Plasma tissue factor pathway inhibitor levels in coronavirus disease 2019 patients: a systematic review and meta-analysis.

Studies have suggested a relationship between tissue factor pathway inhibitor (TFPI) and coronavirus disease 2019 (COVID-19) severity. However, there is inconsistency in the findings of the studies. To enhance comprehension of this relationship, a meta-analysis was conducted. PubMed, Web of Science, and Scopus databases were searched to identify eligible studies. The mean difference was employed as effect measures and the standardized mean difference (SMD) and the 95% confidence interval (CI) were utilized as a summary statistic. Heterogeneity was assessed through the application of the chi-square test and the I2 statistic. The included studies' quality and risk of bias were assessed using the Newcastle-Ottawa assessment scale, adapted for case-control studies. A total of six studies were included with 684 cases and healthy controls (180 healthy controls and 504 COVID-19 patients with different severity, 76 mild, 292 moderate, and 136 severe). The analysis revealed a significant increase in the TFPI level in COVID-19 patients with moderate severity compared with healthy controls (SMD = 0.95 ng/ml, 95% confidence interval (CI) 0.27, 1.63 ng/ml; I2 : 87.2%). The increased TFPI level in mild and moderate COVID-19 was not significant, SMD = 0.68 ng/ml, 95% CI -0.64 to 2.0 ng/ml; I2 92.9% and SMD = 0.62 ng/ml, 95% CI -0.62 to 1.86 ng/ml; I2 91.5%, respectively. In addition, most studies indicate an association of the increased TFPI concentrations with increased markers of inflammation, endothelial damage, and hypercoagulation. Considering the anticoagulant and anti-inflammatory roles of TFPI, its increase seems to be aimed at modulating COVID-19-induced hyper-inflammation and hyper-coagulation state. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023437353.

Expression and Alteration Value of Long Noncoding RNA AB073614 and FER1L4 in Patients with Acute Myeloid Leukemia (AML).

BACKGROUND: Numerous studies have probed the deregulation of the long noncoding RNA AB073614 and FER1L4, which have been discovered in a variety of cancers. However, the precise expression pattern of these lncRNAs and their clinical implications in acute myeloid leukemia (AML) remain elusive. Considering the involvement of the PI3K axis in AML pathogenesis, an investigation into the expression of AB073614 and FER1L4 targets of this pathway has been proposed, aiming to elucidate a potential mechanism underlying AML development. METHODS: The expression levels of lncRNA AB073614 and FER1L4 were assessed in 30 newly diagnosed AML patients and 12 healthy individuals using quantitative reverse transcription-polymerase chain reaction techniques. A statistical analysis was conducted to determine the association of AB073614 and FER1L4 expression levels with clinicopathological features. RESULTS: A significant upregulation of AB073614 was observed in AML patients compared to the control group (p < 0.05). Moreover, a notable increase in AB073614 expression levels coincided with a significant reduction in FER1L4 expression levels in AML samples (p < 0.05). The diagnostic value of these lncRNAs was validated using the receiver operating characteristic (ROC) curve and area under the curve (AUC) calculations. Sensitivity values of AB073614 and FER1L4 gene expression were 96.7% and 100%, respectively, using cut-off relative quantification of 1.045 and 0.770. Additionally, specificity values were observed to be 100%. CONCLUSIONS: The present study indicates that AB073614 and FER1L4 might serve as prognosis biomarkers in AML patients. However, further detailed examinations in this field are warranted. It is proposed that the likely mechanism of imbalanced PI3K and PTEN activity, triggered by the deregulation of AB073614 and FER1L4, may have a crucial role in AML pathogenesis. Any component of this pathway could potentially serve as a new target for more insightful treatment approaches.

Status of major hemostatic components in the setting of COVID-19: the effect on endothelium, platelets, coagulation factors, fibrinolytic system, and complement.

The coagulation, fibrinolytic, anticoagulation, and complement systems are in delicate balance with the vessel wall endothelium ensuring appropriate hemostasis. Coagulopathy in coronavirus disease 2019 (COVID-19) is not a simple disorder of one hemostatic component but a complicated process affecting most of the hemostasis system. COVID-19 disturbs the balance between the procoagulant systems and the regulatory mechanisms. Here, we investigate the effect of COVID-19 on key hemostatic components, including platelets, endothelial cells, coagulation factors, fibrinolytic system, anticoagulant protein system, and complement system, to improve our understanding of the pathophysiological processes underlying COVID-19 coagulopathy based on evidence.

The importance of using routine laboratory tests in the diagnosis and prognosis of patients with coronavirus disease 2019: Shedding light on clinical laboratory data in COVID-19.

BACKGROUND: Novel coronavirus (COVID-19) pandemic has become a global concern and requires early detection, isolation, and treatment. Our purpose is to find some beneficial information by analyzing the COVID-19 laboratory data to provide guidance for clinical practice. MATERIAL AND METHODS: In this study, 174 patients with confirmed COVID-19 infection were admitted. We evaluated the hematological and biochemical parameters in these patients and in 80 healthy individuals. RESULTS: We found that there was significant difference between WBC, LYM, RBC, HB, and HCT parameters of patients and healthy counterparts (p < .001), though there was no remarkable change between NEU, MONO, PLT, and other characteristics of RBC values of patients and the control group (p ≥ .09). Among the evaluated biochemical parameters, the values of CK-MB and LDH in the patient group were significantly different from the control group (p < .01), while other biochemical indicators were in the normal range. CONCLUSION: Several hematological and biochemistry parameters, in particular WBC, LYM, RBC, HB, HCT, CK-MB, and LDH, could be beneficial supplementary approach for COVID-19 infection evaluation to confirm risk stratification and effective management.

NF-κB-dependent Mechanism of Action of c-Myc Inhibitor 10058-F4: Highlighting a Promising Effect of c-Myc Inhibition in Leukemia Cells, Irrespective of p53 Status.

Due to the frequent contribution in the pathogenesis of different human malignancies, c-Myc is among those transcription factors that are believed to be pharmacologically targeted for cancer therapeutic approaches. In the present study, we examined the anti-leukemic effect of a well-known c-Myc inhibitor 10058-F4 on a panel of hematologic malignant cells harboring either mutant or wild-type p53. Notably, we found that the suppression of c-Myc was coupled with the reduction in the survival of all the tested leukemic cells; however, as far as we are aware, this study suggests for the first time that the cytotoxic effect of 10058-F4 was not significantly affected by the molecular status of p53. Delving into the molecular mechanisms of the inhibitor in the most sensitive cell line revealed that 10058-F4 could induce apoptotic cell death in mutant p53-expressing NB4 cells through the suppression of NF-κB pathway coupled with a significant induction of intracellular reactive oxygen species (ROS). In addition, we found that the anti-leukemic effect of 10058-F4 was overshadowed, at least partially, through the compensatory activation of the PI3K signaling pathway; highlighting a plausible attenuating role of this axis on 10058-F4 cytotoxicity. In conclusion, the results of the present study shed light on the favorable anti-leukemic effect of 10058-F4, especially in combination with PI3K inhibitors in acute promyelocytic leukemia; however, further investigations should be accomplished to determine the efficacy of the inhibitor, either as a single agent or in a combined-modal strategy, in leukemia treatment.

c-Myc Inhibition Using 10058-F4 Increased the Sensitivity of Acute Promyelocytic Leukemia Cells to Arsenic Trioxide Via Blunting PI3K/NF-κB Axis.

BACKGROUNDS: Although ATO is widely used to treat acute promelocytic leukemia (APL), the appropriate effects of the drug as a single agent are achieved in high doses which are not clinically achievable without the risk of side effects; highlighting the necessity of its application in a combined-modality. Herein, we aimed to investigate whether c-Myc inhibition could reinforce the anti-leukemic effect of ATO, while reducing its concentration in APL cells. METHODS: NB4 cells were treated with the relevant concentrations of 10058-F4 (c-Myc inhibitor) and ATO, and then the survival of the cells was evaluated using trypan blue, MTT and BrdU assays. Moreover, the mechanism of action of the agents were evaluated using Flow cytometry, qRT-PCR and western blot analysis. RESULTS: We found that the inhibition of c-Myc using 10058-F4 could enhance the anti-leukemic effect of ATO in APL cells through reducing the phosphorylation of IκB, decreasing the expression of the anti-apoptotic genes and in turn, inducing a caspase-3-dependent apoptotic cell death. Moreover, the combination of 10058-F4 and ATO abrogated the activation of the PI3K pathway, while neither agent had significant suppressive impact on this pathway; suggesting for the first time that probably the companionship of c-Myc inhibitor may be an appealing strategy for shifting the resistance condition toward a chemo-sensitive phenotype, without the necessity to elevate the effective dose of ATO. CONCLUSION: Given the efficacy of 10058-F4 in adjuvanting approaches, we suggest this small molecule inhibitor as an impressing agent to be used alongside ATO in the treatment of APL.

The association of right coronary artery conus branch size and course with ST segment elevation of right precordial leads and clinical outcome of acute anterior myocardial infarction.

Introduction: Coronary artery disease is the leading cause of death worldwide and electrocardiogram (ECG) is a reliable diagnostic tool to determine a myocardial infarction. The present study tried to compare the relationship between the ECG findings and angiographic findings in patients with acute anterior myocardial infarction. Methods: Seventy-four patients with acute anterior ST elevation myocardial infarction (Ant- STEMI) presenting to the emergency room in the first 12 hours after the onset of symptoms were studied. Upon admission, a full 14-lead ECG (including leads V3R and V4R) were performed. Angiographic and ECG findings, as well as clinical outcome were compared between two groups. The statistical tests including Chi-square and independent t-test were used for data analysis. Results: Small conus branch was seen in 52 (70.3%) and large conus in 22 ( 29.7%) patients. STE in right-sided leads and heart failure were significantly higher in small conus branch group versus large conus branch (88.6% vs 11.4%, P < 0.001 and 34.6% vs 9.1%, P = 0.02 respectively). There was no significant difference in mortality rate between the two groups (5.8% in small conous group vs 0% in large conus group, P = 0.55). There was a significant difference in major adverse cardiac events (MACE) between the two groups (51.9% in small conous group vs 18.2% in large conus group, P = 0.01). Conclusion: In patients with anterior MI, small conus branch was associated with higher rate of major adverse cardiac events mostly because of increased rate of acute heart failure.

Platelet Transfusion Outcome and Flow Cytometric Monocyte Phagocytic Assay (FMPA).

BACKGROUND: This study was designed to evaluate platelet transfusion outcome via flow cytometric monocyte phagocytic assay (FMPA).   METHODS: Fifteen patients with a history of multiple platelet transfusions and fifteen controls were enrolled in this study. CMFDA-labeled platelets were incubated with patients' sera and were finally incubated with monocytes in a tube and analyzed by flow cytometry. Monocytes that phagocytosed platelets were detected as a CMFDA-positive platelet population via monocyte gate. The FMPA results were compared with CCI results for the patients. RESULTS: The FMPA result correlated with 1-hour (r = -0.885, P = 0.001) and 24-hour (r = -0.884, P = 0.001) CCI. There is a significant difference in means of FMPA results between the patients with immune platelet refractoriness (68.46 ± 10.4%), non-refractory group (37.73 ± 15.21%) and the control group (18.27 ± 2.86%).  CONCLUSION: Our data showed that FMPA has good results in evaluation of platelet transfusion outcome and may be useful as an indicator of platelet transfusion response.