Iron as the concert master in the pathogenic orchestra playing in sporadic Parkinson’s disease

Journal of Neural Transmission, Journal Year: 2021, Volume and Issue: 128(10), P. 1577 - 1598

Published: Oct. 1, 2021

Abstract About 60 years ago, the discovery of a deficiency dopamine in nigro-striatal system led to variety symptomatic therapeutic strategies supplement and substantially improve quality life patients with Parkinson’s disease (PD). Since these seminal developments, neuropathological, neurochemical, molecular biological genetic discoveries contributed elucidate pathology PD. Oxidative stress, consequences reactive oxidative species, reduced antioxidative capacity including loss glutathione, excitotoxicity, mitochondrial dysfunction, proteasomal apoptosis, lysosomal autophagy, suggested be causal for ɑ-synuclein fibril formation aggregation contributing neuroinflammation neural cell death underlying this devastating disorder. However, there are no final conclusions about triggered pathological mechanism(s) follow-up dysfunctions. Nevertheless, it is fact, that iron, major component reactions, as well neuromelanin, intraneuronal chelator undergo an age-dependent increase. And ageing risk factor Iron significantly increased substantia nigra pars compacta (SNpc) Reasons finding include disturbances iron-related import export mechanisms across blood–brain barrier (BBB), localized opening BBB at tract brain vessel pathology. Whether primary or secondary importance not known. We assume better fit top-down hypotheses pathogens entering via olfactory system, then bottom-up (gut-brain) hypothesis PD Triggers bottom-up, dual-hit pathologies chemicals, viruses bacteria. If so, hepcidin, regulator iron absorption its distribution into tissues, play role pathogenesis dyshomeostasis initiating progressing The glial components still unknown. dramatic glutathione (GSH), which mainly synthesized glia, suggests dysfunction process, GSH uptake neurons. Loss increase SNpc concentration have been early, may even pre-symptomatic processes PD, despite fact they progression factors. ferritin isoforms has studied so far detail human post-mortem tissue close insight their called upon. In conclusion, “iron” player Selective chelation excess site nigra, where suggested, peripherally acting chelators contribute portfolio armamentarium anti-Parkinson medications.

Language: Английский

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Optimization and Deoptimization of Codons in SARS‐CoV‐2 and Related Implications for Vaccine Development

Advanced Science, Journal Year: 2023, Volume and Issue: 10(23)

Published: June 2, 2023

The spread of coronavirus disease 2019 (COVID-19), caused by severe respiratory syndrome 2 (SARS-CoV-2), has progressed into a global pandemic. To date, thousands genetic variants have been identified among SARS-CoV-2 isolates collected from patients. Sequence analysis reveals that the codon adaptation index (CAI) values viral sequences decreased over time but with occasional fluctuations. Through evolution modeling, it is found this phenomenon may result virus's mutation preference during transmission. Using dual-luciferase assays, further discovered deoptimization codons in sequence weaken protein expression virus evolution, indicating usage play an important role fitness. Finally, given importance and particularly for mRNA vaccines, designed several codon-optimized Omicron BA.2.12.1, BA.4/5, XBB.1.5 spike vaccine candidates experimentally validated their high levels expression. This study highlights provides guidelines optimization DNA development.

Language: Английский

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Insight into Codon Utilization Pattern of Tumor Suppressor Gene EPB41L3 from Different Mammalian Species Indicates Dominant Role of Selection Force

Cancers, Journal Year: 2021, Volume and Issue: 13(11), P. 2739 - 2739

Published: June 1, 2021

Uneven codon usage within genes as well among genomes is a usual phenomenon across organisms. It plays significant role in the translational efficiency and evolution of particular gene. EPB41L3 tumor suppressor protein-coding gene, present study, pattern was envisaged. The full-length sequences gene for human, brown rat, domesticated cattle, Sumatran orangutan available at NCBI were retrieved utilized to analyze CUB patterns selected mammalian species. Compositional properties, dinucleotide abundance, parity analysis showed dominance A G whilst RSCU indicated G/C-ending codons. neutrality plot plotted between GC12 GC3 determine variation mutation pressure natural selection (R = 0.926; p < 0.00001) over three positions result concordance with adaptation index ENc-GC3 analysis, (P2). Overall dominant acting during

Language: Английский

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First report of the complete mitochondrial genome of 3 beetles (Coleoptera: Scarabaeidae) harming Gastrodia elata (Asparagales: Orchidaceae)

Journal of Insect Science, Journal Year: 2024, Volume and Issue: 24(1)

Published: Jan. 1, 2024

Abstract Gastrodia elata Blume, a valuable traditional Chinese medicine with significant clinical and nutritional importance, is fungal heterotrophic orchid. We present the first report of mitochondrial genome structure characteristics 3 Scarabaeidae pests affecting G. elata: Sophrops peronosporus Gu & Zhang, Anomala rufiventris Kollar Redtenbacher, Callistethus plagiicollis Fairmaire. Each mitogenome contained 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), 2 ribosomal (rRNAs), control region, no gene rearrangements observed. All 21 tRNAs, except trnS1 that lacks dihydrouridine, had stable cloverleaf secondary structure. Maximum likelihood Bayesian inference analyses based on PCGs produced topologically similar phylogenetic trees, both high nodal support. Larvae these cause substantial damage by gnawing tubers roots elata, leading to reduced yield compromised quality. These findings contribute studies Scarabaeidae, expand knowledge pests, offer reference materials for their identification control.

Language: Английский

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Analysis of codon usage bias of exonuclease genes in invertebrate iridescent viruses

Virology, Journal Year: 2024, Volume and Issue: 593, P. 110030 - 110030

Published: Feb. 19, 2024

Language: Английский

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Drug repurposing of argatroban, glimepiride and ranolazine shows anti-SARS-CoV-2 activity via diverse mechanisms

Heliyon, Journal Year: 2025, Volume and Issue: 11(3), P. e41894 - e41894

Published: Jan. 10, 2025

Despite the vast vaccination campaigns against SARS-CoV-2, vaccine-resistant variants have emerged, and COVID-19 is continuing to spread with fear of emergence new that are resistant currently available anti-viral drugs. Hence, there an urgent need discover potential host-directed - rather than virus-directed therapies COVID-19. SARS-CoV-2 enters host cells through binding viral spike (S)-protein angiotensin-converting enzyme 2 (ACE2) receptor, rendering port entry attractive therapeutic target. Accordingly, this study aimed investigate FDA-approved drugs for their repurposing inhibit point SARS-CoV-2. library was enrolled in docking simulations identify bind Spike-ACE2 interface. The list retrieved by shortlisted 19 based on scores safety profiles. These were screened ability prevent between ACE2 S-protein using ELISA-based assay. Five showed statistically significant inhibition S-protein, ranging from 4 % 37 %. Of those five, argatroban, glimepiride ranolazine antiviral activity at IC50 concentrations well below CC50 assessed plaque Their mode action then determined assay some modifications, which revealed argatroban acted mainly a direct virucidal mechanism, while largely inhibited replication, exerted its impact primarily inhibiting adsorption. In conclusion, has identified three could potentially be repurposed used management

Language: Английский

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Codon usage analysis in selected virulence genes of Staphylococcal species

Current Genetics, Journal Year: 2025, Volume and Issue: 71(1)

Published: Jan. 24, 2025

Language: Английский

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Comprehensive analysis of codon usage patterns of porcine deltacoronavirus and its host adaptability

Transboundary and Emerging Diseases, Journal Year: 2022, Volume and Issue: 69(5)

Published: May 8, 2022

The porcine deltacoronavirus (PDCoV) is a newly discovered pig enteric coronavirus that can infect cells from various species. In Haiti, PDCoV infections in children with acute undifferentiated febrile fever were recently reported. Considering the great potential of inter-species transmission PDCoV, we performed comprehensive analysis codon usage patterns and host adaptation profiles 54 representative strains spike (S) gene. Phylogenetic S gene indicates be divided into five genogroups. We found certain bias existed gene, which synonymous codons are often ended U or A. Heat map revealed all shared similar trend. dN/dS ratio lower than 1 reveals negative selection on Neutrality showed natural dominant force shaping Unexpectedly, higher level to Homo sapiens Gallus gallus Sus scrofa. Compared USA lineage, Early China lineage Thailand less adapted their hosts, evolutionary process plays an important role ability PDCoV. These findings this study add our understanding PDCoV's evolution, adaptability, transmission.

Language: Английский

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Natural selection plays a significant role in governing the codon usage bias in the novel SARS-CoV-2 variants of concern (VOC)

PeerJ, Journal Year: 2022, Volume and Issue: 10, P. e13562 - e13562

Published: June 23, 2022

The ongoing prevailing COVID-19 pandemic caused by SARS-CoV-2 is becoming one of the major global health concerns worldwide. genome encodes spike (S) glycoprotein that plays a very crucial role in viral entry into host cell via binding its receptor domain (RBD) to angiotensin converting enzyme 2 (ACE2) receptor. continuously evolving results more severe and transmissible variants characterized emergence novel mutations called ‘variants concern’ (VOC). currently designated alpha, beta, gamma, delta omicron VOC are focus this study due their high transmissibility, increased virulence, for decreased effectiveness available vaccines. In VOC, gene other non-structural protein may affect efficacies approved To understand diversity SARS-CoV-2, several studies have been performed on limited number sequences. However, only few focused codon usage bias (CUBs) pattern analysis all strains. Therefore, evaluate evolutionary divergence S-genes, we CUBs 300,354 sequences relationship with adaptation different hosts, i.e ., humans, bats, pangolins. Base composition RSCU revealed presence 20 preferred AU-ended 10 under-preferred GC-ended codons. addition, CpG was found be depleted, which attributable adaptive response viruses escape from defense process. Moreover, ENC values higher S-gene. Further, neutrality plot demonstrated S-genes analyzed under 83.93% influence natural selection, suggesting pivotal shaping CUBs. similar among Interestingly, observed strains followed trend antagonistic respect human host. identified would help virus evolution adaptation, thus design vaccine strategies against emerging best our knowledge, first report identifying VOC.

Language: Английский

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Evolutionary dynamics and adaptive analysis of Seneca Valley virus

Infection Genetics and Evolution, Journal Year: 2023, Volume and Issue: 113, P. 105488 - 105488

Published: Aug. 7, 2023

Over the past 20 years, Seneca Valley virus (SVV) has emerged in various countries and regions around world. Infected pigs display symptoms similar to foot-and-mouth disease other vesicular diseases, causing severe economic losses affected countries. In recent number of SVV infections been increasing Brazil, China, United States. this study, we comprehensively analyzed genomic sequence data from perspectives evolutionary dynamics, phylogeography, codon usage bias. We aimed gain further insights into SVV's genetic diversity, spatiotemporal distribution patterns, adaptations. Phylogenetic analysis revealed that evolved eight distinct lineages. Based on results phylogeographic analysis, it is speculated States might have source SVV, where subsequently spread different regions. Moreover, our positive selection sites capsid proteins suggests their potential importance process receptor recognition. Finally, preference indicates natural a primary driver influencing conclusion, in-depth investigation origin, dissemination, evolution, adaptation emphasizes significance surveillance control measures.

Language: Английский

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