Hepatitis C virus (HCV) is a widespread dangerous human pathogen. Up to 80% of HCV-infected individuals develop chronic infection, which is often accompanied by liver inflammation and fibrosis and, at terminal stages, liver cirrhosis and cancer. Treatment of patients with end-stage liver disease is often ineffective, and even patients with suppressed HCV replication have higher risk of death as compared with noninfected subjects. Therefore, investigating the mechanisms that underlie HCV pathogenesis and developing treatments for virus-associated liver dysfunction remain an important goal. The effect of individual HCV proteins on the production of proinflammatory and profibrotic cytokines in hepatocellular carcinoma Huh7.5 cells was analyzed in a systematic manner. Cells were transfected with plasmids encoding HCV proteins. Cytokine production and secretion was accessed by immunocytochemistry and ELISA of the culture medium, and transcription of the cytokine genes was assessed using reverse transcription and PCR. HCV proteins proved to differ in effect on cytokine production. Downregulation of interleukin 6 (IL-6) production was observed in cells expressing the HCV core, NS3, and NS5A proteins. Production of transforming growth factor β1 (TGF-β1) was lower in cells expressing the core proteins, NS3, or E1/E2 glycoproteins. A pronounced increase in production and secretion of tumor necrosis factor α (TNF-α) was observed in response to expression of the HCV E1/E2 glycoproteins. A higher biosynthesis, but a lower level in the cell culture medium, was detected for interleukin 1β (IL-1β) in cells harboring NS4 and IL-6 in cells expressing NS5В. The finding was possibly explained by protein-specific retention and consequent accumulation of the respective cytokines in the cell.

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РЕФЕРАТЧастым осложнением при пиометре являются септицемия и септический шок, приводящие к гибели животного. Для профилактики развития осложнений проводят раннюю диагностику. Для этого предложена собственная вариация моделей бaльной оценки (шкaлы PIRО (P = предрасположенность, I = инфекция, R = ответ, O = органная дисфункция) и ПИОМЕТРА). Разработан алгоритм действий при принятии оперативных решений по прогнозу возможных септических осложнений у животных, включающих оценку клинической манифестации воспалительного ответа SIRS, синдромa пoлиорганной недoстаточн MODS и синдрoма компенсаторного противocпалительного ответа CARS. Алгоритм на первом этапе предусматривает определение балла PIRO. Then the PIRO index is determined, which allows you to determine the severity of the disease. При необходимости, если данные PIRO указывают на сомнительный, осторожный или неблагоприятный прогноз, проводится оценка клеточных и гуморальных показателей крови собак по балльной шкале ПИОМЕТРА. Это позволяет определить степень развития клинической манифестации воспалительного ответа (SIRS) и уровень расхода защитных ресурсов организма в результате противовоcпалительного ответа (CARS). Показатель степени тяжести общего состояния больного животного также влияет на достоверность прогноза касающегося исхода заболевания. При оценке шкал PIRO и ПИ ОМЕТ Р А в ис с ле д о ва н и и у о д н и х ж иво т ны х б ыл а ле г ка я с т е пе н ь, др уг и х -cр е д ня я, тя же л aя и л и кр и т иче ск aя c те пе н ь выр a ж е н н о ст и бo лез н и, что по з во л и л о по дт вер д и ть з н ач им о сть и с по льзо ва н и я до по лн и те ль н ы х ш к ал пр и р а зр або т ке с тр а те г и и и т ак т и к и леч е н ия ж и во т н ых .

Hepatitis C virus (HCV) is one of the main triggers of chronic liver disease. Despite tremendous progress in the HCV field, there is still no vaccine against this virus. Potential vaccines can be based on its recombinant proteins. To increase the humoral and, especially, cellular immune response to them, more effective adjuvants are needed. Here, we evaluated a panel of compounds as potential adjuvants using the HCV NS5B protein as an immunogen. These compounds included inhibitors of polyamine biosynthesis and urea cycle, the mTOR pathway, antioxidants, and cellular receptors. A pronounced stimulation of cell proliferation and interferon-γ (IFN-γ) secretion in response to concanavalin A was shown for antioxidant N-acetylcysteine (NAC), polyamine biosynthesis inhibitor 2-difluoromethylornithine (DFMO), and TLR9 agonist CpG ODN 1826 (CpG). Their usage during the immunization of mice with the recombinant NS5B protein significantly increased antibody titers, enhanced lymphocyte proliferation and IFN-γ production. NAC and CpG decreased relative Treg numbers; CpG increased the number of myeloid-derived suppressor cells (MDSCs), whereas neither NAC nor DFMO affected MDSC counts. NAC and DFMO suppressed NO and interleukin 10 (IL-10) production by splenocytes, while DFMO increased the levels of IL-12. This is the first evidence of immunomodulatory activity of NAC and DFMO during prophylactic immunization against infectious diseases.