Cyclic nucleotides in tissues during long-term hypokinesia

Male Wistar rates were kept hypokinetic by placing them in small containers for 22 days. Blood plasma cAMP content was subsequently found increased, and cGMP content decreased, in the experimental animals. Liver and thymus cAMP content was similar in the control and experimental animals. There was a 20 and 38% decrease of cAMP content in the kidneys and spleen, respectively. Hypokinesia's reduction of cyclic nucleotides seems to inhibit RNA and protein synthesis

DIAGNOSTIC DIFFICULTIES OF THE ISOLATED LIVER TUBERCULOSIS

The article describes the case of abdominal tuberculosis – isolated tuberculous lesion of liver. The diagnosis was based on computer tomography of the abdomen and retroperitoneal space with bolus amplification, histological testing of surgery specimens and positive results of diaskintest. This case proves the difficulties of abdominal tuberculosis diagnostics and it justifies the need to perform magnetic resonance tomography of the abdomen, and computer tomography of the abdomen with bolus amplification, special attention is to be paid to the patients with low-grade fever belonging to tuberculosis risk groups

The development of triploid apple cultivars is a priority in breeding

Great attention is paid to preliminary breeding (prebreeding) when developing triploid apple cultivars. Brief characteristics of diploid gamete donors are given. It should be noted that sometimes donors of diploid gametes with necessary important traits not only have to be selected from among existing tetraploid cultivars, but also developed by a breeding way, especially in the case when in nature there are no cultivars and genotypes (donors of diploid gametes) with given traits. The authors of the paper developed form 30-47-88 (Liberty×13-6-106) by a breeding way. 30-47-88 is a complex donor of diploid gametes and scab immunity (Vf ) at once. During 1970–2015, the following work was done in apple breeding using polyploidy: 455 crossing combinations were performed; 660000 flowers were artificially pollinated; 124700 hybrid seeds were obtained and 47900 one-year-old seedlings were grown, from which after multiple rejections 13200 seedlings were planted in breeding orchards. For the first time in Russia ten apple cultivars (Avgusta, Aleksandr Boiko, Bezhin Lug, Vavilovskoye, Dariona, Maslovskoye, Orlovsky Partizan, Osipovskoye, Patriot and Yablochny Spas) have been developed from intervalence crossings and regionalized. It has been stated that apple cultivars developed at the VNIISPK are characterized, as a rule, by high productivity, better fruit marketability, greater resistance to scab and higher autogamy. Apple cultivars combining triploidy and scab immunity have been developed. Promising breeding is being performed for apple cultivars combining triploidy, scab immunity and columnar habit (Co). Brief characteristics of triploid and scab immune cultivars Vavilovskoye and Yablochny Spas developed from the intervalence crossings as well as three triploid cultivars obtained from crossings of diploid cultivars are given. It is noted that triploid apple cultivars developed at the VNIISPK are inferior to none of foreign cultivars in a complex of commercial traits and they significantly excel foreign cultivars in adaptability. Our apple cultivars may contribute to import substitution of fruit production in the country

Genome editing using CRISPR/ Cas9 system: a practical guide

Over the past few years, the CRISPR/Cas techniques have become a revolution in genome editing. Since the original paper on CRIPSR/Cas9 genome editing, researches have proposed numerous modifications of the key components of the CRISPR/Cas9 system to make it extremely efficient. Nowadays, CRISPR/Cas systems can be used not only to modify genomes, but also to control expression levels of defined genes, visualize loci of interest in the space of living cell nuclei, change methylation status of mammalian CpG sites, and to serve many other purposes. Due to an extremely high efficacy and ease of usage, the CRISPR/ Cas system has been employed in a large number of studies in various areas of biology and biotechnology. We have recently published a review describing various CRISPR/Cas systems, mechanisms of their functioning, and applications of the techniques in details. Despite the broad range of potential applications of CRISPR/Cas systems, they are mostly used for genome editing. And, however simple the system may be, there is a number of potential pitfalls on the way towards its use in CRISPR/Cas- naïve laboratory settings. In this article, we describe protocols of CRISPR/Cas9 system generation. We start with a short description of theoretical aspects underlying Cas9-mediated genome editing. Next, we describe a step-by-step protocol of guide RNA vector design and assembly, and several ways of qualitative and quantitative evaluations of the system. Finally, we report protocols of genome editing for modification of embryonic stem cells and zygotes

Antiproliferative activity of PEP005, a novel ingenol angelate that modulates PKC functions, alone and in combination with cytotoxic agents in human colon cancer cells

PEP005 is a novel ingenol angelate that modulates protein kinases C (PKC) functions by activating PKCδ and inhibiting PKCα. This study assessed the antiproliferative effects of PEP005 alone and in combination with several other anticancer agents in a panel of 10 human cancer cell lines characterised for expression of several PKC isoforms. PEP005 displayed antiproliferative effects at clinically relevant concentrations with a unique cytotoxicity profile that differs from that of most other investigated cytotoxic agents, including staurosporine. In a subset of colon cancer cells, the IC50 of PEP005 ranged from 0.01–140 μM. The antiproliferative effects of PEP005 were shown to be concentration- and time-dependent. In Colo205 cells, apoptosis induction was observed at concentrations ranging from 0.03 to 3 μM. Exposure to PEP005 also induced accumulation of cells in the G1 phase of the cell cycle. In addition, PEP005 increased the phosphorylation of PKCδ and p38. In Colo205 cells, combinations of PEP005 with several cytotoxic agents including oxaliplatin, SN38, 5FU, gemcitabine, doxorubicin, vinorelbine, and docetaxel yielded sequence-dependent antiproliferative effects. Cell cycle blockage induced by PEP005 in late G1 lasted for up to 24 h and therefore a 24 h lag-time between PEP005 and subsequent exposure to cytotoxics was required to optimise PEP005 combinations with several anticancer agents. These data support further evaluation of PEP005 as an anticancer agent and may help to optimise clinical trials with PEP005-based combinations in patients with solid tumours

Changes of photosynthesis and carbon metabolism in Typha angustifolia L grown in conditions of nitrate nitrogen overload

Nitrates may induce alterations in NO-signaling system and change photosynthesisin plants. Significant reduction of 14CO2 fixation was noted at concentration of 3.96mM NaNO3 in an aquatic macrophyte (Typha angustifolia L.). Assimilation of 14CO2 seven days after the introduction of nitrates did not differ between control and experimental samples. There were changes in distribution of 14C among products of 4CO2 fixation 4 h after NaNO3 addition, resulting in increased sugar radioactivity in experimental plants. It was suggested that the observed changes may have regulatory importance

Thrombosis in unvaccinated and Gam-COVID-Vac-vaccinated patients with COVID-19

Aim. To analyze the incidence of thrombotic events in unvaccinated and GamCOVID-Vac-vaccinated patients with coronavirus disease 2019 (COVID-19).Material and methods. This prospective study included 316 patients (group 1) vaccinated with two doses of Sputnik V (Gam-COVID-Vac) hospitalized between November 20, 2020 and June 1, 2021 for COVID-19. Group 2 included 754 unvaccinated patients with a positive polymerase chain reaction test for SARSCoV-2.Results. During inhospital period, deaths were recorded only in unvaccinated patients (group 1 — 0%; group 2 — 10,7% (n=87); p<0,0001). Among unvaccinated patients, the following thrombotic events were more common: upper- extremity deep vein thrombosis (group 1 — 0,63% (n=2); group 2 — 5,4% (n=41); p=0,0003), lower-extremity deep vein thrombosis (group 1 — 2,21% (n=7); group 2 — 11,4% (n=86); p<0,0001), pulmonary embolism (PE) (group 1 — 0%; group 2 — 3,4% (n=26); p=0,0008), lower limb arterial thrombosis followed by thrombectomy (group 1 — 0,31% (n=1); group 2 — 12% (n=91); p <0,0001), lower limb arterial retrombosis after retrombectomy (group 1 — 0,31% (n=1); group 2 — 8,7% (n=66); p<0,0001), lower limb amputation (group 1 — 0%; group 2 — 8,7% (n=66); p<0,0001), composite endpoint (group 1 — 3,8% (n=12); group 2 — 55,2% (n=416); p<0,0001). In the long-term follow-up period (125,5±26,5 days), recurrent COVID-19 developed significantly more often in unvaccinated patients (group 1 — 0,63% (n=2); group 2 — 3,6% (n=24); p=0,007). All arterial and venous thromboses, limb amputations were diagnosed only among unvaccinated patients.Conclusion. Vaccination with Sputnik V (Gam-COVID-Vak) prevents the severe COVID-19 with the development of deaths, pulmonary embolism, venous and arterial thrombosis

Фотодинамическая терапия больных с внутрикожными метастазами меланомы

Results of treating 114 skin metastases of melanoma in 21 patients are represented. Melanoma progression with cutaneous metastases after previous treatment was diagnosed in all patients. The method of prolonged photodynamic therapy developed by authors with fotosens administrated intravenously at dose of 0.4 mg/kg of body weight was used in the study. First session of tumor irradiation was performed 2 h after injection of photosensitizer. Patients underwent superfi cial or contact irradiation depending on topography and type of growth of metastatic foci. Course of treatment accounted for 7–10 sessions of photodynamic therapy with 24 h interval, light dose delivered to tumor for one session – 350 J/cm2. Signifi cant clinical effect (complete and partial tumor regression) was obtained in 89% of cases for developed method. Представлены результаты лечения 114 метастатических очагов меланомы в кожу у 21 пациента. У всех больных было диагностировано прогрессирование меланомы с метастазированием в кожу после предшествующего противоопухолевого лечения. В исследовании использована разработанная авторами методика пролонгированной фотодинамической терапии с препаратом фотосенс, который вводили внутривенно в дозе 0,4 мг/кг массы тела больного. Первый сеанс облучения опухолевых очагов проводили через 2 ч после введения фотосенсибилизатора. Пациентам выполняли поверхностное или контактное облучение в зависимости от топографии и характера роста метастатического узла. Курс лечения – 7–10 сеансов фотодинамической терапии с интервалом в 24 ч, плотность энергии лазерного излучения, подводимой к опухоли за один сеанс – 350 Дж/см2. При применении разработанной методики получен объективный клинический эффект (полная и частичная регрессия опухоли) в 89% наблюдений.

Трудности диагностики изолированного туберкулеза печени

The article describes the case of abdominal tuberculosis – isolated tuberculous lesion of liver. The diagnosis was based on computer tomography of the abdomen and retroperitoneal space with bolus amplification, histological testing of surgery specimens and positive results of diaskintest. This case proves the difficulties of abdominal tuberculosis diagnostics and it justifies the need to perform magnetic resonance tomography of the abdomen, and computer tomography of the abdomen with bolus amplification, special attention is to be paid to the patients with low-grade fever belonging to tuberculosis risk groups.Приведен случай абдоминального туберкулеза - изолированного поражения туберкулезом печени. Диагноз установлен на основании компьютерной томографии органов брюшной полости и забрюшинного пространства с болюсным усилением, гистологического исследования операционного материала и положительного результата на пробу с диаскинтестом. Данное наблюдение показывает, какую трудность представляет диагностика абдоминального туберкулеза и обосновывает необходимость проведения как магнитно-резонансной томографии брюшной полости, так и компьютерной томографии органов брюшной полости с болюсным усилением, обращая особое внимание на лиц с длительной субфебрильной температурой, принадлежащих к группам риска по заболеванию туберкулезом