Effect of a sorbent composition based on aluminum oxide and polydimethylsiloxane on the reproductive system of <i>db/db</i> female mice with genetically determined obesity and type 2 diabetes mellitus

Metabolic syndrome, obesity, type 2 diabetes mellitus are characterized by the accumulation of toxic metabolic products in the internal environment of the organism. The development of innovative medicines based on a sorbent matrix modified with  biologically active molecules remains relevant. The sorbent composition from aluminum oxide and polydimethylsiloxane is considered promising. The aim of the study. To investigate the effect of the sorbent composition from aluminum oxide and polydimethylsiloxane on the uterus and ovaries of db/db  mice with obesity and type 2 diabetes mellitus. Materials and methods. The sorbent composition (0.665 g/kg in 200 μl of distilled water) was administered to 14-week-old animals through an intragastric tube once a day for 7 days. The comparison groups were female rats injected with placebo (daily intragastrical administration of 200 µl of water for 7 days) and intact animals. Digital images of light-optical preparations stained with hematoxylin and eosin were processed using Image-Pro Plus 4.1 software. In the ovaries, the numerical density of primordial, primary, secondary follicles and corpus luteum was determined. The width of the uterus layers, the diameters of the blood and lymphatic vessels, the width of the interstitial fissures in both organs were measured. The statistical significance of differences was determined using the Mann – Whitney test. Results. In the myometrium and endometrium of the uterus of db/db mice, dilatation of arteries, veins, lymphatic vessels and edema were noted due to the accumulation of tissue fluid in the interstitium layers. There were no tertiary follicles in the ovaries. The introduction of the sorbent composition contributed to a decrease in the diameters of arteries, veins, lymphatic vessels of the uterus, a decrease in edema in both organs due to the narrowing of the prelymphatic slits, and stimulated an increase in the numerical density of secondary follicles. Conclusion. A corrective effect of the sorbent composition of aluminum oxide and  polydimethylsiloxane on prelymphatic slits, blood and lymphatic vessels in the uterus and ovaries in db/db mice with obesity and type 2 diabetes mellitus was revealed

Вопросы безопасности и оптимального дозирования ингибитора интерлейкина 17А (секукинумаб) при лечении псориатического артрита у пациента с сопутствующим вирусным гепатитом С

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the group of spondylitides, which is associated with psoriasis. The decisive role is played by the activation of the interleukin (IL)-23/IL-17 axis in the pathogenesis of PsA [1]. Secukinumab (SEC) is a fully human antibody that binds to human IL-17A and neutralizes the activity of this cytokine. That the patient has concomitant diseases, chronic hepatitis B virus infection and hepatitis C viral (HCV) infection in particular, limits the use of tumor necrosis factor- α inhibitors in the treatment of PsA [2, 3]. The paper describes a clinical case that demonstrates the successful treatment with SEC in a patient with PsA and concomitant HCV infection. In addition to the safety aspects of the use of SEC to treat chronic HCV infection, the issues on optimal dosing of the drug are discussed.Псориатический артрит (ПсА) – хроническое воспалительное заболевание из группы спондилоартритов, ассоциированное с псориазом. Решающая роль в патогенезе ПсА отводится активации оси интерлейкин (ИЛ) 23/ИЛ17 [1]. Секукинумаб (СЕК) представляет собой полностью человеческие антитела, которые связываются с ИЛ17А человека и нейтрализуют активность этого цитокина. Наличие у пациента сопутствующих заболеваний, в частности хронического вирусного гепатита В и вирусного гепатита С (ВГС), ограничивает применение ингибиторов фактора некроза опухоли α в лечении ПсА [2, 3].Приведено клиническое наблюдение, демонстрирующее успешное лечение СЕК у пациента с ПсА и сопутствующим ВГС. Помимо аспектов безопасности применения СЕК при хроническом ВГС, обсуждаются вопросы оптимального дозирования препарата

Directional Sensitivity of the NEWSdm Experiment to Cosmic Ray Boosted Dark Matter

We present a study of a directional search for Dark Matter boosted forward when scattered by cosmic-ray nuclei, using a module of the NEWSdm experiment. The boosted Dark Matter flux at the edge of the Earth's atmosphere is expected to be pointing to the Galactic Center, with a flux 15 to 20 times larger than in the transverse direction. The module of the NEWSdm experiment consists of a 10 kg stack of Nano Imaging Trackers, i.e.~newly developed nuclear emulsions with AgBr crystal sizes down to a few tens of nanometers. The module is installed on an equatorial telescope. The relatively long recoil tracks induced by boosted Dark Matter, combined with the nanometric granularity of the emulsion, result in an extremely low background. This makes an installation at the INFN Gran Sasso laboratory, both on the surface and underground, viable. A comparison between the two locations is made. The angular distribution of nuclear recoils induced by boosted Dark Matter in the emulsion films at the surface laboratory is expected to show an excess with a factor of 3.5 in the direction of the Galactic Center. This excess allows for a Dark Matter search with directional sensitivity. The surface laboratory configuration prevents the deterioration of the signal in the rock overburden and it emerges as the most powerful approach for a directional observation of boosted Dark Matter with high sensitivity. We show that, with this approach, a 10 kg module of the NEWSdm experiment exposed for one year at the Gran Sasso surface laboratory can probe Dark Matter masses between 1 keV/c$^2$ and 1 GeV/c$^2$ and cross-section values down to $10^{-30}$~cm$^2$ with a directional sensitive search.Comment: 15 pages, 14 figures, updated references, clarified discussion in intro section. Submitted to JCA

МЕТОДЫ ДИАГНОСТИКИ СТОРОЖЕВОГО ЛИМФАТИЧЕСКОГО УЗЛА У БОЛЬНЫХ РАКОМ МОЛОЧНОЙ ЖЕЛЕЗЫ

Objective: to provide various methods for sentinel lymph node detection considering their advantages and disadvantages.Material and Methods. The search of the relevant articles published in Pubmed, MedLine, RINTs, etc. database was conducted. 49 publications from 1970 to 2018 were analyzed.Results. Currently, sentinel lymph node biopsy (SLN biopsy) has become a worthy alternative to traditional lymphatic surgery for early breast cancer. SLN biopsy significantly decreases the number of postoperative complications caused by lymphadenectomy and improves the quality of life of cancer patients. So far, a large number of SLN detection techniques have accumulated. Each of these techniques has its own advantages and disadvantages.Conclusion. Despite a large number of SLN detection methods, the question of the optimal technique is currently debatable. Цель исследования – представить различные методы диагностики сторожевых лимфатических узлов, рассмотрев их достоинства и недостатки.Материал и методы. Проведен поиск статей, опубликованных в базах Pubmed, MedLine, РИНЦ, РГБ за 1970–2018 гг. Из 150 проанализированных публикаций в обзор вошли 50.Результаты. В настоящее время биопсия сторожевого лимфатического узла (СЛУ) стала достойной альтернативой традиционной хирургии на лимфатических путях при раннем раке молочной железы (РМЖ). Благодаря данной методике снизилось количество послеоперационных осложнений, вызванных лимфодиссекцией, а качество жизни больных значительно возросло. С момента появления и до настоящего времени накопилось большое количество техник определения СЛУ, каждая из которых имеет свои плюсы и минусы.Заключение. Несмотря на большое количество методов детекции СЛУ, вопрос об оптимальной технике в настоящее время остается дискуссионным.

SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b

BACKGROUND: The causative agent of severe acute respiratory syndrome, SARS coronavirus (SARS-CoV) genome encodes several unique group specific accessory proteins with unknown functions. Among them, accessory protein 3b (also known as ORF4) was lately identified as one of the viral interferon antagonist. Recently our lab uncovered a new role for 3b in upregulation of AP-1 transcriptional activity and its downstream genes. Thus, we believe that 3b might play an important role in SARS-CoV pathogenesis and therefore is of considerable interest. The current study aims at identifying novel host cellular interactors of the 3b protein. METHODOLOGY/PRINCIPAL FINDINGS: In this study, using yeast two-hybrid and co-immunoprecipitation techniques, we have identified a host transcription factor RUNX1b (Runt related transcription factor, isoform b) as a novel interacting partner for SARS-CoV 3b protein. Chromatin immunoprecipitaion (ChIP) and reporter gene assays in 3b expressing jurkat cells showed recruitment of 3b on the RUNX1 binding element that led to an increase in RUNX1b transactivation potential on the IL2 promoter. Kinase assay and pharmacological inhibitor treatment implied that 3b also affect RUNX1b transcriptional activity by regulating its ERK dependent phosphorylation levels. Additionally, mRNA levels of MIP-1α, a RUNX1b target gene upregulated in SARS-CoV infected monocyte-derived dendritic cells, were found to be elevated in 3b expressing U937 monocyte cells. CONCLUSIONS/SIGNIFICANCE: These results unveil a novel interaction of SARS-CoV 3b with the host factor, RUNX1b, and speculate its physiological relevance in upregulating cytokines and chemokine levels in state of SARS virus infection

The safety and optimal dosage of an interleukin-17A inhibitor (secukinumab) in the treatment of psoriatic arthritis in a patient with concomitant hepatitis C virus infection

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the group of spondylitides, which is associated with psoriasis. The decisive role is played by the activation of the interleukin (IL)-23/IL-17 axis in the pathogenesis of PsA [1]. Secukinumab (SEC) is a fully human antibody that binds to human IL-17A and neutralizes the activity of this cytokine. That the patient has concomitant diseases, chronic hepatitis B virus infection and hepatitis C viral (HCV) infection in particular, limits the use of tumor necrosis factor- α inhibitors in the treatment of PsA [2, 3]. The paper describes a clinical case that demonstrates the successful treatment with SEC in a patient with PsA and concomitant HCV infection. In addition to the safety aspects of the use of SEC to treat chronic HCV infection, the issues on optimal dosing of the drug are discussed

Association of ankylosing spondylitis activity indicators in a Russian population of patients with STAT4 rs7574865 gene polymorphism

Family and twin studies have shown that ankylosing spondylitis (AS) has a hereditary nature that is based on a strong association with the leukocyte antigen HLA-B27. However, only 1–5% of HLA-B27 carriers develop AS, which indicates that there are other genetic markers involved in the formation of a predisposition to this disease. A number of genome-wide association studies have convincingly confirmed the role of the STAT4 gene. This gene encodes the protein – the signal transducer and activator of transcription (STAT) protein, which is a predisposing factor for the development of many autoimmune diseases. There are not so many studies of the relationship of STAT4 polymorphisms to the predisposition to AS, and there are no these studies regarding the Russian population.Objective: to study whether there is a possible association of STAT4 rs7574865 gene polymorphism with the predisposition to AS and to assess the activity of this disease using BASDAI and ASDAS scores in the Russian patient population.Patients and methods. A cohort of 203 individuals, including 100 patients (79 men and 21 women) with AS, and 103 healthy volunteers (a control group) was surveyed. Age, gender, duration, and specific features of AS onset, ESR, and CRP levels were assessed. BASDAI and ASDAS scores were calculated to evaluate disease activity.Results and discussion. There was a significant relationship between STAT4 polymorphism and C-reactive protein (CRP) levels and BASDAI and ASDAS-CRP scores. The TT genotype carriers had significantly higher mean activity indices compared to the GG (p=0.001) and GT (p=0.005) genotype carriers for CRP, BASDAI (p=0.0001 and p=0.009, respectively) and ASDAS-CRP (p=0.009 and p=0.001, respectively). High disease activity (BASDAI &gt;4 and ASDAS-CRP &gt;3.5) was also associated with the high frequency of the T allele (p=0.046 and p=0.004, respectively). The value of STAT4 rs7574865 gene polymorphism in the pathogenesis of autoimmune diseases is confirmed by a study in which the T allele in STAT4 rs7574865 enhances mRNA transcription and protein expression. Italian authors have shown that there is a relationship between the minor T allele of rs7574865 and the high risk of arthritis. We have previously established a relationship between the T allele and the predisposition to diffuse systemic scleroderma, interstitial lung damage, and elevated anti-topoisomerase I antibody levels.Conclusion. The present study has shown for the first time a significant association of STAT4 rs7574865 polymorphism with the main AS activity indicators: CRP levels, BASDAI and ASDAS-CRP scores. The studied polymorphism may be a new genetic marker for predicting the severity of AS