Rytkin E, Mirzaev KB, Grishina EA, Smirnov VV, Ryzhikova KA, Sozaeva ZA, Giliarov MI, Andreev DA, Sychev DA.

Abstract
AIM:
The aim of this study was to determine the impact of CYP2C19 and ABCB1 gene polymorphisms and CYP3A4 isoenzyme activity on stent implantation complications among patients with an acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI).

PATIENTS AND METHODS:
Seventy-six patients (median age 63, range 37-91 years) with an ACS who underwent PCI were screened for CYP2C19 and ABCB1 gene polymorphisms with real-time polymerase chain reaction: CYP2C19*2, CYP2C19*17, and ABCB1 3435. CYP3A4 isoenzyme activity was determined by urine cortisol and 6-beta-hydroxycortisol levels. Stent implantation complications such as stent thrombosis (n=2) and restenosis (n=1) were observed among drug-eluting stent recipients.

RESULTS:
Low mean 6-beta-hydroxycortisol/cortisol ratio is indicative of impaired CYP3A4 activity and was associated with higher risk of thrombosis (b coefficient=0.022, SE 0.009, p=0.021 in the linear regression model). The increase in the length of the implanted stent was associated with higher risk of restenosis (b coefficient=0.006, SE=0.002, p=0.001 in the linear regression model). The presence of the CYP2C19*2 polymorphism did not affect the incidence of stent thrombosis (b coefficient=-1.626, SE=1.449, p=0.262 in the logistic regression model), nor did the CYP2C19*17 (b coefficient=-0.907, SE=1.438, p=0.528 in the logistic regression model) and ABCB1 3435 polymorphisms (b coefficient=1.270, SE=1.442, p=0.378 in the logistic regression model).

CONCLUSION:
We did not find evidence that the presence of CYP2C19*2, CYP2C19*17, and ABCB1 3435 polymorphisms may jeopardize the safety of stent implantation in patients with an ACS. Patients with low CYP3A4 isoenzyme activity may have increased risk of stent thrombosis.

KEYWORDS:
acute coronary syndrome; clopidogrel; complications; polymorphism; stents

PMID: 29075133 PMCID: PMC5609797 DOI: 10.2147/PGPM.S143250

https://www.sechenov.ru/science_and_innovation/repo/?PAGEN_1=8#135002

Glezer M

Abstract
INTRODUCTION:
The guidelines recommend a beta-blocker or calcium channel blocker as the first-line medication for angina, supplemented by other agents for additional symptoms. One such agent is trimetazidine (TMZ), which has been shown to reduce the frequency of anginal episodes and improve exercise performance without affecting haemodynamic parameters. However, extensive real-world evidence for its efficacy in combination with first-line therapies has been lacking.

METHODS:
The aim of this large-scale, Russian, multicentre, 6-month, open-label, prospective observational study was to assess the effect of adding TMZ modified release 35 mg bid to background antianginal therapy in the real-world clinical setting.

RESULTS:
The study included 896 patients: 54% women, aged 29-90 years (42.6% >65 years), 63% with class II angina, and receiving beta-blockers alone or in combination (93%). Add-on TMZ reduced angina frequency and short-acting nitrate use within 2 weeks (both p < 0.0001) regardless of background therapy and maintained this effect over 6 months. It increased the proportion of patients with class I angina sixfold while decreasing that of class 3 angina almost fourfold. It also improved walking distance and well-being at 6 months (both p < 0.0001). Treatment was well tolerated.

CONCLUSION:
Add-on TMZ is a safe and rapidly effective treatment for reducing angina attacks and nitrate use in the real-world clinical setting. It also increases exercise capacity and well-being. These effects are observed within 2 weeks and persist for at least 6 months.

KEYWORDS:
Antianginal combination therapy; Beta-blocker treatment; Clinical practice; Observational study; Real-world evidence; Stable angina; Trimetazidine

PMID: 28220388 DOI: 10.1007/s12325-017-0490-2

https://www.sechenov.ru/science_and_innovation/repo/?PAGEN_1=8#135004

Kolkhir P, André F, Church MK, Maurer M, Metz M.

Abstract
Chronic spontaneous urticaria (CSU) is a mast cell-driven disease that is defined as the recurrence of weals, angioedema or both for > 6 weeks due to known or unknown causes. As of yet, disease diagnosis is purely clinical. Objective tools are needed to monitor the activity of CSU and the efficacy of treatment. Recently, several reports have suggested that blood parameters may be considered as potential disease-related biomarkers. Here, we reviewed available literature on blood biomarkers for CSU diagnosis, activity monitoring, duration, patient subgroup allocation or response to treatment. We performed a PubMed, Google Scholar and Web of Science search and identified and analysed 151 reports published prior to January 2016. We found strong evidence for significant differences between patients with CSU and healthy controls in blood levels or values of D-dimer, C-reactive protein (CRP), matrix metalloproteinase-9 (MMP-9), mean platelet volume (MPV), factor VIIa, prothrombin fragment 1 + 2 (F1 + 2), tumour necrosis factor, dehydroepiandrosterone sulphate and vitamin D. Also, there is strong evidence for a significant association between CSU activity and blood levels or values of D-dimer, F1 + 2, CRP, IL-6 and MPV. Strong evidence for reduced basophil count and high levels of IgG anti-FcεRI in the subgroup of CSU patients with positive autologous serum skin test was shown. In contrast, the evidence for all reported blood biomarkers for differentiating CSU from other diseases, or a role in prognosis, is weak, inconsistent or non-existent. Taken together, we identified 10 biomarkers that are supported by strong evidence for distinguishing patients with CSU from healthy controls, or for measuring CSU activity. There is a need for further research to identify biomarkers that predict outcome or treatment response in CSU.

PMID: 27926978 DOI: 10.1111/cea.12870

https://www.sechenov.ru/science_and_innovation/repo/?PAGEN_1=26#134638

Gushchin VA, Karlin DG, Makhotenko AV, Khromov AV, Erokhina TN, Solovyev AG, Morozov SY, Agranovsky AA.

Abstract
In infected plant cells, closterovirus replicative polyproteins 1a and 1ab drive membrane remodeling and formation of multivesicular replication platforms. Polyprotein 1a contains a variable Central Region (CR) between the methyltransferase and helicase domains. In a previous study, we have found that transient expression of the Beet yellows virus CR-2 segment (aa 1305-1494) in Nicotiana benthamiana induces the formation of ~1µm mobile globules originating from the ER membranes. In the present study, sequence analysis has shown that a part of the CR named the «Zemlya region» (overlapping the CR-2), is conserved in all members of the Closterovirus genus and contains a predicted amphipathic helix (aa 1368-1385). By deletion analysis, the CR-2 region responsible for the induction of 1-μm globules has been mapped to aa 1368-1432. We suggest that the conserved membrane-modifying region of the BYV 1a may be involved in the biogenesis of closterovirus replication platforms.

KEYWORDS:
Endoplasmic reticulum modification; Membrane vesicles; RNA virus replication; Virus replication factory

PMID: 28027478 DOI: 10.1016/j.virol.2016.12.006

https://www.sechenov.ru/science_and_innovation/repo/?PAGEN_1=26#134639

Atabekova AK, Pankratenko AV, Makarova SS, Lazareva EA, Owens RA, Solovyev AG, Morozov SY.

Abstract
Human B-cell receptor-associated protein BAP31 (HsBAP31) is the endoplasmic reticulum-resident protein involved in protein sorting and transport as well as pro-apoptotic signaling. Plant orthologs of HsBAP31 termed ‘plant BAP-like proteins’ (PBL proteins) have thus far remained unstudied. Recently, the PBL protein from Nicotiana tabacum (NtPBL) was identified as an interactor of Nt-4/1, a plant protein known to interact with plant virus movement proteins and affect the long-distance transport of potato spindle tuber viroid (PSTVd) via the phloem. Here, we have compared the sequences of PBL proteins and studied the biochemical properties of NtPBL. Analysis of a number of fully sequenced plant genomes revealed that PBL-encoding genes represent a small multigene family with up to six members per genome. Two conserved motifs were identified in the C-terminal region of PBL proteins. The NtPBL C-terminal hydrophilic region (NtPBL-C) was expressed in bacterial cells, purified, and used for analysis of its RNA binding properties in vitro. In gel shift experiments, NtPBL-C was found to bind several tested RNAs, showing the most efficient binding to microRNA precursors (pre-miRNA) and less efficient interaction with PSTVd. Mutational analysis suggested that NtPBL-C has a composite RNA-binding site, with two conserved lysine residues in the most C-terminal protein region being involved in binding of pre-miRNA but not PSTVd RNA. Virus-mediated transient expression of NtPBL-C in plants resulted in stunting and leaf malformation, developmental abnormalities similar to those described previously for blockage of miRNA biogenesis/function. We hypothesize that the NtPBL protein represents a previously undiscovered component of the miRNA pathway.

KEYWORDS:
BAP31; Endoplasmic reticulum; Micro RNA; Plant protein; RNA binding; Transient protein expression

PMID: 27770627 DOI: 10.1016/j.biochi.2016.10.009

https://www.sechenov.ru/science_and_innovation/repo/?PAGEN_1=26#134640

Pankratenko AV, Atabekova AK, Lazareva EA, Baksheeva VE, Zhironkina OA, Zernii EY, Owens RA, Solovyev AG, Morozov SY.

Abstract
The plant-specific 4/1 protein interacts, both in yeast two-hybrid system and in vitro, and co-localizes in plant cells with plant BAP-like protein, the orthologue of human protein BAP31. In yeast two-hybrid system, we identified a number of Nicotiana benthamiana protein interactors of Nt-4/1, the protein known to affect systemic transport of potato spindle tuber viroid. For one of these interactors, an orthologue of human B-cell receptor-associated protein 31 (BAP31) termed plant BAP-like protein (PBL), the ability to interact with Nt-4/1 was studied in greater detail. Analyses of purified proteins expressed in bacterial cells carried out in vitro with the surface plasmon resonance (SPR) spectroscopy revealed that the N. tabacum PBL (NtPBL) was able to interact with Nt-4/1 with high-affinity, and that their complex can form at physiologically relevant concentrations of both proteins. Subcellular localization studies of 4/1-GFP and NtPBL-mRFP transiently co-expressed in plant cells revealed the co-localization of the two fusion proteins in endoplasmic reticulum-associated bodies, suggesting their interaction in vivo. The N-terminal region of the Nt-4/1 protein was found to be required for the specific subcellular targeting of the protein, presumably due to a predicted amphipathic helix mediating association of the Nt-4/1 protein with cell membranes. Additionally, this region was found to contain a trans-activator domain responsible for the Nt-4/1 ability to activate transcription of a reporter gene in yeast.

KEYWORDS:
BAP31; Endoplasmic reticulum; Plant protein 4/1; Surface plasmon resonance; Transient protein expression; Yeast two-hybrid system

PMID: 27714454 DOI: 10.1007/s00425-016-2601-8

https://www.sechenov.ru/science_and_innovation/repo/?PAGEN_1=26#134641

Mombo IM, Lukashev AN, Bleicker T, Brünink S, Berthet N, Maganga GD, Durand P, Arnathau C, Boundenga L, Ngoubangoye B, Boué V, Liégeois F, Ollomo B, Prugnolle F, Drexler JF Drosten C, Renaud F, Rougeron V, Leroy E.

Abstract
Enteroviruses (EVs) belong to the family Picornaviridae and are responsible for mild to severe diseases in mammals including humans and non-human primates (NHP). Simian EVs were first discovered in the 1950s in the Old World Monkeys and recently in wild chimpanzee, gorilla and mandrill in Cameroon. In the present study, we screened by PCR EVs in 600 fecal samples of wild apes and monkeys that were collected at four sites in Gabon. A total of 32 samples were positive for EVs (25 from mandrills, 7 from chimpanzees, none from gorillas). The phylogenetic analysis of VP1 and VP2 genes showed that EVs identified in chimpanzees were members of two human EV species, EV-A and EV-B, and those identified in mandrills were members of the human species EV-B and the simian species EV-J. The identification of two novel enterovirus types, EV-B112 in a chimpanzee and EV-B113 in a mandrill, suggests these NHPs could be potential sources of new EV types. The identification of EV-B107 and EV90 that were previously found in humans indicates cross-species transfers. Also the identification of chimpanzee-derived EV110 in a mandrill demonstrated a wide host range of this EV. Further research of EVs in NHPs would help understanding emergence of new types or variants, and evaluating the real risk of cross-species transmission for humans as well for NHPs populations.

PMID: 28081564 PMCID: PMC5233426 DOI: 10.1371/journal.pone.0169067

https://www.sechenov.ru/science_and_innovation/repo/?PAGEN_1=26#134642

Moiseev S, Novikov P, Jayne D, Mukhin N.

Abstract
The outcomes in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis have improved significantly over the past decades, although a significant proportion of them still reach end-stage renal disease (ESRD). Renal replacement therapy (RRT) is associated with a relatively low risk of relapsing vasculitis as a result of anti-rejection treatment after kidney transplantation or quiescence of the autoimmune process in haemodialysis patients, but a flare of vasculitis in the latter setting presents a challenge because the treatment is poorly tolerated. There are benefits of rituximab in haemodialysed patients, as it is more steroid sparing in the treatment of extrarenal disease. More favourable outcomes of kidney transplantation compared with haemodialysis support its use as a preferable method of RRT in patients with vasculitis remission or low disease activity.

KEYWORDS:
ANCA-associated vasculitis; end-stage renal disease; haemodialysis; kidney transplantation

PMID: 28186571 DOI: 10.1093/ndt/gfw046

https://www.sechenov.ru/science_and_innovation/repo/?PAGEN_1=26#134643

Savvateeva LV, Erdes SI, Antishin AS, Zamyatnin AA Jr.

Abstract
Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of dietary gluten from some cereals mainly in individuals carrying the HLA-DQ2 and/or HLA-DQ8 haplotypes. As an autoimmune disease, CD is manifested in the small intestine in the form of a progressive and reversible inflammatory lesion due to immune response to self-antigens. Indeed, CD is one of the most challenging medicosocial problems in current gastroenterology. At present, the global CD prevalence is estimated at approximately 1% based on data sent from different locations and available CD screening strategies used. However, it is impossible to estimate global CD prevalence without all the data from the world, including Russia. In this review, we summarize the data on the incidence and prevalence of CD across geographically distinct regions of Russia, which are mostly present in local Russian scientific sources. Our conclusion is that the situation of CD prevalence in Russia is higher than is commonly believed and follows global tendencies that correspond to the epidemiologic situation in Europe, America, and Southwest Asia.

PMID: 28316996 PMCID: PMC5337843 DOI: 10.1155/2017/2314813

https://www.sechenov.ru/science_and_innovation/repo/?PAGEN_1=26#134644

Deviatkin AA, Lukashev AN, Poleshchuk EM, Dedkov VG, Tkachev SE, Sidorov GN, Karganova GG, Galkina IV, Shchelkanov MY, Shipulin GA.

Abstract
Near complete rabies virus N gene sequences (1,110 nt) were determined for 82 isolates obtained from different regions of Russia between 2008 and 2016. These sequences were analyzed together with 108 representative GenBank sequences from 1977-2016 using the Bayesian coalescent approach. The timing of the major evolutionary events was estimated. Most of the isolates represented the steppe rabies virus group C, which was found over a vast geographic region from Central Russia to Mongolia and split into three groups (C0-C2) with discrete geographic prevalence. A single strain of the steppe rabies virus lineage was isolated in the far eastern part of Russia (Primorsky Krai), likely as a result of a recent anthropogenic introduction. For the first time the polar rabies virus group A2, previously reported in Alaska, was described in the northern part of European Russia and at the Franz Josef Land. Phylogenetic analysis suggested that all currently circulating rabies virus groups in the Russian Federation were introduced within the few last centuries, with most of the groups spreading in the 20th century. The dating of evolutionary events was highly concordant with the historical epidemiological data.

PMID: 28225771 PMCID: PMC5321407 DOI: 10.1371/journal.pone.0171855

https://www.sechenov.ru/science_and_innovation/repo/?PAGEN_1=26#134645