Correlation of Krebs von den Lungen-6 and fibronectin with pulmonary fibrosis in coronavirus disease 2019.

OBJECTIVE: Coronavirus Disease 2019 (COVID-19) caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still spreading worldwide, which may progress to pulmonary fibrosis (PF), leading to the worsen outcome. As the markers of lung injury, the correlation of Krebs von den Lungen-6 (KL-6) and fibronectin (Fn) with pulmonary fibrosis in COVID-19 was still unclear. METHODS: 113 patients diagnosed as COVID-19 were enrolled in this retrospective study, and divided into three categories as mild, moderate and severe cases. The concentrations of serum KL-6 and Fn at hospital admission were tested using the method of latex agglutination assay and immunoturbidimetic assay, respectively. RESULTS: Compared with that in the non-severe COVID-19 cases and normal control subjects, serum KL-6 concentration on admission was significantly higher in the severe group, which was positively correlated with C-reactive protein, and negatively correlated with lymphocytes count. Whereas, no obvious elevation in serum Fn concentration was investigated in COVID-19 patients with the different phenotypes. The severe cases displayed the higher incident rate of pulmonary fibrosis at hospital discharge. Compared with non-PF patients, the COVID-19 cases with PF had the higher serum KL-6 values. CONCLUSION: Serum KL-6 concentration was significantly elevated in severe COVID-19 patients, which may be useful for evaluating the disease severity. For early prevention of the development of pulmonary fibrosis, high concentrations of serum KL-6 in the early stage of COVID-19 should be paid close attention.

Evaluation of serum hepatic enzyme activities in different COVID-19 phenotypes.

Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease. Our understanding of the clinical characteristics of liver damage and the relationship with disease severity in COVID-19 is still limited. To investigate the serum hepatic enzyme activities in different phenotypes of COVID-19 patients, evaluate their relationship with the illness severity and analyze the correlation of glycyrrhizin treatment and abnormal liver enzyme activities, one hundred and forty-seven patients with COVID-19 were enrolled in a retrospective study that investigated hepatic dysfunction. Liver alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), Y-glutamyl transferase (GGT), superoxide dismutase (SOD), and alkaline phosphatase (ALP) were analyzed in these patients. Patients with diammonium glycyrrhizinate (DG) treatment were further investigated. Of the 147 patients, 56 (38.1%) had abnormal ALT activity and 80 (54.4%) had abnormal AST activity. The peak of abnormal hepatic enzyme activities occurred at 3 to 6 days after on admission. Serum AST and LDH levels were elevated, while the SOD level was decreased in severe and critical patients, compared with mild cases. DG treatment may alleviate the abnormal liver enzyme activities in non-critical COVID-19 patients. Abnormal liver functions may be observed in patients with COVID-19, and were associated with SARS-CoV-2-induced acute liver damage. Glycyrrhizin treatment may be an effective therapeutic approach for the outcome of abnormal hepatic enzyme activities in severe COVID-19 cases. Serum hepatic enzyme tests may reflect the illness severity and should be monitored.

Epidermal growth factor alleviates cerebral ischemia-induced brain injury by regulating expression of neutrophil gelatinase-associated lipocalin.

Neutrophil gelatinase-associated lipocalin (NGAL) may be a biomarker candidate for brain injury and a novel therapeutic target in ischemic stroke. Epidermal growth factor (EGF) has protective effects on ischemic injury via activating EGF receptor (EGFR). Whether the protection mechanism of activating EGF-EGFR axis against brain injury is involved in regulating NGAL is still unknown. In the present study, we attempted to explore the expression of NGAL in ischemic brain and the effects of EGF on the NGAL expression in a mouse model of middle cerebral artery occlusion (MCAO). Results suggested that the NGAL expression in ischemic brain was markedly increased after cerebral ischemic damage, and specific NGAL-siRNA can attenuate ischemia-triggered infarct volume and neurological deficit. Then, we found that intracerebroventricular EGF treatment may reduce the level of NGAL in ischemic brain, accompanied by functional improvements. Meanwhile, specific JAK2/STAT3 inhibitor AG490 can reverse EGF-induced reduction of NGAL level. Therefore, the elevated NGAL level in ischemic brain may be an important participant in ischemic brain injury. EGF/EGFR activation ameliorated infarct volume of brain tissues and neurological deficit, and the underlying mechanism is involved in regulating the expression of NGAL via the activation of JAK2/STAT3 pathway.

[Expression of EVI1 in Bone Marrow of Patients with AML and ALL and Its Correlation with Leukemia Subtyping, Clinical Features and Prognosis of Patients].

OBJECTIVE: To explore the expression of EVI1 gene in AML and the ALL patients' bone marrow cells, and its correlation with the leukemic typing, clinical characteristics and prognosis. METHODS: Three hundred and thirty-three cases of leukemia in our hospital from 2012 to 2016 were enrolled in this study. Among them there were 263 cases of AML, 70 cases of ALL, and 13 volunteers were selected as normal controls. The bone marrow samples of the patients and volunteers were aspirated. Firstly, the blood mononuclear cells(PBMNC) were separated from the samples through the Ficoll-Hypaque density gradient centrifugation. Secondly, the total DNA was extracted, and the expression of EVI1 mRNA were assayed by real-ime quantitative PCR, which help to find out the EVI1 mRNA expression difference between AML and ALL. Finally, the correlation of EVI1 expression with the acute leukemia typing, clinical characteristics and prognosis were analyzed by a series of statistical method. RESULTS: Based on the expression levels of the EVI1 mRNA determined by real-time quantitative PCR, the expression levels in AML and ALL were both higher, but without significant difference. The rates of both EVI1 mRNA overexpression and low expression of the EVI1 mRNA in AML patients were higher than those in AML group, however, the rate of normal expression in ALL group was statistically significantly lower than that in the AML. The level of Plt in patients with AML-M1 and T-ALL positively correlated with the level of EVI1 expression（r=0.393,P<0.05；ρ=0.442，P<0.05）while the level of blasts(%) in patients with AML-M3 negatively correlated with the level of EVI1 expression. The expression of EVI1 correlated with the age of patients（χ2 =6.684,P<0.05）. The prognosis of AML patients with high expression of EVI1 mRNA was poor（Log-Rank test，P<0.05）and AML-M3 patients with high expression of EVI1 had a significantly poorer prognosis than that of patients without high expression（Log-Rank test，P<0.01）. CONCLUSION: In expression level of EVI1 no difference has been found in AML and ALL, but the distribution of EVI1 expression shows obvious difference and the difference correlats with the age of patients, at the same time, the some clinical features and subtype of acute leukemia correlate with the expression level of EVI1.

Association between Polymorphisms in MicroRNAs and Risk of Urological Cancer: A Meta-Analysis Based on 17,019 Subjects.

Accumulating evidence has demonstrated that some single nucleotide polymorphisms (SNPs) existing in miRNAs correlate with the susceptibility to urological cancers. However, a clear consensus still not reached due to the limited statistical power in individual study. Thus, we concluded a meta-analysis to systematically evaluate the association between microRNA SNPs and urological cancer risk. Eligible studies were collected from PubMed, Embase, Web of Science, and CNKI databases. Pooled odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated to assess the strength of the relationships between three SNPs (miR-196a2, C>T rs11614913; miR-146a, G>C rs2910164; and miR-499, A>G rs3746444) and the risk of urological cancers. In addition, the stability of our analysis was evaluated by publication bias, sensitivity and heterogeneity analysis. Overall, a total of 17,019 subjects from 14 studies were included in this meta-analysis. We found that CT (miR-196a2, C>T rs11614913) was a risk factor for renal cell carcinoma (CT vs. CC: OR = 1.72, 95%CI = 1.05-2.80, P = 0.03, I2 = 66%), especially in Asian population (CT vs. CC: OR = 1.17, 95%CI = 1.04-1.32, P < 0.01, I2 = 0%). miR-146a G>C rs2910164 was a protective factor of urological cancers (C vs. G: OR = 0.87, 95%CI = 0.81-0.93, P < 0.01, I2 = 0%), especially for bladder cancer. miR-499 A>G rs3746444 was correlated with an increased risk of urological cancers, specifically in Asian population. In conclusion, our meta-analysis suggests that polymorphisms in microRNAs, miR-196a2, C>T rs11614913, miR-146a G>C rs2910164 and miR-499 A>G rs3746444, may be associated with the development of urological cancers and the risks mainly exist in Asian populations.

Hepatitis C Virus Increases Free Fatty Acids Absorption and Promotes its Replication Via Down-Regulating GADD45α Expression.

BACKGROUND Hepatitis C virus (HCV) infection, as a major cause of chronic hepatic diseases, is always accompanied with an abnormality of lipid metabolism. The aim of this study was to investigate the pathogenic role of free fatty acids (FFA) in human HCV infection. MATERIAL AND METHODS Peripheral blood lipid indexes among HCV patients with different viral loads (199 samples) and healthy donors (80 samples) were detected by clinical biochemistry tests. HCV replication and the expression of growth arrest and DNA-damage-inducible gene 45-α (GADD45α) in Huh7 cells and clinical samples were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Lipid accumulation in Huh7 cells was detected by immunofluorescence. RESULTS In this study, we found that FFA showed a significant positive correlation with viral load in peripheral blood of HCV patients, but not total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C). GADD45α expression in HCV patients dramatically decreased with the increase of viral load. In Huh7 cells, FFA treatment significantly enhanced HCV replication. HCV infection inhibited GADD45α expression, and this effect was further enhanced with the presence of FFA treatment. Ectopic expression of GADD45α in HCV-infected Huh7 cells markedly inhibited the absorption of FFA and HCV replication. However, FFA significantly elevated GADD45α expression without HCV infection. CONCLUSIONS These results demonstrated that HCV down-regulates GADD45α expression to enhance FFA absorption and thus facilitate its replication. GADD45α is an essential mediator for the pathogenesis of HCV infection. Thus, our study provides potential clues in the search for novel therapeutics and fatty lipid control options for HCV patients.