scholarly journals The growth factor/cytokine midkine may participate in cytokine storm and contribute to the pathogenesis of severe acute respiratory syndrome coronavirus 2-infected patients

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Sema Ketenci ◽  
A. Şükrü Aynacıoğlu
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Inflammatory Diseases ◽  
Treatment Protocol ◽  
Inflammatory Cells ◽  
Clinical Situation ◽  
Main Body ◽  
Cytokine Storm ◽  
Global Challenge ◽  
Hypoxic Conditions ◽  
Cytokine Levels

Abstract Background The current coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged in Wuhan, China, and has rapidly become a global challenge, creating major challenges to health systems in almost every country in the world it has turned into a pandemic. COVID-19 poses a risky clinical situation that can range from mild illness to severe respiratory failure, requiring admission to intensive care. Main body It is known that SARS-CoV-2 infection causes a cytokine storm in some critically ill patients. However, more and more evidence showed that there is a dramatic increase in cytokine levels in patients diagnosed with COVID-19. Midkine (MK) is involved in various physiological and pathological processes, which some of them are desired and beneficial such as controlling tissue repair and antimicrobial effects, but some others are harmful such as promoting inflammation, carcinogenesis, and chemoresistance. Also, MK is expressed in inflammatory cells and released by endothelial cells under hypoxic conditions. Conclusions Considering all this information, there are strong data that midkine, an important cytokine known to increase in inflammatory diseases, may be overexpressed in patients who are positive for COVID-19. The overexpression of MK reveals a picture leading to fibrosis and damage in the lung. Therefore, questions arise about how the expression  of  MK  changes in COVID-19 patients and can we use it as an inflammation biomarker or in the treatment protocol in the future.

scholarly journals The growth factor/ cytokine midkine may participate to cytokine storm and contribute to the pathogenesis of SARS-CoV-2 infected patients

2021 ◽  
Author(s):  
Sema Ketenci ◽  
Şükrü Aynacıoğlu
Keyword(s):  
Tissue Repair ◽  
Inflammatory Diseases ◽  
Treatment Protocol ◽  
Inflammatory Cells ◽  
Clinical Situation ◽  
Lung Damage ◽  
Cytokine Storm ◽  
Hypoxic Conditions ◽  
Cytokine Levels ◽  
Important Cytokine

The current coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged in Wuhan, China and has rapidly become global challenges, creating major challenges to health systems in almost every country in the world it has turned into a pandemic. COVID-19 poses a risky clinical situation that can range from mild illness to severe respiratory failure requiring admission to intensive care. It is known to cause cytokine storm in some critically ill patients. However, more and more evidence showed that there is a dramatic increase in cytokine levels in patients diagnosed with COVID-19. Midkine (MK) is involved in various physiological and pathological processes, which some of them are desired and beneficial such as controlling tissue repair and antimicrobial effects, but some others are harmful such as promoting inflammation, carcinogenesis and chemo-resistance. Also, MK is expressed in inflammatory cells and released by endothelial cells under hypoxic conditions. Considering all this information, there are strong data that MK, an important cytokine known to increase in inflammatory diseases, may overexpressed in patients who are positive for COVID-19. The overexpression of MK reveals a picture leading to fibrosis in the lung damage. Therefore, questions arise about how the concentration of MK changes in CoVID-19 patients and can we use it as an inflammation biomarker or in the treatment protocol in the future.

scholarly journals Cavidine protects against asthma in neonatal asthmatic mice model by attenuating PI3Ks/NF-κB signaling pathway

2021 ◽  
Vol 18 (3) ◽  
pp. 513-518
Author(s):  
Qin Hao ◽  
Juan Shen ◽  
Lin Zhao
Keyword(s):  
Signaling Pathway ◽  
Treatment Protocol ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Specific Ige ◽  
Mice Model ◽  
Altered Expression ◽  
Neonatal Mice ◽  
Cytokine Levels ◽  
Asthmatic Group

Purpose: To evaluate the protective effect of cavidine against asthma in neonatal mice. Methods: Neonatal mice were treated with cavidine at doses of 5 and 10 mg/kg, po, 2 h prior to asthma induction with ovalbumin (OVA) on the 1st and 14th days of the treatment protocol. The anti-asthma activity of cavidine was evaluated by determining the number of inflammatory cells and cytokine levels in broncho-alveolar lavage fluid (BALF) and OVA-specific IgE and TGF-β 1 in the serum of OVAsensitized mice. The levels of NF-ƙB and PI3K protein expression were determined in the lung tissues of OVA-sensitized mice. Results: Cavidine attenuated the number of inflammatory cells and cytokines in BALF of OVAsensitized mice. The levels of OVA-specific IgE and TGF-β 1 decreased significantly in cavidine-treated groups, when compared to asthmatic group of mice, while NF-ƙB was significantly downregulated (p < 0.01). The altered expression of PI3K signaling protein was attenuated in the lung tissues of cavidinetreated mice sensitized with OVA. Conclusion: These results reveal that the anti-asthma effect of cavidine in OVA-induced asthmatic neonatal mice occurs via reduction of inflammation and immune responsive cells linked to PI3Ks/ NF-κB signaling pathway in lung tissues. These findings suggest that cavidine may be clinically suitable for the management of asthma.

scholarly journals May Medium Cut-Off Dialysis Membranes Have Impact on Outcome of COVID-19 Hemodialysis Patients?

2020 ◽  
Author(s):  
SERKAN FEYYAZ YALIN ◽  
AHMET MURT ◽  
MEVLUT TAMER DINCER ◽  
ERGUN PARMAKSIZ ◽  
SERAP YADIGAR ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Inflammatory Cytokines ◽  
Medical Records ◽  
Kidney Diseases ◽  
Hemodialysis Patients ◽  
Cytokine Storm ◽  
Radiologic Findings ◽  
Middle Molecules ◽  
Cytokine Levels ◽  
Dialysis Membranes

Abstract Purpose: Severe acute respiratory syndrome coronavirus 2 which is a novel type of coronavirus, may lead to high levels of expression of inflammatory cytokines. Medium cut-off membranes may make greater clearances for large-middle molecules (including cytokines) than low flux membranes. In this study, we aimed to evaluate impact of type of hemodialysis membranes on outcome of COVID 19+ hemodialysis patients.Methods: Forty nine COVID 19 + hemodialysis patients were included into study. The patients were categorized into two groups regarding type of hemodialysis membranes. Clinical data, etiologies of kidney diseases, comorbidities, laboratory and radiologic findings, antiviral, anti-cytokine treatments, and hemodialysis data were taken from medical records. Results: Medium cut-off membranes were used in 15 patients and low flux membranes were used in 34 patients. There were significantly more patients with comorbidities in medium cut-off group compare to low flux group (p=0,014). CRP and ferritin which are each surragates of cytokine storm in COVID-19, were significantly higher in medium cut-off membrane group compare to low flux group (p=0,00, 0,01, respectively).Conclusion: It may be an option to use medium cut-off membranes in hemodialysis patients with COVID 19 in order to reduce cytokine levels and prevent cytokine storm.

scholarly journals Ethnobotanical, phytochemistry, and pharmacological property of Waltheria Indica Linn

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
C Nirmala ◽  
M Sridevi
Keyword(s):  
Inflammatory Diseases ◽  
Biological Activities ◽  
Perennial Herb ◽  
Main Body ◽  
Biological Targets ◽  
Traditional Uses ◽  
Whole Plant ◽  
Anti Cancer ◽  
Microbial Infections ◽  
Anti Fungal

Abstract Background In modern therapeutics, various human pathological disturbances were treated with the plant-based products. Waltheria indica Linn, a perennial herb, was commonly used in traditional medicine worldwide against various ailments such as cough, dysentery, diarrhea, bladder disorder, hemoptysis, inflammations, neuralgia, wounds, and ulcers. Main body The shrub was majorly distributed in tropical, subtropical regions and exists in many distinct local forms. Both the crude extracts and purified compounds from the whole plant and its parts showed wide pharmacological properties like antioxidant, analgesic, sedative, anti-bacterial, anti-fungal, and anti-parasitic. The phytochemical profile and traditional usage highlight the potency of the plant in the treatment of microbial infections and inflammatory diseases. Yet, additional studies are required for the confirmations of its traditional uses against other diseases. More detailed understanding of anti-cataract, anti-diabetics, asthma, anemia, and anti-cancer mechanism has to be explored. Though many research articles on the proposed plant are available, there has been a rising concern in the therapeutic property, especially on the alkaloids and flavonoids from this plant for drug design. Conclusion This article aims in a systematic and updated review on distribution, botany, traditional uses, phytocompounds, and relevant biological activities from each part of the plant. The information was collected from databases like PubMed, ScienceDirect, Web of Science, Google Scholar, books, dissertation, and reports via academic libraries that included more than 100 articles published since 1937. This ethnopharmacological study of the plant may create new insight into drug discovery to develop important novel leads against various biological targets.

scholarly journals LGK974 suppresses lipopolysaccharide-induced endotoxemia in mice by modulating the crosstalk between the Wnt/β-catenin and NF-κB pathways

2021 ◽  
Vol 53 (3) ◽  
pp. 407-421
Author(s):  
Jaewoong Jang ◽  
Jaewon Song ◽  
Hyunji Lee ◽  
Inae Sim ◽  
Young V. Kwon ◽  
...  
Keyword(s):  
Animal Model ◽  
Survival Rate ◽  
Wnt Pathway ◽  
Cytokine Production ◽  
Cytokine Storm ◽  
Plasma Cytokine ◽  
Gram Negative ◽  
Multiple Organs ◽  
Expression Of Genes ◽  
Cytokine Levels

AbstractEndotoxemia, a type of sepsis caused by gram-negative bacterial endotoxin [i.e., lipopolysaccharide (LPS)], is associated with manifestations such as cytokine storm; failure of multiple organs, including the liver; and a high mortality rate. We investigated the effect and mechanism of action of LGK974, a Wnt signaling inhibitor, in mice with LPS-induced endotoxemia, an animal model of sepsis. LGK974 significantly and dose-dependently increased the survival rate and reduced plasma cytokine levels in mice with LPS-induced endotoxemia. Transcriptome analysis of liver tissues revealed significant changes in the expression of genes associated with the Wnt pathway as well as cytokine and NF-κB signaling during endotoxemia. LGK974 treatment suppressed the activation of NF-κB signaling and cytokine expression as well as the Wnt/β-catenin pathway in the livers of endotoxemic mice. Coimmunoprecipitation of phospho-IκB and β-transducin repeat-containing protein (β-TrCP) was increased in the livers of endotoxemic mice but was reduced by LGK974 treatment. Moreover, LGK974 treatment decreased the coimmunoprecipitation and colocalization of β-catenin and NF-κB, which were elevated in the livers of endotoxemic mice. Our results reveal crosstalk between the Wnt/β-catenin and NF-κB pathways via interactions between β-TrCP and phospho-IκB and between β-catenin and NF-κB during endotoxemia. The results of this study strongly suggest that the crosstalk between the Wnt/β-catenin and NF-κB pathways contributes to the mutual activation of these two pathways during endotoxemia, which results in amplified cytokine production, liver damage and death, and that LGK974 suppresses this vicious amplification cycle by reducing the crosstalk between these two pathways.

High cytokine levels and cytokine storm in the novel coronavirus infection

2021 ◽  
pp. 38-47
Author(s):  
Maksim Leonidovich Maksimov ◽  
Albina Ayratovna Zvegintseva ◽  
Lyudmila Yurievna Kulagina ◽  
Albina Zainutdinovna Nigmedzyanova ◽  
Elvina Ramisovna Kadyseva
Keyword(s):  
Peripheral Blood ◽  
High Frequency ◽  
The Novel ◽  
Cytokine Storm ◽  
The Public ◽  
Systemic Inflammatory Reaction ◽  
Scientific World ◽  
Cytokine Levels ◽  
Coronavirus Infection ◽  
Novel Coronavirus

A review article is based on current foreign sources. The level of cytokines in the peripheral blood can be increased in many diseases, but in some cases there may be an excess of their normal concentration in tens, hundreds or more times with the development of a peculiar clinical picture, which is based on a systemic inflammatory reaction. In the literature this condition has received the figurative name «cytokine storm», which highlights an extremely violent reaction of the immune system with an unknown (often unfavorable) outcome. Close attention of the scientific world and the public to the problem of extremely high levels of cytokines in the peripheral blood (hypercytokinemia) was drawn due to the high frequency of the cytokine storm in the novel coronavirus infection.

In Support of Initial Parenteral Medical Management of Intrathecal Baclofen Withdrawal in Spasticity Patients

2021 ◽  
pp. 875512252110392
Author(s):  
Brian L. LaRowe ◽  
Vicki M. Nussbaum
Keyword(s):  
Case Reports ◽  
Treatment Plan ◽  
Correct Diagnosis ◽  
Treatment Protocol ◽  
Patient Characteristics ◽  
Clinical Problem ◽  
Clinical Situation ◽  
Intrathecal Baclofen ◽  
Wide Range ◽  
Baclofen Withdrawal

Background: Spasticity may present as a wide range of symptoms and conditions. With this protean presentation, a consensus regarding the best course of treatment does not exist. Those patients most severely affected may receive significant benefit from intrathecal baclofen delivery. However, this therapy may itself lead to patient injury in the event of withdrawal. Objective: Withdrawal from intrathecal baclofen may devolve rapidly into a situation in which the patient may incur significant morbidity and even death. A focused, prompt treatment plan would afford the patient the best possible outcome. Methods: The medical literature was reviewed for reports of plans of treatment of baclofen withdrawal and the results obtained. The nature of this problem does not lend itself to a typical study design, depending on case reports and basic pharmacological science application. The paucity of such reports severely limits categorical comparison of patient characteristics and clinical circumstances. Clinical situations, patient characteristics, and therapies were considered and compared. Outcomes of the varied treatments were evaluated for efficacy. Results: Inaccurate diagnoses, delayed correct diagnoses, and the absence of a consistent, treatment plan contributed to widely disparate outcomes. Prompt, correct diagnosis and intensive care unit–based continuous benzodiazepine infusion with titration led to a controlled clinical situation and maximized patient outcomes. Conclusions: Patients going through withdrawal from intrathecal baclofen achieved best outcomes when treated with a continuous infusion and titration of an intravenous benzodiazepine. A well-defined treatment protocol employing this management, reporting serial outcomes, would enable further refinement of the treatment of this clinical problem.

scholarly journals Adventitial Alterations Are the Main Features in Pulmonary Artery Remodeling due to Long-Term Chronic Intermittent Hypobaric Hypoxia in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Julio Brito ◽  
Patricia Siques ◽  
Silvia M. Arribas ◽  
Angel L. López de Pablo ◽  
M. Carmen González ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Right Ventricle ◽  
Inflammatory Cells ◽  
Cell Number ◽  
Hypoxic Conditions ◽  
Artery Remodeling ◽  
Medial Hypertrophy ◽  
The Right ◽  
Pulmonary Artery Remodeling

Long-term chronic intermittent exposure to altitude hypoxia is a labor phenomenon requiring further research. Using a rat model, we examined whether this type of exposure differed from chronic exposure in terms of pulmonary artery remodeling and other features. Rats were subjected to chronic hypoxia (CH,n=9) and long-term intermittent hypoxia (CIH2x2; 2 days of hypoxia/2 days of normoxia,n=10) in a chamber (428 Torr, 4,600 m of altitude) for 46 days and compared to rats under normoxia (NX,n=10). Body weight, hematocrit, and right ventricle ratio were measured. Pulmonary artery remodeling was assessed using confocal microscopy of tissues stained with a nuclear dye (DAPI) and CD11b antibody. Both hypoxic conditions exhibited increased hematocrit and hypertrophy of the right ventricle, tunica adventitia, and tunica media, with no changes in lumen size. The medial hypertrophy area (larger in CH) depicted a significant increase in smooth muscle cell number. Additionally, CIH2x2 increased the adventitial hypertrophy area, with an increased cellularity and a larger prevalence of clustered inflammatory cells. In conclusion, CIH2x2 elicits milder effects on pulmonary artery medial layer muscularization and subsequent right ventricular hypertrophy than CH. However, CIH2x2 induces greater and characteristic alterations of the adventitial layer.

scholarly journals Costimulation of TLR8 responses by CXCL4 in Human Monocytes Mediated by TBK1-IRF5 Signaling and Epigenomic Remodeling

2021 ◽  
Author(s):  
Lionel B. Ivashkiv ◽  
Chao Yang ◽  
Mahesh Bachu ◽  
Caroline Brauner ◽  
Ruoxi Yuan ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Immune Cells ◽  
De Novo ◽  
Inflammatory Diseases ◽  
Human Monocytes ◽  
Cytokine Storm ◽  
New Paradigm ◽  
Inflammatory Genes ◽  
Synergistic Activation ◽  
Fibrotic Diseases

Abstract CXCL4 regulates responses of immune cells to endosomal TLRs and has been implicated in the pathogenesis of inflammatory and fibrotic diseases. However, mechanisms by which CXCL4 modulates TLR responses, and its functions in monocytes/macrophages, are still unclear. Here we report that CXCL4 changes the profile of the TLR8 response in human monocytes by selectively and dramatically amplifying inflammatory gene transcription and IL-1β production while partially attenuating the IFN response. Mechanistically, costimulation by CXCL4 and TLR8 synergistically activated TBK1/IKKε and repurposed these kinases towards an inflammatory response via coupling with IRF5, and by activating the NLRP3 inflammasome without the need for a second signal. CXCL4 strongly induced chromatin remodeling in a cooperative and synergistic manner with TLR8 signaling, inducing de novo enhancers associated with inflammatory genes. These findings identify signaling and epigenomic mechanisms that underly synergistic activation of inflammatory genes by CXCL4 and TLR8, provide a new paradigm for modulation of TLR responses that is relevant for cytokine storm, and suggest targeting the TBK1/IKKε-IRF5 axis may be beneficial in inflammatory diseases.

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