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1.
Curr Pharm Des ; 29(14): 1105-1120, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37073656

RESUMEN

INTRODUCTION: Apoptosis and autophagy are the two fundamental processes involved in maintaining homeostasis, and a common stimulus may initiate the processes. Autophagy has been implicated in various diseases, including viral infections. Genetic manipulations leading to altered gene expression might be a strategy to check virus infection. AIM: Determination of molecular patterns, relative synonymous codon usage, codon preference, codon bias, codon pair bias, and rare codons so that genetic manipulation of autophagy genes may be done to curb viral infection. METHODS: Using various software, algorithms, and statistical analysis, insights into codon patterns were obtained. A total of 41 autophagy genes were envisaged as they are involved in virus infection. RESULTS: The A/T and G/C ending codons are preferred by different genes. AAA-GAA and CAG-CTG codon pairs are the most abundant codon pairs. CGA, TCG, CCG, and GCG are rarely used codons. CONCLUSION: The information generated in the present study helps manipulate the gene expression level of virus infection-associated autophagy genes through gene modification tools like CRISPR. Codon deoptimization for reducing while codon pair optimization for enhancing is efficacious for HO-1 gene expression.


Asunto(s)
Virosis , Humanos , Codón/genética , Virosis/genética , Evolución Molecular
2.
Sci Rep ; 13(1): 6453, 2023 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-37081125

RESUMEN

The purpose of this work was to study the effect of selenium nanoparticles (Se NPs) on the biological and morphofunctional parameters of barley seeds (Hordéum vulgáre L.) We used seeds of Hordéum vulgáre L. with reduced morphofunctional characteristics. For the experiment, Se NPs were synthesized and stabilized with didecyldimethylammonium chloride. It was found that Se NPs have a spherical shape and a diameter of about 50 nm. According to dynamic light scattering data, the average hydrodynamic radius of the particles was 28 ± 8 nm. It is observed that the nanoparticles have a positive ζ-potential (+ 27.3 mV). For the experiment, we treated Hordéum vulgáre L. seeds with Se NPs (1, 5, 10 and 20 mg/L). The experiment showed that treatment of Hordéum vulgáre L. seeds with Se NPs has the best effect on the length of roots and sprout at concentration of 5 mg/L and on the number and thickness of roots at 10 mg/L. Germinability and germination energy of Hordéum vulgáre L. seeds were higher in group treated with 5 mg/L Se NPs. Analysis of macrophotographs of samples, histological sections of roots and 3D visualization of seeds by microcomputing tomography confirmed the best effect at 5 mg/L Se NPs. Moreover, no local destructions were detected at concentrations > 5 mg/L, which is most likely due to the inhibition of regulatory and catalytic processes in the germinating seeds. the treatment of Hordéum vulgáre L. seeds with > 5 mg/L Se NPs caused significant stress, coupled with intensive formation of reactive oxygen species, leading to a reorientation of root system growth towards thickening. Based on the results obtained, it was concluded that Se NPs at concentrations > 5 mg/L had a toxic effect. The treatment of barley seeds with 5% Se NPs showed maximum efficiency in the experiment, which allows us to further consider Se NPs as a stimulator for the growth and development of crop seeds under stress and reduced morphofunctional characteristics.


Asunto(s)
Hordeum , Nanopartículas , Selenio , Selenio/farmacología , Semillas , Germinación
3.
Vaccines (Basel) ; 11(2)2023 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-36851364

RESUMEN

The SARS-CoV-2 delta variant (B.1.617.2) appeared for the first time in December 2020 and later spread worldwide. Currently available vaccines are not so efficacious in curbing the viral pathogenesis of the delta strain of COVID; therefore, the development of a safe and effective vaccine is required. In the present study, we envisaged molecular patterns in the structural genes' spike, nucleoprotein, membrane, and envelope of the SARS-CoV-2 delta variant. The study was based on determining compositional features, dinucleotide odds ratio, synonymous codon usage, positive and negative codon contexts, rare codons, and insight into relatedness between the human host isoacceptor tRNA and preferred codons from the structural genes. We found specific patterns, including a significant abundance of T nucleotide over all other three nucleotides. The underrepresentation of GpA, GpG, CpC, and CpG dinucleotides and the overrepresentation of TpT, ApA, CpT, and TpG were observed. A preference towards ACT- (Thr), AAT- (Asn), TTT- (Phe), and TTG- (Leu) initiated codons and aversion towards CGG (Arg), CCG (Pro), and CAC (His) was present in the structural genes of the delta strain. The interaction between the host tRNA pool and preferred codons of the envisaged structural genes revealed that the virus preferred the codons for those suboptimal numbers of isoacceptor tRNA were present. We see this as a strategy adapted by the virus to keep the translation rate low to facilitate the correct folding of viral proteins. The information generated in the study helps design the attenuated vaccine candidate against the SARS-CoV-2 delta variant using a synthetic biology approach. Three strategies were tested: changing TpT to TpA, introducing rare codons, and disrupting favored codons. It found that disrupting favored codons is a better approach to reducing virus fitness and attenuating SARS-CoV-2 delta strain using structural genes.

4.
Pathogens ; 12(2)2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36839597

RESUMEN

Hepatitis C virus (HCV) is enveloped RNA virus, encoding for a polyprotein that is processed by cellular proteases. The virus is responsible for liver cirrhosis, allograft rejection, and human hepatocellular carcinoma. Based on studies including compositional analysis, odds ratio analysis, parity analysis, skew analysis, relative synonymous codon usage, codon bias, and protein properties, it was evident that codon usage bias in HCV is dependent upon the nucleotide composition. Codon context analysis revealed CTC-CTG as a preferred codon pair. While CGA and CGT codons were rare, none of the codons were rare in HCV-like viruses envisaged in the present study. Many of the preferred codon pairs were valine amino acid-initiated, which possibly infers viral infectivity; hence the role of selection forces appears to act on the HCV genome, which was further validated by neutrality analysis where selection accounted for 87.28%, while mutation accounted for 12.72% force shaping codon usage. Furthermore, codon usage was correlated with the length of the genome. HCV viruses prefer valine-initiated codon pairs, while HCV-like viruses prefer alanine-initiated codon pairs. The HCV host range is very narrow and is confined to only humans and chimpanzees. Based on indices including codon usage correlation analysis, similarity index, and relative codon deoptimization index, it is evident in the study that the chimpanzee is the primary host of the virus. The present study helped elucidate the preferred host for HCV. The information presented in the study paved the way for generating an attenuated vaccine candidate through viral recoding, with finely tuned nucleotide composition and a perfect balance of preferred and rare codons.

5.
Mol Neurobiol ; 60(4): 2252-2267, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36637744

RESUMEN

Neurodegenerative disorders are often a culmination of the accumulation of abnormally folded proteins and defective organelles. Autophagy is a process of removing these defective proteins, organelles, and harmful substances from the body, and it works to maintain homeostasis. If autophagic removal of defective proteins has interfered, it affects neuronal health. Some of the autophagic genes are specifically found to be associated with neurodegenerative phenotypes. Non-functional, mutated, or gene copies having silent mutations, often termed synonymous variants, might explain this. However, these synonymous variant which codes for exactly similar proteins have different translation rates, stability, and gene expression profiling. Hence, it would be interesting to study the pattern of synonymous variant usage. In the study, synonymous variant usage in various transcripts of autophagic genes ATG5, ATG7, ATG8A, ATG16, and ATG17/FIP200 reported to cause neurodegeneration (if dysregulated) is studied. These genes were analyzed for their synonymous variant usage; nucleotide composition; any possible nucleotide skew in a gene; physical properties of autophagic protein including GRAVY and AROMA; hydropathicity; instability index; and frequency of acidic, basic, neutral amino acids; and gene expression level. The study will help understand various evolutionary forces acting on these genes and the possible augmentation of a gene if showing unusual behavior.


Asunto(s)
Evolución Molecular , Mutación Silenciosa , Codón , Nucleótidos/genética
6.
Vaccines (Basel) ; 10(11)2022 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-36366382

RESUMEN

The overexpression of SARS-CoV-2 primary receptors and co-receptors (ACE2, TMPRSS2, FURIN, and CD147) enhance the likeliness of SARS-CoV-2 infection. The genes for same receptors are overexpressed in the periodontal tissues of periodontitis patients. On the other hand, BMAL1 is recognized to play a crucial role in regulating pulmonary inflammation and enhancing susceptibility to viral infection. Silenced BMAL1 disrupts circadian transcriptional regulations, enhances vulnerability to SARS-CoV-2 infections, and may trigger the further production of TNF-α and other pro-inflammatory cytokines that propagate the cytokine storm and exacerbate periodontal inflammation. Therefore ACE2, TMPRSS2, FURIN, CD147, and BMAL1 are the crossroads between SARS-CoV-2 and Periodontitis genes. The enhanced expression of ACE2, TMPRSS2, FURIN, and CD147 and the diminished expression of BMAL1 may be a strategy to check both ailments simultaneously. In gene manipulation techniques, oligos are introduced, which contain all the necessary information to manipulate gene expression. The data are derived from the studies on genes' molecular patterns, including nucleotide composition, dinucleotide patterns, relative synonymous codon usage, codon usage bias, codon context, and rare and abundant codons. Such information may be used to manipulate the overexpression and underexpression of the genes at the time of SARS-CoV-2 infection and periodontitis to mitigate both ailments simultaneously; it can be explored to uncover possible future treatments.

7.
Genes (Basel) ; 13(11)2022 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-36360171

RESUMEN

Genome-wide association studies showed the relationship of NIN, ABHD12B, WHAMM, AP3B2, and SIGLEC5 with chronic periodontitis. The study's objective was to investigate different molecular patterns and evolutionary forces acting on the mentioned genes. The investigation of molecular patterns encompasses the study of compositional parameters, expression profile, physical properties of genes, codon preferences, degree of codon bias, determination of the most influential codons, and assessment of actions of evolutionary forces, such as mutations and natural selection. The overall compositional analysis revealed the dominance of A and G nucleotides compared to T and C. A relatively low codon usage bias is observed. The CTG codon is the most overused codon, followed by TCC. The genes, AP3B2 and SIGLEC5, preferred GC-ending codons, while NIN, ABHD12B, and WHAMM preferred AT-ending codons. The presence of directional mutational force and natural selection was found to operate codon usage in genes envisaged, and selective forces were dominant over mutational forces. Apart from mutation and selection forces, compositional constraints also played imperative roles. The study enriched our knowledge of specific molecular patterns associated with the set of genes significantly associated with chronic periodontitis. Further studies are warranted to identify more genetic signatures associated with the disease.


Asunto(s)
Periodontitis Crónica , Humanos , Periodontitis Crónica/genética , Estudio de Asociación del Genoma Completo , Codón/genética , Selección Genética , Uso de Codones , Proteínas de la Membrana/genética , Proteínas Asociadas a Microtúbulos/genética
8.
Micromachines (Basel) ; 13(7)2022 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-35888922

RESUMEN

In this work, we obtained silver nanoparticles stabilized with polyvinylpyrrolidone, ranging in size from 70 to 110 nm, which exhibits good crystallinity and anisotropic structure. For the first time, we studied the influence of the molar ratio of silver between silver and peroxide on the oxidation process of the nanoparticles and determined the regularities of this process by analyzing changes in absorption spectra. Our results showed that at molar ratios of Ag:H2O2 = 1:1 and 1:5, dependences of changes in the intensity, position and half-width of the absorption band of the plasmon resonance are rectilinear. In vivo studies of silver nanoparticles have shown that silver nanoparticles belong to the toxicity class III (moderately hazardous substance) and to the third group according to the degree of accumulation. We established that silver nanoparticles and oxidized silver nanoparticles form a uniform layer on the surface of the suture material. We found that the use of the suture material with silver nanoparticles and oxidized silver nanoparticles does not cause allergic reactions in the organisms of laboratory animals.

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