Immune responses in COVID-19 patients: Insights into cytokine storms and adaptive immunity kinetics

Heliyon, Journal Year: 2024, Volume and Issue: 10(14), P. e34577 - e34577

Published: July 1, 2024

SARS-CoV-2 infection can trigger cytokine storm in some patients, which characterized by an excessive production of cytokines and chemical mediators. This hyperactive immune response may cause significant tissue damage multiple organ failure (MOF). The severity COVID-19 correlates with the intensity storm, involving elements such as IFN, NF-κB, IL-6, HMGB1, etc. It is imperative to rapidly engage adaptive immunity effectively control disease progression. CD4

Language: Английский

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Advances in inflammatory senescence in liver disease

Journal of Zhejiang University (Medical Sciences), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Inflammatory senescence is a process of cellular dysfunction associated with chronic inflammation, which plays significant role in the onset and progression liver diseases,and research on its mechanisms becomes hotspot currently. In viral hepatitis, inflammatory primarily involve oxidative stress, cell apoptosis necrosis, as well gut microbiota dysbiosis. non-alcoholic fatty disease, are more complex, involving insulin resistance, fat deposition, lipid metabolism disorders, dysbiosis, NAD+ abnormalities. tumors, characterized by weakening tumor suppressive mechanisms, remodeling microenvironment, metabolic reprogramming, enhanced immune evasion. Therapeutic strategies targeting have been developing recently, antioxidant therapy, disorder improvement, immunotherapy emerging important interventions for diseases. This review focuses secescence diseases, aiming to provide novel insights prevention treatment

Language: Английский

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Activity of the apoptosis-inducing ligand TRAIL in the blood of patients with chronic obstructive pulmonary disease who had COVID-19

Bulletin physiology and pathology of respiration, Journal Year: 2025, Volume and Issue: 95, P. 18 - 25

Published: March 19, 2025

Aim. To assess the serum level of apoptosis-inducing ligand TRAIL in patients with chronic obstructive pulmonary disease (COPD) 12 months after COVID-19 relationship to measures systemic inflammation. Materials and methods. The study included 90 aged 46 79 years stable COPD who had experienced (regardless severity) hospital discharge. comparison group consisted 43 no history COVID-19. was measured by enzymelinked immunosorbent assay using specific antibodies (RayBiotech, Human, USA). Levels interleukin (IL)-6, IL-10, vascular endothelial growth factor (VEGF) (Vector-Best, Russia), C-reactive protein (CRP) (Biochemmack, Austria) were determined direct serological “sandwich-type” assays mono- polyclonal antibodies. Results. Twelve COVID-19, showed intensified apoptosis inflammation, evidenced a 33.7% increase TRAIL, 71.3% IL-6, 57.5% CRP, 69.0% VEGF compared without A strong association found between IL-10 levels (p < 0.01), moderate positive correlation noted IL-6 0.05), weak CRP > 0.05). Conclusion. This is first report significantly higher activity those inflammation markers (IL-10, IL-6), reflecting apoptosis-dependent mechanisms COPD. Measuring may be useful for comprehensive evaluations recovering from

Language: Английский

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Pharmacological mechanisms of probenecid for SARS-CoV-2 and RSV co-infection: findings of system pharmacology, molecular docking, molecular dynamics simulation, and structure–activity relationship

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: April 30, 2025

Background The clinical consequences of the co-infection with novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and syncytial virus (RSV) are not optimistic. Nevertheless, there is currently no approved therapeutic regimen specifically targeting SARS-CoV-2/RSV co-infection, existing monotherapies showing limited efficacy. According to recent studies, probenecid has both anti-SARS-CoV-2 anti-RSV effects. Therefore, as one probable molecular candidate for SARS-CoV-2 RSV, was researched in this exploration. Methods Using systems pharmacology bioinformatics, we characterized targets associated treatment focusing on their biological functions, mechanisms binding activities. To further validate these findings, conducted docking, MD simulations, electrostatic potential mapping, SAR analysis explore interactions between identified core targets. Results We 141 that overlapped probenecid, used shared construct a protein-protein interaction (PPI) network. Subsequently, obtained top 16 hub namely, AKT1, ALB, EGFR, CASP3, CTNNB1, SRC, HSP90AA1, so on. enrichment analysis, might affect inflammation, immunity, oxidative stress, defenses; Toll-like receptor, TNF, IL-17, NOD-like cytokine-cytokine among others. Additionally, based docking effectively bound related co-infection. Meanwhile, according dynamics (MD) simulations structure-activity relationship (SAR) speculated SRC HSP90AA1 more likely be target proteins than other proteins. Conclusion Our findings from bioinformatics indicate immune inflammatory responses play pivotal role effects probenecid. Infectious disease-related pathways also contribute significantly its effectiveness treating Further validation through analysis. These analyses suggest This study provides valuable preliminary insights into It establishes strong foundation future research strategy

Language: Английский

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Characterization of host substrates of SARS-CoV-2 main protease

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 21, 2023

The main protease (M pro ) plays a crucial role in coronavirus, as it cleaves viral polyproteins and host cellular proteins to ensure successful replication. In this review, we discuss the preference recognition sequence of M based on sequence-based studies structural information highlight recent advances computational experimental approaches that have aided discovering novel substrates. addition, provide an overview current understanding substrates their implications for replication pathogenesis. As has emerged promising target development antiviral drugs, further insight into its substrate specificity may contribute design specific inhibitors.

Language: Английский

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Apoptosis and pyroptosis in the nasal mucosa of Syrian hamster during SARS-CoV-2 infection and reinfection

APOPTOSIS, Journal Year: 2024, Volume and Issue: 29(7-8), P. 1246 - 1259

Published: Feb. 28, 2024

Language: Английский

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Cerebral small vessel injury in mice with damage to ACE2‐expressing cerebral vascular endothelial cells and post COVID‐19 patients

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Abstract Introduction The angiotensin‐converting enzyme 2 (ACE2), which is expressed in cerebral vascular endothelial cells (CVECs), has been currently identified as a functional receptor for SARS‐CoV‐2. Methods We specifically induced injury to ACE2‐expressing CVECs mice and evaluated the effects of such targeted damage through magnetic resonance imaging (MRI) cognitive behavioral tests. In parallel, we recruited single‐center cohort COVID‐19 survivors further assessed their brain microvascular based on cognition emotional scales, cranial MRI scans, blood proteomic measurements. Results Here, show an array pathological alterations characteristic small vessel disease (CSVD) that CVECs, survivors. These CSVD‐like manifestations persist at least 7 months post‐recovery from COVID‐19. Discussion Our findings suggest SARS‐CoV‐2 may induce with persistent sequelae, underscoring imperative heightened clinical vigilance mitigating or treating SARS‐CoV‐2‐mediated throughout infection convalescence. HIGHLIGHTS Cerebral disease–associated changes were observed after 2–expressing cells. sequelae. Clinical needed preventing SARS‐CoV‐2–induced during recovery.

Language: Английский

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The role of reactive oxygen species in severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection-induced cell death

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: Nov. 8, 2024

Coronavirus disease 2019 (COVID-19) represents the novel respiratory infectious disorder caused by severe acute syndrome coronavirus 2 (SARS-CoV-2) and is characterized rapid spread throughout world. Reactive oxygen species (ROS) account for cellular metabolic by-products, excessive ROS accumulation can induce oxidative stress due to insufficient endogenous antioxidant ability. In case of stress, production exceeds capacity, thus leading cell death. SARS-CoV-2 activate different death pathways in context infection host cells, such as neutrophil extracellular trap (NET)osis, ferroptosis, apoptosis, pyroptosis, necroptosis autophagy, which are closely related signalling control. this review, we comprehensively elucidated relationship between generation cells after infection, leads development COVID-19, aiming provide a reasonable basis existing interventions further therapies against SARS-CoV-2.

Language: Английский

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Differential activation of programmed cell death in patients with severe SARS-CoV-2 infection

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Nov. 20, 2023

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe lower airway disease and death in a subset of patients. Knowledge on the relative contribution programmed cell (PCD) to lung pathology is limited few human autopsy studies with small sample size/scope, vitro culture, experimental model systems. In this study, we sought identify, localize, quantify activation apoptosis, ferroptosis, pyroptosis, necroptosis FFPE tissues from patients that died SARS-CoV-2 infection ( n = 28) uninfected controls 13). Immunofluorescence (IF) staining, whole-slide imaging, Image J software was used localize expression nucleoprotein following PCD protein markers: cleaved Caspase-3, pMLKL, Gasdermin D, CD71, respectively. IF showed differential each pathway infected lungs dichotomous staining for enabling distinction between high 9) vs low viral burden 19). No differences were observed apoptosis ferroptosis controls. However, both pyroptosis significantly increased SARS-CoV-2-infected lungs. Increased lungs, irrespective burden, suggesting an inflammation-driven mechanism. contrast, exhibited very strong positive correlation R 0.9925), direct mediated effect. These data indicate possible novel mechanism viral-mediated potential role lytic pathways, mediating outcome.

Language: Английский

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Cathepsins and SARS‐CoV‐2 infection: From pathogenic factors to potential therapeutic targets

British Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 180(19), P. 2455 - 2481

Published: July 5, 2023

Abstract Coronavirus disease‐19 (COVID‐19) is caused by severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) infection. The COVID‐19 pandemic began in March 2020 and has wrought havoc on health economic systems worldwide. Efficacious treatment for lacking: Only preventive measures as well symptomatic supportive care are available. Preclinical clinical studies have indicated that lysosomal cathepsins might contribute to the pathogenesis disease outcome of COVID‐19. Here, we discuss cutting‐edge evidence pathological roles SARS‐CoV‐2 infection, host immune dysregulations, possible underlying mechanisms. Cathepsins attractive drug targets because their defined substrate‐binding pockets, which can be exploited binding sites pharmaceutical enzyme inhibitors. Accordingly, potential modulatory strategies cathepsin activity discussed. These insights could shed light development cathepsin‐based interventions

Language: Английский

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