Andrei E. Siniavin  Mikhail S. Novikov  Vladimir A. Gushchin  Alexander A. Terechov  Igor A. Ivanov  Maria P. Paramonova  Elena S. Gureeva  Leonid I. Russu  Nadezhda A. Kuznetsova  Elena V. Shidlovskaya  Sergei I. Luyksaar  Daria V. Vasina  Sergei A. Zolotov  Nailya A. Zigangirova  Denis Y. Logunov  Alexander L. Gintsburg 《International journal of molecular sciences》2022,23(17)

Despite the widespread use of the COVID-19 vaccines, the search for effective antiviral drugs for the treatment of patients infected with SARS-CoV-2 is still relevant. Genetic variability leads to the continued circulation of new variants of concern (VOC). There is a significant decrease in the effectiveness of antibody-based therapy, which raises concerns about the development of new antiviral drugs with a high spectrum of activity against VOCs. We synthesized new analogs of uracil derivatives where uracil was substituted at the N₁ and N₃ positions. Antiviral activity was studied in Vero E6 cells against VOC, including currently widely circulating SARS-CoV-2 Omicron. All synthesized compounds of the panel showed a wide antiviral effect. In addition, we determined that these compounds inhibit the activity of recombinant SARS-CoV-2 RdRp. Our study suggests that these non-nucleoside uracil-based analogs may be of future use as a treatment for patients infected with circulating SARS-CoV-2 variants.  相似文献   

    

Giuseppina Biondi  Nicola Marrano  Anna Borrelli  Martina Rella  Giuseppe Palma  Isabella Calderoni  Edoardo Siciliano  Pasquale Lops  Francesco Giorgino  Annalisa Natalicchio 《International journal of molecular sciences》2022,23(10)

The dysregulation of the β-cell functional mass, which is a reduction in the number of β-cells and their ability to secure adequate insulin secretion, represents a key mechanistic factor leading to the onset of type 2 diabetes (T2D). Obesity is recognised as a leading cause of β-cell loss and dysfunction and a risk factor for T2D. The natural history of β-cell failure in obesity-induced T2D can be divided into three steps: (1) β-cell compensatory hyperplasia and insulin hypersecretion, (2) insulin secretory dysfunction, and (3) loss of β-cell mass. Adipose tissue (AT) secretes many hormones/cytokines (adipokines) and fatty acids that can directly influence β-cell function and viability. As this secretory pattern is altered in obese and diabetic patients, it is expected that the cross-talk between AT and pancreatic β-cells could drive the maintenance of the β-cell integrity under physiological conditions and contribute to the reduction in the β-cell functional mass in a dysmetabolic state. In the current review, we summarise the evidence of the ability of the AT secretome to influence each step of β-cell failure, and attempt to draw a timeline of the alterations in the adipokine secretion pattern in the transition from obesity to T2D that reflects the progressive deterioration of the β-cell functional mass.  相似文献   

    

Rita Del Giudice  Paola Imbimbo  Federico Pietrocola  Isabelle Martins  Fatima Domenica Elisa De Palma  Jos Manuel Bravo-San Pedro  Guido Kroemer  Maria Chiara Maiuri  Daria Maria Monti 《International journal of molecular sciences》2022,23(7)

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Irina Zh. Zhalsanova  Ekatherina G. Ravzhaeva  Anna E. Postrigan  Gulnara N. Seitova  Daria I. Zhigalina  Vasilisa Yu. Udalova  Maryana M. Danina  Ilya V. Kanivets  Nikolay A. Skryabin 《International journal of molecular sciences》2022,23(18)

Rafiq syndrome (RAFQS) is a congenital disorder of glycosylation (CDG) that is caused by mutations in the MAN1B1 gene and characterized by impaired protein and lipid glycosylation. RAFQS is characterized by a delay in intellectual and motor development, facial and other dysmorphism, truncal obesity, behavior problems, and hypotonia. We describe a Russian patient with delayed intellectual and motor development, a lack of speech, disorientation in space and time, impaired attention and memory, and episodes of aggression. Screening for lysosomal, amino acid, organic acid, and mitochondrial disorders was normal. The patient was referred for the targeted sequencing of the “Hereditary Metabolic Disorders” panel. The genetic testing revealed two heterozygous pathogenic variants in the MAN1B1 gene: the previously reported c.1000C > T (p.Arg334Cys) and the novel c.1065 + 1 G > C. Thus, the patient’s clinical picture and genetic analysis confirmed RAFQS in the patient.  相似文献   

    

Rosanna Lucignano  Alessandro Pratesi  Paola Imbimbo  Daria Maria Monti  Delia Picone  Luigi Messori  Giarita Ferraro  Antonello Merlino 《International journal of molecular sciences》2022,23(22)

Auranofin (AF), a gold(I) compound that is currently used for the treatment of rheumatoid arthritis and is in clinical trials for its promising anticancer activity, was encapsulated within the human H-chain and the horse spleen ferritin nanocages using the alkaline disassembly/reassembly protocol. The aim of the work was to highlight possible differences in their drug loading capacity and efficacy. The drug-loaded ferritins were characterized via UV-vis absorption spectroscopy and inductively coupled plasma-atomic emission spectroscopy to assess AF encapsulation and to define the exact amount of gold atoms trapped in the Ft cavity. The crystal structures allowed us to define the nature of AF interaction with both ferritins and to identify the gold binding sites. Moreover, the biological characterization let us to obtain preliminary information on the cytotoxic effect of AF when bound to the human H-chain.  相似文献   

    

Daria Chlebek  Tomasz P&#x;ociniczak  Sara Gobetti  Agata Kumor  Katarzyna Hupert-Kocurek  Magdalena Pacwa-P&#x;ociniczak 《International journal of molecular sciences》2022,23(1)

The Pseudomonas qingdaonensis ZCR6 strain, isolated from the rhizosphere of Zea mays growing in soil co-contaminated with hydrocarbons and heavy metals, was investigated for its plant growth promotion, hydrocarbon degradation, and heavy metal resistance. In vitro bioassays confirmed all of the abovementioned properties. ZCR6 was able to produce indole acetic acid (IAA), siderophores, and ammonia, solubilized Ca₃(PO₄)₂, and showed surface active properties and activity of cellulase and very high activity of 1-aminocyclopropane-1-carboxylic acid deaminase (297 nmol α-ketobutyrate mg⁻¹ h⁻¹). The strain degraded petroleum hydrocarbons (76.52% of the initial hydrocarbon content was degraded) and was resistant to Cd, Zn, and Cu (minimal inhibitory concentrations reached 5, 15, and 10 mM metal, respectively). The genome of the ZCR6 strain consisted of 5,507,067 bp, and a total of 5055 genes were annotated, of which 4943 were protein-coding sequences. Annotation revealed the presence of genes associated with nitrogen fixation, phosphate solubilization, sulfur metabolism, siderophore biosynthesis and uptake, synthesis of IAA, ethylene modulation, heavy metal resistance, exopolysaccharide biosynthesis, and organic compound degradation. Complete characteristics of the ZCR6 strain showed its potential multiway properties for enhancing the phytoremediation of co-contaminated soils. To our knowledge, this is the first analysis of the biotechnological potential of the species P. qingdaonensis.  相似文献   

    

Polina V. Zhdanova  Alexander A. Lomzov  Daria V. Prokhorova  Grigory A. Stepanov  Alexander A. Chernonosov  Vladimir V. Koval 《International journal of molecular sciences》2022,23(16)

Most processes of the recognition and formation of specific complexes in living systems begin with collisions in solutions or quasi-solutions. Then, the thermodynamic regulation of complex formation and fine tuning of complexes come into play. Precise regulation is very important in all cellular processes, including genome editing using the CRISPR–Cas9 tool. The Cas9 endonuclease is an essential component of the CRISPR–Cas-based genome editing systems. The attainment of high-specificity and -efficiency Cas9 during targeted DNA cleavage is the main problem that limits the practical application of the CRISPR–Cas9 system. In this study, we analyzed the thermodynamics of interaction of a complex’s components of Cas9–RNA/DNA through experimental and computer simulation methods. We found that there is a small energetic preference during Cas9–RNA/DNA formation from the Cas9–RNA and DNA/DNA duplex. The small difference in binding energy is relevant for biological interactions and could be part of the sequence-specific recognition of double-stranded DNA by the CRISPR–Cas9 system.  相似文献   

    

Ekaterina M. Sogorina  Ekaterina R. Kim  Alexey V. Sorokin  Dmitry N. Lyabin  Lev P. Ovchinnikov  Daria A. Mordovkina  Irina A. Eliseeva 《International journal of molecular sciences》2022,23(1)

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Svetlana R. Derkach  Yuliya A. Kuchina  Daria S. Kolotova  Ludmila A. Petrova  Vasily I. Volchenko  Andrei Yu. Glukharev  Vladimir A. Grokhovsky 《International journal of molecular sciences》2022,23(22)

Protein isolates were obtained from marine hydrobionts by the method of isoelectric precipitation with a preliminary stage of protein alkaline solubilisation. Northern blue whiting was chosen as the raw material. Various technological modes of the solubilisation stage were used: the temperature of the reaction mixture was 4 or 20 °C, and the duration was 4 or 16 h. The yield of the product was 44–45% with a high content of the main component (protein) equal to about 95%. It has been shown that a decrease in the temperature and duration of the alkaline solubilisation stage provides the production of protein isolates with good technological properties, a low solubility, high swelling and high emulsifying ability, necessary for its use in the production of functional food products, including therapeutic and prophylactic effects. These technological properties are explained by a change in the composition and structure of the protein, the change being an increase in the content of essential amino acids and the proportion of α-helices in the polypeptide chain. The main patterns obtained will be used to obtain protein isolates from marine molluscs.  相似文献   

    

Vasileios Stavropoulos  Peter Wilson  Daria Kuss  Mark Griffiths  Douglas Gentile 《Behaviour & Information Technology》2017,36(5):524-539

Presence describes the feeling of reality and immersion that users of virtual/Internet environments have. Importantly, it has been suggested that there are individual and contextual differences regarding susceptibility to presence. These aspects of presence have been linked to both beneficial and disadvantageous uses of the Internet, such as online therapeutic applications and addictive Internet behaviours. In the present study, presence was studied in relation to individual anxiety symptoms and classroom-level openness to experience (OTE) using a normative sample of 648 adolescents aged between 16 and 18 years. Presence was assessed with the Presence II questionnaire, anxiety symptoms with the relevant subscales of the SCL-90-R, and OTE with the Five-Factor Questionnaire. A three-level hierarchical linear model was calculated. Results showed that experiencing presence in virtual environments dropped between the ages of 16 and 18 years. Additionally, although anxiety symptoms were associated with higher presence at 16 years, this association decreased with age. Results also demonstrated that adolescents in classrooms higher on OTE reported reduced level of experiencing presence. The practical and theoretical implications of these findings are discussed.  相似文献