Safety and efficacy of herbal extracts to restore respiratory health and improve innate immunity in COVID-19 positive patients with mild to moderate severity: A structured summary of a study protocol for a randomised controlled trial.
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ABSTRACT:
SUBMITTER: Rangnekar H
PROVIDER: S-EPMC7680979 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A safe and effective direct acting anti-hepatitis C virus (HCV) agent is still needed. In this study, human single chain variable fragments of antibody (scFvs) that bound to HCV NS3/4A protein were produced by phage display technology. The engineered scFvs were linked to nonaarginines (R9) for making them cell penetrable. HCV-RNA-transfected Huh7 cells treated with the transbodies produced from four different transformed E. coli clones had reduced HCV-RNA inside the cells and in the cell spent media, as well as fewer HCV foci in the cell monolayer compared to the transfected cells in culture medium alone. The transbodies-treated transfected cells also had up-expression of the genes coding for the host innate immune response, including TRIF, TRAF3, IRF3, IL-28B, and IFN-β. Computerized homology modeling and intermolecular docking predicted that the effective transbodies interacted with several critical residues of the NS3/4A protease, including those that form catalytic triads, oxyanion loop, and S1 and S6 pockets, as well as a zinc-binding site. Although insight into molecular mechanisms of the transbodies need further laboratory investigation, it can be deduced from the current data that the transbodies blocked the HCV NS3/4A protease activities, leading to the HCV replication inhibition and restoration of the virally suppressed host innate immunity. The engineered antibodies should be tested further for treatment of HCV infection either alone, in combination with current therapeutics, or in a mixture with their cognates specific to other HCV proteins.
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Project description:While mitochondrial function is essential for life in all multicellular organisms, a mild impairment of mitochondrial function can extend longevity in model organisms. By understanding the molecular mechanisms involved, these pathways might be targeted to promote healthy aging. In studying two long-lived mitochondrial mutants in C. elegans, we found that disrupting subunits of the mitochondrial electron transport chain results in upregulation of genes involved in innate immunity, which is driven by the mitochondrial unfolded protein response (mitoUPR) but also dependent on the canonical p38-mediated innate immune signaling pathway. Both of these pathways are required for the increased resistance to bacterial pathogens and extended longevity of the long-lived mitochondrial mutants, as is the FOXO transcription factor DAF-16. This work demonstrates that both the p38-mediated innate immune signaling pathway and the mitoUPR act in concert on the same innate immunity genes to promote pathogen resistance and longevity, and that input from the mitochondria can extend longevity by signaling through these pathways. This indicates that multiple evolutionarily conserved genetic pathways controlling innate immunity also function to modulate lifespan.
| S-SCDT-EMBOR-2021-52964V1 | biostudies-other
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| S-EPMC8080998 | biostudies-literature
Project description:BACKGROUND:In models of COPD, environmental stressors induce innate immune responses, inflammasome activation and inflammation. However, the interaction between these responses and their role in driving pulmonary inflammation in stable COPD is unknown. OBJECTIVES:To investigate the activation of innate immunity and inflammasome pathways in the bronchial mucosa and bronchoalveolar lavage (BAL) of patients with stable COPD of different severity and control healthy smokers and non-smokers. METHODS:Innate immune mediators (interleukin (IL)-6, IL-7, IL-10, IL-27, IL-37, thymic stromal lymphopoietin (TSLP), interferon ? and their receptors, STAT1 and pSTAT1) and inflammasome components (NLRP3, NALP7, caspase 1, IL-1? and its receptors, IL-18, IL-33, ST2) were measured in the bronchial mucosa using immunohistochemistry. IL-6, soluble IL-6R, sgp130, IL-7, IL-27, HMGB1, IL-33, IL-37 and soluble ST2 were measured in BAL using ELISA. RESULTS:In bronchial biopsies IL-27+ and pSTAT1+ cells are increased in patients with severe COPD compared with control healthy smokers. IL-7+ cells are increased in patients with COPD and control smokers compared with control non-smokers. In severe stable COPD IL-7R+, IL-27R+ and TSLPR+ cells are increased in comparison with both control groups. The NALP3 inflammasome is not activated in patients with stable COPD compared with control subjects. The inflammasome inhibitory molecules NALP7 and IL-37 are increased in patients with COPD compared with control smokers. IL-6 levels are increased in BAL from patients with stable COPD compared with control smokers with normal lung function whereas IL-1? and IL-18 were similar across all groups. CONCLUSIONS:Increased expression of IL-27, IL-37 and NALP7 in the bronchial mucosa may be involved in progression of stable COPD.
| S-EPMC4219154 | biostudies-literature
Project description:While mitochondrial function is essential for life in all multicellular organisms, a mild impairment of mitochondrial function can extend longevity in model organisms. By understanding the molecular mechanisms involved, these pathways might be targeted to promote healthy aging. In studying two long-lived mitochondrial mutants in C. elegans, we found that disrupting subunits of the mitochondrial electron transport chain results in upregulation of genes involved in innate immunity, which is driven by the mitochondrial unfolded protein response (mitoUPR) but also dependent on the canonical p38-mediated innate immune signaling pathway. Both of these pathways are required for the increased resistance to bacterial pathogens and extended longevity of the long-lived mitochondrial mutants, as is the FOXO transcription factor DAF-16. This work demonstrates that both the p38-mediated innate immune signaling pathway and the mitoUPR act in concert on the same innate immunity genes to promote pathogen resistance and longevity and that input from the mitochondria can extend longevity by signaling through these pathways. This indicates that multiple evolutionarily conserved genetic pathways controlling innate immunity also function to modulate lifespan.
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Project description:The immune system is one of the most important adaptations that has evolved to protect animals from a wide range of pathogens they encounter from early life onwards. During the early developmental period this is particularly true for the innate immunity, as other components of the immune system are, as yet, poorly developed. But innate immunity may not only be crucial for early life survival, but may also have long-lasting effects, for example if early life immunity reflects the functioning of the immune system as a whole. For this reason, we investigated the importance of four constitutive innate immune parameters (natural antibodies, complement activity, concentrations of haptoglobin, and concentrations of nitric oxide) for recruitment in free-living great tits. We compared nestling immunity of recruits with nestling immunity of their nonrecruited siblings. We also investigated within individual consistency of these innate immune parameters for those individuals that recruited, which may be taken as a measure of immune capacity. In accordance with previous studies, we found a clear effect of tarsus length and a trend for body mass on the likelihood to recruit. Nevertheless, we found no evidence that higher levels of constitutive innate immunity as a nestling facilitated local recruitment. Furthermore, individual innate immunity was not consistent across life stages, that is to say, nestling immune parameters did not determine, or respectively, reflect adult innate immune parameters. This plasticity in innate immune components may explain why we did not find long-lasting survival benefits.
| S-EPMC4759050 | biostudies-other
Project description:Induction of GLUT4 translocation in the absence of insulin is considered a key concept to decrease elevated blood glucose levels in diabetics. Due to the lack of pharmaceuticals that specifically increase the uptake of glucose from the blood circuit, application of natural compounds might be an alternative strategy. However, the effects and mechanisms of action remain unknown for many of those substances. For this study we investigated extracts prepared from seven different plants, which have been reported to exhibit anti-diabetic effects, for their GLUT4 translocation inducing properties. Quantitation of GLUT4 translocation was determined by total internal reflection fluorescence (TIRF) microscopy in insulin sensitive CHO-K1 cells and adipocytes. Two extracts prepared from purslane (Portulaca oleracea) and tindora (Coccinia grandis) were found to induce GLUT4 translocation, accompanied by an increase of intracellular glucose concentrations. Our results indicate that the PI3K pathway is mainly responsible for the respective translocation process. Atomic force microscopy was used to prove complete plasma membrane insertion. Furthermore, this approach suggested a compound mediated distribution of GLUT4 molecules in the plasma membrane similar to insulin stimulated conditions. Utilizing a fluorescent actin marker, TIRF measurements indicated an impact of purslane and tindora on actin remodeling as observed in insulin treated cells. Finally, in-ovo experiments suggested a significant reduction of blood glucose levels under tindora and purslane treated conditions in a living organism. In conclusion, this study confirms the anti-diabetic properties of tindora and purslane, which stimulate GLUT4 translocation in an insulin-like manner.
| S-EPMC4731058 | biostudies-literature
Project description:ObjectivesTo investigate the potential efficacy of Nigella sativa (NS) oil supplementation on the outcomes of patients with mild Coronavirus Disease 2019 (COVID-19).Trial designProspective, two-arm, parallel-group, randomised (1:1 allocation ratio), open-label, controlled, exploratory phase II clinical trial of oral NS oil in patients with mild COVID-19.ParticipantsInclusion Criteria: - Patients with mild COVID19 (defined as upper respiratory tract infection symptoms in the absence of clinical or radiological signs of pneumonia). - Adult (18 - 65 years old). - Written informed consent by the patient (or legally authorized representative) prior to initiation of any study procedures. - All patients should understand and agree to comply with planned study procedures. - Polymerase chain reaction (PCR)-confirmed infection with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) from throat swab.Exclusion criteria- Patients with pneumonia or severe illness requiring admission to intensive care unit. - Severe chronic kidney disease (i.e. estimated glomerular filtration rate [eGFR] < 30 mL / min ) or end stage renal disease requiring dialysis - Severe chronic liver disease (Alanine transaminase [AlT] or Aspartate transaminase [AST] > 5 times the upper limit of normal). - Pregnancy or breast feeding. - Anticipated transfer within 72 hours to another hospital that is not a study site. - Allergy to the study medication The trial is currently conducted on patients recruited from King Abdulaziz University Hospital, Jeddah, Saudi Arabia.Intervention and comparatorIntervention group: Nigella sativa oil (MARNYS® Cuminmar) 500 mg softgel capsules, one capsule orally twice daily for 10 days plus standard of care treatment (antipyretic, antitussive). Comparator group: standard of care treatment.Main outcomesProportion of patients who clinically recovered (defined as 3 days of no symptoms) within 14 days after randomisation.RandomisationPatients will be randomly assigned to treatment or control groups in a 1:1 ratio using a computer-generated randomization scheme (Random permuted blocks of 10) developed using the web-based program: http://www.randomization.com .Blinding (masking)No blinding.Numbers to be randomised (sample size)Up to 200 eligible patients will be randomly assigned to either treatment or control groups.Trial statusProtocol version 1, as of July 14, 2020. Recruitment was started on May 21, 2020. The intended completion date is December 31, 2020.Trial registrationClinicalTrials.gov Identifier: NCT04401202 . Date of trial registration: May 26, 2020.Full protocolThe full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.
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