ABSTRACT
Background: Coronavirus disease 2019 (COVID-19) individuals with varied severity group are affected by the cytokine storm brought on by SARS-CoV2 infection, which is a significant cause of acute respiratory distress syndrome. Objective: The goal of the current study was to examine tumor necrosis factor (TNF-α) gene expression in COVID-19 at various severity levels. Materials and Methods: The study includes 140 divided into 105 COVID-19-positive patients (35 for each mild, moderate, and severe group) and 35 COVID-19-negative healthy people as control. COVID-19 positive patients had 46 males and 59 females, while COVID-19-negative healthy people included 16 males and 19 females. The separation of peripheral blood mononuclear cells (PBMC) was achieved using Ficoll, and then Ribonucleic acid was extracted and converted to cDNA and the gene expression using glyceraldehyde-3-phosphate dehydrogenase as the housekeeping gene. Results: The results revealed non-significant differences at P < 0.05 in age among different COVID-19 groups and control (F-ratio value is 0.54257 and P-value is 0.65397). The results revealed over-expression of TNF-α gene among COVID-19 patients and the relative quantification (fold change) (mean ± standard deviation) values were 6.542 ± 7.29, 5.740 ± 6.41, 7.306 ± 8.85, and 6.580 ± 6.47 for all, mild, moderate, and severe COVID-19 patients, respectively. One-way analysis of variance test relative quantification (fold change) TNF-α (mean ± standard deviation) for mild, moderate, and severe groups revealed non-significant at P < 0.05, the F-ratio value is 0.39889 and the P-value is 0.672109. Conclusion: The present study concludes upregulation of TNF-α gene in PBMC of COVID-19-positive patients without significant differences among different severity groups. © 2023 Medical Journal of Babylon ;Published by Wolters Kluwer - Medknow.
ABSTRACT
Introduction: The preferred treatment for COVID-19 cases is Convalescent Plasma. In COVID-19 patients, cytokine storms are caused by high levels of cytokines including: Inflammatory cytokines such as (IL-10, IL-12, IL-27, IL-21, TNF-α and IFN-γ, IL-2, and IL-6), are triggered by T cell responses. The goal of this research is to determine Does administration of convalescent plasma affect the TNF-α and IFN-γ cases of COVID-19 sufferers. Materials and methods: The experimental research method uses (a post-test only control group design). The study material in the form of serum from the blood of COVID-19 patients as many as 38 samples selected randomly with details of COVID-19 patients as many as 19 samples were not given convalescent plasma treatment and 19 samples of COVID-19 patients receiving convalescent plasma therapy. Results: This study showed that there was no effect on TNF-α levels before and after convalescent plasma administration (P> 0.05), while IFN-γ levels showed an effect between before and after convalescent plasma administration (P< 0.05). Conclusion: Although in this study there were differences in the results of statistical analysis of TNF-α and IFN-γ levels in convalescent plasma treatment of COVID-19 patients, this study proved to be able to improve the clinical condition of COVID-19 cases. © 2023 UPM Press. All rights reserved.
ABSTRACT
In spite of various and extensive studies known for pyrazolo[1,5-a]pyrimidines the synthesis, in silico studies and biological evaluation of their 5-(het)aryl analogs remained underexplored. The TNF-α inhibitors on the other hand has considerable therapeutic potential for autoimmune and inflammatory diseases in addition to cancer, diabetes and possibly COVID-19. In the current study 5-aryl pyrazolo[1,5-a]pyrimidines were explored as potential inhibitors of TNF-α that was supported by the in silico studies. This class of compounds was accessed via a sonochemical synthesis involving the acid catalyzed cyclocondensation reaction of aminopyrazoles with acrylophenones in the presence of aerial oxygen. The study indicated that the overall rate of the reaction was enhanced by ultrasound in the absence of which a longer duration and higher temperature was necessary. The current catalyst/promoter/ligand free and scalable method afforded a range of compounds. Some of these compounds showed good inhibition of TNF-α in vitro where ester/amide moiety at the C-3 position played a key role in interacting with the protein dimer as suggested by the in silico studies. Indeed, these groups formed H-bonds with A: GLY121 and B: TYR151 residues of TNF-α dimer in silico. A brief SAR within the series and in silico ADME/toxicity prediction for best active compounds is presented. Compounds 3a-c were identified as initial hits for further pharmacological evaluations. A sonochemical method has been developed for the facile synthesis of pyrazolo[1,5-a]pyrimidines that were evaluated as potential inhibitors of TNF-α. [ABSTRACT FROM AUTHOR] Copyright of Polycyclic Aromatic Compounds is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
ABSTRACT
Background: Coronavirus Disease 2019 (COVID-19) is an easily contagious disease, and not much is known about the characteristics of COVID-19, both in terms of susceptibility, severity, and spreadability of various SARS-CoV-2 strains. Patient genomic factors, especially related to genomic polymorphisms that affect the body's immune system, can influence the course of infectious diseases. The aim of this study is to get an adequate picture regarding gene polymorphisms, both susceptibility and related to the clinical degree in COVID-19 patients. Methods: The PCR preparations were carried out in the Biomedical laboratory of the Faculty of Medicine, Universitas Sebelas Maret. The qualitative PCR (qPCR) examination was sent to the Genetica Science laboratory, Tangerang, West Java. The research subjects were divided into 3 groups, namely COVID-19 patients with no symptoms, COVID-19 patients with mild-moderate symptoms, COVID-19 patients with severe-critical symptoms. The research subjects were taken 6 cc of venous blood (3 cc for examination of serum IL-6 and TNFα levels and 3 cc for DNA examination). Results: Serum levels of IL-6 and TNF-α in the clinical grade group were almost all above normal values. The frequency of TNF-α polymorphisms (-376G/A) all showed homozygote GG. TNF-α (-308G/A) also showed homozygote GG was dominant for SARS CoV2. IL-6 (-572G/C) polymorphism for cases requiring medium and severe clinical degree hospitalization was found to have more C allele than G allele. IL-6 polymorphism (intron A/G) the G allele is less common in cases requiring hospitalization. Conclusion: TNF-α(−308A) allele has an influence on the development of clinical symptoms of SARS CoV2 infection. The rs1800796GG genotype in the IL-6 promoter contributes to milder symptoms in SARS CoV2 infection. Allelic variants of the gene under study may show different effects in other races depending on their interactions with other risk factors. © 2022, Sanglah General Hospital. All rights reserved.
ABSTRACT
It is well established that HCQ has anti-inflammatory and immunosuppressive, but it has stopped as treatment for Covid-19 because it affect increase heart rhythm. So this research aimed to demonstrate the effect of HCQ treatment on concentrations of plasma TNF-α and IL-6 in mice and its relationship with glucocorticoids level which could explain the arrhythmias. In this research, 30 adult male Balb/C mice were used. The mice aged 2-3months were divided into 3groups;one treated with high-dosage of HCQ (8.1mg/kg body-weight, twice for 10days);second with low-dosage (6.4mg/kg body-weight, twice on one day and once on other 4days);and third was left without treatment to be serve as a control group. At different points time, the mice were sacrificed by cervical distraction. A blood sample is taken from the eye and the serum is separated to determine cortisol level by cobas e411 analyzers. Brain, spleen, and kidney were taken and homogenized. Aliquot and serum were be used to determine TNF-α and IL-6 level by sandwich ELISA using murine IL-6 and TNF-α kits (Melsin/China). The results showed a significantly lower cortisol, IL-6, and TNF-α level in serum and tissues of both treated groups compared to control. The reduction of cytokines are believed to inhibit the HPA axis resulting in decrease glucocorticoids level which could be good prove of the interplay between immune and endocrine systems. So it is very important to check cortisol level during HCQ treatment and it is preferred to use a combined treatment between HCQ and glucocorticoid. © 2022 American Institute of Physics Inc.. All rights reserved.
ABSTRACT
SARS CoV-2 gets over more than four million people all over the world. The challenges for developing vaccines in overwhelming pandemic situations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developing and screening of unique antiviral agents are peremptorily necessitated. In this study, we aimed to identify the chemical constituents of Citrus clementine peel essential oil (CCPEO) and to investigate its activities as anti-SARS-CoV-2 and anti-inflammatory activities. The chemical profile of CCPEO was identified via Gas chromatography-mass spectrometry analysis (GC/MS). The in-vitro cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and the 50% cytotoxic concentration (CC50) of CCPEO was determined. The antiviral effect of citrus clementine extract was determined by plaque reduction assay. A geometry-based molecular docking approach (Patchdock) was performed to create docking modifications that result in good molecular shape complementarity. The antiviral effect of CCPEO was attributed to the downregulation of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) released from Huh7cells, and thus attenuating the SARSCoV-2 infection-associated cytokine storm in severe cases. ©2022 National Information and Documentation Center (NIDOC)
ABSTRACT
The new coronavirus SARS-CoV-2 is responsible for the COVID-19 epidemic. SARS-CoV-2 accesses host cells by ACE2, which is abundantly expressed in the heart, kidneys, and lungs and shed into the plasma. Many SARS-CoV-2 patients' neutralizing antibody titers and memory B cell responses may be transient, exposing them to re-infection. Notably, neutralizing antibody titers and the number of virus-specific T cells had a substantial relationship. Our findings lay the groundwork for additional research into protective immunity against SARS-CoV-2 and the etiology of COVID-19, particularly in severe instances. The most important characteristic of our findings a positive correlation between all parameters (cellular and humoral) and COVID-19 patients compared with healthy group excepting neutrophil cells where no significant difference was observed between the two groups. Lymphopenia and elevated levels of specific cytokines, such as IL-6, IL-10, and TNF-α, have been linked to illness severity in general. T cells are thought to play a key role in the first immune response. In extreme situations, a significant drop in T cell counts is virtually always detected. We observed that lymphocytes were significantly decreased (p < 0.001) in COVID-19 patients (630±0.7678) cells/mm3, as compared to healthy controls (2247±0.1497), Generally COVID-19 patients at severe stage suffering leucopenia and stimulate neutrophils to reduce formazan dye. On the other hand significant increase was recorded in cytokines storm that Hyper-production of mostly pro-inflammatory cytokines, such as IL-6, IL-10, and TNF-, which selectively target lung tissue, can significantly impair the prognosis in the most severe cases. Average of IL6, IL-10, TNF- α were significantly increased (p < 0.001) in COVID-19 patients (38.2±6.228, 94.87±8.426, 23.61±4.13 pg/ml), as compared to healthy controls (2.66±0.21, 8.06±0.85, 10.53±1.13 pg/ml) respectively. Gene expression of ACE2 significantly decreased at P <0.001 in severe patients to (0.1262±0.0072) whereas reported (1) for healthy controls, thus Fold of expression 7.92 (down regulation). Their impact on results will aid in the development of more effective COVID-19 management strategies. © 2022 Universidad Tecnica de Manabi. All Rights Reserved.
ABSTRACT
Cytokine storms, an overaggressive immune response due to the overexpression of pro-inflammatory cytokines, have been identified to play a significant role in COVID-19 infections. Studies have shown that TNF-α and IFN-γ are integral to the process, however, its genetic mechanisms have yet to be fully elucidated. Herein, the key changes in the gene expression of TNF-α and IFN-γ induced cytokine storms are identified through differential gene analysis on the publicly available GEO GSE160163 dataset. GO and KEGG enrichment were used to annotate identified DEGs, and a PPI network was constructed based on the STRING database. A total of 446 differentially expressed genes were identified. Up-regulated genes and downregulated genes were enriched in viral immune response and infection pathways, and steroid biosynthesis and metabolic pathways, respectively. PPI construction revealed 1,834 interactions between 428 proteins, indicating their biological connectivity. Module analysis identified nine (9) hub genes: STAT1, CXCL10, CD274, CXCL9, IRF1, PSMB9, CD86, STAT3, and CXCR4, involved in viral immune response and three (3) significant modules involved in NOD-like receptor signaling, steroid biosynthesis, and viral infections. These identified DEGs, hub genes, and their respective enriched pathways aid us in understanding the molecular mechanisms of cytokine storms, as well as provide potential gene targets and druggable receptors for the treatment of cytokine storms. © 2022 IEEE.
ABSTRACT
The COVID-19 pandemic demands changes in using of medicinal plants. Empirically, the medicinal plants of Curcuma xanthorrhiza (CX) and black cumin (BC) have been used massively in the era of the COVID-19 pandemic. Curcuma xanthorrhiza and black cumin (CXBC) preparations have been developed with the main ingredients of BC oil and CX extract. The purpose of the study was to determine the antioxidant and immune-modulatory activities of CXBC preparations active substances (polyphenols, flavonoids, thymoquinone). We conducted experimental laboratory research. The immunomodulatory activity test was carried out on human large lung cancer cell line (HTB-183 cells) by observing the expression of tumor necrosis factor alfa (TNF-α) and interleukine 10 (IL-10). The results showed that the CXBC preparation contained 4% thymoquinone, 25.87 mg/ml polyphenols, and 41.86 mg/dl flavonoids. CXBC preparations contain vitamins (A, C, and E) and minerals (potassium, calcium). The antioxidant activity of the CXBC preparation was included in the strong category with IC50=54.87 ppm. CXBC preparations increased TNF-a expression and decreased IL-10 expression in HTB-183 cells. Based on the study results, it can be concluded that the CXBC preparation contains 4% thymoquinone, 25.87 mg/ml polyphenol, 41.86 mg/dl flavonoid, and a high level of vitamin and minerals. CXBC preparations have potent antioxidant activity, increase TNF-α and decrease IL-10 expression. © 2022, Intelektual Pustaka Media Utama. All rights reserved.
ABSTRACT
Objective: Hypoxia has an important role in the disruption of intestinal mucosal integrity because of inflammation and apoptosis induced by inflammatory cytokines such as TNF-a (Tumor necrosis factor-alpha), IL-6 and IFN-y, and apoptotic regulatory proteins. Chloroquine (CLQ) is a drug used in the novel coronavirus disease (COVID-19) and is widely used for the treatment of many inflammatory diseases such as malaria and rheumatoid arthritis. In this study, we aimed to reduce the destructive effects of hypoxia-induced inflammation and apoptosis in the intestinal mucosa of rats with CLQ applications. Methods: For this purpose, a total of 24 Wistar Albino rats were randomly divided into three groups;Group I: Control group (n=8), Group II: Hypoxia (n=8) and Group III: Hypoxia + CLQ (n=8). The control group was housed in plexiglass cages to keep the oxygen levels at 10% levels for 28 days, while the hypoxia and hypoxia+CLQ groups were housed in a normal atmospheric environment (21% O2), and the hypoxia+CLQ group was administered CLQ at a dose of 50 mg/kg every day for 28 days. At the end of the experiment, the intestinal tissues of the experimental animals, were extracted under the anesthesia and they were sacrificed. Results: As a result of histopathological evaluations, it was determined that CLQ applications showed healing properties on the histopathological effects induced by hypoxia in the intestine. While an increase in TNF-α expression was observed in the hypoxia group, a statistically significant decrease was detected in the hypoxia+CLQ group. In addition, Bax expression was found to be statistically significantly lower in the hypoxia+CLQ group when compared to the hypoxia group. On the contrary, it was observed that Bcl-2 expression was statistically significantly increased in the hypoxia+CLQ group compared to the Hypoxia group. Conclusion: We observed that hypoxia causes significant damage to the intestinal mucosa and triggers a severe inflammation that drives cells to apoptosis. Considering the curative effects of chloroquine on the intestinal mucosa, we suggest that this anti-inflammatory drug has a potential to use clinically to alleviate the deleterious effects of hypoxia in the intestine. © 2022. All Rights Reserved.
ABSTRACT
In spite of various and extensive studies known for pyrazolo[1,5-a]pyrimidines the synthesis, in silico studies and biological evaluation of their 5-(het)aryl analogs remained underexplored. The TNF-α inhibitors on the other hand has considerable therapeutic potential for autoimmune and inflammatory diseases in addition to cancer, diabetes and possibly COVID-19. In the current study 5-aryl pyrazolo[1,5-a]pyrimidines were explored as potential inhibitors of TNF-α that was supported by the in silico studies. This class of compounds was accessed via a sonochemical synthesis involving the acid catalyzed cyclocondensation reaction of aminopyrazoles with acrylophenones in the presence of aerial oxygen. The study indicated that the overall rate of the reaction was enhanced by ultrasound in the absence of which a longer duration and higher temperature was necessary. The current catalyst/promoter/ligand free and scalable method afforded a range of compounds. Some of these compounds showed good inhibition of TNF-α in vitro where ester/amide moiety at the C-3 position played a key role in interacting with the protein dimer as suggested by the in silico studies. Indeed, these groups formed H-bonds with A: GLY121 and B: TYR151 residues of TNF-α dimer in silico. A brief SAR within the series and in silico ADME/toxicity prediction for best active compounds is presented. Compounds 3a-c were identified as initial hits for further pharmacological evaluations. A sonochemical method has been developed for the facile synthesis of pyrazolo[1,5-a]pyrimidines that were evaluated as potential inhibitors of TNF-α. A sonochemical method has been developed for the facile synthesis of pyrazolo[1,5-a]pyrimidines that were evaluated as potential inhibitors of TNF-α.
ABSTRACT
Introduction: Patients infected with covid-19 coronavirus and even influenza can die because of an overreaction of the immune system called cytokine storms. Previous research has said that turmeric (curcumin) has the ability to suppress viral infection condition where cytokine increase and continuing by increased of cytokine storm. This condition showed that curcumin potentially to using for healing Ebola patients. Curcumin seems to have very low bioavailability on our human body. In order to increase absorption, nanocurcumin which has smaller particle substrate was used. Our previous research has said that nanocurcumin increase mitochondrial biogenesis in skeletal muscles. This study aims to look at the effect of nanocurcumin administration on Il-6 and TNF-α which increase on high intensity endurance exercise. Methods: Wistar rats 10 weeks old used on this experiment and entered into non-exercise and exercise groups. Furthermore, every group divided with control and nanocurcumin. Curcumin doses was one hundred mg/ kilogram/day peroral on both groups for 28 days to known effect of nanocurcumin itself and nanocurcumin together with exercise. Two hours swimming exercise per-day used to determine effect of endurance training. Western blotting (WB) was used to detect of proteins expression IL-6 and TNF-α. Results: Compared to non-exercise group, exercise group showed enhance IL-6 and TNF-α protein expression and interested that nanocurcumin significant abolish this effect. Conclusion: Taken together, these results suggest that nanocurcumin treatment ability decreased inflammation involved on endurance training induced cytokine storm and potentially to be one of candidate drugs to decrease cytokine storm condition. © 2021 UPM Press. All rights reserved.