Ischemic Heart Disease Pathophysiology Paradigms Overview: From Plaque Activation to Microvascular Dysfunction

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(21), P. 8118 - 8118

Published: Oct. 30, 2020

Ischemic heart disease still represents a large burden on individuals and health care resources worldwide. By conventions, it is equated with atherosclerotic plaque due to flow-limiting obstruction in large-medium sized coronary arteries. However, clinical, angiographic autoptic findings suggest multifaceted pathophysiology for ischemic just some cases are caused by severe or complicated plaques. Currently there no well-defined assessment of that satisfies all the observations sometimes underlying mechanism everyday ward misleading. In order better examine this provide future perspectives, important know analyze pathophysiological mechanisms underline it, because not always determined complication. Therefore, have more complete comprehension we propose an overview available paradigms, from activation microvascular dysfunction.

Language: Английский

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HIV–Host Cell Interactions

Cells, Journal Year: 2023, Volume and Issue: 12(10), P. 1351 - 1351

Published: May 9, 2023

The development of antiretroviral drugs (ARVs) was a great milestone in the management HIV infection. ARVs suppress viral activity host cell, thus minimizing injury to cells and prolonging life. However, an effective treatment has remained elusive for four decades due successful immune evasion mechanisms virus. A thorough understanding molecular interaction with cell is essential both preventive curative therapies This review highlights several inherent that promote its survival propagation, such as targeting CD4+ lymphocytes, downregulation MHC class I II, antigenic variation envelope complex minimizes antibody access, how they collaboratively render system unable mount response.

Language: Английский

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Macrophages: Key Cellular Players in HIV Infection and Pathogenesis

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 288 - 288

Published: Feb. 13, 2024

Although cells of the myeloid lineages, including tissue macrophages and conventional dendritic cells, were rapidly recognized, in addition to CD4+ T lymphocytes, as target HIV-1, their specific roles pathophysiology infection initially largely neglected. However, numerous studies performed over past decade, both vitro cell culture systems vivo monkey humanized mouse animal models, led growing evidence that play important direct indirect HIV-1 pathogenesis. It has been recently proposed are likely involved all stages pathogenesis, virus transmission dissemination, but above all, viral persistence through establishment, together with latently infected reservoirs many host tissues, major obstacle eradication people living HIV. Infected indeed found, very often multinucleated giant expressing antigens, almost lymphoid non-lymphoid tissues HIV-1-infected patients, where they can probably persist for long period time. In addition, also participate, directly targets or indirectly key regulators innate immunity inflammation, chronic inflammation associated clinical disorders observed HIV, even patients receiving effective antiretroviral therapy. The main objective this review is therefore summarize recent findings, revisit older data, regarding critical functions infection, found well during different

Language: Английский

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Sensor Sensibility—HIV-1 and the Innate Immune Response

Cells, Journal Year: 2020, Volume and Issue: 9(1), P. 254 - 254

Published: Jan. 20, 2020

Innate immunity represents the human immune system's first line of defense against a pathogenic intruder and is initiated by recognition conserved molecular structures known as pathogen-associated patterns (PAMPs) specialized cellular sensors, called pattern receptors (PRRs). Human immunodeficiency virus type 1 (HIV-1) unique RNA that causes acquired syndrome (AIDS) in infected individuals. During replication cycle, HIV-1 undergoes reverse transcription its genome integrates resulting DNA into genome. Subsequently, integrated provirus results production new virions spreading infection virus. Throughout viral numerous nucleic acid derived PAMPs can be recognized diverse set innate sensors cells. However, has evolved efficient strategies to evade or counteract this surveillance downstream responses. Understanding underpinnings concerted actions system, well corresponding evasion mechanisms during infection, critical understanding transmission pathogenesis, may provide important guidance for design appropriate adjuvant vaccine strategies. Here, we summarize current knowledge basis sensing cells, including CD4+ T dendritic macrophages. Furthermore, discuss underlying which regulated, describe developed

Language: Английский

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The Role of Toll-Like Receptors in Retroviral Infection

Microorganisms, Journal Year: 2020, Volume and Issue: 8(11), P. 1787 - 1787

Published: Nov. 14, 2020

Toll-like receptors (TLRs) are key pathogen sensing that respond to diverse microbial ligands, and trigger both innate adaptive immune responses infection. Since their discovery, a growing body of evidence has pointed an important role for TLRs in retroviral infection pathogenesis. These data suggest multiple contribute the anti-retroviral response, TLR engagement by retroviruses can have complex divergent outcomes Despite this progress, numerous questions remain about In review, I summarize existing TLR-retrovirus interactions functional roles these play immunity pathogenesis, with particular focus on human immunodeficiency virus (HIV).

Language: Английский

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Innate Immune Response to Viral Vectors in Gene Therapy

Viruses, Journal Year: 2023, Volume and Issue: 15(9), P. 1801 - 1801

Published: Aug. 24, 2023

Viral vectors play a pivotal role in the field of gene therapy, with several related drugs having already gained clinical approval from EMA and FDA. However, numerous viral therapy are currently undergoing pre-clinical research or participating trials. Despite advancements, innate response remains significant barrier impeding development therapy. The immune to transgenes is still an important reason hindering its development. Extensive studies have demonstrated that different DNA RNA sensors can detect adenoviruses, adeno-associated viruses, lentiviruses, thereby activating various pathways such as Toll-like receptor (TLR), cyclic GMP-AMP synthase–stimulator interferon genes (cGAS-STING), retinoic acid-inducible I–mitochondrial antiviral signaling protein (RLR-MAVS). This review focuses on elucidating mechanisms underlying induced by three widely utilized vectors: adenovirus, virus, lentivirus, well strategies employed circumvent immunity.

Language: Английский

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Long noncoding RNA MIR4435-2HG enhances metabolic function of myeloid dendritic cells from HIV-1 elite controllers

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(9)

Published: May 2, 2021

Restriction of HIV-1 replication in elite controllers (ECs) is frequently attributed to T cell-mediated immune responses, while the specific contribution innate cells less clear. Here, we demonstrate an upregulation host long noncoding RNA (lncRNA) MIR4435-2HG primary myeloid dendritic (mDCs) from ECs. Elevated expression this lncRNA mDCs was associated with a distinct immunometabolic profile, characterized by increased oxidative phosphorylation and glycolysis activities response TLR3 stimulation. Using functional assays, show that directly influenced metabolic state mDCs, likely through epigenetic mechanisms involving H3K27ac enrichment at intronic enhancer RPTOR gene locus, main component mammalian target rapamycin complex 1 (mTORC1). Together, these results suggest role for enhancing ECs targeted modifications member mTOR signaling pathway.

Language: Английский

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IFI27 is a potential therapeutic target for HIV infection

Annals of Medicine, Journal Year: 2022, Volume and Issue: 54(1), P. 314 - 325

Published: Jan. 22, 2022

Therapeutic studies against human immunodeficiency virus type 1 (HIV-1) infection have become one of the important works in global public health.Differential expression analysis was performed between HIV-positive (HIV+) and HIV-negative (HIV-) patients for GPL6947 GPL10558 GSE29429. Coexpression common genes with same direction differential identified modules. Module were subjected to enrichment analysis, Short Time-series Expression Miner (STEM) PPI network analysis. The top 100 most connected screened construct LASSO model, AUC values calculated identify key genes. Methylation modification by chAMP package. Differences immune cell infiltration HIV + HIV- patients, as well antiretroviral therapy (ART) using ssGSEA.We obtained 3610 genes, clustered into nine coexpression significantly enriched interferon signalling, helper T-cell immunity, HIF-1-signalling pathways. We out module gradual changes increasing time from enrolment STEM software. 12 significant through regression especially proteasome 20S subunit beta 8 (PSMB8) alpha inducible protein 27 (IFI27). PSMB8 IFI27 then detected quantitative real-time PCR. Interestingly, also a persistently dysregulated gene STEM. In addition, 10 be modified methylation. infiltrated cells restored after ART, associated cells.The above results provided potential target early diagnosis treatment patients. may progression powerful immunotherapy.

Language: Английский

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Host Cell Restriction Factors Blocking Efficient Vector Transduction: Challenges in Lentiviral and Adeno-Associated Vector Based Gene Therapies

Cells, Journal Year: 2023, Volume and Issue: 12(5), P. 732 - 732

Published: Feb. 24, 2023

Gene therapy relies on the delivery of genetic material to patient’s cells in order provide a therapeutic treatment. Two currently most used and efficient systems are lentiviral (LV) adeno-associated virus (AAV) vectors. vectors must successfully attach, enter uncoated, escape host restriction factors (RFs), before reaching nucleus effectively deliver instructions cell. Some these RFs ubiquitously expressed mammalian cells, while others cell-specific, still only upon induction by danger signals as type I interferons. Cell have evolved protect organism against infectious diseases tissue damage. These can be intrinsic, directly acting vector, or related with innate immune response system, indirectly through interferons, but both intertwined. The immunity is first line defense pathogens and, such derived from myeloid progenitors (but not only), well equipped detect pathogen-associated molecular patterns (PAMPs). In addition, some non-professional epithelial endothelial fibroblasts, play major roles pathogen recognition. Unsurprisingly, foreign DNA RNA molecules among detected PAMPs. Here, we review discuss identified that block LV AAV vector transduction, hindering their efficacy.

Language: Английский

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New Approaches to Dendritic Cell-Based Therapeutic Vaccines Against HIV-1 Infection

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 4, 2022

Due to the success of combined antiretroviral therapy (cART) in recent years, pathological outcome Human Immunodeficiency Virus type 1 (HIV-1) infection has improved substantially, achieving undetectable viral loads most cases. Nevertheless, presence a reservoir formed by latently infected cells results patients having maintain treatment for life. In absence effective eradication strategies against HIV-1, research efforts are focused on obtaining cure. One these approaches is creation therapeutic vaccines. this sense, promising one up now based establishing immunological synapse between dendritic (DCs) and T lymphocytes (TL). DCs first immune system encounter HIV-1 acting as antigen presenting cells, bringing about interaction innate adaptive responses mediated TL. Furthermore, TL end effector, their response capacity essential elimination pathogens. review, we summarize knowledge with TL, well characterization specific T-cell infection. The use nanotechnology design improvement vaccines been researched presented here special emphasis.

Language: Английский

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