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Objective To explore the potential common mechanism and active ingredients of Reduning Injection against SARS, MERS and COVID-19 through network pharmacology and molecular docking technology. Methods The TCMSP database was used to retrieve the chemical components and targets of Artemisiae Annuae Herba, Lonicerae Japonicae Flos and Gardeniae Fructus in Reduning Injection. The gene corresponding to the target was searched by UniProt database, and Cytoscape 3.8.2 was used to build a medicinal material-compound-target (gene) network. Three coronavirus-related targets were collected in the Gene Cards database with the key words of "SARS""MERS" and "COVID-19", and common target of three coronavirus infection diseases were screened out through Venny 2.1.0 database. The common targets of SARS, MERS and COVID-19 were intersected with the targets of Reduning Injection, and the common targets were selected as research targets. Protein-protein interaction (PPI) network map were constructed by Cytoscape3.8.2 software after importing the common targets into the STRING database to obtain data. R language was used to carry out GO biological function enrichment analysis and KEGG signaling pathway enrichment analysis, histograms and bubble charts were drew, and component-target-pathway network diagrams was constructed. The key compounds in the component-target-pathway network were selected for molecular docking with important target proteins, novel coronavirus (SARS-CoV-2) 3CL hydrolase, and angiotensin-converting enzyme II (ACE2). Results 31 active compounds and 207 corresponding targets were obtained from Reduning Injection. 2 453 SARS-related targets, 805 MERS-related targets, 2 571 COVID-19-related targets, and 786 targets for the three diseases. 11 common targets with Reduning Injection: HSPA5, CRP, MAPK1, HMOX1, TGFB1, HSP90AA1, TP53, DPP4, CXCL10, PLAT, PRKACA. GO function enrichment analysis revealed 995 biological processes (BP), 71 molecular functions (MF), and 31 cellular components (CC). KEGG pathway enrichment analysis screened 99 signal pathways (P < 0.05), mainly related to prostate cancer, fluid shear stress and atherosclerosis, hepatocellular carcinoma, proteoglycans in cancer, lipid and atherosclerosis, human T-cell leukemia virus 1 infection, MAPK signaling pathway, etc. The molecular docking results showed that the three core active flavonoids of quercetin, luteolin, and kaempferol in Reduning Injection had good affinity with key targets MAPK1, PRKACA, and HSP90AA1, and the combination of the three active compounds with SARS-CoV-2 3CL hydrolase and ACE2 was less than the recommended chemical drugs. Conclusion Reduning Injection has potential common effects on the three diseases of SARS, MERS and COVID-19. This effect may be related to those active compounds such as quercetin, luteolin, and kaempferol acting on targets such as MAPK1, PRKACA, HSP90AA1 to regulate multiple signal pathways and exert anti-virus, suppression of inflammatory storm, and regulation of immune function.Copyright © 2022 Drug Evaluation Research. All rights reserved.
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Objective: Immunohistochemistry of post-mortem lung tissue from Covid-19 patients with diffuse alveolar damage demonstrated marked increases in chondroitin sulfate and CHST15 and decline in N-acetylgalactosamine-4-sulfatase. Studies were undertaken to identify the mechanisms involved in these effects. Method(s): Human primary small airway epithelial cells (PCS 301-010;ATCC) were cultured and exposed to the SARSCoV- 2 spike protein receptor binding domain (SPRBD;AA: Lys310-Leu560;Amsbio). Expression of the spike protein receptor, angiotensin converting enzyme 2 (ACE2), was enhanced by treatment with Interferon-beta. Promoter activation, DNA-binding, RNA silencing, QPCR, Western blots, ELISAs, and specific enzyme inhibitors were used to elucidate the underlying molecular mechanisms. Result(s): Treatment of the cultured cells by the SPRBD led to increased CHST15 and CHST11 expression and decline in ARSB expression. Sulfotransferase activity, total chondroitin sulfate, and sulfated glycosaminoglycan (GAG) content were increased. Phospho-T180/T182-p38-MAPK and phospho- S423/S425-Smad3 were required for the activation of the CHST15 and CHST11 promoters. Inhibition by SB203580, a phospho-p38 MAPK inhibitor, and by SIS3, a Smad3 inhibitor, blocked the CHST15 and CHST11 promoter activation. SB203580 reversed the SPRBD-induced decline in ARSB expression, but SIS3 had no effect on ARSB expression or promoter activation. Phospho-p38 MAPK was shown to reduce retinoblastoma protein (RB) S807/S811 phosphorylation and increase RB S249/T252 phosphorylation. E2F-DNA binding declined following exposure to SPRBD, and SB203580 reversed this effect. This indicates a mechanism by which SPRBD, phospho-p38 MAPK, E2F, and RB can regulate ARSB expression and thereby impact on chondroitin 4-sulfate and dermatan sulfate and molecules that bind to these sulfated GAGs, including Interleukin-8, bone morphogenetic protein-4, galectin-3 and SHP-2 (Src homology region 2-containing protein tyrosine phosphatase 2). Conclusion(s): The enzyme ARSB is required for the degradation of chondroitin 4-sulfate and dermatan sulfate, and accumulation of these sulfated GAGs can contribute to lung pathophysiology, as evident in Covid-19. Some effects of the SPRBD may be attributable to unopposed Angiotensin II, when Ang1-7 counter effects are diminished due to binding of ACE2 with the SARS-CoV-2 spike protein and reduced production of Ang1-7. Aberrant cell signaling and activation of the phospho-p38 MAPK and Smad3 pathways increase CHST15 and CHST11 production, which can contribute to increased chondroitin sulfate in infected cells. Decline in ARSB may occur as a consequence of effects of phospho-p38 MAPK on RB phosphorylation and E2F1 availability. Decline in ARSB and the resulting impaired degradation of sulfated GAGs have profound consequences on cellular metabolic, signaling, and transcriptional events. Funding is VA Merit Award.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
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Background: Aging and binge alcohol abuse are both known as independent risk factors for both atrial and ventricular arrhythmias. With the COVID-19 pandemic, increased social isolation has significantly increased alcohol consumption worldwide. Older adults are a high-risk drinking group and alcohol significantly enhances the risk of arrhythmia onset. Yet, how alcohol (a secondary stressor) drives spontaneous atrial and ventricular arrhythmia onset in the aged heart (a primary stressor) remains unclear. Objective(s): We recently reported the stress-response kinase c-jun N-terminal kinase 2 (JNK2) underlies alcohol-enhanced atrial arrhythmia vulnerability (pacing-induced) in healthy young hearts. Here, we reveal a critical role of JNK2 in alcohol-driven arrhythmia onset in the aged heart in vivo. Method(s): Ambulatory ECGs were recorded using wireless telemeters in binge alcohol-exposed aged (24 months) and young mice (2 months). Spontaneous premature atrial and ventricular contractions (PACs, PVCs), atrial and ventricular tachycardia (AT, VT) were quantified as previously described. The role of JNK2 in triggered arrhythmic activities was assessed using a well-evaluated JNK2-specific inhibitor and our unique cardiac-specific MKK7D and MKK7D-JNK2dn mouse models with tamoxifen inducible overexpression of constitutively active MKK7 (a JNK upstream activator) or co-expression of MKK7D and inactive dominant negative JNK2 (JNK2dn). Result(s): We found that binge alcohol exposure in aged mice (n=14) led to spontaneous PACs/PVCs (75% of the mice), and AT/VT episodes (50%) along with a 21% mortality rate. However, alcohol-exposed young (n=5) and non-alcohol-exposed aged mice (n=11) were absent of any spontaneous arrhythmic activities or premature death. Intriguingly, JNK2-specific inhibition in vivo abolished those alcohol-associated triggered activities and mortality in aged mice. The causative role of JNK2 in triggered arrhythmias and premature death was further supported by the high frequency of spontaneous PACs/PVCs and nonsustained AT/VT episodes along with a 50% mortality rate in MKK7D mice (n=10), which was strikingly alleviated in MKK7D-JNK2dn mice (n=5) with cardiac-specific JNK2 competitive inhibition. Conclusion(s): Our findings are the first to reveal that stress kinase JNK2 underlies binge alcohol-evoked atrial and ventricular arrhythmia initiation in aged mice. Modulating JNK2 could be a novel therapeutic strategy to treat and/or prevent binge drinking-evoked cardiac arrhythmias.Copyright © 2023
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Coronavirus-induced disease-19 (COVID-19), caused by SARS-CoV-2, is still a major global health challenge. Human endogenous retroviruses (HERVs) represent retroviral elements that were integrated into the ancestral human genome. HERVs are important in embryonic development as well as in the manifestation of diseases, including cancer, inflammation, and viral infections. Here, we analyze the expression of several HERVs in SARS-CoV-2-infected cells and observe increased activity of HERV-E, HERV-V, HERV-FRD, HERV-MER34, HERV-W, and HERV-K-HML2. In contrast, the HERV-R envelope is downregulated in cell-based models and PBMCs of COVID-19 patients. Overexpression of HERV-R inhibits SARS-CoV-2 replication, suggesting its antiviral activity. Further analyses demonstrate the role of the extracellular signal-regulated kinase (ERK) in regulating HERV-R antiviral activity. Lastly, our data indicate that the crosstalk between ERK and p38 MAPK controls the synthesis of the HERV-R envelope protein, which in turn modulates SARS-CoV-2 replication. These findings suggest the role of the HERV-R envelope as a prosurvival host factor against SARS-CoV-2 and illustrate a possible advantage of integration and evolutionary maintenance of retroviral elements in the human genome.Copyright © 2023 The Authors.
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Background: Viral infections pose some of the most serious human health concerns worldwide. The infections caused by several viruses, including coronavirus, hepatitis virus, and human immunodeficiency virus, are difficult to treat. Method(s): This review details the findings of a literature search performed on the antiviral properties of luteolin. The keywords engaged in the search are "virus" along with "luteolin." Results: Luteolin possesses antiviral properties, which is the basis for the current review. It is an important natural flavonoid with numerous important biological properties, including anti-inflammatory, immune regulatory, and antitumor effects, and is found in vegetables, fruits, and several medicinal plants. Recent studies have revealed that many traditional Chinese medicines that contain luteolin inhibit the replication of coronaviruses. Conclusion(s): Luteolin effectively inhibits the replication of coronavirus, influenza virus, enterovirus, rotavirus, herpes virus, and respiratory syncytial virus, among others. In particular, it prevents viral infection by improving the body's nonspecific immunity and antioxidation capacity and inhibiting many pathways related to virus infection and replication, such as MAPK, PI3K-AKT, TLR4/8, NF-kappaB, Nrf-2/hemeoxygenase-1, and others. It also regulates the expression of some receptors and factors, including hepatocyte nuclear factor 4alpha, p53, NLRP3, TNF-alpha, and interleukins, thereby interfering with the replication of viruses in cells. Luteolin also promotes the repair of damaged cells induced by proinflammatory factors by regulating the expression of inflammatory molecules. The overall effect of these processes is the reduction in viral replication and, consequently, the viral load. This review summarizes the antiviral effect of luteolin and the mechanism underlying this property.Copyright © The Author(s) 2023.
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Objective: Pneumonia is an infectious inflammation of the alveoli,distal airway,and interstitium caused by bacterial,viral,and other pathogens. Maxing Shigantang,originated from Treatise On Cold Damage Diseases,is a classic prescription for treating pneumonia,with significant clinical efficacy. However,its treatment mechanism is still elusive. Method(s): In that paper,the transcriptome-based multi-scale network pharmacology was used to reveal the overall pharmacological mechanism of Maxing Shigantang in treating pneumonia from six scales of tissue,cell,pathological process,biological process,signaling pathway, and target. Result(s):At the tissue level,Maxing Shigantang mainly acted on the focal tissue of pneumonia-lung and the main inflammatory immune tissues-blood and spleen. Analysis of cell,pathological process and biological process suggested that Maxing Shigantang could treat pneumonia by reversing inflammatory and immune functions and improving cardiopulmonary and vascular injury caused by pneumonia. Analysis of signaling pathway and target showed that Maxing Shigantang regulated inflammatory immune response pathways such as "coronavirus disease-COVID-19" and "Toll-like receptor signaling pathway",and related targets such as "MAPKAPK3" and "NRG1". Conclusion(s):This paper,from molecular to tissue levels,indicated Maxing Shigantang treated pneumonia mainly by regulating inflammatory immune response and improving cardiopulmonary and vascular injury.Copyright © 2023, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.
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Obesity is associated with several diseases, including mental health. Adipose tissue is distributed around the internal organs, acting in the regulation of metabolism by storing and releasing fatty acids and adipokine in the tissues. Excessive nutritional intake results in hypertrophy and proliferation of adipocytes, leading to local hypoxia in adipose tissue and changes in these adipokine releases. This leads to the recruitment of immune cells to adipose tissue and the release of pro-inflammatory cytokines. The presence of high levels of free fatty acids and inflammatory molecules interfere with intracellular insulin signaling, which can generate a neuroinflammatory process. In this review, we provide an up-to-date discussion of how excessive obesity can lead to possible cognitive dysfunction. We also address the idea that obesity-associated systemic inflammation leads to neuroinflammation in the brain, particularly the hypothalamus and hippocampus, and that this is partially responsible for these negative cognitive outcomes. In addition, we discuss some clinical models and animal studies for obesity and clarify the mechanism of action of anti-obesity drugs in the central nervous system.Copyright © 2023 Wolters Kluwer Medknow Publications. All rights reserved.
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The proceedings contain 63 papers. The topics discussed include: doxorubicin cardiotoxicity in human organotypic cardiac slices is modulated by P38 MAPK inhibition in a sex- and isoform-specific manner;validation of a modified response evaluation criteria in solid tumors after stereotactic ablative radiosurgery for lung cancer;safer use of aspirin in older adults, need for a consensus;efficacy of facemasks in prevention of COVID-19: a systematic review;practice patterns of rapid influenza diagnostic test;equity and inclusion in patient centered outcomes research: lessons from the adaptable study at Montefiore site;a solution to decrease potentially inappropriate medications (PIM) use during hospitalization;predictors of misperceptions, risk perceptions, and personal risk perceptions about COVID-19 by country, education and income;cognitive function and the consumption of probiotic foods in older adults: an NHANES study;and registered dietitian nutritionist care impacts nutrition-related outcomes for patients with cancer in the outpatient setting.
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COVID-19 has been found to affect the expression profile of several mRNAs and miRNAs, leading to dysregulation of a number of signaling pathways, particularly those related to inflammatory responses. In the current study, a systematic biology procedure was used for the analysis of high-throughput expression data from blood specimens of COVID-19 and healthy individuals. Differentially expressed miRNAs in blood specimens of COVID-19 vs. healthy specimens were then identified to construct and analyze miRNA-mRNA networks and predict key miRNAs and genes in inflammatory pathways. Our results showed that 171 miRNAs were expressed as outliers in box plot and located in the critical areas according to our statistical analysis. Among them, 8 miRNAs, namely miR-1275, miR-4429, miR-4489, miR-6721-5p, miR-5010-5p, miR-7110-5p, miR-6804-5p and miR-6881-3p were found to affect expression of key genes in NF-KB, JAK/STAT and MAPK signaling pathways implicated in COVID-19 pathogenesis. In addition, our results predicted that 25 genes involved in above-mentioned inflammatory pathways were targeted not only by these 8 miRNAs but also by other obtained miRNAs (163 miRNAs). The results of the current in silico study represent candidate targets for further studies in COVID-19.Copyright © 2023 Elsevier B.V.
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Mitogen-activated protein kinase (MAPK) cascades are crucial in extracellular signal transduction to cellular responses. The classical three-tiered MAPK cascades include signaling through MAP kinase kinase kinase (MAP3K) that activates a MAP kinase kinase (MAP2K), which in turn induces MAPK activation and downstream cellular responses. The upstream activators of MAP3K are often small guanosine-5'-triphosphate (GTP)-binding proteins, but in some pathways, MAP3K can be activated by another kinase, which is known as a MAP kinase kinase kinase kinase (MAP4K). MAP4K4 is one of the widely studied MAP4K members, known to play a significant role in inflammatory, cardiovascular, and malignant diseases. The MAP4K4 signal transduction plays an essential role in cell proliferation, transformation, invasiveness, adhesiveness, inflammation, stress responses, and cell migration. Overexpression of MAP4K4 is frequently reported in many cancers, including glioblastoma, colon, prostate, and pancreatic cancers. Besides its mainstay pro-survival role in various malignancies, MAP4K4 has been implicated in cancer-associated cachexia. In the present review, we discuss the functional role of MAP4K4 in malignant/non-malignant diseases and cancer-associated cachexia and its possible use in targeted therapy.
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2019-novel coronavirus (2019-nCoV) is a highly pathogenic human CoV that first emerged in Wuhan in 2019. 2019-nCoV has a zoonotic origin and poses a major threat to public health. However, little is known about the viral factors contributing to the high virulence of 2019-nCoV. Many animal viruses, including CoVs, encode proteins that interfere with host gene expression, including those involved in antiviral immune responses, and these viral proteins are often major virulence factors. Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory infection. In the past 17 years, the onset of 2019-nCoV, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans. The recent study of HCoVs-host interactions has contributed extensively to our understanding of infection pathogenesis of 2019-nCoV. This review discuss various host physiopathologic mechanism, such as apoptosis, innate immunity, endoplasmic reticulum (ER) stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-kappaB) pathway that may be modulated by HCoVs and provides evidence for the intensive investigate of 2019-nCoV infection.Copyright © 2020 by the Chinese Medical Association.
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Metabolic associated fatty liver disease (MAFLD) is a chronic liver disease with the highest incidence in the world, which affects 1/4-1/3 of the world population and has a serious effect on people's health. As is a multi-systemic disease, MAFLD is closely related to the occurrence and prognosis of many diseases. Studies have shown that MAFLD is associated with viral infectious diseases, and their interaction affects the prognosis of the disease. This paper reviews the research progress in this field in recent years.Copyright © The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
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Objective: To explore the mechanism of Xiyanping injection in the treatment of human coronavirus infection based on network pharmacology and molecular docking method. Methods: The active components and targets of Xiyanping injection were screened by CNKI, SwissTarget Prediction and Targetnet. The Human Gene Database (Genecards), Online Human Mendelian Inheritance Database (OMIM) and Therapeutic Target Database (TTD) were searched to predict disease targets. Venny 2.1.0, Cytoscape 3.8.2 and STRING11.5 were used to construct "drug target-disease target Venn diagram", "drug-active ingredient-target-disease network" and "protein interaction network". The Database for Annotation, Visualization and Integrated Discovery (DAVID) and Bioinformatics, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for the enrichment analysis and visualization. Finally, molecular docking was performed by AutoDock Vina and PyMOL. Results: The active ingredient of Xiyanping injection was andrographolide, andrographolide had 140 targets, 1 812 potential targets of human coronavirus infection, and 35 common targets of Xiyanping and human coronavirus infection;PPI network analysis and molecular docking showed that MAPK9, MAPK8, TYK2, CDKI and interleukin (IL)-6 among the 35 common targets might be the key targets of Xiyanping injection in the treatment of human coronavirus infection. Lactone was tightly bound;enrichment analysis showed that key targets were closely related to protein phosphorylation, cell signal transduction, and gene expression regulation, and key targets were NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, FOXO signaling pathway, there was also an important link in the TNF signaling pathway. Conclusion: The active ingredient of Xiyanping injection was andmgrapholide, and its treatment of human coronavirus infection might affect NOD-like receptor signaling pathway, Toll-like receptor signaling pathway and FOXO signaling by inhibiting the activities of MAPK9, MAPK8, TYK2, CDK1 and IL-6. The activation of the pathway and the TNF signaling pathway regulates protein phosphorylation, cell signal transduction and gene expression, thereby exerting anti-inflammatory effects.
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Objective: COVID19 is associated with vascular inflammation. IFN-alpha (IFNa) and IFN-lambda3 (IFNl3) are potent cytokines produced in viral infections. Their effects involve interferon-stimulated genes (ISGs) and may influence expression of angiotensin-converting enzyme 2 (ACE2), the receptor for S-protein (S1P) of SARS-CoV-2. We hypothesized that S1P-induced immune/inflammatory responses in endothelial cells (EC) are mediated via IFN-activated pathways Design and methods: Human ECs were stimulated with S1P (1 mg/mL), IFNa (100ng/mL) or IFNl3 (100IU/mL). Because ACE2, ADAM17 and TMPRSS2 are important for SARS-CoV-2 infection, we used inhibitors of ADAM17 (marimastat, 3.8 nM), ACE2 (MLN4760, 440pM), and TMPRSS2 (camostat, 50 mM). Gene and protein expression was investigated by real-time PCR and immunoblotting, respectively. Vascular function was assessed in mesenteric arteries from wild-type (WT) normotensive and hypertensive (LinA3) mice and in ISG15-deficient (ISG15KO) mice. Results: S1P increased expression of IFNa (3-fold), IFNl3 (4-fold) and ISGs (2-fold) in EC (p < 0.05). EC responses to IFNa (ISG15: 16-fold) were greater than to IFNl3 (ISG15: 1.7-fold) (p < 0.05). S1P increased gene expression of IL-6 (1.3-fold), TNFa (6.2-fold) and IL-1b (3.3-fold), effects that were amplified by IFNs. Only the ADAM17 inhibitor marimastat inhibited S1P effects. IFNa and IFNl3 increase protein expression of ADAM17 (27%) and TMPRSS2 (38%). No changes were observed on ACE2 expression. This was associated with increased phosphorylation of Stat1 (134%), Stat2 (102%), ERK1/2 (42%). EC production of IL-6 was increased by IFNa (1,230pg/mL) and IFNl3 (1,124pg/mL) vs control (591pg/mL). Nitric oxide generation and eNOS phosphorylation (Ser1177) were reduced by IFNa (40%) and IFNl3 (40%). Vascular functional responses demonstrated that endothelium-dependent vasorelaxation (% Emax) in vessels from WT-mice stimulated with IFNa (67%) and IFNl3 (71%) were reduced vs control (82%) (p < 0.05). Responses were not altered in vessels from ISG15KO mice. Increased contraction was observed only in vessels from hypertensive mice treated with IFNa (9.1 ± 0.5mN vs control: 7.3 ± 0.3mN) (p < 0.05). Conclusions: In ECs, S1P, IFNa and IFNl3 increased ISG15 and IL-6 by mechanisms dependent on ADAM17. IFNs amplifies endothelial cell inflammatory responses and induced vascular dysfunction through ISG15-dependent mechanisms, with augmented effects in hypertension. Our findings demonstrate that S1P induces immune/inflammatory responses that may be important in endotheliitis associated with COVID-19. This may be especially important in the presence of cardiovascular risk factors, including hypertension.
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Background: Acute respiratory distress syndrome (ARDS) is a distinctive feature of severe COVID-19 infections that occurs mainly in patients with coexisting health problems, such as hypertension, atherosclerosis, and diabetes. Endothelial dysfunction is a major contributing factor during ARDS development in COVID- 19 patients with pre-existing comorbidities. Objective: Studying the mechanism by which endothelial activation and dysfunction could provide a therapeutic target for COVID-19 treatment. Design and method: The current study measured endothelial dysfunction and oxidative stress by incubating human umbilical vein endothelial cells (HUVECs) with plasma from patients with mild, moderate, severe and extremely severe COVID- 19. Using flow cytometry, wound-healing assays and phosphokinase arrays, Results: We detected increases in cell apoptosis;reactive oxygen species (ROS) formation;hypoxia-inducible factor-1 alpha (HIF-1 alpha), vascular cell adhesion molecule-1 (VCAM-1), and vascular endothelial growth factor receptor-1 (VEGFR-1) expression;viral entry;and inflammatory-related protein activity. We also found an impairment in the wound-healing process. Moreover, we found that AT1R blockade and P38 MAPK inhibition reversed all of these effects, especially in the severe group. Conclusions: These findings indicate that AT1R/P38 MAPK-mediated oxidative stress and endothelial dysfunction occur during COVID-19 infection.
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Background: Glycine is an endogenous, non-essential, simple amino acid produced in the human body. A 1.5% solution is commonly used for irrigation in gynecologic and urologic procedures as it is a sterile, clear, non-irritating liquid. It is neutral, mildly acidic and nonpyrogenic, and as it is produced by the human body it does not cause allergic reactions. If an excessive amount is absorbed during a procedure it can result in electrolyte abnormalities, such as hyponatremia or hypocalcemia. It can also result in transient vision disturbances, changes in heart rate, hypotension, hyperammonemia, or encephalopathy. Glycine has been used as a diluent in certain inhaled therapies for COVID-19 infections, such as epoprostenol. We describe a case where a 1.5% glycine solution was inadvertently used for humidified oxygen via high flow nasal cannula as opposed to distilled water. Case report: The patient was a 70-year-old male who was admitted to the hospital for hypoxia related to a COVID-19 infection with O2 saturations in the 70-80% range. He was placed on high flow nasal cannula to improve his oxygen levels. During his inpatient stay it was discovered that a 3-L bag of 1.5% glycine solution had been connected to the high flow nasal cannula instead of distilled water. This ran from Friday evening to the following Monday morning before the error was discovered. There was only 100mL of the glycine solution remaining in the bag when it was found. The patient continued to do well and had no new complaints during his stay. The case was called to the regional poison center which recommended monitoring electrolytes, watching for any possible respiratory symptoms and continuing supportive care. Initial lab work on admission showed a chemistry panel of Na 146, K 3.6, Cl 102, CO2 25.3, BUN 9, Cr 0.70, Glucose 106, Ca 9.3. Repeat lab work immediately after the mistake was found showed: Na 137, K 4.8 Cl 100, CO2 28, BUN 15, Cr 0.70, Glucose 129, Ca 9.0. On recommendations from poison control, electrolytes were monitored with repeat lab work 10 h after discontinuation of the glycine solution, showing: Na 135, K 4.3, Cl 97, CO2 26.8, Glucose 175, Ca 9.2. The patient did not develop any new complaints, had no reported altered mental status, epistaxis, nasal irritation or other symptoms related to the inhalation. He was eventually discharged home on oxygen for his persistent hypoxia related to his COVID-19 lung infection. Discussion(s): This case demonstrates that prolonged continuous inhalational exposure to a 1.5% glycine irrigation solution does not result in any mucosal irritation, metabolic or systemic toxic reactions, even though its pH is reportedly between 4.5 and 6.5. Thus, glycine solutions up to this concentration appear to be safely tolerated for its increasing use as an excipient for aerosolized medications. Conclusion(s): We describe a case where 1.5% glycine solution was inadvertently used in place of distilled water for humidified oxygen via high flow nasal cannula for approximately 3 days in a patient being treated for COVID-19 related pneumonia with no notable adverse effects.
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Objective To explore the application pattern and mechanism of medicine and food homologous traditional Chinese medicine (TCM) against modern viral diseases. Methods The method of literature mining was applied based on the characteristics of modern viral diseases, combining with ancient books and modern prescriptions for the prevention and treatment of viral diseases to build a relevant prescription database. Then SPSS and R language were used to analyze the high-frequency medicine and food homologous TCM and high confidence medicine and food homologous prescriptions in these prescriptions, and cluster analysis was carried out. The antiviral characteristic active ingredients of high-frequency medicinal and food homologous TCN were identified and analyzed, and the action mechanism of active ingredients against modern viral diseases was evaluate by network pharmacology. Results In the prevention and treatment of modern viral diseases, Gancao (Glycyrrhizae Radix et Rhizoma)-Chenpi (Citri Reticulatae Pericarpium)-Fuling (Poria) had the highest confidence, Glycyrrhizae Radix et Rhizoma-Jiegeng (Platycodonis Radix) had the highest support. At the same time, the prescriptions were clustered and analyzed to obtain Jinyinhua (Lonicerae Japonicae Flos)-Huangqi (Astragali Radix)-Huoxiang (Agastache rugosa), Glycyrrhizae Radix et Rhizoma-Xingren (Armeniacae Semen Amarum)-Poria-Platycodonis Radix-Citri Reticulatae Pericarpium, Ganjiang (Zingiberis Rhizoma)-Renshen (Ginseng Radix et Rhizoma), Zisu (Perilla frutescens)-Gegen (Puerariae Lobatae Radix), Lugen (Phragmitis Rhizoma)-Sangye (Mori Folium), Shengjiang (Zingiberis Rhizoma Recens)-Dazao (Jujubae Fructus) clustering new prescription. The core action targets of EGFR, CASP3, VEGFA, STAT3, MMP9, HSP90AA1, mTOR, PTGS2, MMP2, TLR4, MAPK14, etc were identified. The action mechanism involved human cytomegalovirus infection, coronavirus disease-coronavirus disease 2019 (COVID-19), etc. The core action pathway were phosphatidylinositol-3/kinase protein kinase B (PI3K/Akt) signal pathway, mitogen activated protein kinase (MAPK) signal pathway, interleukin-17 (IL-17) signal pathway, Janus kinase/signal transducer and activator of transcription (JAK/STAT) signal pathway, etc. Conclusion Through data mining, six new prescriptions for preventing and controlling modern viral diseases were obtained, and the mechanism of action was preliminarily discussed, which provided some reference for the research and development of medicine and food homologous TCM prescriptions for the prevention and treatment of viral epidemics and related health products.
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Donepezil hydrochloride is an acetylcholine esterase inhibitor studied and approved to treat Alzheimer’s disease (AD). However, this drug can have positive therapeutic potential in treating different conditions, including various neurodegenerative disorders such as other types of dementia, multiple sclerosis, Parkinson’s disease, psychiatric and mood disorders, and even infectious diseases. Hence, this study reviewed the therapeutic potential of this drug in treating Alzheimer’s and other diseases by reviewing the articles from databases including Web of Science, Scopus, PubMed, Cochrane, and Science Direct. It was shown that donepezil could affect the pathophysiology of these diseases via mechanisms such as increasing the concentration of acetylcholine, modulating local and systemic inflammatory processes, affecting acetylcholine receptors like nicotinic and muscarinic receptors, and activating various cellular signaling via receptors like sigma-1 receptors. Despite many therapeutic potentials, this drug has not yet been approved for treating non-Alzheimer’s diseases, and more comprehensive studies are needed.
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Purpose: The field of osteoarthritis (OA) biology is rapidly evolving and brilliant progress has been made this year as well. Methods: Landmark studies of OA biology published in 2021 and early 2022 were selected through PubMed searches and classified by their molecular mechanisms, and it was largely divided into the intra-cellular mechanisms and the inter-compartment or inter-cellular interaction in OA progression. Results: The intra-cellular mechanisms involving OA progression included 1) Piezo1/TRPV4-mediated calcium signaling, 2) low grade inflammation by TLR-CD14-LBP complex and IKKβ-NFkB signaling, 3) PGRN/TNFR2/14-3-3ε/Elk-1 anabolic cascade, 4) G protein-coupled receptor (GPCR) signaling, 5) mechanical loading-cilia/Ift88-hedgehog signaling, 6) mitochondrial fission by ERK1/2-DRP1 pathway, and 7) hypoxia-DOT1L-H3K79 methylation pathway. The studies on inter-compartment or inter-cellular interaction in OA progression included the following subjects: 1) the anabolic role of Lubricin, a proteoglycan from superficial zone cells, 2) osteoclast-chondrocyte interaction via exosomal miRNA and sphingosine 1-phosphate (S1P), 3) αV integrin-mediated TGFβ activation by mechanical loading, 4) TGFβ-mediated suppression of sclerostin in osteocytes, 5) catabolic role of Flightless I as a DAMPs-triggering molecule, and 6) catabolic role of paracrine signaling from fat. Conclusions: Despite the disastrous Covid-19 pandemic situation, many outstanding studies have expanded the boundary of OA biology. They give us not only critical insight on pathophysiology, but also clue for the treatment of OA.
ABSTRACT
Clinical Information Patient Initials or Identifier Number: Mr. AL Relevant Clinical History and Physical Exam: 59-year-old gentleman. CAD risk factors: Hypertension, Diabetes Mellitus, Dyslipidaemia, Positive family history of CAD. Admitted with Acute Anterior MI & got Tenecteplase. Relevant Test Results Prior to Catheterization: Troponin-I: >50000 ng/L, ECG: ST Elevation in V1-V6, Echo: Anterior wall is hypokinetic with Mild LV systolic dysfunction (EF- 45%). Hb-14.2 gm/dl, Creatinine: 1.12 mg/dl, Na- 135, K- 4.0, Cl- 100 m mol/L, Plasma BNP: 235 pg/ml, COVID-19 RT-PCR- Negative, S. Bilirubin- 0.3 mg/dl, ALT- 45 IU/L, AST- 107 IU/L, Anti-HCV- Negative, Anti-HIV- Negative, HbsAg- Negative, Relevant Catheterization Findings: LMCA: Normal. LAD: Got 90-99% narrowing in its proximal segment followed by 90-99% diffuse disease. DG1 is small and diseased. DG2 has got sub-total occlusion at its origin. LCX: Good size artery with mild ostial narrowing & 50% narrowing in its mid segment. Principal OM has got 50% narrowing in its ostium. RCA: Dominant artery has got 60% narrowing in its proximal segment. PDA is a good size artery & got mild irregular narrowing in its proximal segment. Recommendation: PCI to LAD [Formula presented] [Formula presented] [Formula presented] Interventional Management Procedural Step: LCA was engaged with guiding catheter EBU -3.5 (6F). Sion Blue wire crossed the lesion of LAD, another wire crossed the lesion of Diagonal branch and pre-dilatation was done with 2.0 x 15 mm balloon at 08-10 ATM. Proximal lesion was stented with a 2.75 mm x 18 mm stent (Xience Alpine) at 12-14 ATM. After withdrawing the wire following angiogram showed proximal LAD was well dilated but mid LAD having a long dissection which interrupted the distal flow. So, decided to put stent in mid LAD. Again, repeated ballooning was done in mid LAD to prepare the lesion and a 2.25 mm x 28 mm stent (Xience Xpedition) was taken for mid LAD but stent didn't cross the mid LAD lesion. During stent withdrawal, it was struck in the previous Proximal stent and proximal calcified segment. When trying to pull it back, the delivery system shaft was tear off. Tried to get the shaft by coronary snare but failed to get it back. Finally, he was recommended to retrieve the torn delivery system & stent surgically. [Formula presented] [Formula presented] [Formula presented] Conclusions: • Stent with torn delivery system entrapment might not be rare. • In this situation, emergency decision to tackle the situation and Bail out decision to send the patient for surgical retrieval of the delivery system & stent saved the life of the patient. Take Home Message: • No case is simple in intervention. • Preparedness to tackle any untoward consequence is the key to success and save lives.