scholarly journals Abnormal upregulation of cardiovascular disease biomarker PLA2G7 induced by proinflammatory macrophages in COVID-19 patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yang Li ◽  
Yongzhong Jiang ◽  
Yi Zhang ◽  
Naizhe Li ◽  
Qiangling Yin ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Normal Limit ◽  
Genomic Analysis ◽  
High Rate ◽  
Hub Gene ◽  
Viral Loads ◽  
Protein Levels ◽  
Nasal Swabs ◽  
Positive Rate ◽  
Validation Stage

AbstractHigh rate of cardiovascular disease (CVD) has been reported among patients with coronavirus disease 2019 (COVID-19). Importantly, CVD, as one of the comorbidities, could also increase the risks of the severity of COVID-19. Here we identified phospholipase A2 group VII (PLA2G7), a well-studied CVD biomarker, as a hub gene in COVID-19 though an integrated hypothesis-free genomic analysis on nasal swabs (n = 486) from patients with COVID-19. PLA2G7 was further found to be predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, RNA level of PLA2G7 was identified in nasal swabs from both COVID-19 and pneumonia patients, other than health individuals. The positive rate of PLA2G7 were correlated with not only viral loads but also severity of pneumonia in non-COVID-19 patients. Serum protein levels of PLA2G7 were found to be elevated and beyond the normal limit in COVID-19 patients, especially among those re-positive patients. We identified and validated PLA2G7, a biomarker for CVD, was abnormally enhanced in COVID-19 at both nucleotide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in patients with COVID-19. PLA2G7 could be a potential prognostic and therapeutic target in COVID-19.

scholarly journals Abnormal Upregulation of Cardiovascular Disease Biomarker PLA2G7 Induced by Proinflammatory Macrophages in COVID-19 patients

2020 ◽  
Author(s):  
Yang LI ◽  
Yongzhong JIANG ◽  
Yi ZHANG ◽  
Naizhe LI ◽  
Qiangling YIN ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Influenza Infection ◽  
Severe Pneumonia ◽  
H1n1 Influenza ◽  
Tissue Type ◽  
Cross Sectional ◽  
Viral Loads ◽  
Protein Levels ◽  
Biomarker Analysis ◽  
Nasal Swabs

BACKGROUND. Coronavirus disease 2019 (COVID-19) triggers distinct patterns of pneumonia progression with multiorgan disease, calling for cell- and/or tissue-type specific host injury markers. METHODS. An integrated hypothesis-free single biomarker analysis framework was performed on nasal swabs (n=484) from patients with COVID-19 in GSE152075. The origin of candidate biomarker was assessed in single-cell RNA data (GSE145926). The candidate biomarker was validated in a cross-sectional cohort (n=564) at both nucletide and protein levels. RESULTS. Phospholipase A2 group VII (PLA2G7) was identified as a candidate biomarker in COVID-19. PLA2G7 was predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, PLA2G7 was found in patients with COVID-19 and pneumonia, especially in severe pneumonia, rather than patients suffered mild H1N1 influenza infection. The positive rates of PLA2G7 ranging from 29.37% to 100.00% were positively correlated with not only viral loads in patients with COVID-19 but also severity of pneumonia in non COVID-19 patients. Although Ct values of PLA2G7 in severe pneumonia was siginificantly lower than that in moderate pneumonia (P=7.2e-11), no differences were observed in moderate pneumonia with COVID-19 between severe pneumonia without COVID-19 (P=0.81). Serum protein levels of PLA2G7, also known as lipoprotein-associated phospholipase A2 (Lp-PLA2), were further found to be elevated and beyond the upper limit of normal in patients with COVID-19, especially among the re-positive patients. CONCLUSIONS. We firstly identified and validated PLA2G7, a biomarker for cardiovascular diseases (CVDs), was abnormally enhanced in COVID-19 patients at both nucletide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in COVID-19 patients. PLA2G7 could be a hallmark of COVID-19 for monitoring disease progress and therapeutic response.

scholarly journals Author Correction: Individual variations in cardiovascular-disease-related protein levels are driven by genetics and gut microbiome

2018 ◽  
Vol 50 (12) ◽  
pp. 1752-1752
Author(s):  
Daria V. Zhernakova ◽  
◽  
Trang H. Le ◽  
Alexander Kurilshikov ◽  
Biljana Atanasovska ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Gut Microbiome ◽  
Related Protein ◽  
Protein Levels ◽  
Individual Variations

scholarly journals Growth and feed utilization of Boer x Kacang crossbred goats offered total mixed rations of different protein and energy levels

2018 ◽  
Vol 22 (4) ◽  
pp. 188
Author(s):  
Simon P. Ginting ◽  
Kiston Simanihuruk ◽  
Antonius Antonius ◽  
Andi Tarigan
Keyword(s):  
Energy Density ◽  
Protein Level ◽  
Crude Protein ◽  
Energy Levels ◽  
Dietary Treatment ◽  
Feed Utilization ◽  
Metabolizable Energy ◽  
High Rate ◽  
Protein Levels ◽  
Crude Protein Level

The aim of this study was to evaluate the growth of and feed utilization by Boer x Kacang crosses goats fed on total mixed ration differing in protein and energy levels. Four total mixed rations combination were formulated to contain 16 and 18% crude protein and 2650 and 2850 Kcal ME/ kg DM (dried matter) energy density. Twenty-eight male Boer x Kacang crosses goats (14.5 ± 1.14 kg) and of age ranging from 4 to 5 months were randomly allocated to one of these four TMRs (total mixed rations) (7 animals/TMR). The effects of dietary treatment were assessed using the general linear model and significance of the diet effects was detected using Duncan’s multiple range test. Dry matter intake increased as metabolizable energy density of diet increased from 2650 to 2850 Kcal/kg DM, but it is not affected by increasing crude protein level from 16 to 18%. The average daily gains were not improved (P>0.05) as the crude protein levels and metabolizable energy density of diet increased. Crude protein levels and ME density did not affect (P>0.05) the DM, OM and energy digestibility, but NDF digestibility was affected by the ME density of diets (P<0.05). Daily N intakes were greater (P<0.0%) in goats received diets higher in the crude protein and metabolizable energy levels. At this high rate of feed intake this type of goats are able to gain optimally when offered feed with crude protein level of 16% and metabolizable energy density of 2850 Kcal/kg DM.

scholarly journals Ten Representative Saponins on Tissue Factor Expression in Human Monocytes: Structure–Activity Relationships and Molecular Docking

2020 ◽  
Vol 15 (3) ◽  
pp. 1934578X2091368
Author(s):  
Yongjiang Zeng ◽  
Xuhua He ◽  
Wenwen Jiang ◽  
Junping Kou ◽  
Boyang Yu
Keyword(s):  
Cardiovascular Disease ◽  
Molecular Docking ◽  
Tissue Factor ◽  
Inhibitory Effect ◽  
Coagulation Cascade ◽  
Human Monocytes ◽  
Messenger Ribonucleic Acid ◽  
Structure Activity Relationships ◽  
Protein Levels ◽  
Structure Activity

Saponins have significant bioactivities in treating cardiovascular disease. Whereas there is a lack of in-depth knowledge about how saponins prevent cardiovascular disease. Tissue factor (TF) is the major initiator of the coagulation cascade and plays an important role in hemostasis and thrombosis. However structure–activity relationships (SARs) of saponins inhibiting TF activity have not been discussed in detail at present. To further clarify the relationships between saponins and TF, in this study, 10 representative saponins were selected to study the inhibitory effect on TF procoagulant activity of monocytes by an improved chromogenic substrate method, and the possible SARs were preliminarily analyzed. Furthermore, molecular docking analysis suggested that 4 representative saponins had a good affinity with TF/FVIIa. In addition, a representative saponin, ruscogenin, decreased both messenger ribonucleic acid and protein levels of TF in human monocytes partly due to its downregulation of nuclear factor kappa-light-chain-enhancer of activated B cells and c-Jun N-terminal kinase pathways. In conclusion, this study provides further explanation for the cardiovascular protection of saponins, and the analysis of SARs between inhibiting TF activity and saponins will be helpful to explore the therapeutic TF inhibitors.

scholarly journals Dynamic Structural Modeling Revealed That Nilotinib Inhibits Smoothened Signaling

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Kirti Kandhwal Chahal ◽  
Jie Li ◽  
Irina Kufareva ◽  
Donald Durden ◽  
Robert Wechsler Reya ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Computational Modeling ◽  
Kinase Inhibitor ◽  
Acquired Resistance ◽  
Protein Docking ◽  
High Rate ◽  
Protein Levels ◽  
Matching Criteria

Abstract INTRODUCTION Dysregulation of the 7-transmembrane receptors Smoothened (SMO) and other components of the Hedgehog (Hh) signaling pathway causes several cancers, including medulloblastoma (MB) and glioblastoma. However, SMO-specific antagonists produced mixed results in clinical trials, marked by a limited efficacy and a high rate of acquired resistance in tumors. METHODS Computational modeling of protein docking sites, analytical configuration modeling of crystallographic data, and in Vitro and in Vivo xenograft experiments. RESULTS Using computational modeling of SMO structure, we discovered that Nilotinib, an FDA-approved receptor tyrosine kinase inhibitor, directly binds to SMO. Furthermore, Nilotinib was more efficacious than the SMO-specific antagonist Vismodegib in inhibiting cell growth and Gli-1 mRNA and protein levels in Hh-dependent MB cells and glioblastoma cells. It also reduced tumor growth in the Hh-dependent MB and glioblastoma mouse xenograft models. These results indicate that in addition to its ability to inhibit several tyrosine kinase-mediated proliferative pathways, Nilotinib is active against the Hh pathway. CONCLUSION The newly discovered extension of Nilotinib target profile holds promise for the treatment of Hh-dependent cancers. It also calls for comprehensive characterization of pharmacology for other drugs and incorporation of their multitarget profiles into drug-disease matching criteria for personalized medicine.

scholarly journals Dysfunction of the β2-spectrin-based pathway in human heart failure

2016 ◽  
Vol 310 (11) ◽  
pp. H1583-H1591 ◽  
Author(s):  
Sakima A. Smith ◽  
Langston D. Hughes ◽  
Crystal F. Kline ◽  
Amber N. Kempton ◽  
Lisa E. Dorn ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Left Ventricle ◽  
Small Animal ◽  
Left Ventricular ◽  
Effector Proteins ◽  
Human Heart Failure ◽  
Protein Levels ◽  
Ankyrin B

β2-Spectrin is critical for integrating membrane and cytoskeletal domains in excitable and nonexcitable cells. The role of β2-spectrin for vertebrate function is illustrated by dysfunction of β2-spectrin-based pathways in disease. Recently, defects in β2-spectrin association with protein partner ankyrin-B were identified in congenital forms of human arrhythmia. However, the role of β2-spectrin in common forms of acquired heart failure and arrhythmia is unknown. We report that β2-spectrin protein levels are significantly altered in human cardiovascular disease as well as in large and small animal cardiovascular disease models. Specifically, β2-spectrin levels were decreased in atrial samples of patients with atrial fibrillation compared with tissue from patients in sinus rhythm. Furthermore, compared with left ventricular samples from nonfailing hearts, β2-spectrin levels were significantly decreased in left ventricle of ischemic- and nonischemic heart failure patients. Left ventricle samples of canine and murine heart failure models confirm reduced β2-spectrin protein levels. Mechanistically, we identify that β2-spectrin levels are tightly regulated by posttranslational mechanisms, namely Ca2+- and calpain-dependent proteases. Furthermore, consistent with this data, we observed Ca2+- and calpain-dependent loss of β2-spectrin downstream effector proteins, including ankyrin-B in heart. In summary, our findings illustrate that β2-spectrin and downstream molecules are regulated in multiple forms of cardiovascular disease via Ca2+- and calpain-dependent proteolysis.

scholarly journals Effect of Magnesium Supplementation on Circulating Biomarkers of Cardiovascular Disease

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1697
Author(s):  
Alvaro Alonso ◽  
Lin Y. Chen ◽  
Kyle D. Rudser ◽  
Faye L. Norby ◽  
Mary R. Rooney ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Serum Magnesium ◽  
Interleukin 1 ◽  
Multiple Comparisons ◽  
Tartrate Resistant Acid Phosphatase ◽  
Magnesium Supplementation ◽  
Double Blind ◽  
Baseline Serum ◽  
Protein Levels ◽  
Oral Magnesium

(1) Background: Magnesium supplementation may be effective for the prevention of cardiometabolic diseases, but the mechanisms are unclear. Proteomic approaches can assist in identifying the underlying mechanisms. (2) Methods: We collected repeated blood samples from 52 individuals enrolled in a double-blind trial which randomized participants 1:1 to oral magnesium supplementation (400 mg magnesium/day in the form of magnesium oxide) or a matching placebo for 10 weeks. Plasma levels of 91 proteins were measured at baseline with follow-up samples using the Olink Cardiovascular Disease III proximity extension assay panel and were modeled as arbitrary units in a log2 scale. We evaluated the effect of oral magnesium supplementation for changes in protein levels and the baseline association between serum magnesium and protein levels. The Holm procedure was used to adjust for multiple comparisons. (3) Results: Participants were 73% women, 94% white, and had a mean age of 62. Changes in proteins did not significantly differ between the two intervention groups after correction for multiple comparisons. The most statistically significant effects were on myoglobin [difference −0.319 log2 units, 95% confidence interval (CI) (−0.550, −0.088), p = 0.008], tartrate-resistant acid phosphatase type 5 (−0.187, (−0.328, −0.045), p = 0.011), tumor necrosis factor ligand superfamily member 13B (−0.181, (−0.332, −0.031), p = 0.019), ST2 protein (−0.198, (−0.363, −0.032), p = 0.020), and interleukin-1 receptor type 1 (−0.144, (−0.273, −0.015), p = 0.029). Similarly, none of the associations of baseline serum magnesium with protein levels were significant after correction for multiple comparisons. (4) Conclusions: Although we did not identify statistically significant effects of oral magnesium supplementation in this relatively small study, this study demonstrates the value of proteomic approaches for the investigation of mechanisms underlying the beneficial effects of magnesium supplementation. Clinical Trials Registration: ClinicalTrials.gov NCT02837328.

scholarly journals Genomic analysis of coxsackieviruses A1, A19, A22, enteroviruses 113 and 104: viruses representing two clades with distinct tropism within enterovirus C

2013 ◽  
Vol 94 (9) ◽  
pp. 1995-2004 ◽  
Author(s):  
Rafal Tokarz ◽  
Saddef Haq ◽  
Stephen Sameroff ◽  
Stephen R. C. Howie ◽  
W. Ian Lipkin
Keyword(s):  
Phylogenetic Analysis ◽  
Sequence Analysis ◽  
Genomic Analysis ◽  
The Other ◽  
High Rate ◽  
Structural Genes ◽  
Genome Sequences ◽  
Capsid Region ◽  
High Degree ◽  
Degree Of Similarity

Coxsackieviruses (CV) A1, CV-A19 and CV-A22 have historically comprised a distinct phylogenetic clade within Enterovirus (EV) C. Several novel serotypes that are genetically similar to these three viruses have been recently discovered and characterized. Here, we report the coding sequence analysis of two genotypes of a previously uncharacterized serotype EV-C113 from Bangladesh and demonstrate that it is most similar to CV-A22 and EV-C116 within the capsid region. We sequenced novel genotypes of CV-A1, CV-A19 and CV-A22 from Bangladesh and observed a high rate of recombination within this group. We also report genomic analysis of the rarely reported EV-C104 circulating in the Gambia in 2009. All available EV-C104 sequences displayed a high degree of similarity within the structural genes but formed two clusters within the non-structural genes. One cluster included the recently reported EV-C117, suggesting an ancestral recombination between these two serotypes. Phylogenetic analysis of all available complete genome sequences indicated the existence of two subgroups within this distinct Enterovirus C clade: one has been exclusively recovered from gastrointestinal samples, while the other cluster has been implicated in respiratory disease.

scholarly journals Survival curve identifies critical period for postoperative mortality in cardiac patients undergoing emergency general surgery

2020 ◽  
Author(s):  
Diego Martines ◽  
Fernanda Nii ◽  
Kayo Medeiros ◽  
Barbara Carvalho ◽  
Leonardo Pipek ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Survival Curve ◽  
Postoperative Mortality ◽  
Acute Mesenteric Ischemia ◽  
Cardiac Surgical Procedures ◽  
Clinical Severity ◽  
High Rate ◽  
Postoperative Phase ◽  
Emergency General Surgery ◽  
Cardiovascular Comorbidity

Abstract Introduction: The number of non-cardiac major surgeries carried out has significantly increased in recent years to around 200 million procedures carried out annually. Approximately 30% of patients submitted to non-cardiac surgery present some form of cardiovascular comorbidity. In emergency situations, with less surgery planning time and greater clinical severity, the risks become even more significant. The aim of this study is to determine the incidence and clinical outcomes in patients with cardiovascular disease submitted to non-cardiac surgical procedures in a single cardiovascular referral center. Methods: This is a prospective cohort study of patients with cardiovascular disease submitted to non-cardiovascular surgery. All procedures were carried out by the same surgeon, between January 2006 and January 2018. Results: 240 patients included were elderly, 154 were male (64%), 8 patients presented two diagnoses. Of the resulting 248 procedures carried out, 230 were emergency (92.8%). From the data obtained it was possible to estimate the day from which the occurrence of mortality is less probable in the postoperative phase. Conclusion: Our research evaluated the epidemiological profile of the surgeries and we were able to estimate the survival and delimit the period of greatest risk of mortality in these patients. The high rate of acute mesenteric ischemia was notable, a serious and frequently fatal condition.

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