Sub-cellular biochemistry/Subcellular biochemistry, Journal Year: 2023, Volume and Issue: unknown, P. 77 - 112
Published: Jan. 1, 2023
Language: Английский
International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(16), P. 9089 - 9089
Published: Aug. 13, 2022
Cathepsins encompass a family of lysosomal proteases that mediate protein degradation and turnover. Although mainly localized in the endolysosomal compartment, cathepsins are also found cytoplasm, nucleus, extracellular space, where they involved cell signaling, matrix assembly/disassembly, processing trafficking through plasma nuclear membrane between intracellular organelles. Ubiquitously expressed body, play regulatory roles wide range physiological processes including coagulation, hormone secretion, immune responses, others. A dysregulation cathepsin expression and/or activity has been associated with many human diseases, cancer, diabetes, obesity, cardiovascular inflammatory kidney dysfunctions, neurodegenerative disorders, as well infectious diseases. In viral infections, may promote (1) activation attachment glycoproteins entry virus into target cells; (2) antigen presentation, enabling to replicate infected (3) up-regulation heparanase facilitates release progeny spread infection; (4) death either favor clearance or assist propagation. this review, we report most relevant findings on molecular mechanisms underlying involvement infection physiopathology, discuss potential inhibitors for therapeutical applications
Language: Английский
Citations
49
Advanced Science, Journal Year: 2024, Volume and Issue: unknown
Published: Sept. 23, 2024
Abstract The efficacy and safety of self‐amplifying mRNA (saRNA) have been demonstrated in COVID‐19 vaccine applications. Unlike conventional non‐replicating (nrmRNA), saRNA offers a key advantage: its self‐replication mechanism fosters efficient expression the encoded protein, leading to substantial dose savings during administration. Consequently, there is growing interest further optimizing efficiency saRNA. In this study, vitro adaptive passaging conducted under exogenous interferon pressure, which revealed several mutations nonstructural protein (NSP). Notably, two stable mutations, Q48P I113F, situated NSP3 macrodomain (MD), attenuated mono adenosine diphosphate ribose (MAR) hydrolysis activity exhibited decreased replication but increased payload compared wild‐type (wt saRNA). Transcriptome sequencing analysis unveils diminished activation double‐stranded RNA (dsRNA) sensor and, consequently, significantly reduced innate immune response wt Furthermore, mutant less translation inhibition cell apoptosis than saRNA, culminating higher both vivo. These findings underscore potential reducing replication‐dependent dsRNA‐induced responses through genetic modification as valuable strategy for enhancing efficiency, mitigating cytotoxicity.
Language: Английский
Citations
8
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 798 - 798
Published: Jan. 8, 2024
Lagovirus europaeus/GI.2 causes severe and highly fatal Rabbit Hemorrhagic Disease (RHD). Because of its characteristics, this infection is used as an animal model for acute liver failure (ALF). Apoptosis one the key processes underlying ALF has been described mechanisms RHD pathogenesis. Apoptotic cell death quite well characterized in with different variants GI.1 strains, but so far, GI.2 genotype not widely studied. In study, we performed evaluation apoptotic hepatocytes rabbits infected europaeus/GI.2. We analyzed expression genes involved by real-time PCR immunohistochemical (IHC) assays. showed a significant increase caspase-3 proapoptotic Bax anti-apoptotic Bcl-2 animals. addition, recorded increased Bax/Bcl-2 ratios. IHC analyses presence morphological signs apoptosis rabbits. Our results indicate that proteins from families play role induced infection.
Language: Английский
Citations
5
Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(46)
Published: Aug. 2, 2024
Abstract The sulfane sulfur pool, comprised of persulfide (RS‐SH) and polysulfide (RS‐S n H) derived from hydrogen sulfide (H 2 S), has emerged as a major player in redox biochemistry. Mitochondria, besides energy generation, serve significant cellular hubs, mediate stress response health. However, the effects endogenous mitochondrial (MSS) remain largely uncharacterized compared with their cytosolic counterparts, (CSS). To investigate this, we designed novel artificial substrate for 3‐mercaptopyruvate sulfurtransferase (3‐MST), key enzyme involved MSS biosynthesis. Using cells expressing mitochondrion‐localized biosensor, demonstrate this tool's ability to selectively enhance MSS. While H S was previously known suppress human immunodeficiency virus (HIV‐1), found that profoundly affected HIV‐1 life cycle, mediating viral reactivation latency. Additionally, provide evidence role host's state, membrane potential, apoptosis, respiration rates managing latency reactivation. Together, dynamic fluctuations pool have possibly conflicting effect on precision tools developed herein allow orthogonal generation within both mitochondria cytosol will be useful interrogating disease biology.
Language: Английский
Citations
5
Antioxidants, Journal Year: 2022, Volume and Issue: 12(1), P. 100 - 100
Published: Dec. 31, 2022
Glutathione peroxidase 4 (GPX4)-dependent ferroptosis in pancreatic acinar cells plays a critical role acute pancreatitis (AP). However, potential upstream regulators of GPX4 are not well defined. Here, we observed marked reduction expression and ferroptotic cell death mice with cerulein-induced AP. To determine the factors involved ferroptosis, pancreas transcriptome data from an AP mouse model were analyzed overlapped predicted transcription Gpx4, upregulated factor active protein 1 (AP-1) protein, Jun, was identified. The administration specific inhibitor liproxstatin-1 alleviated pathology significantly decreased Jun levels. Bioinformatic analysis indicated that Gpx4 promoter contains putative AP-1 binding site. binds directly to inhibits under conditions. inhibition by selective SR11302 reversed ameliorated GPX4-dependent manner. Collectively, our study demonstrates downregulation is aggravation during progression Strategies targeting AP-1/GPX4 axis may be potentially effective for prevention treatment
Language: Английский
Citations
21
International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12648 - 12648
Published: Aug. 10, 2023
Long COVID, also called post-acute sequelae of SARS-CoV-2, is characterized by a multitude lingering symptoms, including impaired cognition, that can last for many months. This symptom, often "brain fog", affects the life quality numerous individuals, increasing medical complications as well healthcare expenditures. The etiopathogenesis SARS-CoV-2-induced cognitive deficit unclear, but most likely cause chronic inflammation maintained viral remnant thriving in select body reservoirs. These sanctuaries are comprised fused, senescent cells, microglia and astrocytes, pathogen convert into neurotoxic phenotypes. Moreover, enteric nervous system contains neurons glia, virus lingers gastrointestinal tract well, accounting intestinal symptoms long COVID. Fusogens proteins overcome repulsive forces between cell membranes, allowing to coalesce with host cells enter cytoplasm. In intracellular compartment, hijacks actin cytoskeleton, fusing each other engendering pathological syncytia. Cell-cell fusion enables infect healthy neighboring cells. We surmise syncytia formation drives impairment facilitating "seeding" hyperphosphorylated Tau, documented COVID-19. our previous work, we hypothesized SARS-CoV-2 induces premature endothelial senescence, permeability blood-brain barrier. migration microbes and/or their components circulation, eventually reaching brain where they may induce dysfunction. For example, translocated lipopolysaccharides or microbial DNA Tau hyperphosphorylation, memory problems. this perspective article, examine pathogenetic mechanisms potential biomarkers cell-free DNA, interleukin 22, phosphorylated beneficial effect transcutaneous vagal nerve stimulation.
Language: Английский
Citations
12
Aquaculture, Journal Year: 2025, Volume and Issue: unknown, P. 742365 - 742365
Published: March 1, 2025
Language: Английский
Citations
0
Viruses, Journal Year: 2025, Volume and Issue: 17(4), P. 503 - 503
Published: March 31, 2025
Infectious bronchitis virus (IBV) poses a major challenge to poultry health and productivity. This study examined how inflammatory cell death pathways influence the replication pathogenesis of two IBV strains—respiratory Connecticut (Conn) A5968 nephropathogenic Delmarva (DMV)/1639—in chicken macrophages. Low serum conditions enhanced viral replication, reduced viability, promoted apoptosis necroptosis, with DMV/1639 showing more pronounced effects. Modulation cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) pathway displayed strain-specific effects, mitigating necroptosis in DMV/1639-infected cells but exacerbating Conn A5968-infected cells. Broad caspase inhibition (z-VAD-FMK) while selective caspase-1/4 heightened apoptotic responses. Caspase-8 selectively infections increased infections. NLRP3 inflammasome RIPK1 decreased viability both strains had distinct effects on necroptosis. These findings reveal regulation apoptosis, underscoring intricate interplay between host pathways. Understanding these mechanisms provides novel insights into highlights potential therapeutic strategies mitigate its impact health.
Language: Английский
Citations
0
ACS Biomaterials Science & Engineering, Journal Year: 2025, Volume and Issue: unknown
Published: April 3, 2025
Cell-free DNA (cfDNA) holds significant promise for diagnostic and therapeutic advancements in medicine. This review delineates the utility of cfDNA diagnostics its potential through clearance mechanisms an array diseases. Damage-associated molecular patterns (DAMPs) are endogenous molecules released by host cells during stress, or injury. As a trigger inflammatory responses via damage-associated (DAMPs), cfDNA's removal nanotechnological approaches can attenuate inflammation promote tissue repair. While application is particularly auspicious cancer, sepsis, conditions, it confronted with challenges including toxicity, specificity, rigors clinical trial validation. Collectively, this novel targets to inform development innovative treatment strategies.
Language: Английский
Citations
0
Molecular Biology and Evolution, Journal Year: 2023, Volume and Issue: 40(2)
Published: Jan. 17, 2023
Abstract Some viruses (e.g., human immunodeficiency virus 1 and severe acute respiratory syndrome coronavirus 2) have been experimentally proposed to accelerate features of aging cellular senescence. These observations, along with evolutionary considerations on viral fitness, raised the more general puzzling hypothesis that, beyond documented sources in genetics, our species may also depend virally encoded interactions distorting benefits diverse viruses. Accordingly, we designed systematic network–based analyses protein interactomes, which unraveled dozens encoding proteins demonstrated interact from pathways associated aging, including We further corroborated predictions that specific interfere using published experimental evidence transcriptomic data; identifying influenza A (subtype H1N1) as a major candidate age distorter, notably through manipulation By providing original convergently contribute evolution numerous age-associated co-evolution, network-based bipartite methodologies support an ecosystemic study searching for genetic causes outside focal species. Our findings, predicting distorters targets anti-aging therapies among viruses, could fundamental practical implications biology, study, virology, medicine, demography.
Language: Английский
Citations
9