EXPRESSION OF TLR2, TLR3, TLR4 AND PROINFLAMMATORY TNF AND IL-6 CYTOKINES IN LIVER BIOPSIES OF NONALCOHOLIC FATTY LIVER DISEASE PATIENTS

Non-alcoholic fatty liver disease (NAFLD) is a group of conditions closely associated with obesity that are among the most common and socially significant liver diseases in the modern Western world. The emergence and progression of NAFLD from simple steatosis to non-alcoholic steatohepatitis with the subsequent development of fibrosis are the leading factors in the pathogenesis of a significant proportion of the most severe liver pathologies, such as cirrhosis and hepatocellular carcinoma, as well as extrahepatic metabolic complications of NAFLD, such as insulin resistance and type 2 diabetes mellitus. The inflammatory component is one of the most important factors in the pathogenesis of NAFLD, particularly in the context of the progression of simple steatosis to non-alcoholic steatohepatitis. At the same time, the role of the most important mediators of the inflammatory response, innate immunity receptors and the Toll-like receptors in particular, in the pathogenesis of NAFLD has been poorly studied. In the present work, we first used the bioinformatics analysis of the publicly available gene expression databases to demonstrate that only TLR1, TLR2, TLR3 and TLR4 were significantly expressed in the healthy human liver. We then used the reverse transcription PCR to measure the mRNA expression levels of TLR2, TLR3, and TLR4, as well as those of the important pro-inflammatory mediators tumor necrosis factor (TNF) and interleukin-6 (IL-6), in the liver biopsy specimens obtained from 20 patients with NAFLD (simple steatosis, n = 10; non-alcoholic steatohepatitis, n = 10), as well as from 4 obese patients with clinical suspicion for NAFLD but no histological signs of NAFLD in their liver biopsies. We found a significant increase in the expression of TLR2, TLR3 and TLR4 mRNA in liver biopsy samples obtained from patients with non-alcoholic steatohepatitis as compared to those obtained from controls without histological signs of NAFLD. We were also able to demonstrate the association between the hepatic levels of TLR2, TLR3 and TLR4 mRNAs with the histological degree of liver damage as evidenced by the degree of steatosis and balloon dystrophy of hepatocytes, as well as with the plasma levels of uric acid, the important endogenous stimulator of innate immunity. Our data indicate the possible involvement of innate immunity, particularly the Toll-like receptors, in the pathogenesis of NAFLD

Перспективы применения пробиотических препаратов при острых инфекциях респираторного тракта

Аcute respiratory infection (ARI) is one of the most prevalent diseases worldwide. The disease occurs in any age, so its course could be associated with complications  and poor outcome.  Prevention  and treatment of ARI and complications  are important  problems in clinical practice.  Recent researches of human microbiome  composition  and functions have aroused a great interest to this field in order to prevent ARIs.In this review, the authors discuss non-specific  mechanisms  of human  innate antiviral defense and available data about a role of symbiontic intestinal microf lora for ARI prevention. Typically, main biological properties of probiotic bacteria are considered in the context of modulating effects on the inf lammatory immune response. Published data demonstrated reduction in the risk, severity and duration of ARI under the treatment with probiotic agents both in the children and in adults. The strain-specific effect and potential molecular antiviral mechanisms of probiotics enhancing the antiviral response of symbiontic bacteria are also discussed in the review.Острые  вирусные  инфекции верхних  дыхательных  путей  (ВДП)  являются  одним  из самых  распространенных заболеваний в мире. Заболевание возникает  у лиц всех возрастных  групп и в некоторых случаях может иметь неблагоприятные осложнения и исходы. Одна из приоритетных задач практического здравоохранения состоит в возможности профилактики и лечения  острой респираторной вирусной инфекции и ее осложнений. В представленном обзоре рассмотрены собственные механизмы  неспецифической защиты человеческого организма  от вирусной инфекции. Обобщены  результаты исследований по изучению роли симбионтной кишечной микрофлоры в профилактике острой инфекции ВДП. На основании имеющихся литературных  данных представлены  основные  аспекты биологических свойств пробиотических бактерий,  которые,  как правило,  рассматриваются в контексте  их модулирующего  влияния на воспалительную иммунную реакцию.  Проведен  анализ имеющихся данных о снижении риска возникновения, продолжительности и выраженности симптомов  респираторной инфекции при приеме пробиотических препаратов  (ПБП) как в детском возрасте,  так и во взрослой популяции. Обсуждается  вопрос  штаммоспецифического эффекта  ПБП.  В статье рассмотрены основные  возможные  молекулярные противовирусные механизмы  ПБП, за счет которых симбионтные бактерии усиливают противовирусный ответ

Apophis Planetary Defense Campaign

We describe results of a planetary defense exercise conducted during the close approach to Earth by the near-Earth asteroid (99942) Apophis during 2020 December–2021 March. The planetary defense community has been conducting observational campaigns since 2017 to test the operational readiness of the global planetary defense capabilities. These community-led global exercises were carried out with the support of NASA’s Planetary Defense Coordination Office and the International Asteroid Warning Network. The Apophis campaign is the third in our series of planetary defense exercises. The goal of this campaign was to recover, track, and characterize Apophis as a potential impactor to exercise the planetary defense system including observations, hypothetical risk assessment and risk prediction, and hazard communication. Based on the campaign results, we present lessons learned about our ability to observe and model a potential impactor. Data products derived from astrometric observations were available for inclusion in our risk assessment model almost immediately, allowing real-time updates to the impact probability calculation and possible impact locations. An early NEOWISE diameter measurement provided a significant improvement in the uncertainty on the range of hypothetical impact outcomes. The availability of different characterization methods such as photometry, spectroscopy, and radar provided robustness to our ability to assess the potential impact risk. © 2022. The Author(s). Published by the American Astronomical Society.Brinson Foundation of ChicagoMoscow CenterNASA’s Planetary Defense Coordination Office, (80NSSC18K0284, 80NSSC18K1575, NN12AR55G)NEOOPlanetary Data SystemNational Aeronautics and Space Administration, NASA, (80NSSC18K0971)University of Maryland, UMDHorizon 2020 Framework Programme, H2020, (870403)Planetary Science Division, PSDNational Research Foundation, NRFMinistry of Education and Science of the Russian Federation, Minobrnauka, (075-15-2019-1623)National Research Foundation of Korea, NRFMinistry of Science and Higher Education of the Russian Federation, (80NSSC18K0849, FEUZ-2020-0030)Overall, the campaign successfully demonstrated the capability of the planetary defense community to respond in real time to a potentially impacting object and obtain data sufficient to characterize its orbit, brightness, size, spectrum, rotation period, and hazard to Earth. Timely reporting of astrometry and preliminary physical property analyses, with appropriate error bars, significantly improved our knowledge of the potential impact consequences. Human factors, such as the end-of-year holiday season, had a distinct impact on rapidly constraining the rotation period of Apophis and demonstrate the importance of building a broad coalition for planetary defense spanning continents and cultures. Future planetary defense campaigns should focus on targets with less-favorable apparitions that might better simulate a future discovery of a hazardous object. Acknowledgments The Apophis campaign was conducted as part of the International Asteroid Warning Network (IAWN). IAWN is supported by the Planetary Data System (PDS) Small Bodies Node (SBN) at the University of Maryland College Park. The work at the Jet Propulsion Laboratory, California Institute of Technology, was performed under a contract with the National Aeronautics and Space Administration (NASA). This material is based in part on work supported by NASA under the Science Mission Directorate Research and Analysis Programs. This publication makes use of data products from NEOWISE, which is a joint project of the University of Arizona and the Jet Propulsion Laboratory/California Institute of Technology, funded by the Planetary Science Division of NASA. Pan-STARRS is supported by the National Aeronautics and Space Administration under Grant No. 80NSSC18K0971 issued through the SSO Near Earth Object Observations Program. Part of this work was supported by the Russian Ministry of Science and Higher Education via the State Assignment Project FEUZ-2020-0030. Part of the observations performed with the Zeiss-1000 telescope of the Terskol Observatory Shared Research Centre of the Institute of Astronomy of the Russian Academy of Sciences. We are extremely grateful to the IRTF and GTC Observatories’ night and day staff for their overwhelming support and assistance that made the observations possible. D.P. & M.M. are thankful to Richard Binzel and Francesca DeMeo for sharing their experience and wisdom while planning and conducting the measurements. D.P. is grateful to the Israeli Space Agency. M.M. was supported by the National Aeronautics and Space Administration under grant No. 80NSSC18K0849 issued through the Planetary Astronomy Program. J.d.L., J.L., and M.P. acknowledge financial support from the NEOROCKS project, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 870403. This work was funded by NASA’s Planetary Defense Coordination Office. Supercomputing resources supporting this work were provided by the NASA High End Computing (HEC) Program through the NASA Advanced Supercomputing (NAS) Division at Ames Research Center. This work has made use of data from the Asteroid Terrestrial-impact Last Alert System (ATLAS) project. ATLAS is primarily funded to search for NEAs through NASA grants NN12AR55G, 80NSSC18K0284, and 80NSSC18K1575byproducts of the NEA search include images and catalogs from the survey area. The ATLAS science products have been made possible through the contributions of the University of Hawaii Institute for Astronomy, the Queen’s University Belfast, the Space Telescope Science Institute, and the South African Astronomical Observatory. This work is partially supported by the South African National Research Foundation (NRF). Spacewatch is supported by NASA/NEOO grants and the Brinson Foundation of Chicago, IL. We thank TUBITAK National Observatory for partial support in using the T100 telescope with project number 20CT100-1743. This work was supported by the Moscow Center of Fundamental and Applied Mathematics, Agreement with the Ministry of Science and Higher Education of the Russian Federation, No. 075-15-2019-1623. This work made extensive use of Python, specifically the NumPy (Harris et al. 2020), Astropy (Astropy Collaboration et al. 2013, 2018), Matplotlib (Hunter 2007), and SciPy (Virtanen et al. 2020b) packages

Experience of applying azelaic acid in dermatology

The article presents current published data on 30 years of experience in applying of azelaic acid in dermatology. Data on pharmacokinetics, efficacy and safety in the international practice; results of study and therapeutic efficacy of different dosage forms are presented

15 year experience of tacrolimus application in medical practice

The review presents modern literature data on the use of tacrolimus in medical practice. The results of national and international research on the effectiveness and safety of the drug at various dermatoses are presented

A comparative analysis of the efficacy of a combined topical therapy in patients suffering from mild to moderate papulopustular acne

The goal of this study was to compare the efficacy and safety of Azelic (15% gel of azelaic acid), 1% Clindamycin gel and 0.1% Adapalene gel as a complex therapy in patients suffering from mild to moderate acne. Materials and methods. An open-label comparative study involving 40 patients suffering from mild to moderate papulopustular acne. The study was based on the medical history, a questionnaire form, physical examination results, assessment of morphological and functional skin parameters and dynamics of the life quality index (DLQI). Key findings and conclusions. Positive dynamics of the skin process was observed by the end of Week 6 of the treatment depending on the combination treatment type. The administration of Azelic gel resulted in an increased moisture level of the skin and reduced sebometry indices, skin relief intensity and pigmentation level

Severe Clostridium diffi cile infection after liver and kidney transplantation

Recent statistics have shown increased rates of morbidity and mortality from Clostridium difficile infection worldwide. This problem is mainly typical for surgical patients and is associated with an antibiotic therapy and a prolonged hospital stay. Recipients of solid organs are at a high risk of developing severe forms of C. difficile infection due to immunosupression. Existing recommendations for the treatment of C. difficile infection are based on the severity of the disease and do not consider patients after liver transplantation. The aim of this work is to determine an actual tactics for the diagnosis and treatment of C. difficile in organ recipients in clinical practice

CHRONIC HEPATITIS B VIRUS INFECTION IN PREGNANCY: STRATEGIES OF ANTIVIRAL THERAPY

Treatment of chronic hepatitis B during pregnancy is an extremely complicated issue. Despite  implementation of immune prophylaxis, a significant proportion of babies born by mothers with  high viral load are infected by hepatitis B virus.  Cumulative data suggest that antiviral therapy in  the 3  trimester of pregnancy is an effective intervention in the event of unsuccessful immune prord phylaxis. To minimize fetal effects of nucleoside  and nucleotide analogues, antiviral therapy during  pregnancy should be administered to mothers with high risk of disease progression and/or uncontrolled hepatitis B virus infection. The safety  data obtained indicate that telbivudine and tenofovir can be used during pregnancy. Nevertheless,  antiviral therapy requires a  thorough assessment of the risk to benefit ratio

THE DIFFERENCES OF BONE METABOLISM IN MALES WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND POSTMENOPAUSAL FEMALES

Aim — to compare bone metabolism activity in males with chronic obstructive pulmonary disease (COPD) and postmenopausal females.Materials and methods. The prospective cohort study was conducted. 33 male patients with COPD over 55 years old and 33 female patients without respiratory diseases over 55 were included. General examination, clinical and biochemical blood analyses, densitometry of lumbar spine and proximal part of left femoral bone, respiratory function, osteocalcin and C-telopeptids blood levels have been performed to the patients.Results. Male patients with COPD had lower T-score for the femoral neck than postmenopausal female patients without pulmonary disorders,(–1.05 ± 0.85 SD and –0.36 ± 1.24 SD respectively, р &lt; 0.05). Osteocalcin level in males with COPD was significantly higher and C‑telopeptids level was significantly lower than in postmenopausal females (р &lt; 0.05).Conclusion. Male patients with COPD have lower T‑score for the femoral neck than postmenopausal females without pulmonary disorders of the same age. Furthermore osteoclasts in COPD patients seem to be more activated than in postmenopausal females, on the contrary osteoblasts activity is significantly depressed. Therefore it is necessary to use another approach of prevention and treatment of osteoporosis in patients with COPD.</p