Publications by authors named "Musa R Khaitov"

9 Publications

  • Page 1 of 1

Genotoxicity of cationic lipopeptide nanoparticles.

Toxicol Lett 2020 Aug 19;328:1-6. Epub 2020 Apr 19.

Laboratory of pharmacology and mutagenesis, FSBI Zakusov Research Institute of Pharmacology, Baltiyskaya str., 8, 125315, Moscow, Russia. Electronic address:

The genotoxicity of cationic lipopeptide nanoparticles (cLPNPs) was evaluated in vivo and in vitro comet assay and the in vivo chromosome aberrations test. In vitro comet assay, human blood cells were exposed to cLPNPs at the concentration of 2.5, 5, 10, 20, 40 and 100 μg/mL. Significant DNA damage was observed after 1 h exposure, but no effects were detected after 3 h. In vivo, cLPNPs were administered in single or five daily injection doses at 8, 20 and 40 mg/kg of body weight by subcutaneous injection to male mice. The cLPNPs caused DNA damage in the liver, lung and kidney, but not in the spleen. The kidney was more prone to genotoxic effects that persisted from 24 h to 14d after a single injection of cLPNPs. No statistically significant increase in the percentage of cells with chromosomal aberrations above the vehicle control was observed in mice bone marrow after a single or repeated injection of cLPNPs. In summary, cLPNPs shown to be genotoxic both in vivo and in vitro. The results suggest the importance of the use of highly sensitive methods, such as the comet assay, in order to determine the full genotoxic potential of nanoparticles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxlet.2020.04.011DOI Listing
August 2020

Highly sensitive ELISA-based assay for quantification of allergen-specific IgE antibody levels.

Allergy 2020 10 27;75(10):2668-2670. Epub 2020 May 27.

Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/all.14325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687237PMC
October 2020

Linear and dendrimeric antiviral peptides: design, chemical synthesis and activity against human respiratory syncytial virus.

J Mater Chem B 2020 04;8(13):2607-2617

NRC Institute Immunology FMBA, Kashirskoe shosse 24, Moscow, 115522, Russian Federation.

Respiratory syncytial virus (RSV) is one of the most common viral pathogens. It is especially dangerous for newborns and young children. In some cases it could lead to severe bronchiolitis, pneumonia with hospitalization or even a lethal outcome. Despite decades of investigation of RSV biology, effective and safe therapeutics are still under development. Certain natural peptides have been found to exhibit antiviral activity against respiratory viruses, but their implementation is limited by low stability in biological media. One of the current approaches to enhance the peptide therapeutic opportunities is chemical synthesis of peptide dendrimers with hyperbranched structures. Taking into account the recent data of bioactive cationic and helical regions of natural peptides and the structure features of nucleolin identified as an RSV cellular receptor, the main goal of this study was to design relatively short linear and dendrimeric cationic peptides and to test their antiviral activity against RSV. As a result 3 linear cationic peptides and 4 peptide dendrimers were synthesized and compared with known LL-37 (cathelicidin family) and anti-F0 monoclonal antibodies in terms of cytotoxicity and antiviral activity. Their affinity to the supposed molecular target - nucleolin (C23) - was estimated in silico by molecular docking analysis. Four synthesized peptides demonstrated a cytotoxic effect, two of them were even more cytotoxic than LL-37, which could be explained by a combination of a high amount of positive charge and amphipathicity. Contrariwise, non-hydrophobic dendrimer peptides did not exhibit cytotoxicity in mammalian cells in the studied concentration range. Two of the seven synthesized peptides, LTP (dendrimer) and SA-35 (linear), used in this study had a stronger antiviral effect than natural peptide LL-37, and three others showed slightly lower activity than anti-F0 monoclonal antibodies. The data obtained in this study suggest that evenly distributed positive charge, and low or medium amphipathicity play a key role in the antiviral activity of the studied peptides. Moreover, the calculated free energy values of the peptide/nucleolin complex for the most active peptides supported the idea that the peptide ability of nucleolin interaction promotes the anti-RSV properties of the molecules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9tb02485aDOI Listing
April 2020

Cell-Type-Specific Responses to Interleukin-1 Control Microbial Invasion and Tumor-Elicited Inflammation in Colorectal Cancer.

Immunity 2019 01;50(1):166-180.e7

Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA. Electronic address:

Chronic inflammation drives the progression of colorectal cancer (CRC). Increased expression of interleukin (IL)-17A is associated with poor prognosis, and IL-17A blockade curbs tumor progression in preclinical models of CRC. Here we examined the impact of IL-1 signaling, a key regulator of the IL-17 pathway, in different cell types within the CRC microenvironment. Genetic deletion of the IL-1 receptor (IL-1R1) in epithelial cells alleviated tumorigenesis in the APC model of CRC, demonstrating a cell-autonomous role for IL-1 signaling in early tumor seed outgrowth. T cell specific ablation of IL-1R1 decreased tumor-elicited inflammation dependent on IL-17 and IL-22, thereby reducing CRC progression. The pro-tumorigenic roles of IL-1 were counteracted by its effects on myeloid cells, particularly neutrophils, where IL-1R1 ablation resulted in bacterial invasion into tumors, heightened inflammation and aggressive CRC progression. Thus, IL-1 signaling elicits cell-type-specific responses, which, in aggregate, set the inflammatory tone of the tumor microenvironment and determine the propensity for disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.immuni.2018.11.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490968PMC
January 2019

A novel peptide dendrimer LTP efficiently facilitates transfection of mammalian cells.

Org Biomol Chem 2018 11;16(43):8181-8190

NRC Institute of Immunology FMBA, Moscow, Russian Federation.

One of the urgent problems of gene therapy is the search for effective transfection methods. Synthetic cationic peptides (CPs) are considered to be one of the most promising approaches for intracellular transport of oligonucleotides. Almost unlimited possibilities of the architectural design of CPs (linear and cyclic structures with a variation of chirality as well as dendrimers) make CPs an effective tunable carrier in this field. Cationic peptide dendrimers (PDs), as a relatively new direction, have significant advantages as gene delivery vehicles by virtue of non-natural ε-amide bonds that significantly increase their resistance to proteolysis. Moreover they also possess much lower cytotoxicity than linear peptides, which is crucial for the potential clinical application of CPs. In a further development of oligonucleotide delivery systems, we have synthesized a collection of 14 CPs, including linear peptides, lipopeptides and PDs. Their activity was evaluated by transfection of 293T cells with plasmids containing reporter genes encoding luciferase or a green fluorescent protein. The obtained results demonstrated that the greatest activity was exhibited by PDs, particularly LTP, an arginine-rich peptide dendrimer, which possesses low cytotoxic and hemolytic activity. The peptide exhibited high cell-penetrating activity, confirmed by fast dissipation of the membrane potential of cells probed by dis-C3-(5). The quantitative analysis of labelled LTP in tissue samples of mice revealed that the Cy5-LTP/siRNA complexes have a reasonable tropism to lung tissues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8ob02039fDOI Listing
November 2018

Cross-sectional study on Asthma Insights and Management in the Gulf and Russia.

Allergy Asthma Proc 2018 Nov 16;39(6):430-436. Epub 2018 Oct 16.

Real-World & Analytics Solutions, IQVIA, Dubai, United Arab Emirates.

Asthma is a chronic and complex lung disease that is not completely understood. It involves airway inflammation, reversible airflow obstruction, and bronchial hyperresponsiveness. The most common symptoms are recurrent wheezing, chest tightness, shortness of breath, and coughing. The Asthma Insights and Management study gathered information on the burden of asthma in the Gulf region (United Arab Emirates, Kuwait, Saudi Arabia) and Russia. This was a cross-sectional, multinational, noninterventional, two-phase study that collected data from patients ages ≥ 12 years, through interviews and a survey questionnaire. Phase 1 consisted of survey questions focused on estimating the asthma prevalence in the community. Phase 2 was designed to assess the level of asthma control, asthma-related perceptions and behaviors, and presentation patterns. Data were summarized by using descriptive analyses. Analysis of data of 711 patients revealed that the prevalence of asthma among patients who lived in the community was 7.9% and that 66% subjectively perceived their asthma as being controlled. However, 97% of the patients' asthma were partially controlled or uncontrolled based on the Global initiative for Asthma control classification. Troubling symptoms were daytime coughing (33.3%) and shortness of breath (20.3%). With respect to medications for asthma, 76.2% of the patients reported the use of quick relief medication and 80.8% of maintenance medication during the past 4 weeks. Asthma exacerbation in the past year was reported by 40% of adults and adolescents in the study. The results showed that a significant proportion of the patients experienced bothersome symptoms and that many had a lack of knowledge about asthma control and treatment recommendations, which indicated that there is a need for improvements in patient education and asthma care in the Gulf and Russia regions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2500/aap.2018.39.4180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212633PMC
November 2018

Efficacy of novel antibody-based drugs against rhinovirus infection: In vitro and in vivo results.

Antiviral Res 2017 06 27;142:185-192. Epub 2017 Mar 27.

Research Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia. Electronic address:

Rhinoviruses (RVs) cause the common cold and are associated with exacerbations of chronic inflammatory respiratory diseases, especially asthma and chronic obstructive pulmonary disease (COPD). We have assessed the antiviral drugs Anaferon for Children (AC) and Ergoferon (containing AC as one of the active pharmaceutical ingredients) in in vitro and in vivo experimental models, in order to evaluate their anti-rhinoviral and immunomodulatory potential. HeLa cells were pretreated with AC, and levels of the interferon-stimulated gene (ISG), 2'-5'-oligoadenylate synthetase 1 (OAS1-A) and viral replication were analyzed. In a mouse model of RV-induced exacerbation of allergic airway inflammation we administered Ergoferon and analyzed its effect on type I (IFN-β), type II (IFN-γ) and type III (IFN-λ) IFNs induction, cell counts in bronchoalveolar lavage (BAL), cytokine (interleukin (IL)-4; IL-6) and chemokine (CXCL10/IP-10; CXCL1/KC) levels. It was shown that AC increased OAS1-А production and significantly decreased viral replication in vitro. Increased IFNs expression together with reduced neutrophils/lymphocytes recruitment and correlated IL-4/IL-6 declination was demonstrated for Ergoferon in vivo. However, there was no effect on examined chemokines. We conclude that AC and Ergoferon possess effects against RV infection and may have potential as novel therapies against RV-induced exacerbations of asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.antiviral.2017.03.017DOI Listing
June 2017

Small interfering RNAs targeted to interleukin-4 and respiratory syncytial virus reduce airway inflammation in a mouse model of virus-induced asthma exacerbation.

Hum Gene Ther 2014 Jul 22;25(7):642-50. Epub 2014 May 22.

1 National Research Center Institute of Immunology of Federal Medicobiological Agency , Moscow 115478, Russia .

Asthma exacerbations are caused primarily by viral infections. Antisense and small interfering RNA (siRNA) technologies have gained attention as potential antiasthma and antiviral approaches. In this study we analyzed whether gene silencing of interleukin (IL)-4 expression and respiratory syncytial virus (RSV) replication by RNA interference is able to suppress allergen- and virus-induced responses in a mouse model of virus-induced asthma exacerbation. Knockdown efficacy of IL-4 siRNA molecules was analyzed in the human HEK293T cell line by cotransfection of six different siRNAs with a plasmid carrying mouse IL-4. The most potent siRNA was then used in a mouse model of RSV-induced asthma exacerbation. BALB/c mice were sensitized intraperitoneally with ovalbumin (OVA) and then infected 12 days later intranasally with RSV Long strain (1×10(6) TCID50/mouse), followed 1 day later by intranasal challenge with OVA for 3 days. Mice were pretreated intranasally three times with either siRNA to IL-4 or GFP control, 2 days before, and on the first two OVA challenge days. siRNAs to RSV or rhinovirus control were inoculated intranasally once, 3 hr before RSV infection. Combined anti-IL-4 and anti-RSV siRNAs were able to significantly reduce total cell counts and eosinophilia in bronchoalveolar lavage fluid, development of airway hyperresponsiveness, and airway inflammation and to downregulate IL-4 mRNA expression and RSV viral RNA, but to upregulate IFN-γ levels in lung tissues. We conclude that anti-helper T cells type 2 and antiviral siRNAs may constitute a new therapeutic approach for treatment of virus induced asthma exacerbations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2013.142DOI Listing
July 2014