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共4篇 平均IF=4.8 (2.2-4.9)更多分析
  • 2区Q1影响因子: 4.7
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    1. Mouse Norovirus Infection Arrests Host Cell Translation Uncoupled from the Stress Granule-PKR-eIF2α Axis.
    作者:Fritzlar Svenja , Aktepe Turgut E , Chao Yi-Wei , Kenney Nathan D , McAllaster Michael R , Wilen Craig B , White Peter A , Mackenzie Jason M
    期刊:mBio
    日期:2019-06-18
    DOI :10.1128/mBio.00960-19
    The integrated stress response (ISR) is a cellular response system activated upon different types of stresses, including viral infection, to restore cellular homeostasis. However, many viruses manipulate this response for their own advantage. In this study, we investigated the association between murine norovirus (MNV) infection and the ISR and demonstrate that MNV regulates the ISR by activating and recruiting key ISR host factors. We observed that during MNV infection, there is a progressive increase in phosphorylated eukaryotic initiation factor 2α (p-eIF2α), resulting in the suppression of host translation, and yet MNV translation still progresses under these conditions. Interestingly, the shutoff of host translation also impacts the translation of key signaling cytokines such as beta interferon, interleukin-6, and tumor necrosis factor alpha. Our subsequent analyses revealed that the phosphorylation of eIF2α was mediated via protein kinase R (PKR), but further investigation revealed that PKR activation, phosphorylation of eIF2α, and translational arrest were uncoupled during infection. We further observed that stress granules (SGs) are not induced during MNV infection and that MNV can restrict SG nucleation and formation. We observed that MNV recruited the key SG nucleating protein G3BP1 to its replication sites and intriguingly the silencing of G3BP1 negatively impacts MNV replication. Thus, it appears that MNV utilizes G3BP1 to enhance replication but equally to prevent SG formation, suggesting an anti-MNV property of SGs. Overall, this study highlights MNV manipulation of SGs, PKR, and translational control to regulate cytokine translation and to promote viral replication. Viruses hijack host machinery and regulate cellular homeostasis to actively replicate their genome, propagate, and cause disease. In retaliation, cells possess various defense mechanisms to detect, destroy, and clear infecting viruses, as well as signal to neighboring cells to inform them of the imminent threat. In this study, we demonstrate that the murine norovirus (MNV) infection stalls host protein translation and the production of antiviral and proinflammatory cytokines. However, virus replication and protein translation still ensue. We show that MNV further prevents the formation of cytoplasmic RNA granules, called stress granules (SGs), by recruiting the key host protein G3BP1 to the MNV replication complex, a recruitment that is crucial to establishing and maintaining virus replication. Thus, MNV promotes immune evasion of the virus by altering protein translation. Together, this evasion strategy delays innate immune responses to MNV infection and accelerates disease onset.
  • 3区Q1影响因子: 4.9
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    2. Challenges and Future Trends in Atopic Dermatitis.
    期刊:International journal of molecular sciences
    日期:2023-07-12
    DOI :10.3390/ijms241411380
    Atopic dermatitis represents a complex and multidimensional interaction that represents potential fields of preventive and therapeutic management. In addition to the treatment armamentarium available for atopic dermatitis, novel drugs targeting significant molecular pathways in atopic dermatitis biologics and small molecules are also being developed given the condition's complex pathophysiology. While most of the patients are expecting better efficacy and long-term control, the response to these drugs would still depend on numerous factors such as complex genotype, diverse environmental triggers and microbiome-derived signals, and, most importantly, dynamic immune responses. This review article highlights the challenges and the recently developed pharmacological agents in atopic dermatitis based on the molecular pathogenesis of this condition, creating a specific therapeutic approach toward a more personalized medicine.
  • 3区Q3影响因子: 2.2
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    3. Pathophysiology of atopic dermatitis: Clinical implications.
    期刊:Allergy and asthma proceedings
    日期:2019-03-01
    DOI :10.2500/aap.2019.40.4202
    Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Genetic predisposition, epidermal barrier disruption, and dysregulation of the immune system are some of the critical components of AD. An impaired skin barrier may be the initial step in the development of the atopic march as well as AD, which leads to further skin inflammation and allergic sensitization. Type 2 cytokines as well as interleukin 17 and interleukin 22 contribute to skin barrier dysfunction and the development of AD. New insights into the pathophysiology of AD have focused on epidermal lipid profiles, neuroimmune interactions, and microbial dysbiosis. Newer therapeutic strategies focus on improving skin barrier function and targeting polarized immune pathways found in AD. Further understanding of AD pathophysiology will allow us to achieve a more precision medicine approach to the prevention and the treatment of AD.
  • 3区Q1影响因子: 4.9
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    4. Molecular Mechanisms of Atopic Dermatitis Pathogenesis.
    作者:Sroka-Tomaszewska Jowita , Trzeciak Magdalena
    期刊:International journal of molecular sciences
    日期:2021-04-16
    DOI :10.3390/ijms22084130
    Atopic dermatitis is a chronic, non-infectious inflammatory dermatosis. Acharacteristic feature is persistent itching of the skin. The chronic, relapsing course of the disease, economic burden, and the whole family's involvement in the treatment process immensely reduce the quality of life of patients and their families. The disease emerges as a social problem by increasing indirect costs, such as visiting a doctor, absenteeism from work and school, and avoiding social interactions. Thepathophysiology of atopic dermatitis is complex and multifactorial. It includes genetic disorders, a defect in the epidermal barrier, an altered immune response, anddisruption of the skin's microbial balance. The numerous complex changes at thegenetic level and innate and adaptive immunity provide the basis for characterizing the various phenotypes and endotypes of atopic dermatitis. Emerging therapies rely on the action of specific molecules involved in the disease's pathogenesis. It may be the starting point for the individualization of atopic dermatitis treatment. This paper will try to present some molecular mechanisms of atopic dermatitis and their clinical implications.

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