Clinical Significance of miRNA-145 and -126 in Chronic Obstructive Pulmonary Disease with Pulmonary Embolism.

BACKGROUND: Pulmonary embolism (PE) a consequence of hypercoagulability status associated with chronic obstructive pulmonary disease (COPD) and worsens its course. Recently, microRNAs (miRNAs) have been linked to PE in COPD settings. We aimed to measure expression levels of miRNAs145 and 126 in COPD patients with and without PE. METHODS: Herein, miRNA (145 and 126) expression levels were measured in 250 COPD patients with PE by quan-titative real-time PCR, and their data were compared with 300 COPD patients without PE. RESULTS: Our results showed that miRNA-145 expression was downregulated in COPD patients with PE compared to those without PE. The reverse was observed in miRNA-126 expression that was higher in COPD patients with PE than in those without PE. miRNA-145 correlated positively with FEV1/FVC and correlated negatively with D-dimer in all patients regardless of the presence of PE. In addition, miRNA-126 positively correlated with D-dimer and negatively correlated with FEV1/FVC in all studied COPD patients. CONCLUSIONS: Lower levels of miRNA-145 and higher levels of miRNA-126 associated with worse diagnosis PE in patients with COPD. Extensive studies are mandated to bring a better understanding of the role of these miRNAs in the mechanism of thrombosis in COPD patients.

Association of follicular helper T and follicular regulatory T cells with severity and hyperglycemia in hospitalized COVID-19 patients.

We aimed to determine the levels of follicular helper T (Tfh) and follicular regulatory T (Tfr) cells in COVID-19 patients and determine whether their levels correlated with disease severity and presence of hyperglycemia. This study was carried out in 34 hospitalized COVID-19 patients and 20 healthy controls. Levels of total circulating Tfh, inducible T-cell costimulator (ICOS)+ activated Tfh, and Tfr cells were assessed in all participants by flow cytometry. Total CD4+CXCR5+ Tfh cells and ICOS+Foxp3-activated Tfh cells increased and ICOS+Foxp3+ Tfr cells decreased in COVID-19 patients, especially in diabetic patients and those with severe disease. Activated ICOS+ Tfh cells were directly correlated with lactate dehydrogenase, D-dimer, ferritin, and respiratory rate and inversely correlated with the partial pressure of carbon dioxide. COVID-19 is associated with marked activation of Tfh cells and a profound drop in Tfr cells, especially in severe and diabetic patients. Future studies on expanded cohorts of patients are needed to clarify the relationship between SARS-CoV-2 and acute-onset diabetes.

Diagnostic value of monocyte chemoattractant Protein-1, soluble mannose receptor, Presepsin, and Procalcitonin in critically ill children admitted with suspected sepsis.

INTRODUCTION: The differentiation between systemic inflammatory response syndrome and sepsis is very important as it determines essential treatment decisions, such as selection, initiation, and duration of antibiotic therapy. OBJECTIVES: We aimed to investigate the diagnostic value of Procalcitonin, Monocyte Chemoattractant Protein-1, soluble Mannose Receptor, Presepsin as early biomarkers of pediatric sepsis in comparison to systemic inflammatory response syndrome in severely ill children. PATIENTS AND METHODS: This study included 58 children diagnosed as sepsis (group 1), 24 children with systemic inflammatory response syndrome without infection (group 2), and 50 healthy children as controls (group 3). All the plasma levels of the studied biomarkers were measured and ROC curves were created for all the tested parameters to discriminate between sepsis and SIRS. RESULTS: The area under the curve for Monocyte Chemoattractant Protein-1 was 0.926 (0.846-0.927) with sensitivity 100% and specificity 62.5%. The soluble Mannose Receptor had the highest sensitivity (100%), with AUC equals 1(.0.956-1.0) and specificity of 100%. The cut-off values for Procalcitonin, Presepsin, soluble Mannose Receptor, and Monocyte Chemoattractant Protein-1 and were: 0.62 ng/ml, 100 pg/ml, 13 ng/ml and 90 pg/ml, respectively. In septic cases, both soluble Mannose Receptor and Procalcitonin have positive correlations with the severity of sepsis, low Glasgow Coma Scale, ventilatory support, use of inotropic drugs and mortality rate (r = 0.950, 0.812, 0.795, 0.732 and 0.861respectively) for soluble Mannose Receptor and (0.536, 0.473, 0.422, 0.305 and 0.474 respectively) for Procalcitonin. CONCLUSION: Soluble Mannose Receptor, Presepsin, and Monocyte Chemoattractant Protein-1 can be used to differentiate between sepsis and SIRS in critically ill children.

Differential alterations in peripheral lymphocyte subsets in COVID-19 patients: upregulation of double-positive and double-negative T cells.

BACKGROUND: Viral infections cause alteration in the total number of lymphocytes and their subset distribution. We aimed to study peripheral blood lymphocyte subsets in COVID-19 patients and to correlate these subsets with clinical and laboratory data, which may help in clarifying the pathogenesis to develop novel diagnostic and prognostic biomarkers for COVID-19. METHODS: Twenty-six reverse-transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 patients were subjected to medical history-taking and a thorough clinical examination. Laboratory tests included complete blood count, D dimer, ferritin, and C-reactive protein (CRP). Chest CT was used to diagnose COVID-19 pneumonia. Lymphocyte subsets were compared with those in 20 healthy controls using flow cytometry. RESULTS: Leucopenia, relative neutrophilia, lymphopenia, eosinopenia together with marked elevation in neutrophil/lymphocyte ratio were observed in our COVID-19 patients. A marked reduction was observed in T cells, including both CD4 and CD8 cells, natural killer (NK), and natural killer T cells (NKT). Double-positive T (DPT) cells, double-negative T (DNT) cells, and B cells were elevated in the patients relative to the other lymphocyte subsets. CONCLUSION: Immune-inflammatory parameters are of utmost importance in understanding the pathogenesis and in the provisional diagnosis of COVID-19. Yet, adequate care must be taken during their interpretation because of the vast discrepancies observed between studies even in the same locality. Further studies are needed to clarify the role of B cells, DPT, and DNT cells in the pathogenesis and control of COVID-19.

Matrix Metalloproteinase-2 Single Nucleotide Polymorphism in Egyptian Non-Hodgkin Lymphoma Patients: Correlation with Clinicopathological Characteristics and Outcome.

Non-Hodgkin's lymphoma (NHL) is an exceedingly diversified group of lymphoproliferative neoplasms emerging from B-, T- or natural killer -lymphocytes. This study was done to detect Matrix metalloproteinase-2 (MMP2)-735C/T gene polymorphism in patients with NHL and its relation to the clinicopathological characteristics of the studied patients in addition to detection the association between it and NHL disease susceptibility and progression. Clinico-hematological profiles were done on 50 NHL patients. The genotypes and allelic frequencies of MMP-2 polymorphisms were recognized utilizing Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). PCR products after adding restriction endonuclease were analyzed using QIAxcel advanced (automated) instrument. The CT + TT genotypes and T allele of MMP2 735C/T were statistically significant in patients having advanced clinical stages III/IV compared to patients with stages I/II. Another significance was observed in patients with intermediate high/high IPI score and BM infiltration. Interestingly, patients with MMP2-735C/T genotype exhibit lower rate of survival. Our results demonstrated that MMP2-735C/T polymorphism may potentially affect the progression of NHL. Further larger scale studies are needed.

Intestinal barrier integrity and function in infants with cholestasis.

BACKGROUND/AIMS: The safety of the human body is maintained by effective monitoring of the mucosal surface integrity and protection against potentially harmful compounds. This function of the gut called intestinal barrier function can be affected by cholestasis and the absence of bile in the intestinal lumen. We aimed to determine whether the gut barrier integrity is impaired in infants with cholestasis by evaluation of the intestinal fatty acid binding proteins (I-FABP) and ileal bile acid binding protein (I-BABP) as markers of intestinal epithelial cell damage and plasma D-lactate level as a marker of gut wall permeability. METHODS: This case-control study included 53 infants with cholestasis and 29 controls. Serum levels of I-FABP, I-BABP, and D-lactate were measured in all subjects. RESULTS: Both groups of patients with neonatal hepatitis and biliary atresia showed significantly higher levels of I-FABP and I-BABP than the controls. There were no differences in the serum D-lactate level between the cases and controls. There was no difference between the two groups of patients (I and II) regarding any of the parameters studied. No significant correlations between serum levels of I-FABP, I-BABP, or D-lactate and total or direct bilirubin levels were found in the cholestatic infants. CONCLUSIONS: The intestinal epithelial barrier integrity is breached nearly in all parts of the intestine in infants with cholestasis. Further research is recommended to determine the impact of this finding on the management of these infants. The relationship between physical intestinal barrier damage and its functional failure remains subject for further research.

Modified Adenovirus Reduces De Novo Peritoneal Adhesions in Rats and Limits Off-Target Transfection. Role of EZH2 in Adhesion Formation.

AIM OF THE STUDY: Adenovector encoding tissue plasminogen activator (tPA) was shown to reduce experimental peritoneal adhesion. We investigated the targeting potential of our modified adenovector, its ability to reduce adhesions and the epigenetic role of histone methyltransferase EZH2 in adhesion formation. MATERIALS AND METHODS: Control lacZ, nonmodified tPA or modified tPA vectors were instilled in the peritoneal cavity after injury in de novo adhesions or after lysis of adhesions in recurrent adhesions. Adhesion severity was scored and adhesions and liver tissues were examined for adenovirus E4 gene and tPA mRNA expression. Levels of tPA, plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-ß1 (TGF-ß1), and EZH2 expression were measured. RESULTS: E4 transcripts were detected in adhesions of nonmodified and modified and in livers of nonmodified but not in livers of modified de novo adhesions. Both nonmodified (p = 0.021) and modified vectors (p = 0.036) reduced the severity of de novo adhesions compared to lacZ vector. Levels of tPA in nonmodified (p = 0.021) and modified adhesions (p = 0.001) were elevated while PAI-1 (p = 0.013 and p = 0.001, respectively) and TGF-ß1 levels (p = 0.002 and p = 0.016, respectively) were reduced compared with lacZ group. All vectors were not expressed in recurrent adhesions and severity score were not different among groups. EZH2 levels were elevated in de novo nontreated (p = 0.001) and was further increased in recurrent (p = 0.001) nontreated adhesions compared with noninjured peritoneum. CONCLUSION: Modified adenovirus successfully targeted de novo adhesions but not liver tissues and reduced the severity of de novo adhesions. EZH2 is involved in the development and progression of peritoneal adhesions.

Adiponectin, leptin and insulin levels at birth and in early postnatal life in neonates with hypoxic ischemic encephalopathy.

BACKGROUND: Hypoxic ischemic encephalopathy (HIE) occurs in one to three per 1000 live full-term births. Fifteen to twenty percent will die in the postnatal period, and an additional 25 % will develop severe and permanent neuropsychological sequalae. The control of growth and nutritional status in the fetus and neonate is a complex mechanism, in which also hormones produced by adipose tissue, such as adiponectin and leptin are involved. The aim of this study was to measure the levels of adiponectin, leptin and insulin in neonates with HIE at birth and in early postnatal life and comparing them with normal healthy AGA and SGA neonates. METHODS: This study carried out on 80 full-term neonates born in Minia university hospital during the period from May 2013 to December 2014. They were divided into group I included 25 neonates with HIE and group II included 55 normal healthy neonates (30 appropriate for gestational age (AGA) and 25 small for gestational age (SGA)). Weight, length, head circumference, body mass index (BMI), glucose, adiponectin, leptin and insulin levels were measured for all neonates. Adiponectin, leptin and insulin levels were compared between neonates with HIE and normal healthy neonates as well as between AGA and SGA neonates at birth, 2nd and 6th days of life. RESULTS: Adiponectin and leptin levels were significantly higher at birth then began to decrease during the first postnatal week in all neonates while insulin level increased during the same period. Serum adiponectin levels were significantly lower while serum leptin and insulin levels were significantly higher in neonates with HIE than healthy neonates. In all neonates, the serum adiponectin level was positively correlated at birth with weight, length, BMI and leptin levels but not with insulin level. In neonates with HIE, serum adiponectin level was not correlated with weight, BMI, leptin level or insulin level. In all neonates, the serum leptin level was positively correlated at birth with body weight, height and BMI. In neonates with HIE serum leptin levels were not correlated with weight, BMI or insulin level after birth. There were no correlations between either leptin or adiponectin serum levels or any of the studied parameters in neonates with HIE. CONCLUSIONS: Neonates who are suffering from HIE had lower serum levels of adiponectin and higher serum levels of leptin and insulin than normal healthy neonates at birth and during the early postnatal period. The decline of leptin and increased the insulin levels after birth in all neonates may be important for the stimulation of feeding behavior and the acquisition of energy homeostasis during the early postnatal life. Positive significant correlations between adiponectin, leptin, body weight and body mass indices were present in normal healthy neonates but not in neonates with HIE reflecting the effect of hypoxia on the regulatory mechanisms controlling the adipose tissue functions.

Human leukocyte antigens as a risk factor for the primary diseases leading to end stage renal disease in Egyptian patients.

The number of patients with end stage renal disease (ESRD) is increasing considerably worldwide. The incidence of ESRD is likely to be higher than that reported from the developed world, with diabetic nephropathy, hypertension and chronic glomerulonephritis being the most common causes in Egypt. The aim of the present study is to investigate the Human leukocyte antigens [HLA-A,-B and -DRB1 antigens] as a risk factor for the primary diseases leading to ESRD in Egyptian patients. Our study included a total of 457 individuals comprising 207 ESRD patients and 250 healthy controls were enrolled into the study. Class I [HLA-A and-B] typing was performed by complement-dependent cytotoxicity (CDC) method, while class II HLA-DRB1 typing was performed by low resolution polymerase chain reaction (PCR)-sequence-specific oligonucleotide probe [PCR-SSOP]. We found that the most common primary disease groups leading to ESRD classified as Diabetic nephropathy, hypertensive nephrosclerosis and chronic glomerulonephritis. HLA-A2, -B8 and DRB1*3 and HLA-DRB1*11 significantly correlated with diabetic nephropathy, respectively. B8-DR3 haplotype is susceptible to DM. In, conclusion, determination of HLA-A,-B and -DRB1 as a risk factor for primary diseases leading to ESRD might be beneficial in preventing progression to ESRD and recurrence of the primary disease post-transplantation.