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Problem: Several large studies have demonstrated that COVID-19 pregnant individuals are at a significant risk for severe disease and adverse pregnancy outcomes. The mechanisms underlying these phenomena remain to be elucidated and are the focus of our project. Although fetal and placental infection is rare, placental abnormalities and adverse pregnancy outcomes associated with placental dysfunction in COVID-19 cases have been widely reported. In particular, placental thrombosis and lesions consistent with maternal vascular malperfusion (MVM) of the placenta are common in individuals with COVID-19. Since thrombotic complications have been associated with COVID-19, it is not surprising that pregnant individuals with COVID- 19 are at risk for placental thrombosis. Method of Study: Placentas were evaluated histologically. Extracellular vesicles were isolated by serial centrifugation. Result(s): Adverse pregnancy outcomes associated with these placental lesions, including hypertensive disorders of pregnancy (gestational hypertension and preeclampsia), small for gestational age (SGA, birthweight < 10th percentile for gestational age), and preterm birth (PTB, < 37 weeks) are significantly increased among pregnant individuals with COVID-19. Placental infection with SARSCoV- 2 is uncommon, but multiple inflammatory and metabolic factors are likely to affect the placenta, including circulating extracellular vesicles (EVs) derived from various organs that have been associated with COVID-19 pathology and disease severity.We have analyzed over 500 placentas from COVID-19 pregnancies and found marked changes in placental morphology, characterized by abnormal maternal and fetal vessels, intervillous thrombi, and fibrin deposition, even in the face of mild or asymptomatic disease. We detected increased levels of small EVs in maternal serum from COVID-19 cases compared to controls and increased levels of mitochondrial DNA in EVs from COVID-19 cases. In in vitro experiments, we found increased oxidative stress in uterine endothelial cells and primary trophoblasts. Syncytialization of trophoblast cells following exposure to EVs from pregnant COVID-19 patients was markedly reduced. RNAseq of trophoblast cells exposed to EVs from pregnant COVID-19 patients revealed disruption of multiple pathways related to mitochondria function, oxidative stress, coagulation defects, and inflammation. Timing of infection during pregnancy (first, second, and third trimester) altered EV size distribution, cargo content, and functional consequences of trophoblast EV exposure. Conclusion(s): Our studies show that COVID-19 infection during pregnancy has profound effects on placenta morphology and function. It remains to be determined what the long-term consequences are on the offspring.
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The coronavirus SARS-CoV-2 was detected in isolates of pneumonia patients in January 2020. The virus cannot multiply extracellularly but requires access to the cells of a host organism. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as a receptor, to which it docks with its spikes. ACE2 belongs to the renin angiotensin system (RAS), whose inhibitors have been used for years against high blood pressure. Renin is an endopeptidase that is predominantly formed in the juxtaglomerular apparatus of the kidney and cleaves the decapeptide angiotensin I (Ang I) from angiotensinogen. Through the angiotensin-converting enzyme (ACE), another 2 C-terminal amino acids are removed from Ang I, so that finally the active octapeptide angiotensin II (Ang II) is formed. The biological effect of Ang II via the angiotensin II receptor subtype 1 (AT1-R) consists of vasoconstriction, fibrosis, proliferation, inflammation, and thrombosis formation. ACE2 is a peptidase that is a homolog of ACE. ACE2 is predominantly expressed by pulmonary alveolar epithelial cells in humans and has been detected in arterial and venous endothelial cells. In contrast to the dicarboxy-peptidase ACE, ACE2 is a monocarboxypeptidase that cleaves only one amino acid from the C-terminal end of the peptides. ACE2 can hydrolyze the nonapeptide Ang-(1-9) from the decapeptide Ang I and the heptapeptide Ang-(1-7) from the octapeptide Ang II. Ang-(1-7) acts predominantly antagonistically (vasodilatory, anti-fibrotic, anti-proliferative, anti-inflammatory, anti-thrombogenetically) via the G protein-coupled Mas receptor to the AT1-R-mediated effects of Ang II. In the pathogenesis of COVID-19 infection, it is therefore assumed that there is an imbalance due to overstimulation of the AT1 receptor in conjunction with a weakening of the biological effects of the Mas receptor.Copyright © 2022 Dustri-Verlag Dr. K. Feistle.
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Problem: Environmental stress during pregnancy has known impacts on both maternal and fetal health. In terms of theCOVID-19 pandemic, the majority of published work has focused on the impact of the infection itself, without considering the potential immune impact of pandemic related-stress.We, therefore, assessed the impact of pandemic stress, independently of SARS-CoV-2 infection, on the circulating and placental immune profiles of pregnant individuals. Method(s): Placentas from 239 patients were collected at the Sainte- Justine Hospital, Montreal, Canada. Of these, 199 patients delivered during the pandemic and were exposed to pandemic stress with (+: 79) or without (-: 120) SARS-CoV-2 infection, the latter exposed to pandemic stress only. Pre-pandemic historic controls (uncomplicated pregnancies, Ctrl: 40), were also included. Placental biopsies were collected to assess cytokine levels by ELISAs and histopathological lesions. A sub-study with 35 pre-pandemic pregnancies (unexposed) and 20 who delivered during the pandemic (exposed) was also conducted. The latter (exposed/unexposed) were all uncomplicated pregnancies. We collected maternal blood prior to delivery for immunophenotyping, and plasma/peripheral blood mononuclear cells (PBMCs) were isolated. Inflammatory mediators in the plasma were quantified by ELISAs. Co-culture assays with PBMCs and human umbilical vein endothelial cells (HUVECs) were performed to assess endothelial activation. Demographical/obstetrical data were obtained through chart review. Result(s): SARS-CoV-2+ patients were multiethnic (63.4%), had higher pre-pregnancyBMI (28.9 vs. 24.8 inCtrl, P<.05), and elevated preterm birth rate (16.5% vs. 5.8% in SARS-CoV-2-, P < .05 and 0.0% in Ctrl, P < .01). In the placentas, we observed an increase in the levels of IL- 1Ra (P < .05) and CRP (P < .05) in both SARS-CoV-2 groups, while IL-6 (P = .0790) and MCP-1 (P < .001) were elevated solely in SARS-CoV- 2-. These changes were predominant in placentas with inflammatory lesions on histopathological analysis. Moreover, we observed elevated CD45+ cells (P < .001) in the placentas from both SARS-CoV-2 groups versus Ctrl. Considering that the differences we observed were important in the SARS-CoV-2- group, we performed a study solely on uncomplicated pregnancies, either exposed or unexposed to pandemic stress. At the systemic level, we observed a decrease in the percentage of Th2 cells (P < .001), leading to a pro-inflammatory Th1/Th2 imbalance in exposed individuals. Decreased Treg (P < .05) and Th17 (P < .05) versus unexposed was also observed. Surprisingly, decreased levels of circulating IL-6 (P < .05), MCP-1 (P < .01), and CRP (P<.05) were seen in exposed versus unexposed individuals. Finally,we observed increased secretion of ICAM, a marker of endothelial activation, solely in endothelial cells co-cultured with PBMCs from exposed individuals. Conclusion(s): Overall, placental inflammatory profiles differed between pregnant individuals exposed to pandemic stress with or without SARS-CoV-2 infection. Moreover, we observed that the pandemic stress exposed group presented a systemic pro-inflammatory bias. This highlights the need to understand the differences between the effects of pandemic-related stress and the added burden of SARS-CoV-2 infection itself on maternal and fetal health. Our work also supports an association between an increased risk of hypertension/ preeclampsia and SARS-CoV-2 infection that might be driven in part by pandemic-related stress.
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Advances in biology have allowed us to substantially deepen our knowledge about hemostasis functioning both in health and disease. ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) and von Willebrand factor (vWF) are components of the hemostasis system, which physiological interaction holds an important place in maintaining homeostasis. ADAMTS-13 is a metalloproteinase mainly acting to release vWF fragments into the blood plasma, as well as regulating its activity by cleaving ultra-large vWF multimers (UL-vWF) into smaller and less active forms. The study of such factors is of great clinical importance, since a decrease in ADAMTS-13 activity and an increase in vWF level can be predictors of microcirculatory disorders that play an important role in developing multiple organ failure. However, very few and fully contradictory studies devoted to the physiological aspects of the ADAMTS-13/vWF axis functioning in the mother-fetus system are available, therefore requiring to be further investigated.Copyright © 2023 Russian Journal of Forensic Medicine. All rights reserved.
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It is now only in the wake of coronavirus disease 2019 (COVID-19) that we are beginning to understand many of the extra-respiratory manifestations of the condition. There is now growing evidence that erectile dysfunction (ED) is closely linked with the disease. We carry out one of the first literature reviews to consolidate the current evidence of the causal link between COVID-19 and ED and explore the proposed mechanisms that underpin this phenomenon. We carried out a literature search of the databases;PubMed (MEDLINE), Scopus, Web of Science and the Cochrane library. Search time frame was between December 2019 and March 2022. Only studies deemed of acceptable quality were included. Five studies were found highlighting the link between COVID-19 and ED. A further Nineteen studies were utilized to illustrate the proposed biological mechanisms underpinning COVID-19 related ED. Clear evidence has been documented through multiple studies internationally recognizing reduction in erectile scores and reduced sexual activity. It appears there is likely indirect and direct cytopathic effects on endothelial cells, in addition to hormonal and psychosocial factors. The associated ED is likely a result of a multitude of mechanisms including direct and indirect endothelial dysfunction, vasoactive cytokines, endocrine dysregulation, and psychosocial factors. This is the first literature review to delve into the likely underpinning mechanisms of the virus that drive ED.Copyright ©2023 The Author(s). Published by MRE Press.
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The pathogenesis of severe coronavirus infection COVID-19 is associated with activation of immune system, cytokine storm, impaired blood clotting, microvascular thrombosis, organ ischemia and multiple organ dysfunction syndrome. The role of various lymphocyte subpopulations in COVID-19 is still debated. The aim of our study was to analyze the subpopulational profile of peripheral blood lymphocytes in COVID-19 patients as compared with healthy donors. The study included 20 COVID-19 patients (11 males and 9 females,) and 26 healthy donors. Average age of the patients was 52 and 56 years, respectively. Clinical examinations were performed by standard laboratory methods. Peripheral blood lymphocytes were isolated in the Ficoll gradient. The cells were stained with antibodies to specific antigens of main lymphocyte populations, endothelial cells, and apoptotic cell markers. The analysis was performed by flow cytometry. The results showed that all patients had elevated C-reactive protein (14- to 35-fold), ferritin (1.2- to 13-fold), D-dimers (1.2- to 90-fold). 55% of men had a decrease in the absolute number of lymphocytes, in women this index was at the low normal limit. Cytometric analysis showed that, among peripheral blood lymphocytes, the proportion of functional cells expressing the CD45 marker ranged from 2 to 12% in 70% of patients, as compared with 80-99% among the donors. The proportion of CD45+ lymphocytes significantly correlated with the level of hemoglobin, but not with the levels of inflammatory biochemical markers. Among the functional lymphocytes of patients, there was a decrease in the proportion of CD3+, CD4+, CD8+T cells, increased proportion of natural killer CD56+ and the apoptotic (AnnexinV+) cell contents, but the proportion of CD19 and HLA-DR+B cells was not changed. Analysis of the lymphocyte (LC) subpopulations that did not express CD45 marker showed that this fraction contained different lymphocyte subsets with reduced expression of CD4, CD8, CD19, CD56 etc. in the blood of patients and donors. Higher percentage of endothelial cells expressing CD62P marker made the difference between patients and donors. Laboratory determination of lymphocyte subsets in blood samples of COVID-19 patients does not reflect the real severity pattern of the disease, thus requiring studies of the CD45-expressing functional cell populations.Copyright © Svirshchevskaya E.V. et al., 2023 The article can be used under the Creative Commons Attribution 4.0 License.
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Background and objectives: SARS-C0V-2 infections have varied manifestations among individuals ranging from asymptomatic or mild symptoms to severe disease and death. This study is done to look into various histopathological changes in lung, liver, and kidney tissues among Covid19 positive autopsies with cellular tropism and viral load among various organs by immunohistochemistry (IHC) for the SARS-C0V-2 viral marker. Method(s): A prospective descriptive study of core biopsies from covid19 positive autopsies from the lung, liver, and kidneys were taken from 20 cases. A routine histopathological examination of the tissues with IHC staining for SARS-CoV-2 cocktail antibodies was performed and assessed. Result(s): Histopathological changes in the lung, liver, and kidney tissues showed changes of varying severity. On IHC, in the lung, the tropism for SARS-CoV-2 was seen in pneumocytes, bronchial epithelial cells, endothelial cells, and macrophages. In the kidney, tropism was seen towards tubular epithelial cells and endothelial cells. In the liver, hepatocytes and bile duct epithelial cells were positive. Variable viral density was seen in different organs which varied from case to case. The density of the viral load was highest in the lung and lower in the kidney and least in the liver. Conclusion(s): In this study the various histopathological changes and cellular tropism of the SARS-CoV-2 among Lung, liver, and kidney tissues have been described and compared with various similar studies across the globe.Copyright © 2023 International Journal of Life Sciences Biotechnology and Pharma Research. All rights reserved.
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INTRODUCTION: Glioblastoma (GBM) is the most common and deadliest primary brain tumor, characterized by chemoradiation resistance and an immunosuppressive tumor microenvironment (TME). SARS-CoV-2, the COVID-19 virus, produces a significant proinflammatory response and a spectrum of clinical presentations after central nervous system infection. METHOD(S): Patient-derived GBM tissue, primary cell lines, and organoids were analyzed with immunohistochemistry and pixel-line intensity quantification. Data from tumor-bulk and single-cell transcriptomics served to describe the cell-specific expression of SARS-CoV-2 receptors in GBM and its association with the immune TME phenotype. Normal brain and iPSC-derived organoids served as controls. RESULT(S): We demonstrate that patient-derivedGBMtissue and cell cultures express SARS-CoV2 entry factors such as ACE2, TMPRSS2, and NRP1. NRP1 expression was higher in GBM than in normal brains (p<0.05), where it plays a crucial role in SARS-CoV-2 infection. NRP1 was expressed in a cell-type and phenotype-specific manner and correlated with TME infiltration of immunosuppressive cells: M2 macrophages (r = 0.229), regulatory T cells (r = 0.459), NK cells (r = -0.346), and endothelial cells (r = 0.288) (p < 0.05). Furthermore, gene ontology enrichment analysis showed that leukocyte migration and chemotaxis are among the top 5 biological functions mediated by NRP1 (p < 0.05). We found our GBM organoids recapitulate tumoral expression of SARSCoV- 2 entry factors, which varies based on distance from surface as surrogate of TME oxygenation (p < 0.05). CONCLUSION(S): GBM cancer cells and immune TME cells express SARS-CoV-2 entry factors. Glioblastoma organoids recapitulate this expression and allow for currently undergoing studies analyzing the effect of SARS-CoV-2 infection in GBM. Our findings suggest that SARSCoV- 2 could potentially target GBM, opening the door to future studies evaluating SARS-CoV-2-driven immune modulation.
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The pathogenesis of severe coronavirus infection COVID-19 is associated with activation of immune system, cytokine storm, impaired blood clotting, microvascular thrombosis, organ ischemia and multiple organ dysfunction syndrome. The role of various lymphocyte subpopulations in COVID-19 is still debated. The aim of our study was to analyze the subpopulational profile of peripheral blood lymphocytes in COVID-19 patients as compared with healthy donors. The study included 20 COVID-19 patients (11 males and 9 females,) and 26 healthy donors. Average age of the patients was 52 and 56 years, respectively. Clinical examinations were performed by standard laboratory methods. Peripheral blood lymphocytes were isolated in the Ficoll gradient. The cells were stained with antibodies to specific antigens of main lymphocyte populations, endothelial cells, and apoptotic cell markers. The analysis was performed by flow cytometry. The results showed that all patients had elevated C-reactive protein (14- to 35-fold), ferritin (1.2- to 13-fold), D-dimers (1.2- to 90-fold). 55% of men had a decrease in the absolute number of lymphocytes, in women this index was at the low normal limit. Cytometric analysis showed that, among peripheral blood lymphocytes, the proportion of functional cells expressing the CD45 marker ranged from 2 to 12% in 70% of patients, as compared with 80-99% among the donors. The proportion of CD45+ lymphocytes significantly correlated with the level of hemoglobin, but not with the levels of inflammatory biochemical markers. Among the functional lymphocytes of patients, there was a decrease in the proportion of CD3+, CD4+, CD8+T cells, increased proportion of natural killer CD56+ and the apoptotic (AnnexinV+) cell contents, but the proportion of CD19 and HLA-DR+B cells was not changed. Analysis of the lymphocyte (LC) subpopulations that did not express CD45 marker showed that this fraction contained different lymphocyte subsets with reduced expression of CD4, CD8, CD19, CD56 etc. in the blood of patients and donors. Higher percentage of endothelial cells expressing CD62P marker made the difference between patients and donors. Laboratory determination of lymphocyte subsets in blood samples of COVID-19 patients does not reflect the real severity pattern of the disease, thus requiring studies of the CD45-expressing functional cell populations.Copyright © Svirshchevskaya E.V. et al., 2023 The article can be used under the Creative Commons Attribution 4.0 License.
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Objectives: The aim of this study was to explore the association of the plasma levels of coagulation proteins with venous thromboembolic events (VTE) in COVID-19 and identify candidate early markers of VTE. Background(s): Coagulopathy and thromboembolism are known complications of SARS-CoV-2 infection. The mechanisms of COVID-19-associated hematologic complications involve endothelial cell and platelet dysfunction and immunothrombosis and have been intensively studied. Yet, a full understanding of the pathogenesis and factors that lead to COVID-19 associated coagulopathy is lacking. Previous studies investigated only small numbers of coagulation proteins together, and they were limited in their ability to adjust for confounders. Method(s): This study was a post-hoc analysis of a previously published dataset (Filbin et al., 2021). We included in our analysis 305 subjects with confirmed SARS-CoV-2 infection who presented to an urban Emergency Department with acute respiratory distress during the first COVID-19 surge in 2020;13 (4.2%) were subsequently diagnosed with venous thromboembolism during hospitalization. Serial samples were obtained on days 0, 3, and 7 and assays were performed on two highly-multiplexed proteomic platforms, that in combination cover 1472 + 4776 proteins. We included 31 coagulation proteins in our analysis. Result(s): Nine coagulation proteins were differentially expressed in patients with thromboembolic events. In multivariable models, day 0 levels of P-selectin, a cell adhesion molecule on the surface of activated endothelial cells, displayed the strongest association with the diagnosis of VTE, independent of disease severity and other confounders (p=0.0025). P-selectin together with D-dimer upon hospital presentation provided better discriminative ability for VTE diagnosis than D-dimer alone (AUROC = 0.834 vs. 0.783). Conclusion(s): Our results suggest that plasma P-selectin is a potential early biomarker for the risk stratification of VTE in COVID-19 disease. Our findings support the importance of endothelial activation in the mechanistic pathway of venous thromboembolism in COVID-19.Copyright © 2023
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Objective: To investigate the laboratory and instrumental characteristics of fetal growth restriction (FGR) secondary to novel coronavirus infection (NCI) to identify pathogenetically relevant predictive markers. Material(s) and Method(s): During the epidemic activity of the NCI Delta strain, 140 high-risk pregnant women were tested at 18-21 weeks and 26-34 weeks of gestation. Retrospectively, taking into account the fact of NCI disease and the exclusion of severe somatic and obstetric comorbidities, 2 groups were formed. Group 1 (n=32) included pregnant women with FGR, without a history of NCI. Group 2 (n=41) included pregnant women with FGR who recovered from NCI by the end of the second and third trimesters. Thirty healthy pregnant women served as the controls. In addition to ultrasound assessment of the fetal placental unit, patients underwent testing for markers of inflammation, endothelial hemostasis dysfunction, decidualization, placental angiogenesis, and pathological insulin resistance. Result(s): Pregnant women with a history of NCI had a higher incidence of FGR (1.3 times;OR 2.41 [95% CI 1.12-5.17]), more severe forms of FGR (2 times;OR 3.27 [95% CI 1.22-8.76]), more severe fetal-placental blood flow abnormalities (3.5-fold;OR 11.07 [95% CI 3.68-33.27]), and oligohydramnios (4.5-fold;OR 8.94 [95% CI 3.65-30.17]). The impact of NCI on the formation of placental insufficiency was expressed by an increase in systemic changes (thrombopoiesis, apoptosis), modulation of local processes (decidualization, placental angiogenesis), and the development of pathological insulin resistance and hyperinsulinemia, an immunopathological process of endotheliocytes. The identification of the most informative markers of FGR due to NCI allowed the development of a predictive index. Conclusion(s): An in-depth study of the impact of NCI on the formation of FGR has important scientific and practical implications for the optimization of FGR prediction, which may help identify appropriate patient management strategies for high-risk pregnant women.Copyright © 2023, Bionika Media Ltd.. All rights reserved.
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Objective: To investigate the laboratory and instrumental characteristics of fetal growth restriction (FGR) secondary to novel coronavirus infection (NCI) to identify pathogenetically relevant predictive markers. Material(s) and Method(s): During the epidemic activity of the NCI Delta strain, 140 high-risk pregnant women were tested at 18-21 weeks and 26-34 weeks of gestation. Retrospectively, taking into account the fact of NCI disease and the exclusion of severe somatic and obstetric comorbidities, 2 groups were formed. Group 1 (n=32) included pregnant women with FGR, without a history of NCI. Group 2 (n=41) included pregnant women with FGR who recovered from NCI by the end of the second and third trimesters. Thirty healthy pregnant women served as the controls. In addition to ultrasound assessment of the fetal placental unit, patients underwent testing for markers of inflammation, endothelial hemostasis dysfunction, decidualization, placental angiogenesis, and pathological insulin resistance. Result(s): Pregnant women with a history of NCI had a higher incidence of FGR (1.3 times;OR 2.41 [95% CI 1.12-5.17]), more severe forms of FGR (2 times;OR 3.27 [95% CI 1.22-8.76]), more severe fetal-placental blood flow abnormalities (3.5-fold;OR 11.07 [95% CI 3.68-33.27]), and oligohydramnios (4.5-fold;OR 8.94 [95% CI 3.65-30.17]). The impact of NCI on the formation of placental insufficiency was expressed by an increase in systemic changes (thrombopoiesis, apoptosis), modulation of local processes (decidualization, placental angiogenesis), and the development of pathological insulin resistance and hyperinsulinemia, an immunopathological process of endotheliocytes. The identification of the most informative markers of FGR due to NCI allowed the development of a predictive index. Conclusion(s): An in-depth study of the impact of NCI on the formation of FGR has important scientific and practical implications for the optimization of FGR prediction, which may help identify appropriate patient management strategies for high-risk pregnant women.Copyright © 2023, Bionika Media Ltd.. All rights reserved.
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Objective: To investigate the laboratory and instrumental characteristics of fetal growth restriction (FGR) secondary to novel coronavirus infection (NCI) to identify pathogenetically relevant predictive markers. Material(s) and Method(s): During the epidemic activity of the NCI Delta strain, 140 high-risk pregnant women were tested at 18-21 weeks and 26-34 weeks of gestation. Retrospectively, taking into account the fact of NCI disease and the exclusion of severe somatic and obstetric comorbidities, 2 groups were formed. Group 1 (n=32) included pregnant women with FGR, without a history of NCI. Group 2 (n=41) included pregnant women with FGR who recovered from NCI by the end of the second and third trimesters. Thirty healthy pregnant women served as the controls. In addition to ultrasound assessment of the fetal placental unit, patients underwent testing for markers of inflammation, endothelial hemostasis dysfunction, decidualization, placental angiogenesis, and pathological insulin resistance. Result(s): Pregnant women with a history of NCI had a higher incidence of FGR (1.3 times;OR 2.41 [95% CI 1.12-5.17]), more severe forms of FGR (2 times;OR 3.27 [95% CI 1.22-8.76]), more severe fetal-placental blood flow abnormalities (3.5-fold;OR 11.07 [95% CI 3.68-33.27]), and oligohydramnios (4.5-fold;OR 8.94 [95% CI 3.65-30.17]). The impact of NCI on the formation of placental insufficiency was expressed by an increase in systemic changes (thrombopoiesis, apoptosis), modulation of local processes (decidualization, placental angiogenesis), and the development of pathological insulin resistance and hyperinsulinemia, an immunopathological process of endotheliocytes. The identification of the most informative markers of FGR due to NCI allowed the development of a predictive index. Conclusion(s): An in-depth study of the impact of NCI on the formation of FGR has important scientific and practical implications for the optimization of FGR prediction, which may help identify appropriate patient management strategies for high-risk pregnant women.Copyright © 2023, Bionika Media Ltd.. All rights reserved.
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The pathogen of COVID-19 is 2019-nCoV, which belongs to the beta coronavirus. Angiotensin-converting enzyme 2 (ACE2) is the receptor of 2019-nCoV as the same of SARS-CoV. Most of the severe patients were the elderly with underlying diseases, which may be related to the decrease in the number of naive T cells. In addition to pulmonary symptoms, COVID-19 can also cause multiple organ dysfunction and even multiple organ failure (liver, nervous system, heart, kidney, etc.). Pathogenic mechanisms such as direct virus invasion, cytokine storm, endothelial cells damage, and down-regulation of ACE2 may play important roles in the severity of the disease.Copyright © 2021 Chinese Medical Association
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Introduction: (IFITM3) is an innate immune protein that has been identified as a novel gamma-secretase (gammas) modulator. FYN is a kinase that stabilizes IFITM3 on the membrane, primes APP for amyloidogenic gammas processing and mediates tau oligomerization. The purpose of this study is to explore the role of FYN and IFITM3 in AD and COVID-19, expanding on previous research from our group. Method(s): A 520 gene signature containing FYN and IFITM3 (termed Ia) was extracted from a previously published meta-analysis of Alzheimer's disease (AD) bulk- and single nuclei sequencing data. Exploratory analyses involved meta-analysis of bulk and single cell RNA data for IFITM3 and FYN differential expression per CNS site and cellular type. Confirmatory analyses, gene set enrichment analysis (GSEA) on Ia was performed to detect overlapping enriched biological networks between COVID-19 with AD. Result(s): Bulk RNA data analysis revealed that IFITM3 and FYN were overexpressed in two CNS regions in AD vs. Controls: the temporal cortex Wilcoxon p-value=1.3e-6) and the parahippocampal cortex Wilcoxon p-value=0.012). Correspondingly, single cell RNA analysis of IFITM3 and FYN revealed that it was differentially expressed in neurons, glial and endothelial cells donated b AD patients, when compared to controls. Discussion(s): IFITM3 and FYN were found as interactors within biological networks overlapping between AD and SARS-CoV-2 infection. Within the context of SARS-CoV-2 induced tau aggregation and interactions between tau and Ab1-42, the FYN - IFITM3 regulome may outline an important innate immunity element responsive to viral infection and IFN-I signaling in both AD and COVID-19.Copyright © 2021 The Authors
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The clinical outcomes of COVID-19 patients highlight a significant minority of subjects with very rapid lethal outcomes subsequent to the almost complete healing after coronavirus infections for most of the subjects involved. In addition, the reckless use of some drugs and therapeutic protocols that have not shown any efficacy in reducing mortality in those patients where the progression of the disease was unstoppable suggests a different interpretative model in the pathogene-sis of severe cases. Starting from the clinical data already known for almost twenty years on the be-havior of human SARS coronaviruses, it is possible to develop a new hypothesis. The reference points taken into consideration are: i) the comparison of the histological evidence of the autoptic material;ii) the poor pharmacological response in subjects with severe phenotypes of the patholo-gy;iii) the common element of endotheliitis in a subgroup of the population characterized by harm-ful clinical outcomes during the evolution of the pathology. The tendency to develop widespread, massive endothelial lesions not responding to any drug therapy or other interventions necessarily plays a crucial role in the onset of the systemic and severe stage of the disease. The present perspective opens the door to a different therapeutic approach both to the full-blown phase of COVID-19 and to the preventive phase or the very first manifestations of the disease. It is imperative to pay more attention to the protection of the vascular endothelium in subjects who already have a predis-position to the development of a severe evolution of this ailment rather than to give a simple antiviral therapy together with symptomatic drugs.Copyright © 2021 Bentham Science Publishers.
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Background: The current Covid-19 pandemic has resulted in significant global impacts for healthcare systems and beyond. Age and or co-morbidities which are often chronic in nature are the main risk factors for severe Covid-19 infection with strong further associations with mortality. IL-6 is reported to be greatly elevated in patients with severe Covid-19 infection. As a key positive regulator for hepcidin biosynthesis this may suggest impacts for iron metabolism in these patients;elevated serum ferritin further reinforces this notion. Aim(s): To investigate the effects of IL-6 and hepcidin on ACE2 gene expression in pulmonary artery endothelial cells (PAECs). Method(s): PAECs were treated with IL-6 (1-10 ng/mL) and hepcidin (0.1-1 mug/mL). Gene expression was identified by RT-PCR and Western Blot (WB). Result(s): When challenged with either IL-6 or hepcidin, significant upregulation of ACE2 mRNA was observed in hPAECs (n= 3;*p<0.05). Significant elevated levels of ACE2 protein expression were also observed by western blot (n= 3;*p<0.05). In addition, knock-down of the ferroportin gene (SLC40A1) in these cells resulted in significant loss of ferroportin mRNA coupled with a strong significant up-regulation of ACE2 mRNA (n= 3;*p<0.05). Conclusion(s): Whilst our results demonstrate upregulation of ACE2 gene and protein in hPAECs in response to iron regulatory elements, such as hepcidin and IL-6, further studies need to be undertaken to establish if such effects result in enhanced SARS-CoV-2 infection and whether modulation of this axis may be protective.
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Introduction: In the natural conditions first and major target for respiratory viruses (RVs) are epithelial cells. Nonetheless, recently we have demonstrated that RVs are able to infect not only epithelium, but also Human Microvascular Lung Endothelial Cells (HMVEC-L) which increased network is observed during severe asthma due to increased angiogenesis. Furthermore, on the surface of HMVEC-L we observed intense expression of aminopeptidase N (AP-N)- an entry receptor for Human Coronavirus 229E (HCoV-229E). Due to the facts, that possibility of being infected by HCoV-229E should be considered and there is no research based on this model the aim of this study was to assess the vulnerability of HMVEC-L to HCoV-229E infection. Method(s): HMVEC-L was incubated with HCoV-229E (MOI 0,1;1,0;3,0) for 3 hours, 3x PBS washed and cultured for 120 hours. In relevant time points (5;24;48;72;96 and 120h) viral copy number and mRNA expression of inflammatory, anti-viral and receptor factors were evaluated in Real-Time PCR. Confocal microscopy (CM) and flow cytometry (FACS) were used to measure AP-N surface expression. Result(s): FACS and CM confirmed intense surface expression of AP-N on HMVEC-L. HCoV-229E efficiently infected HMVEC-L (604 945,5 +/-194 930,2 viral copies/mul) in 48h cultures (MOI 0,1) and induced relatively late (between 72- 96h) mRNA expression of RANTES (1181,12);IL-6 (89,6);IFN-beta (53,7);OAS-1 (64,3);PKR (11,4) and TLR-3 (42,4). Increased mRNA expression was also accompanied by protein release to the supernatants. Conclusion(s): HCoV-229E may efficiently infect HMVEC-L and induce delayed inflammatory and anti-viral response.
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Cardiovascular disease (CVD) is the sixth mos common human disease that causes about 17.3 million deaths yearly Advancement in nanomedicine enables the usage of nanomaterials fo treating cardiac disorders. Among these, Cerium Oxide (CeO2 nanoparticle is gaining attention due to their irreversible oxidativ states (Ce3+ and Ce4+), which provide them with many unique physiologically important traits like antioxidant property, Anti inflammatory property, free radicle scavenging potential etc. All thes features make CeO2 an excellent agent for treating many cardia related disorders. We have used the search engines PubMed an Google scholar to identify the relevant papers in last 5 years on thi topic. Some old classical articles were also identified, and the review was written based on these relevant papers. Cerium nanoparticle (CeNPs) are being used in the therapy of CVD mainly for reducin oxidative stress, inflammation, and damage caused by free radicals CeO2 can also protect endothelial cells (ECs) from apoptosis. It can b used as a wound-healing agent during cardiac surgeries. This i because of its potential to enhance endothelialization. In this article we reviewed various applications of CeO2 in the field of CVD.Copyright © 2023 Society of Pharmaceutical Sciences and Research. All rights reserved.