Artificial COVID-19 T-Cell Immunogen.

An artificial T-cell immunogen consisting of conserved fragments of different proteins of the SARS-CoV-2 virus and its immunogenic properties were studied in BALB/c mice. To create a T-cell immunogen, we used an approach based on the design of artificial antigens that combine many epitopes from the main proteins of the SARS-CoV-2 virus in the one molecule. The gene of the engineered immunogen protein was cloned as part of the pVAX1 plasmid in two versions: with an N-terminal ubiquitin and without it. The obtained plasmids were analyzed for their ability to provide the synthesis of the immunogen protein in vitro and in vivo. It has been shown that protein product of the created artificial genes is actively processed in HEK293T cells and induces cellular immunity in mice.

Immunogenicity of the DNA/Protein Combined Vaccine against COVID-19.

During the COVID-19 pandemic, the development of prophylactic vaccines, including those based on new platforms, became highly relevant. One such platform is the creation of vaccines combining DNA and protein components in one construct. For the creation of DNA vaccine, we chose the full-length spike protein (S) of the SARS-CoV-2 virus and used the recombinant receptor-binding domain (RBD) of the S protein produced in CHO-K1 cells as a protein component. The immunogenicity of the developed combined vaccine and its individual components was compared and the contribution of each component to the induction of the immune response was analyzed. The combined DNA/protein vaccine possesses the advantages of both underlying approaches and is capable of inducing both humoral (similar to subunit vaccines) and cellular (similar to DNA vaccines) immunity.

Mitochondrial DNA analysis of ancient sheep from Altai.

A comparative analysis of the genetic diversity of ancient and modern sheep can shed light on the origin of these animals and their distribution as well as help to evaluate the role of humans at each formation stage of different sheep breeds. Here we isolated ancient DNA and performed sequencing of the mitochondrial DNA D-loop from 17 sheep bone remains (~4000-1000 years old) found in the archaeological complexes in the south of Altai (Western Siberia). The length of the sequences obtained ranged between 318 and 586 bp. The haplotype diversity and nucleotide diversity were 0.801 ± 0.081 and 0.0096 ± 0.0014 respectively. The average number of nucleotide differences was ~3.1. Nucleotide sequence analysis revealed that 15 specimens were nested within previously described A,B,C,D and E lineages and that two specimens had a basal position relative to the rest of the analyzed samples. A relatively high diversity of sheep haplotypes, including the presence of two basal haplotypes, indicates that the Altai region may have been a transport route of human migration. Further ancient DNA analysis of other specimens and deeper genome sequencing of samples with novel haplotypes is needed to better understand the demographic history of sheep in Southern Siberia.

Primary non-Hodgkin's lymphoma of the stomach: three radical modalities of treatment in 75 patients.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) remains a rare form of gastric malignancy, with a rising incidence. Approaches to treatment vary from surgery alone to conservative management. METHODS: To determine the optimal scheme of treatment, a randomized clinical trial was undertaken. Seventy-five patients were randomized into three groups: A-surgery alone (25), B-surgery followed by chemotherapy (29), and C-radiation therapy followed by surgery and chemotherapy (21). Forty-nine patients had stage IE and 26 had stage IIE disease. Chemotherapy (COP and COPP) consisted of 6 courses during a 1-year period, with the courses being 6 weeks apart. RESULTS: Subtotal gastrectomy was performed in 26 patients. Forty-nine patients underwent total gastrectomy. Postoperative complications occurred in 6 (8%) patients: 3 (12%) in group A, 2 (6.9%) in group B, and 1 (4.7%) in group C. Postoperative mortality occurred in 2 (8%) patients in group A (2.7% of all patients). An increase in hospital admissions number per year and decrease of mean age of patients with NHL of the stomach after the Chernobyl accident on April 26, 1986 was noted. CONCLUSIONS: Improved survival in gastric NHL was achieved by a combination of preoperative radiation with surgery and postoperative chemotherapy, presumptively through the management of local and systemic disease.

Radical treatment of locally recurrent gastric cancer.

Locally recurrent gastric cancer develops in 45 per cent of resected patients. This study assessed the impact of an aggressive search for recurrence after radical operations and the use of reoperative and adjuvant therapy in this setting. From 1983 to 1990, 75 patients were explored for regionally recurrent gastric cancer. Resection was possible in 40 (53.5%), and palliative bypass was possible in 19 (25.3%); exploration only was performed in 16 (21.4%). Among resectable patients, gastrectomy was performed in 22 (55%) and gastrectomy with adjacent organ resection in 18 (45%) with an overall operative mortality of 15% (6 patients). Mean duration of life after bypass was 3.1 months; after exploration 4.5 months. Fifteen (40.6%) were not candidates for radiation or chemotherapy, 13 (31.2%) received preoperative radiotherapy (20 Gy), and 12 (28.2%) received postoperative systemic chemotherapy. Two-year survival after radical treatment was as follows: surgery alone 20%; radiotherapy and surgery 31.3%; surgery and chemotherapy 66.4%. These preliminary results indicate that re-excision benefits selected patients with recurrent gastric cancer. Patients receiving radiotherapy and chemotherapy tended toward improved survival.