ДОСТИЖЕНИЯ И ПЕРСПЕКТИВЫ МЕЖДИСЦИПЛИНАРНОГО ПОДХОДА В БОРЬБЕ С ТУБЕРКУЛЕЗОМ КАК ПОЛИОРГАННОЙ И КОМОРБИДНОЙ ПАТОЛОГИЕЙ В РЕСПУБЛИКЕ МОЛДОВА

Despite that the turning point was achieved in tuberculosis control in the world, still there is on-going interest to this social disease.Goal: to evaluate changes of main epidemiological rates, to publish achievements and prospects of the implementation of National tuberculosis control programme for the period after 2015.Materials and methods. Comparative analysis included evolution of tuberculosis in various localizations in 2011-2015.Results. Tuberculosis situation has been gradually improving in the Republic of Moldova for the last 5 years. The data evidence about the number of tuberculosis cases going down but the global burden of the disease remains fairly high. The success in tuberculosis control supported by WHO and other international organizations is also related to certain Moldavian research achievements.Conclusion. Due to diversity of clinical forms of tuberculosis and the growing problem of comorbidity the cross-disciplinary approach to tuberculosis control can assure success of these activities. Несмотря на то что в борьбе с туберкулезом (ТБ) в мире наступил переломный момент, к этому социально значимому заболеванию сохраняется неослабевающий интерес.Цель: оценка динамики основных эпидемиологических показателей, освещение достижений и перспектив реализации Национальной программы по борьбе с ТБ на период после 2015 г.Материалы и методы. Проведен сравнительный анализ эволюции ТБ различных локализаций в 2011-2015 гг. Результаты. Последнее пятилетие характеризуется постепенным улучшением эпидемической ситуации по ТБ в Республике Молдова. Приведенные данные свидетельствуют о том, что число заболевших ТБ продолжает уменьшаться, но глобальное бремя болезни в целом остается еще весомым. Отмечаемые успехи в борьбе с ТБ при поддержке ВОЗ и других международных организаций связаны в том числе и с отечественными научными достижениями.Заключение. В связи с многообразием клинических форм ТБ и нарастающей проблемой коморбидности залогом успеха борьбы с этим заболеванием может быть междисциплинарный подход

ЭПИДЕМИОЛОГИЯ ТУБЕРКУЛЕЗА И КОНСОЛИДАЦИЯ УСИЛИЙ СПЕЦИАЛИСТОВ РАЗЛИЧНЫХ ЗВЕНЬЕВ ЗДРАВООХРАНЕНИЯ В БОРЬБЕ С ЭТИМ ЗАБОЛЕВАНИЕМ В РЕСПУБЛИКЕ МОЛДОВА

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Стратегии обеспечения интегрированной комплексной медицинской помощи, ориентированной на больных туберкулезом и другими социально значимыми заболеваниями легких

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ACHIEVEMENTS AND PROSPECTS OF CROSS-DISCIPLINARY APPROACH TO TUBERCULOSIS CONTROL AS A MULTI-ORGAN AND COMORBID PATHOLOGY IN MOLDOVA REPUBLIC

Despite that the turning point was achieved in tuberculosis control in the world, still there is on-going interest to this social disease.Goal: to evaluate changes of main epidemiological rates, to publish achievements and prospects of the implementation of National tuberculosis control programme for the period after 2015.Materials and methods. Comparative analysis included evolution of tuberculosis in various localizations in 2011-2015.Results. Tuberculosis situation has been gradually improving in the Republic of Moldova for the last 5 years. The data evidence about the number of tuberculosis cases going down but the global burden of the disease remains fairly high. The success in tuberculosis control supported by WHO and other international organizations is also related to certain Moldavian research achievements.Conclusion. Due to diversity of clinical forms of tuberculosis and the growing problem of comorbidity the cross-disciplinary approach to tuberculosis control can assure success of these activities

Combined Analysis of Metabolomes, Proteomes, and Transcriptomes of Hepatitis C Virus-Infected Cells and Liver to Identify Pathways Associated With Disease Development

BACKGROUND & AIMS: The mechanisms of hepatitis C virus (HCV) infection, liver disease progression, and hepatocarcinogenesis are only partially understood. We performed genomic, proteomic, and metabolomic analyses of HCV-infected cells and chimeric mice to learn more about these processes. METHODS: Huh7.5.1(dif) (hepatocyte-like cells) were infected with culture-derived HCV and used in RNA sequencing, proteomic, metabolomic, and integrative genomic analyses. uPA/SCID (urokinase-type plasminogen activator/severe combined immunodeficiency) mice were injected with serum from HCV-infected patients; 8 weeks later, liver tissues were collected and analyzed by RNA sequencing and proteomics. Using differential expression, gene set enrichment analyses, and protein interaction mapping, we identified pathways that changed in response to HCV infection. We validated our findings in studies of liver tissues from 216 patients with HCV infection and early-stage cirrhosis and paired biopsy specimens from 99 patients with hepatocellular carcinoma, including 17 patients with histologic features of steatohepatitis. Cirrhotic liver tissues from patients with HCV infection were classified into 2 groups based on relative peroxisome function; outcomes assessed included Child-Pugh class, development of hepatocellular carcinoma, survival, and steatohepatitis. Hepatocellular carcinomas were classified according to steatohepatitis; the outcome was relative peroxisomal function. RESULTS: We quantified 21,950 messenger RNAs (mRNAs) and 8297 proteins in HCV-infected cells. Upon HCV infection of hepatocyte-like cells and chimeric mice, we observed significant changes in levels of mRNAs and proteins involved in metabolism and hepatocarcinogenesis. HCV infection of hepatocyte-like cells significantly increased levels of the mRNAs, but not proteins, that regulate the innate immune response; we believe this was due to the inhibition of translation in these cells. HCV infection of hepatocyte-like cells increased glucose consumption and metabolism and the STAT3 signaling pathway and reduced peroxisome function. Peroxisomes mediate beta-oxidation of very long-chain fatty acids; we found intracellular accumulation of very long-chain fatty acids in HCV-infected cells, which is also observed in patients with fatty liver disease. Cells in livers from HCV-infected mice had significant reductions in levels of the mRNAs and proteins associated with peroxisome function, indicating perturbation of peroxisomes. We found that defects in peroxisome function were associated with outcomes and features of HCV-associated cirrhosis, fatty liver disease, and hepatocellular carcinoma in patients. CONCLUSIONS: We performed combined transcriptome, proteome, and metabolome analyses of liver tissues from HCV-infected hepatocyte-like cells and HCV-infected mice. We found that HCV infection increases glucose metabolism and the STAT3 signaling pathway and thereby reduces peroxisome function; alterations in the expression levels of peroxisome genes were associated with outcomes of patients with liver diseases. These findings provide insights into liver disease pathogenesis and might be used to identify new therapeutic targets