Endothelioprotective property of the combination of the thioctic acid and rosuvastatin shown in the endothelial dysfunction models

During the experiment, the modeling of endothelial dysfunction of male rats was performed by intraperitoneal administration of L-NAME at a dose of 25 mg/kg for 7 days, and the same of female rats was performed by bilateral ovarioectomy and further intraperitoneal administration of L-NAME at a dose of 25 mg/kg for 7. The deficiency of nitric oxide as a result of the NO-synthase blockade was accompanied by the impairment of the endotheliumdependent and independent vasodilatation estimated in the pharmacological tests, which was expressed in the increasing coefficient of endothelial dysfunctio

Pharmacological blockade of cannabinoid type II receptors and mesenchymal stem cell transplantation in a model of peripheral neuropathic pain

Objective. To evaluate the anti-nociceptive and reparative effects of adipose-derived mesenchymal stem cells (ADMSCs) under the pharmacological blockade of cannabinoid CB2 receptors in a model of peripheral neuropathic pain.Material and methods. In 40 male Wistar rats, modeling of peripheral neuropathy (NP) was performed by excising a sciatic nerve. On day 7 of the study, ADMSCs (1 × 106 cells/kg) were transplanted into the area of sciatic nerve injury without additional influences or after administration of the CB2 receptor antagonist AM630, as well as after incubation with AM630. Within 90  days, nociceptive sensitivity was studied, as well as a detailed analysis of gait using CatWalk XT (Noldus, Netherlands). On day 21 and day 90, histostructure of the distal segment of the sciatic nerve was assessed.Results. Pharmacological blockade of CB2 receptors both on the ADMSCs and in the soft tissues surrounding the site of sciatic nerve injury led to a decrease in withdrawal threshold and withdrawal latency from day 28 of the study compared with the group of rats with NP and transplantation of ADMSCs only. Local injection of AM630 before transplantation of ADMSCs contributed to the development of  NP-induced gait disturbances and increase of the number of damaged nerve fibers in the distal segment of sciatic nerve. Transplantation of ADMSCs pretreated with  AM630 did not significantly affect the rate of recovery of gait parameters, and decreased the number of damaged nerve fibers by day 90 of study.Conclusion. Blockade of CB2 receptors, both on the membranes of MSCs and in the area of damage to the peripheral nerve, has a negative effect on the development of the anti-nociceptive and reparative effects of MSCs

Potent antiviral activity against HSV-1 and SARS-CoV-2 by antimicrobial peptoids

Viral infections, such as those caused by Herpes Simplex Virus-1 (HSV-1) and SARS-CoV-2, affect millions of people each year. However, there are few antiviral drugs that can effectively treat these infections. The standard approach in the development of antiviral drugs involves the identification of a unique viral target, followed by the design of an agent that addresses that target. Antimicrobial peptides (AMPs) represent a novel source of potential antiviral drugs. AMPs have been shown to inactivate numerous different enveloped viruses through the disruption of their viral envelopes. However, the clinical development of AMPs as antimicrobial therapeutics has been hampered by a number of factors, especially their enzymatically labile structure as peptides. We have examined the antiviral potential of peptoid mimics of AMPs (sequence-specific N-substituted glycine oligomers). These peptoids have the distinct advantage of being insensitive to proteases, and also exhibit increased bioavailability and stability. Our results demonstrate that several peptoids exhibit potent in vitro antiviral activity against both HSV-1 and SARS-CoV-2 when incubated prior to infection. In other words, they have a direct effect on the viral structure, which appears to render the viral particles non-infective. Visualization by cryo-EM shows viral envelope disruption similar to what has been observed with AMP activity against other viruses. Furthermore, we observed no cytotoxicity against primary cultures of oral epithelial cells. These results suggest a common or biomimetic mechanism, possibly due to the differences between the phospholipid head group makeup of viral envelopes and host cell membranes, thus underscoring the potential of this class of molecules as safe and effective broad-spectrum antiviral agents. We discuss how and why differing molecular features between 10 peptoid candidates may affect both antiviral activity and selectivity

Bronchodilator reversibility test for broncho-obstructive syndrome detection and differential diagnosis of bronchial asthma and chronic obstructive pulmonary disease

Purpose – to analyze the method of bronchodilator reversibility test (BRT) at different doses of salbutamol in patients with bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD). Materials and methods. We examined 80 patients with broncho-obstructive syndrome, including 50 patients with a mild persistent BA (Group I) and 30 patients with COPD of moderate (course B) severity (Group II). All patients underwent routine methods of investigation: general clinical, laboratory, pulmonary function test, radiography of the chest organs (if needed), and statistical methods were used. Results. Two methods of BRT were performed that differed in the dose of salbutamol to examine the patients with BA and COPD. All 50 patients with BA were first examined for bronchodilator reversibility with 200 micrograms of salbutamol and then, usually in 2 weeks, with 400 micrograms of salbutamol. Reversibility was in all the patients with BA within 15 minutes after 200 micrograms of salbutamol inhalation, but in 30 patients (60 %) it was full (12 % and more than the previous, >200 ml), and in 20 patients it was partial (less than 12 % or 200 ml). Full reversibility was found in 46 out of the 50 patients (92 %) within 30 minutes and it was 12 % or more (>200 ml) in all the patients only within 45 minutes. When using a salbutamol dose of 400 mg in BRT, the following results were obtained: full reversibility was in 47 (94 %) patients within 15 minutes and in another 3 patients within 30 minutes, that is in all the patients with BA. 16 (53.3 %) patients with COPD were considered nonreversible following administration a dose of salbutamol 200 micrograms within 15 minutes and partial reversibility was in 14 (46.7 %) patients with COPD. Partial reversibility was found in 10 patients (33.3 %) after 30 minutes, and 6 patients (20.0 %) were nonreversible or reversibility was within 2–3 %; in 4 out of the 6 patients (93.24 % in total) partial reversibility was only after 45 minutes and the remaining two patients were nonreversible even after 60 minutes of the examination. BRT revealed partial reversibility at a salbutamol dose of 400 micrograms in 26 (86.6 %) patients with COPD within 15 minutes, in another 3 (96.6 %) patients – within 30 minutes and after 45 minutes – in all patients; none of the patients showed full reversibility. Conclusions. According to conducted study, salbutamol for BRT can be used at a dose of 200 and 400 mcg in patients with BA, but the time of repeated spirometry should be different: at 200 mcg – not earlier than 30 minutes, or preferably 45 minutes; and at 400 mcg – 15 minutes after or a maximum of 30 minutes. In patients with COPD, the use of salbutamol at a dose of 200 mcg is impractical, but a dose of 400 mcg should be used and repeated spirometry is needed not earlier than 30 minutes after a test dose of the drug

ALS and Parkinson's disease genes CHCHD10 and CHCHD2 modify synaptic transcriptomes in human iPSC-derived motor neurons

Mitochondrial intermembrane space proteins CHCHD2 and CHCHD10 have roles in motor neuron diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy and axonal neuropathy and in Parkinson's disease. They form a complex of unknown function. Here we address the importance of these two proteins in human motor neurons. We show that gene edited human induced pluripotent stem cells (iPSC) lacking either CHCHD2 or CHCHD10 are viable and can be differentiated into functional motor neurons that fire spontaneous and evoked action potentials. Mitochondria in knockout iPSC and motor neurons sustain ultrastructure but show increased proton leakage and respiration, and reciprocal compensatory increases in CHCHD2 or CHCHD10. Knockout motor neurons have largely overlapping transcriptome profiles compared to isogenic control line, in particular for synaptic gene expression. Our results show that the absence of either CHCHD2 or CHCHD10 alters mitochondrial respiration in human motor neurons, inducing similar compensatory responses. Thus, pathogenic mechanisms may involve loss of synaptic function resulting from defective energy metabolism.Peer reviewe

СЕЛЕКЦИОННАЯ И БИОХИМИЧЕСКАЯ ХАРАКТЕРИСТИКА ФОРМ ЛУКА, СОЗДАННЫХ НА ОСНОВЕ МЕЖВИДОВОЙ ГИБРИДИЗАЦИИ

One of the most important crops among all types of Alliums is onion, the value of which is determined by the nutritional and medicinal properties. It is used not only as a seasoning for food, but also as a source of a number of biologically active substances. The biochemical composition of the bulbs and its green leaves in different periods of growth and development varies, depending on the variety, environmental conditions and agrotechnical methods of cultivation. Creation on the basis of interspecies hybridization of fundamentally new forms of Allium plants with a unique combination of genetic material allows to expand the possibility of selection of valuable genotypes in practical terms. The study was performed on plants of the inbred progenies I4-5 from BC1-2 bulbous forms of interspecific hybrids of Allium crossing combinations F5(A. cepa xA. vavilovii), F5(A. cepa x A. fistulosum). The biometric assessment was carried out after harvesting and drying the bulbs according to the "test Procedure for distinctiveness, uniformity and stability" according to the main breeding characteristics: the color of the dry cover scales of the bulb, the mass of the bulb, the shape of the bulb. As the standard used plant varieties Odintsovets. The biochemical composition of onion samples was determined by the content of dry matter, monosaccharides, the amount of sugars, ascorbic acid, antioxidants. Based on the biometric assessment of the forms of interspecific hybrids of onions, 5 forms were identified according to the uniformity of such features as the color of dry cover scales and the shape of the bulb weighing 50-60 g, which are a qualitatively new source material for breeding. In determining the biochemical composition of the isolated forms of interspecific hybrids of Alliums on the main breeding grounds found that the plants of these forms of onions indicators of dry matter (15%), monosaccharides (1.15-1.71%), the amount of sugars (11.17%), were at the level of the standard, or exceeded it, but the total content of antioxidants (8.22 mg/g) inferior to the standard.Одной из наиболее важных культур среди всех видов лука является лук репчатый, ценность которого определяется пищевкусовыми и лекарственными свойствами. Его используют не только в качестве приправы к пище, но и как источник ряда биологически активных веществ. Биохимический состав луковиц и его зеленых листьев в разные периоды роста и развития изменяется, зависит от сорта, экологических условий и агротехнических приемов возделывания растений. Создание на основе межвидовой гибридизации принципиально новых форм растений лука с уникальным сочетанием генетического материала позволяет расширить возможность отбора ценных в практическом отношении генотипов. Исследования проводили на растениях из инбредных потомств I4-5 от ВС1-2 луковичных форм межвидовых гибридов лука комбинаций скрещивания F5(A.cepa x A.vavilovii), F5(A.cepa x A.fistulosum). Биометрическую оценку проводили после уборки и подсушивания луковиц согласно «Методике проведения испытаний на отличимость, однородность и стабильность» по основным селекционным признакам: окраске сухих покровных чешуй луковицы, массе луковицы, форме луковицы. В качестве стандарта использовали растения сорта Одинцовец. Биохимический состав образцов лука определяли по содержанию сухого вещества, моносахаров, суммы сахаров, аскорбиновой кислоты, антиоксидантов. На основании биометрической оценки форм межвидовых гибридов лука выделено 5 форм по выравненности таких признаков, как окраске сухих покровных чешуй и форме луковицы массой 50-60 г, которые являются качественно новым исходным материалом для селекционной работы. При определении биохимического состава выделенных форм межвидовых гибридов лука по основным селекционным признакам установлено, что у растений данных форм лука показатели содержания сухого вещества (15%), моносахаров (1,15-1,71%), суммы сахаров (11,17%), находились на уровне стандарта, либо превышали его, но по суммарному содержанию антиоксидантов (8,22 мг/г) уступали стандарту

СТАХИС – ПЕРСПЕКТИВНАЯ ОВОЩНАЯ КУЛЬТУРА С ЛЕКАРСТВЕННЫМИ СВОЙСТВАМИ. ТЕХНОЛОГИЯ ВЫРАЩИВАНИЯ СТАХИСА

The technology of cultivation of stachys, the vegetable and officinal crop, in vitro and in vivo is presented in the article. There is a problem of cultivation of this crop on big areas in private farms duo to the lack of specialized machines. The main labor-intensive process of Stachys`s agrotechnology is harvesting of nodules in autumn (in October). In this period, the temperature drops below zero, and heavy rainfall is possible. This problem can be partially solved with the use of biotechnological methods. Stachys is susceptible to viral and fungal diseases. Diseasefree plants and nodules can be obtained through in vitro propagation. The multiplication ratio of Stachys, using method of clonal micropropagation, is very high (1:200). It shows the exploitability of method of tissue culture and plant cells for cultivation of stachys.В статье представлена технология выращивания овощной и лекарственной культуры стахиса in vitro и in vivo. Низкая рентабельность производства стахиса в личных подсобных хозяйствах в условиях Нечерноземной зоны России обусловлена отсутствием комплекса специализированных машин, что не позволяет выращивать эту культуру на больших площадях. Основным трудоемким приемом агротехники стахиса является уборка клубеньков осенью (в октябре). В этот период температура воздуха может опускаться ниже нуля, и возможны обильные осадки.Помимо этого, стахис подвержен вирусным и грибным заболеваниям, поэтому необходимо периодически оздоравливать клубеньки и размножать их с использованием биотехнологических методов. Показан высокий коэффициент размножения стахиса способом клонального микроразмножения (1:200), что свидетельствует о перспективности выращивания его с использованием метода культуры тканей и клеток растений

ХАРАКТЕРИСТИКА ГИБРИДОВ МЕЖДУ ALLIUM СЕРА L. И ALLIUM NUTANS L. ПО БИОХИМИЧЕСКОМУ СОСТАВУ

Wild species of Allium L. genus are not only a harbor of resistance to biotic factors such as pathogens and pests and abiotic factor such as drought, cold and freezing, but also have the biochemical composition differed from cultural species. Crosses between wild and cultured species in Allium genus are usually performed to develop breeding forms with improved content of biochemically valuable compounds. Hybrids F1 obtained from combination Allium сера x Allium nutans, where varieties ‘Stuttgarter Riesen’ and ‘Strigunovskiy’ served as parental forms from A.cepa were studied. Biochemical contents and morphological descriptions of obtained plants were also given in the article. NO3, К+, ascorbic acid, dry matter and total watersoluble antioxidants were analyzed in the plants. Increased content of NO3- was found in accession N13 F1 of A. cepa x A. nutans combination that was higher than in other accessions, including control plants. The accession N15 had a much higher content of Cl- and K+ in leaves than in other accessions. The content of ascorbic acid in all hybrids was 2-3 times less than in control accessions and varied from 15.8 to 28.6 mg%. All hybrid accessions had less dry matter content than in control accessions, achieving 9.3 to 11.7%, in control plants, 12.7. The lowest antioxidant content, 15.3 mg/g (conc. in ascorbic acid units), was found out in accession N3, but the highest antioxidant content 37.3 mg/g (conc. in ascorbic acid units) was in accession N16; it was twice higher than in control plants. The obtained hybrid F1 plants from combination A. cepa x A. nutans can be then selected for their best biochemical composition.Дикорастущие виды рода Allium L. являются источниками не только устойчивости к биотическим (болезням, вредителям) и абиотическим факторам окружающей среды (морозо-, зимостойкость, засухоустойчивость), но также отличаются по биохимическим показателям от культурного вида лука. Проведение скрещиваний с участием дикорастущих видов лука может увеличить содержание биохимических веществ у гибридов в сравнении с культурными. Во ВНИИССОК проводили скрещивания между дикорастущими и культурными видами рода Allium L. Для создания исходных форм для селекции с более высоким содержанием ценных биохимических веществ. Изучали растения межвидовых гибридов лука F1 в комбинации скрещивания A. cepa x A. nutans и растения родительских видов: Allium cepa L. (сорта лука репчатого – Штутгартер ризен, Стригуновский) и Allium nutans L. В работе представлена морфологическая характеристика растений межвидовых гибридов лука F1 Allium сера x Allium nutans и дана биохимическая оценка межвидовых гибридов лука. У растений определяли содержание NO3-, К+, аскорбиновой кислоты, сухого вещества, суммарного содержания водорастворимых антиоксидантов. Повышенное содержание NO3-наблюдалось у №13 F1 A. cepa x A. nutans в сравнении с другими вариантами и стандартом. У №15 F1 A. cepa x A. nutans содержание K+ в листьях значительно превышало накопление этих элементов у растений других вариантов. Содержание аскорбиновой кислоты у всех гибридов A. cepa x A. nutans было меньшим, по сравнению с контролем в два-три раза и варьировало от 15,8 до 28,6 мг%. Все гибридные растения также уступали растениям стандарта по содержанию сухого вещества (9,3-11,7%, в стандарте – 12,7%). Самыми низким содержанием антиоксидантов характеризовался образец №3 – 15,3 мг/г (ЕАК), самые высокие значения были получены в варианте №16 – 37,3 мг/г (ЕАК), превосходящие стандарт в два раза. У полученных растений F1 A. cepa x A. nutans через индивидуальный отбор целесообразно направленно отбирать формы, лучшие по биохимическому составу

Software platform virtualization in chemistry research and university teaching

<p>Abstract</p> <p>Background</p> <p>Modern chemistry laboratories operate with a wide range of software applications under different operating systems, such as Windows, LINUX or Mac OS X. Instead of installing software on different computers it is possible to install those applications on a single computer using Virtual Machine software. Software platform virtualization allows a single guest operating system to execute multiple other operating systems on the same computer. We apply and discuss the use of virtual machines in chemistry research and teaching laboratories.</p> <p>Results</p> <p>Virtual machines are commonly used for cheminformatics software development and testing. Benchmarking multiple chemistry software packages we have confirmed that the computational speed penalty for using virtual machines is low and around 5% to 10%. Software virtualization in a teaching environment allows faster deployment and easy use of commercial and open source software in hands-on computer teaching labs.</p> <p>Conclusion</p> <p>Software virtualization in chemistry, mass spectrometry and cheminformatics is needed for software testing and development of software for different operating systems. In order to obtain maximum performance the virtualization software should be multi-core enabled and allow the use of multiprocessor configurations in the virtual machine environment. Server consolidation, by running multiple tasks and operating systems on a single physical machine, can lead to lower maintenance and hardware costs especially in small research labs. The use of virtual machines can prevent software virus infections and security breaches when used as a sandbox system for internet access and software testing. Complex software setups can be created with virtual machines and are easily deployed later to multiple computers for hands-on teaching classes. We discuss the popularity of bioinformatics compared to cheminformatics as well as the missing cheminformatics education at universities worldwide.</p

West Nile Fever: Results of Monitoring over the Causative Agent in the Russian Federation in 2021, the Incidence Forecast for 2022

The epidemiological situation on West Nile fever (WNF) in Russia in 2021 was characterized by an increase in the incidence relative to 2020 (more than 6-fold increase). The peculiarities of the WNF epidemic process have been determined: the territorial distribution of cases (75 % – in the constituent entities of the Central Federal District), the expansion of the causative agent’s areal with the involvement of new territories (official registration of cases in Moscow and the Tula Region for the first time ever), the early end of the epidemic season. An increase in the proportion of neuroinvasive forms, an increase in the share of male patients and the age group of 30–39 years, a decrease in the proportion of the population in contact with the pathogen in natural places of mass recreation were observed in the incidence structure. According to the results of the monitoring studies carried out by the Reference Center, intensive circulation of the pathogen was established on the territory of the Central Federal District, Southern Federal District, and the North Caucasian Federal District. The low reported incidence was due to insufficient detection of WNF patients. The results of moleculargenetic study showed that in the European part of Russia, WNV lineage 2 circulated in both epizootic and epidemic cycles, lineage 2 in the south of Western Siberia (Omsk Region) and lineage 4 in the Volgograd Region – in the epizootic cycle only. Phylogenetic analysis revealed that strains isolated from the Astrakhan, Volgograd, Rostov, Voronezh Regions and the Republic of Dagestan in 2021 belong to the genovariant of WNV lineage 2 not registered in Russia previously.  The topology of the phylogenetic tree indicates the possible African origin of the isolates, probably imported into Russia by migratory birds across the coast of the Caspian Sea. In the Volgograd Region, WNV of both the entrenched clade of lineage 2 (since 2007) and new genovariant circulated. The specialists of the Reference Center developed a forecast of WNF epidemiological situation development in the Volgograd Region in 2022 on the basis of the neural network modeling technique, according to which an increase in the incidence is expected, comparable to that in 2010 and 2012. Based on the climate projections, an increase in the incidence is possible in all Federal Districts of the European part of Russia, the southern territories of the Urals, Western Siberia, and the Far East