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1.
Sex Transm Infect ; 96(8): 601-607, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32188772

RESUMEN

To estimate the prevalence and factors associated with HIV and five other STIs among outdoor female sex workers (OSFW) and indoor FSW (IFSW). METHODS: Cross-sectional survey using respondent-driven sampling methodology. Participants answered a bio-behavioural questionnaire and were tested for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV), syphilis (lifetime contact) and Mycoplasma genitalium (MG). Weighted HIV and other STIs prevalence and 95% CIs were calculated. Weighted multivariate logistic regression was performed to identify factors associated with having at least one STI (including HIV). RESULTS: Between October 2017 and July 2018, 385 FSW participants were recruited, among whom 206 (53.5%) were IFSW and 179 (46.5%) were OFSW. The mean age was 31.4 years. Weighted HIV prevalence was 3.1% (95% CI 1.5 to 7.0). Weighted prevalence of other STIs was: 4.1% (95% CI 2.2 to 8.0) for NG, 8.8% (95% CI 5.9 to 13.0) for CT, 12.7% (95% CI 8.6 to 18.0) for TV, 13.9% (95% CI 9.9 to 19.0) for syphilis (lifetime contact) and 14.9% (95% CI 10.5 to 21.0) for MG. STI prevalence was significantly higher among OFSW for CT, TV and MG (p<0.001). In total, 43.2% of the participants had at least one HIV/STI. Factors associated with having HIV/STI were being an OFSW (OR 3.29; 95% CI 1.72 to 6.27); being registered in another Russian region (2.61 (95% CI 1.05 to 6.48)); having never been tested for HIV (2.51 (95% CI 0.98 to 6.41)) and having a low level of knowledge regarding HIV transmission (4.88 (95% CI 0.96 to 24.78)). CONCLUSION: Prevalence of HIV and STIs was high among FSW in Moscow. OFSW were more vulnerable to STIs. There is an urgent need to tailor programmes for sexual and reproductive health for FSW in Russia.


Asunto(s)
Infecciones por VIH/epidemiología , Trabajadores Sexuales/estadística & datos numéricos , Enfermedades de Transmisión Sexual/epidemiología , Adulto , Estudios Transversales , Femenino , Infecciones por VIH/psicología , Conocimientos, Actitudes y Práctica en Salud , Humanos , Persona de Mediana Edad , Moscú/epidemiología , Prevalencia , Factores de Riesgo , Conducta Sexual , Enfermedades de Transmisión Sexual/psicología , Adulto Joven
2.
J Org Chem ; 84(21): 13430-13446, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31547663

RESUMEN

The reactions of thioamides with azides in water were studied. It was reliably shown that the reaction of 2-cyanothioacetamides 1 with various types of azides 2 in water in the presence of alkali presents an efficient, general, one-step, atom-economic, and eco-friendly method for the synthesis of 1,2,3-thiadiazol-4-carbimidamides 5 and 1,2,3-triazole-4-carbothioamides 4. This method can be extended to the one-pot reaction of sulfonyl chlorides and 6-chloropyrimidines 2'o with sodium azide, leading to final products in higher yields, that is, avoiding the isolation of unsafe sulfonyl azides. The method was furthermore applied to the reaction of N,N'-bis-(2-cyanothiocarbonyl)pyrazine 1h with sulfonyl azides to afford bicyclic 1,2,3-thiadiazoles 8 and 1,2,3-triazoles 9 connected via a 1,1'-piperazinyl linker. 2-Cyanothioacetamides 1 were also shown to react with aromatic azides in water in the presence of alkali to afford 1-aryl-5-amino-1,2,3-triazole-4-carbothioamides 11. In contrast to aromatic azides and similarly to sulfonyl azides, 6-azidopyrimidine-2,4-diones 2o-q react with cyanothioacetamides to form N-pyrimidin-6-yl-5-dialkylamino-1,2,3-thiadiazole-4-N-l-carbimidamides 12. A mechanism was proposed to rationalize the role of water in changing the reactivity of azides toward 2-cyanothioacetamides.

3.
Beilstein J Org Chem ; 12: 2390-2401, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-28144307

RESUMEN

Reactions of ß-azolyl enamines and nitrile oxides were studied by both experimental and theoretical methods. (E)-ß-(4-Nitroimidazol-5-yl), (5-nitroimidazol-4-yl) and isoxazol-5-yl enamines smoothly react regioselectively at room temperature in dioxane solution with aryl, pyridyl, and cyclohexylhydroxamoyl chlorides without a catalyst or a base to form 4-azolylisoxazoles as the only products in good yields. The intermediate 4,5-dihydroisoxazolines were isolated as trans isomers during the reaction of (E)-ß-imidazol-4-yl enamines with aryl and cyclohexylhydroxamoyl chlorides. Stepwise and concerted pathways for the reaction of ß-azolyl enamines with hydroxamoyl chlorides were considered and studied at the B3LYP/Def2-TZVP level of theory combined with D3BJ dispersion correction. The reactions of benzonitrile oxide with both E- and Z-imidazolyl enamines have been shown to proceed stereoselectively to form trans- and cis-isoxazolines, respectively. The preference of E-isomers over Z-isomers, driven by the higher stability of the former, apparently controls the stereoselectivity of the investigated cycloaddition reaction with benzonitrilе oxide. Based on the reactivity of azolyl enamines towards hydroxamoyl chlorides, a novel, effective catalyst-free method was elaborated to prepare 4-azolyl-5-substituted isoxazoles that are otherwise difficult to obtain.

4.
J Biol Chem ; 289(29): 20158-69, 2014 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-24878957

RESUMEN

The distinguishing feature of self-inactivating (SIN) retroviral vectors is the deletion of the enhancer/promoter sequences in the U3 region of the 3' long terminal repeat. This design is used to overcome transcriptional interference and prevent downstream transcription from the 3' long terminal repeat. SIN vectors were derived from a number of different retroviruses. Studies of SIN vectors show that extensive U3 deletions in HIV-based vectors do not alter viral titers or the in vitro and in vivo properties of the vectors. However, deletion of the U3 sequences in γ- and α-retroviruses correlates with defects in 3' RNA processing and reduces viral titers by >10-fold. Here, we studied the steps in the retroviral life cycle that are affected by the deletion of sequences in the 3' U3 region of Moloney murine leukemia virus-derived retroviral vectors. The results show that the amounts of both full-length and internal RNA transcripts of U3-minus vectors are reduced in the nuclei of transfected cells, an effect that is probably due to a general defect in 3' RNA processing. Furthermore, full-length RNA transcripts were also defective in terms of nuclear export. This defect was complemented by transferring the U3 region to another position within the retroviral vector, indicating that the U3 region contains position-independent cis-acting sequences that are required for the transport of full-length viral transcripts. The results also suggest that the leader region of Moloney murine leukemia virus contains inhibitory/regulatory sequences, which prevent export and mediate nuclear retention of full-length viral RNA.


Asunto(s)
Virus de la Leucemia Murina de Moloney/genética , Secuencias Repetidas Terminales , Transporte Activo de Núcleo Celular , Animales , Elementos de Facilitación Genéticos , Expresión Génica , Vectores Genéticos , Ratones , Virus de la Leucemia Murina de Moloney/metabolismo , Células 3T3 NIH , Regiones Promotoras Genéticas , Procesamiento Postranscripcional del ARN , ARN Viral/genética , ARN Viral/metabolismo , Eliminación de Secuencia , Transfección , Replicación Viral
5.
Animals (Basel) ; 14(2)2024 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-38254427

RESUMEN

The aim of the current study was to assess the female metabolic rate and test the hypothesis that there is a relationship between the egg productivity of Japanese quails from eight breeds and their morphometric, or growth, parameters. Parameters measured were body weight (B), volume (V), and surface area (S), as well as the metabolism level expressed by the ratio S/V. The collected egg performance traits were as follows: the number of eggs produced (N), the average egg weight (W), and the total egg mass (M) (i.e., N multiplied by W). To measure the S and V values, a novel technique was developed that takes into account the similarity of the quail's body to an ellipsoid. An analysis of the relationships between productivity indicators allowed us to introduce a new index called the metabolic index, B·S/V, based on all three main growth parameters in quails. Using the values of this index, we were then able to judge indirectly the level of quails' egg productivity. We went on to assess the N, W, and M values, not only depending on the size of the bird's growth parameters but also according to the degree of their changes during quail growth. These changes were expressed as the slope angles of trend lines describing the growth process data. This approach produced more accurate results for predicting the egg productivity in terms of W and M.

6.
Eur J Med Chem ; 275: 116596, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38889610

RESUMEN

The increasing frequency of filovirus outbreaks in African countries has led to a pressing need for the development of effective antifilovirus agents. In continuation of our previous research on the antifilovirus activity of monoterpenoid derivatives, we synthesized a series of (+)-fenchol and (-)-isopinocampheol derivatives by varying the type of heterocycle and linker length. Derivatives with an N-alkylpiperazine cycle proved to be the most potent antiviral compounds, with half-maximal inhibitory concentration (IC50) 1.4-20 µÐœ against Lenti-EboV-GP infection and 11.3-47 µÐœ against Lenti-MarV-GP infection. Mechanism-of-action experiments revealed that the compounds may exert their action by binding to surface glycoproteins (GPs). It was demonstrated that the binding of the synthesized compounds to the Marburg virus GP is less efficient as compared to the Ebola virus GP. Furthermore, it was shown that the compounds possess lysosomotropic properties. Thus, the antiviral activity may be due to dual effects. This study offers new antiviral agents that are worthy of further exploration.


Asunto(s)
Antivirales , Antivirales/farmacología , Antivirales/química , Antivirales/síntesis química , Humanos , Internalización del Virus/efectos de los fármacos , Relación Estructura-Actividad , Ebolavirus/efectos de los fármacos , Estructura Molecular , Relación Dosis-Respuesta a Droga , Animales , Pruebas de Sensibilidad Microbiana , Chlorocebus aethiops , Marburgvirus/efectos de los fármacos
7.
Genes (Basel) ; 15(4)2024 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-38674458

RESUMEN

Breeding improvements and quantitative trait genetics are essential to the advancement of broiler production. The impact of artificial selection on genomic architecture and the genetic markers sought remains a key area of research. Here, we used whole-genome resequencing data to analyze the genomic architecture, diversity, and selective sweeps in Cornish White (CRW) and Plymouth Rock White (PRW) transboundary breeds selected for meat production and, comparatively, in an aboriginal Russian breed of Ushanka (USH). Reads were aligned to the reference genome bGalGal1.mat.broiler.GRCg7b and filtered to remove PCR duplicates and low-quality reads using BWA-MEM2 and bcftools software; 12,563,892 SNPs were produced for subsequent analyses. Compared to CRW and PRW, USH had a lower diversity and a higher genetic distinctiveness. Selective sweep regions and corresponding candidate genes were examined based on ZFST, hapFLK, and ROH assessment procedures. Twenty-seven prioritized chicken genes and the functional projection from human homologs suggest their importance for selection signals in the studied breeds. These genes have a functional relationship with such trait categories as body weight, muscles, fat metabolism and deposition, reproduction, etc., mainly aligned with the QTLs in the sweep regions. This information is pivotal for further executing genomic selection to enhance phenotypic traits.


Asunto(s)
Pollos , Polimorfismo de Nucleótido Simple , Selección Genética , Animales , Pollos/genética , Sitios de Carácter Cuantitativo , Cruzamiento , Federación de Rusia , Secuenciación Completa del Genoma/métodos
8.
Genes (Basel) ; 15(10)2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39457370

RESUMEN

BACKGROUND/OBJECTIVES: For genomic selection to enhance the efficiency of broiler production, finding SNPs and candidate genes that define the manifestation of main selected traits is essential. We conducted a genome-wide association study (GWAS) for growth and meat productivity traits of roosters from a chicken F2 resource population (n = 152). METHODS: The population was obtained by crossing two breeds with contrasting phenotypes for performance indicators, i.e., Russian White (slow-growing) and Cornish White (fast-growing). The birds were genotyped using the Illumina Chicken 60K SNP iSelect BeadChip. After LD filtering of the data, 54,188 SNPs were employed for the GWAS analysis that allowed us to reveal significant specific associations for phenotypic traits of interest and economic importance. RESULTS: At the threshold value of p < 9.2 × 10-7, 83 SNPs associated with body weight at the age of 28, 42, and 63 days were identified, as well as 171 SNPs associated with meat qualities (average daily gain, slaughter yield, and dressed carcass weight and its components). Moreover, 34 SNPs were associated with a group of three or more traits, including 15 SNPs significant for a group of growth traits and 5 SNPs for a group of meat productivity indicators. Relevant to these detected SNPs, nine prioritized candidate genes associated with the studied traits were revealed, including WNT2, DEPTOR, PPA2, UNC80, DDX51, PAPPA, SSC4D, PTPRU, and TLK2. CONCLUSIONS: The found SNPs and candidate genes can serve as genetic markers for growth and meat performance characteristics in chicken breeding in order to achieve genetic improvement in broiler production.


Asunto(s)
Pollos , Estudio de Asociación del Genoma Completo , Carne , Polimorfismo de Nucleótido Simple , Animales , Pollos/genética , Pollos/crecimiento & desarrollo , Fenotipo , Sitios de Carácter Cuantitativo , Peso Corporal/genética , Masculino , Cruzamiento , Genotipo , Femenino
9.
Genes (Basel) ; 15(3)2024 02 25.
Artículo en Inglés | MEDLINE | ID: mdl-38540354

RESUMEN

The search for SNPs and candidate genes that determine the manifestation of major selected traits is one crucial objective for genomic selection aimed at increasing poultry production efficiency. Here, we report a genome-wide association study (GWAS) for traits characterizing meat performance in the domestic quail. A total of 146 males from an F2 reference population resulting from crossing a fast (Japanese) and a slow (Texas White) growing breed were examined. Using the genotyping-by-sequencing technique, genomic data were obtained for 115,743 SNPs (92,618 SNPs after quality control) that were employed in this GWAS. The results identified significant SNPs associated with the following traits at 8 weeks of age: body weight (nine SNPs), daily body weight gain (eight SNPs), dressed weight (33 SNPs), and weights of breast (18 SNPs), thigh (eight SNPs), and drumstick (three SNPs). Also, 12 SNPs and five candidate genes (GNAL, DNAJC6, LEPR, SPAG9, and SLC27A4) shared associations with three or more traits. These findings are consistent with the understanding of the genetic complexity of body weight-related traits in quail. The identified SNPs and genes can be used in effective quail breeding as molecular genetic markers for growth and meat characteristics for the purpose of genetic improvement.


Asunto(s)
Coturnix , Estudio de Asociación del Genoma Completo , Masculino , Animales , Coturnix/genética , Polimorfismo de Nucleótido Simple/genética , Carne/análisis , Peso Corporal/genética
10.
BMC Psychol ; 11(1): 293, 2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37759263

RESUMEN

BACKGROUND: Innovation competence has been found to constitute distinct innovative abilities that must be analyzed together to get a more comprehensive picture of their effectiveness in various targeted groups. Drawn from the componential theory of creativity, such personal traits as individual resilience and self-monitoring play a critical role in developing innovation competence across students. This research aims to investigate the innovation competence profiles of students from various educational levels and study the role of individual resilience and self-monitoring in predicting the memberships of these profiles. METHODS: A cross-sectional survey was conducted among university and college students, studying in a metropolitan area of the North-West region. The sampling scheme was stratified by the level of education and age. The questionnaire included items on the participants' demographics, including gender, age, and level of education, measures of innovative abilities, individual resilience, and self-monitoring. This study sought to create innovation competence profiles in the student population using latent profile analysis. Multinomial logistic regression was employed to identify the impact of individual resilience and self-monitoring on innovation competence profile membership. RESULTS: A sample of 638 university and college students was analyzed. The latent profile analysis classified students into three different innovation competence profiles - strong, moderate, and weak - with college and female students being identified as the typical members of the weak profile. Individual resilience increases the odds of membership into the strong profile than to moderate and weak profiles. High self-monitors have higher chances of being profiled into the strong profile than the weak and moderate profiles compared to the low self-monitors. CONCLUSIONS: Training investment aimed at boosting the innovative abilities of employees should consider the innovation competence profile of the beneficiaries to inform decisions about the appropriate level of intervention required. Likewise, educators could enrich their courses devoted to improving the innovative abilities of students with content that aims to improve their level of resilience accompanied by social support. Theoretical and practical implications are also discussed.


Asunto(s)
Apoyo Social , Estudiantes , Humanos , Femenino , Estudios Transversales , Universidades , Poder Psicológico
11.
World J Clin Pediatr ; 12(2): 45-56, 2023 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-37034429

RESUMEN

BACKGROUND: Patients with immune-mediated diseases, such as juvenile idiopathic arthritis (JIA) and inflammatory bowel disease (IBD) are at increased risk of developing infections, due to disease-related immune dysfunction and applying of immunosuppressive drugs. AIM: To evaluate vaccine coverage in patients with IBD and JIA, and compare it with healthy children. METHODS: In the cross-sectional study we included the data from a questionnaire survey of 190 Legal representatives of children with JIA (n = 81), IBD (n = 51), and healthy children (HC, n = 58). An electronic online questionnaire was created for the survey. RESULTS: There were female predominance in JIA patients and younger onset age. Parents of JIA had higher education levels. Employment level and family status were similar in the three studied groups. Patients with JIA and IBD had lower vaccine coverage, without parental rejection of vaccinations in IBD, compare to JIA and healthy controls. The main reason for incomplete vaccination was medical conditions in IBD and JIA. IBD patients had a lower rate of normal vaccine-associated reactions compared to JIA and HC. The encouraging role of physicians for vaccinations was the lowest in JIA patients. IBD patients had more possibilities to check antibodies before immune-suppressive therapy and had more supplementary vaccinations compared to JIA and HC. CONCLUSION: JIA and IBD patients had lower vaccine coverage compared to HC. Physicians' encouragement of vaccination and the impossibility of discus about future vaccinations and their outcomes seemed the main factors for patients with immune-mediated diseases, influencing vaccine coverage. Further investigations are required to understand the reasons for incomplete vaccinations and improve vaccine coverage in both groups, especially in rheumatic disease patients. The approaches that stimulate vaccination in healthy children are not always optimal in children with immune-mediated diseases. It is necessary to provide personalized vaccine-encouraging strategies for parents of chronically ill children with the following validation of these technics.

12.
Animals (Basel) ; 13(1)2023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-36611792

RESUMEN

Negative heterosis can occur on different economically important traits, but the exact biological mechanisms of this phenomenon are still unknown. The present study focuses on determining the genetic factors associated with negative heterosis in interspecific hybrids between domestic sheep (Ovis aries) and argali (Ovis ammon). One locus (rs417431015) associated with viability and two loci (rs413302370, rs402808951) associated with meat productivity were identified. One gene (ARAP2) was prioritized for viability and three for meat productivity (PDE2A, ARAP1, and PCDH15). The loci associated with meat productivity were demonstrated to fit the overdominant inheritance model and could potentially be involved int negative heterosis mechanisms.

13.
Biology (Basel) ; 12(7)2023 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-37508409

RESUMEN

A study for genomic variation that may reflect putative selective signaling and be associated with economically important traits is instrumental for obtaining information about demographic and selection history in domestic animal species and populations. A rich variety of the Russian chicken gene pool breeds warrants a further detailed study. Specifically, their genomic features can derive implications from their genome architecture and selective footprints for their subsequent breeding and practical efficient exploitation. In the present work, whole genome genotyping of 19 chicken breeds (20 populations with up to 71 samples each) was performed using the Chicken 50 K BeadChip DNA chip. The studied breed sample included six native Russian breeds of chickens developed in the 17th-19th centuries, as well as eight Russian chicken breeds, including the Russian White (RW), created in the 20th century on the basis of improving local chickens using breeds of foreign selection. Five specialized foreign breeds of chickens, including the White Leghorn (WL), were used along with other breeds representing the Russian gene pool. The characteristics of the genetic diversity and phylogenetic relationships of the native breeds of chickens were represented in comparison with foreign breeds. It was established that the studied native breeds demonstrate their own genetic structure that distinguishes them from foreign breeds, and from each other. For example, we previously made an assumption on what could cause the differences between two RW populations, RW1 and RW2. From the data obtained here, it was verified that WL was additionally crossed to RW2, unlike RW1. Thus, inherently, RW1 is a purer population of this improved Russian breed. A significant contribution of the gene pool of native breeds to the global genetic diversity of chickens was shown. In general, based on the results of a multilateral survey of this sample of breeds, it can be concluded that phylogenetic relationships based on their genetic structure and variability robustly reflect the known, previously postulated and newly discovered patterns of evolution of native chickens. The results herein presented will aid selection and breeding work using this gene pool.

14.
J Anim Sci Biotechnol ; 14(1): 35, 2023 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-36829208

RESUMEN

BACKGROUND: The genomes of worldwide poultry breeds divergently selected for performance and other phenotypic traits may also be affected by, and formed due to, past and current admixture events. Adaptation to diverse environments, including acclimation to harsh climatic conditions, has also left selection footprints in breed genomes. RESULTS: Using the Chicken 50K_CobbCons SNP chip, we genotyped four divergently selected breeds: two aboriginal, cold tolerant Ushanka and Orloff Mille Fleur, one egg-type Russian White subjected to artificial selection for cold tolerance, and one meat-type White Cornish. Signals of selective sweeps were determined in the studied breeds using three methods: (1) assessment of runs of homozygosity islands, (2) FST based population differential analysis, and (3) haplotype differentiation analysis. Genomic regions of true selection signatures were identified by two or more methods or in two or more breeds. In these regions, we detected 540 prioritized candidate genes supplemented them with those that occurred in one breed using one statistic and were suggested in other studies. Amongst them, SOX5, ME3, ZNF536, WWP1, RIPK2, OSGIN2, DECR1, TPO, PPARGC1A, BDNF, MSTN, and beta-keratin genes can be especially mentioned as candidates for cold adaptation. Epigenetic factors may be involved in regulating some of these important genes (e.g., TPO and BDNF). CONCLUSION: Based on a genome-wide scan, our findings can help dissect the genetic architecture underlying various phenotypic traits in chicken breeds. These include genes representing the sine qua non for adaptation to harsh environments. Cold tolerance in acclimated chicken breeds may be developed following one of few specific gene expression mechanisms or more than one overlapping response known in cold-exposed individuals, and this warrants further investigation.

15.
Animals (Basel) ; 13(22)2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-38003057

RESUMEN

Traces of long-term artificial selection can be detected in genomes of domesticated birds via whole-genome screening using single-nucleotide polymorphism (SNP) markers. This study thus examined putative genomic regions under selection that are relevant to the development history, divergence and phylogeny among Japanese quails of various breeds and utility types. We sampled 99 birds from eight breeds (11% of the global gene pool) of egg (Japanese, English White, English Black, Tuxedo and Manchurian Golden), meat (Texas White and Pharaoh) and dual-purpose (Estonian) types. The genotyping-by-sequencing analysis was performed for the first time in domestic quails, providing 62,935 SNPs. Using principal component analysis, Neighbor-Net and Admixture algorithms, the studied breeds were characterized according to their genomic architecture, ancestry and direction of selective breeding. Japanese and Pharaoh breeds had the smallest number and length of homozygous segments indicating a lower selective pressure. Tuxedo and Texas White breeds showed the highest values of these indicators and genomic inbreeding suggesting a greater homozygosity. We revealed evidence for the integration of genomic and performance data, and our findings are applicable for elucidating the history of creation and genomic variability in quail breeds that, in turn, will be useful for future breeding improvement strategies.

16.
Vaccines (Basel) ; 11(4)2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37112720

RESUMEN

Despite the rapid development and approval of several COVID vaccines based on the full-length spike protein, there is a need for safe, potent, and high-volume vaccines. Considering the predominance of the production of neutralizing antibodies targeting the receptor-binding domain (RBD) of S-protein after natural infection or vaccination, it makes sense to choose RBD as a vaccine immunogen. However, due to its small size, RBD exhibits relatively poor immunogenicity. Searching for novel adjuvants for RBD-based vaccine formulations is considered a good strategy for enhancing its immunogenicity. Herein, we assess the immunogenicity of severe acute respiratory syndrome coronavirus 2 RBD conjugated to a polyglucin:spermidine complex (PGS) and dsRNA (RBD-PGS + dsRNA) in a mouse model. BALB/c mice were immunized intramuscularly twice, with a 2-week interval, with 50 µg of RBD, RBD with Al(OH)3, or conjugated RBD. A comparative analysis of serum RBD-specific IgG and neutralizing antibody titers showed that PGS, PGS + dsRNA, and Al(OH)3 enhanced the specific humoral response in animals. There was no significant difference between the groups immunized with RBD-PGS + dsRNA and RBD with Al(OH)3. Additionally, the study of the T-cell response in animals showed that, unlike adjuvants, the RBD-PGS + dsRNA conjugate stimulates the production of specific CD4+ and CD8+ T cells in animals.

17.
Pharmaceutics ; 14(11)2022 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-36365078

RESUMEN

Vaccination against SARS-CoV-2 and other viral infections requires safe, effective, and inexpensive vaccines that can be rapidly developed. DNA vaccines are candidates that meet these criteria, but one of their drawbacks is their relatively weak immunogenicity. Electroporation (EP) is an effective way to enhance the immunogenicity of DNA vaccines, but because of the different configurations of the devices that are used for EP, it is necessary to carefully select the conditions of the procedure, including characteristics such as voltage, current strength, number of pulses, etc. In this study, we determined the optimal parameters for delivery DNA vaccine by electroporation using the BEX CO device. BALB/c mice were used as a model. Plasmid DNA phMGFP was intramuscular (I/M) injected into the quadriceps muscle of the left hind leg of animals using insulin syringes, followed by EP. As a result of the experiments, the following EP parameters were determined: direct and reverse polarity rectangular DC current in three pulses, 12 V voltage for 30 ms and 950 ms intervals, with a current limit of 45 mA. The selected protocol induced a low level of injury and provided a high level of GFP expression. The chosen protocol was used to evaluate the immunogenicity of the DNA vaccine encoding the receptor-binding domain (RBD) of the SARS-CoV-2 protein (pVAXrbd) injected by EP. It was shown that the delivery of pVAXrbd via EP significantly enhanced both specific humoral and cellular immune responses compared to the intramuscular injection of the DNA vaccine.

18.
Viruses ; 14(5)2022 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-35632800

RESUMEN

Currently, SARS-CoV-2 spike receptor-binding-domain (RBD)-based vaccines are considered one of the most effective weapons against COVID-19. During the first step of assessing vaccine immunogenicity, a mouse model is often used. In this paper, we tested the use of five experimental animals (mice, hamsters, rabbits, ferrets, and chickens) for RBD immunogenicity assessments. The humoral immune response was evaluated by ELISA and virus-neutralization assays. The data obtained show hamsters to be the least suitable candidates for RBD immunogenicity testing and, hence, assessing the protective efficacy of RBD-based vaccines.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Inmunogenicidad Vacunal , Glicoproteína de la Espiga del Coronavirus , Animales , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Pollos , Cricetinae , Modelos Animales de Enfermedad , Hurones , Ratones , Ratones Endogámicos BALB C , Conejos , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunas de Subunidad/inmunología
19.
Gels ; 7(4)2021 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-34698152

RESUMEN

We investigated the water sorption properties of macroporous cryogels of gelatine (Gel) and dextran dialdehyde (DDA) prepared via cryogelation at 260 K and following the freeze drying processes. Water vapour sorption isotherms for aerogels were studied at 293 K by two independent methods: static-gravimetric and dynamic vapour sorption (DVS) over a water activity range of 0.11-1.0. Experimental data were fitted by use of the Brunauer-Emmett-Teller (BET) and Guggenheim-Anderson-de Boer (GAB) models. The BET model (for a water activity range of 0.1 ≤ p/po ≤ 0.5) was used to calculate the sorption parameters of the studied cryogels (the monolayer capacity, surface area and energy of interaction). In comparison with BET, the GAB model can be applied for the whole range of water activities (0.1 ≤ p/po ≤ 0.95). This model gave an almost perfect correlation between the experimental and calculated sorption isotherms using nonlinear least squares fitting (NLSF). Confocal Laser Scanning Microscopy (CLSM) was used to confirm the structural differences between various DDA:Gel cryogel compositions. Thermogravimetric analysis and DSC data for aerogels DDA:Gel provided information regarding the bonded water loss, relative remaining water content of the material and the temperature of decomposition. Estimation of the amount of bound water in the cryogels after the freeze drying process as well as after the cycle of treatment of cryogels with high humidity and drying was performed using DSC. The results of the DSC determinations showed that cryogels with higher gelatin content had higher levels of bonded water.

20.
Eur J Ophthalmol ; 31(5): 2397-2404, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33176495

RESUMEN

PURPOSE: To report on impact of Nd:YAG laser goniopuncture (LGP) timing on hypotensive efficacy of deep sclerectomy (DS) for open-angle glaucoma (OAG) patients. METHODS: 228 patients who underwent DS followed by Nd:YAG LGP between January 2010 and December 2013, (follow up - 5 years) were enrolled into a single-center, retrospective, non-randomized, consecutive study. Subjects were divided into two groups (1 - delayed LGP, n = 116; 2 - early LGP, n = 112). Demographic variables, preoperative glaucoma medications, preceding surgeries and glaucoma severity were analyzed. Intraoperative and postoperative complications, intraocular pressure (IOP), ultrasound biomicroscopy (UBM) values were recorded. Success rate was analyzed using Kaplan-Meier curve. UBM data were the criteria for early or delayed LGP. RESULTS: LGP was performed 3.46 ± 1.9 (1.5-6.7) months after DS in group 1, 1.12 ± 0.08 (0.9-1.5) months in group 2 (p = 0.0001). Mean IOP before LGP in group 1 was 18.5 ± 4.7 (11.2-22.9) mm Hg; 15.7 ± 4.1 (9.1-18.5) mm Hg in group 2 (p = 0.001). Choroidal effusion occurred in 8.6% of group 1 and 3.5% of group 2 (p = 0.0001). Postoperative IOP: 15.6 ± 4.6 (group 1) and 15.7 ± 4.3 mm Hg (group 2) at 12 months (p = 0.98), 16.7 ± 4.3 and 14.9 ± 1.6 mm Hg at 24 months (p = 0.004), 16.8 ± 3.9 and 14.5 ± 3.2 mm Hg at 60 months, respectively (p = 0.0001). Complete success rates: 68.07% and 92.59% at 12 months, 40.7% and 75.8% at 24 months, 15.2% and 48.93% at 36, 48, 60 months in groups respectively (p = 0.0001). CONCLUSION: Early LGP after DS excludes TDM influence on further formation of intrascleral canal cavity and outflow pathways demonstrating pronounced hypotensive success in a long-term follow-up.


Asunto(s)
Glaucoma de Ángulo Abierto , Terapia por Láser , Láseres de Estado Sólido , Esclerostomía , Estudios de Seguimiento , Glaucoma de Ángulo Abierto/cirugía , Humanos , Láseres de Estado Sólido/uso terapéutico , Punciones , Estudios Retrospectivos
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