The role of programmed cell death in organ dysfunction induced by opportunistic pathogens

Critical Care, Год журнала: 2025, Номер 29(1)

Опубликована: Янв. 24, 2025

Sepsis is a life-threatening condition resulting from pathogen infection and characterized by organ dysfunction. Programmed cell death (PCD) during sepsis has been associated with the development of multiple dysfunction syndrome (MODS), impacting various physiological systems including respiratory, cardiovascular, renal, neurological, hematological, hepatic, intestinal systems. It well-established that infections lead to immune dysregulation, which subsequently contributes MODS in sepsis. However, recent evidence suggests sepsis-related opportunistic pathogens can directly induce failure promoting PCD parenchymal cells each affected organ. This study provides an overview damaged induction host pathogens, proposing innovative strategies for preventing

Язык: Английский

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SARS-CoV-2 mitochondriopathy in COVID-19 pneumonia exacerbates hypoxemia

Redox Biology, Год журнала: 2022, Номер 58, С. 102508 - 102508

Опубликована: Окт. 13, 2022

Язык: Английский

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Perturbation of the host cell Ca2+ homeostasis and ER-mitochondria contact sites by the SARS-CoV-2 structural proteins E and M

Cell Death and Disease, Год журнала: 2023, Номер 14(4)

Опубликована: Апрель 29, 2023

Abstract Coronavirus disease (COVID-19) is a contagious respiratory caused by the SARS-CoV-2 virus. The clinical phenotypes are variable, ranging from spontaneous recovery to serious illness and death. On March 2020, global COVID-19 pandemic was declared World Health Organization (WHO). As of February 2023, almost 670 million cases 6,8 deaths have been confirmed worldwide. Coronaviruses, including SARS-CoV-2, contain single-stranded RNA genome enclosed in viral capsid consisting four structural proteins: nucleocapsid (N) protein, ribonucleoprotein core, spike (S) envelope (E) membrane (M) embedded surface envelope. In particular, E protein poorly characterized viroporin with high identity amongst all β-coronaviruses (SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-OC43) low mutation rate. Here, we focused our attention on study M proteins, found general perturbation host cell calcium (Ca 2+ ) homeostasis selective rearrangement interorganelle contact sites. vitro vivo biochemical analyses revealed that binding specific nanobodies soluble regions reversed observed phenotypes, suggesting might be an important therapeutic candidate not only for vaccine development, but also management COVID designing drug regimens that, so far, very limited.

Язык: Английский

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Mitochondrial oxidative stress, mitochondrial ROS storms in long COVID pathogenesis

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Дек. 22, 2023

Significance This review discusses the coronavirus disease 2019 (COVID-19) pathophysiology in context of diabetes and intracellular reactions by COVID-19, including mitochondrial oxidative stress storms, ROS long COVID. Recent advances The COVID is suffered ~10% COVID-19 patients. Even virus does not exist, patients suffer for even over a year, could be mitochondria dysregulation disease. Critical issues Patients who recover from can develop new or persistent symptoms multi-organ complications lasting weeks months, called underlying mechanisms involved still unclear. Once persist, they cause significant damage, leading to numerous, symptoms. Future directions A comprehensive map stages pathogenetic related effective drugs treat prevent it are required, which will aid development future treatments symptom relief.

Язык: Английский

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Metabolomics combined with network pharmacology reveals a role for astragaloside IV in inhibiting enterovirus 71 replication via PI3K-AKT signaling

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Июнь 10, 2024

Язык: Английский

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Unveiling the Role of Protein Kinase C θ in Porcine Epidemic Diarrhea Virus Replication: Insights from Genome-Wide CRISPR/Cas9 Library Screening

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(6), С. 3096 - 3096

Опубликована: Март 7, 2024

Porcine epidemic diarrhea virus (PEDV), a member of the Alpha-coronavirus genus in Coronaviridae family, induces acute diarrhea, vomiting, and dehydration neonatal piglets. This study aimed to investigate genetic dependencies PEDV identify potential therapeutic targets by using single-guide RNA (sgRNA) lentiviral library screen host factors required for infection. Protein kinase C θ (PKCθ), calcium-independent PKC family localized cell membrane, was found be crucial factor The investigation infection limited Vero porcine epithelial cell-jejunum 2 (IPEC-J2) due defective interferon production poor replication IPEC-J2. Therefore, identifying suitable cells is crucial. findings this reveal that human embryonic kidney (HEK) 293T L929 cells, but not IPEC-J2 were investigating PKCθ played significant role endocytosis PEDV, regulated expression phosphorylation PKCθ. Apoptosis involved replication, as activated PKCθ-B-cell lymphoma (BCL-2) ovarian killer (BOK) axis HEK293T increase viral via mitochondrial apoptosis. demonstrated suitability identified essential These provide valuable insights development strategies drug

Язык: Английский

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Taurine Improved Autism-Like Behaviours and Defective Neurogenesis of the Hippocampus in BTBR Mice through the PTEN/mTOR/AKT Signalling Pathway

Folia Biologica, Год журнала: 2024, Номер 70(1), С. 45 - 52

Опубликована: Янв. 1, 2024

Effective treatment of patients with autism spectrum disorder (ASD) is still absent so far. Taurine exhibits therapeutic effects towards the autism-like behaviour in ASD model animals. Here, we determined mechanism taurine effect on hippocampal neurogenesis genetically inbred BTBR T + tf/J (BTBR) mice, a proposed ASD. In this mouse model, explored oral supplementation ASD-like behaviours an open field test, elevated plus maze, marble burying self-grooming and three-chamber test. The mice were divided into four groups normal controls (WT) models (BTBR), who did or not receive 6-week water (WT, WT+ Taurine, BTBR, BTBR+Taurine). Neurogenesis-related by Ki67 immunofluorescence staining. Western blot analysis was performed to detect expression phosphatase tensin homologue deleted from chromosome 10 (PTEN)/mTOR/AKT pathway-associated proteins. Our results showed that improved behaviour, increased proliferation cells, promoted PTEN expression, reduced phosphorylation mTOR AKT tissue mice. conclusion, partially inherited which may be associa­ted improving defective neural precursor cell enhancing PTEN-associated pathway tissue.

Язык: Английский

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Mitochondria in COVID-19: from cellular and molecular perspective

Frontiers in Physiology, Год журнала: 2024, Номер 15

Опубликована: Июнь 21, 2024

The rapid development of the COVID-19 pandemic resulted in a closer analysis cell functioning during β-coronavirus infection. This review will describe evidence for as syndrome with strong, albeit still underestimated, mitochondrial component. Due to sensitivity host mitochondria coronavirus infection, SARS-CoV-2 affects signaling, modulates immune response, modifies cellular energy metabolism, induces apoptosis and ageing, worsening symptoms which can sometimes be fatal. Various aberrations across human systems tissues their relationships were reported. In this review, particular attention is given characterization multiple alterations gene expression pattern metabolism COVID-19; complexity interactions between proteins presented. participation mitogenome fragments signaling occurrence subgenomic RNA within membranous compartments, including widely discussed. As severely quality system mitochondria, background dynamics additionally characterized. Finally, perspectives on mitigation by affecting biogenesis numerous compounds therapeutic treatments are briefly outlined.

Язык: Английский

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Visualization of BOK pores independent of BAX and BAK reveals a similar mechanism with differing regulation

Cell Death and Differentiation, Год журнала: 2022, Номер 30(3), С. 731 - 741

Опубликована: Окт. 26, 2022

Abstract BOK is a poorly understood member of the BCL-2 family proteins that has been proposed to function as pro-apoptotic, BAX-like effector. However, molecular mechanism and structural properties pores remain enigmatic. Here, we show thermal stability pore activity depends on presence its C-terminus well mitochondrial lipid cardiolipin. We directly visualized in liposomes by electron microscopy, which appeared similar those induced BAX, line with comparable oligomerization quantified single molecule imaging. In addition, super-resolution STED imaging revealed organized into dots ring-shaped assemblies apoptotic mitochondria, also reminiscent found for BAX BAK. Yet, unlike BAK, was limited partial localization independent unaffected other proteins. These results suggest that, while kept check subcellular instead interaction members, resulting are structurally

Язык: Английский

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COVID‐19 and neurodegeneration: The mitochondrial connection

Aging Cell, Год журнала: 2022, Номер 21(11)

Опубликована: Окт. 11, 2022

Abstract There is still a significant lack of knowledge regarding many aspects the etiopathology and consequences severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in humans. For example, variety molecular mechanisms mediating this infection, long‐term disease remain poorly understood. It first seemed like SARS‐CoV‐2 primarily caused serious syndrome. However, over last years, an increasing number studies also pointed towards damaging effects has on central nervous system (CNS). In fact, evidence suggests possible disruption blood–brain barrier deleterious CNS, especially patients who already suffer from other pathologies, such as neurodegenerative disorders. The behind these CNS could involve dysregulation mitochondrial physiology, well‐known early marker neurodegeneration hallmark aging. Moreover, mitochondria are involved activation inflammatory response, which been broadly described COVID‐19. Here, we critically review current bibliography presence symptoms COVID‐19 patients, with special emphasis

Язык: Английский

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