in the high galectin-3 group. ( P = .008, P = .004, P = .002, respectively). High galectin-3 levels were also associated with heart failure development and re-hospitalization at both 1 year ( P = .029, P = .009, respectively) and 2 years ( P = .019, P = .036, respectively). According to Cox multivariate analysis, left ventricular ejection fraction (LVEF) was an independent predictor of 2-year cardiovascular mortality ( P = .009), whereas galectin-3 was not ( P = .291). Although high galectin-3 levels were not independent predictors of long-term CV mortality in patients with acute STEMI who underwent primary PCI, it was associated with short-term and long-term development of adverse CV events, heart failure, and re-hospitalization.

Coronary artery ectasia (CAE) is characterized by inappropriate dilation of the coronary vasculature. The underlying mechanisms of CAE formation are not yet entirely known. A polymorphism in the endothelial nitric oxide synthase (eNOS) gene, which reduces eNOS activity, might be a risk factor for coronary heart diseases. However, its role in CAE is unknown. One of the most studied eNOS gene polymorphisms is a c.894G>T polymorphism that results in the conversion of Glu (GAG) to Asp (GAT) at position 298. In this study, we investigated the potential association between the c.894G>T (Glu298Asp) polymorphism and CAE. The present study included 84 subjects from 2,980 consecutive patients in whom elective diagnostic coronary angiography was performed. Forty patients with isolated CAE and 44 subjects with normal coronary arteries were enrolled. The frequencies of the G allele were 78.4% in the control and 57.5% in CAE patients. The TT genotype was more frequent in patients with CAE than that in the controls (20% vs. 4.5%, p = 0.013). Furthermore, the risk of developing CAE in the presence of the homozygous TT genotype was significantly higher in the patients than that in the controls (OR = 7.7, 95% CI = 1.44-41.3). The presence of an 894T allele increased the risk of CAE 2.8-fold (95% CI = 1.15-6.73; p = 0.027). The frequencies of the T allele were 65% in CAE patients and 38.6% in the controls. In conclusion, the c.894G>T polymorphism in the eNOS gene may be a risk factor for CAE.

The objective of this study is to determine the effect of intravenous (i.v.) or oral N-acetylcysteine (NAC) in preventing contrast-induced nephropathy (CIN) in patients with moderate-to-severe renal insufficiency undergoing intra-arterial interventions. We studied 307 patients with estimated glomerular filtration rate of less than 60 ml/min/1.73 m undergoing an elective intra-arterial procedure. Patients were assigned randomly to three groups according to the prophylactic regimen used. In group 1, patients were administered an i.v. infusion of 0.9% saline (n=103); in group 2, patients were administered oral NAC in addition to an i.v. saline infusion (n=102); and in group 3, patients were administered i.v. NAC in addition to an i.v. saline infusion (n=102). Serum creatinine (SCr) and cystatin C levels were measured at baseline and 4, 24, and 48 h after the application of contrast media. The primary endpoint was defined as an increase in the SCr or cystatin C concentration of at least 0.5 mg/dl and/or of at least 25% from the baseline value at 48 h after administration of the contrast dye. The overall incidence of SCr-based CIN was 11.1%: 6.8% in the saline group, 13.7% in the oral NAC group, and 12.7% in the i.v. NAC group (P=0.231). That of cystatin C-based CIN was 8.1%: 6.8% in the saline group, 6.9% in the oral NAC group, and 10.8% in the i.v. NAC group (P=0.491). In this study, there was no detectable benefit of either high-dose oral or i.v. NAC over an aggressive hydration protocol in patients with moderate-to-severe renal insufficiency.

The diagnostic role of serum cytokines depends on the etiology and pathogenesis of acute appendicitis but the clinical significance of these cytokines in the differential diagnosis of complicated acute appendicitis remains unclear. To investigate the prediction of progression and diagnostic values of interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha in complicated acute appendicitis. This study was conducted in 100 patients with a definitive diagnosis of acute appendicitis and 20 individuals assigned for the control group. Venous blood was collected to assess biochemical tests, as well as interleukin-6, interleukin-1β, and tumor necrosis factor-α levels. Serum levels of all parameters were dramatically higher in the complicated group compared with uncomplicated. Duration of hospitalization, rates of postoperative infection, intraabdominal abscess, and re-hospitalization were higher in complicated group. Cut-off points of WBC, CRP, NLR, interleukin-6, interleukin-1β and tumor necrosis factor-α were 13.5x103/µL, 1.92 mg/dL, 6.09, 23.4 pg/mL, 5.6 pg/mL and 24 pg/mL (p=0.0014, p<0.001, p=0.009, respectively and p<0.001 for the rest). AUC of interleukin-6 was larger than AUCs of all other parameters, suggesting the highest predicting power of interleukin-6 among other parameters. Serum interleukin-6, interleukin-1β, and tumor necrosis factor-α levels are valuable diagnostic parameters to predict a complicated acute appendicitis.