Reproductive effects of the tumor necrosis factor (TNF) deficiency in mice

TNF is a multifunctional cytokine that, at physiological concentrations, maintains the balance between apoptosis and survival of male germ cells and, at higher concentrations, has adverse effects on various stages of the reproductive process. Although ant-cytokine therapies have been used in millions of patients, the consequences of cytokine deficiency for reproductive functions are poorly understood and need attention. In this work, we have studied behavioral interactions between males and females, spermatogenesis, male fertility, and embryonic developmental characteristics of the progeny in TNFα knockout mice (TNF-/-). We have demonstrated that TNF is involved in the regulation of sexual behavior, spermatogenesis, pre- and postimplantation development. Complete TNF deficiency led to decreased reproductive efficiency: a lower number of viable embryos were observed in TNF-/- mice than in wild-type mice. The decrease in fertility was caused by preimplantation embryo loss in TNF-/- mice. Preimplantation loss in females might be caused by asospermia in TNF-/- males. Additionally, the sensitivity of reproductive functions to female stimuli was different between TNF-/- mice and wild-type mice, while interactions with females increased the concentrations of sper­matozoids in both TNF-/- and wild-type mice. Still higher levels were observed in knockout animals, which led to increase in the number of immature spermatozoids in epididymides

Evaluation of the impact of unhealthy nutrition on the intestinal microbiota, mitochondrial function and the formation of multiple organ metabolic syndrome, ways of correction

BACKGROUND: The problem of metabolic syndrome is considered a demographic catastrophe. According to WHO experts,«by 2025, the prevalence of metabolic syndrome (MS) in the world will amount to more than 300 million people, and in the next 25 years it is expected to increase by 50%.» The pathophysiological mechanisms of MS formation and the role of unhealthy diet on the development of intestinal dysbiosis, mitochondrial insufficiency remain unclear.AIM: To study the effect of unhealthy diet on the state of the intestinal microbiota and the development of metabolicmitochondrial insufficiency in the formation of a multi-organ metabolic syndrome, evaluation of ways of correction.MATERIALS AND METHODS: Clinical picture assessment, anthropometric data (body mass index), laboratory results (glucose, cholesterol and fractions) were carried out in patients with MS, triglycerides, aspartate aminotransferase, alanine aminotransferase, C-reactive protein, lipid peroxidation indicators: malondialdehyde, diene conjugates, schiff bases, hydroperoxides, catalase, superoxide dismutase, succinate dehydrogenase (ASDH), α-glycerophosphate dehydrogenase (α-AGFDH). Hemorheological parameters were evaluated by the apparent viscosity of blood, the yield strength, the aggregation coefficient of erythrocytes and platelets. The microbiota and microbiome of the intestine were evaluated by species, strain composition and the level of metabolites-propionic, butyric, acetic acid, lipopolysaccharides, peptidoglycans. A questionnaire was conducted to study the nature of nutrition.RESULTS: The study included 128 patients with MS and 25 healthy individuals. According to medical outpatient records from anamnesis, questioning of each patient, complaints and clinical picture, 26.2% of patients had type 2 diabetes, 3.74% of men had erectile dysfunction, 7.5% of women had polycystic ovaries, 15.1% had night apnea syndrome, 8.7% hyperuricemic syndrome, 96.5% of patients had metabolic fatty liver steatosis. According to the results of the survey, it was revealed that 99.8% of patients adhered to an unhealthy and unbalanced, high-calorie diet, 46.4% of patients had a low level of physical activity, 48.7% had an average. The revealed disorders of lipid, carbohydrate metabolism, microbiota and intestinal microbiome were associated with increased lipid peroxidation, decreased levels of antioxidant defense enzymes, indicators reflecting mitochondrial function against the background of hemorheological disorders.CONCLUSION: In multi-organ MS, unhealthy diet can be considered as a targeted risk factor triggering pathophysiological mechanisms at the level of the intestinal microbiota, followed by a cascade of metabolic disorders in the form of activation of lipid peroxidation with inhibition of antioxidant defense enzymes, the development of multi-organ mitochondrial insufficiency and the development of latent hemorheological syndrome. The revealed metabolic complex obviously constitutes a multiorgan morphological cluster underlying the development of multi-organ metabolic syndrome. Based on the identified disorders, pathogenetically justified correction of MS should include a balanced diet with mitochondrial protective therapy

QCD in the nuclear medium and effects due to Cherenkov gluons

The equations of in-medium gluodynamics are proposed. Their classical lowest order solution is explicitly shown for a color charge moving with constant speed. For nuclear permittivity larger than 1 it describes emission of Cherenkov gluons resembling results of classical electrodynamics. The values of the real and imaginary parts of the nuclear permittivity are obtained from the fits to experimental data on the double-humped structure around the away-side jet obtained at RHIC. The dispersion of the nuclear permittivity is predicted by comparing the RHIC, SPS and cosmic ray data. This is important for LHC experiments. Cherenkov gluons may be responsible for the asymmetry of dilepton mass spectra near rho-meson, observed in the SPS experiment with excess in the low-mass wing of the resonance. This feature is predicted to be common for all resonances. The "color rainbow" quantum effect might appear according to higher order terms of in-medium QCD if the nuclear permittivity depends on color.Comment: 29 p., 4 figs; for "Phys. Atom. Nucl." volume dedicated to 80th birthday of L.B. Okun; minor corrections on pp. 11 and 13 in v

CD-1 mice females recognize male reproductive success via volatile organic compounds in urine

Sexual selection is considered as one of the leading factors of evolutionary development. In the conditions of incessant competition, specialized methods of attracting individuals of the opposite sex as well as criteria for assessing the quality of a sexual partner have been formed. In order for animals to rely on signaling from sexual partners, the signal must reflect the morpho-physiological status of animals. A high reproductive efficiency of male mice is a good advantage for mate selection and thus must be somehow demonstrated to potential mates. The aim of our study was to find out if male mice could demonstrate their reproductive efficiency through urine volatile organic compounds. The experiment implies cohabiting one male with two mature females for 6 days. The reproductive success of the male was assessed by the presence or absence of pregnant females. At the same time, naive females, who did not participate in reproduction, assessed the urine of the successful males as more attractive, which was expressed in shorter Latency time of sniffs in the Olfactory test. Using a rapid headspace GC/MS analysis, we have found volatile organic compounds (VOCs) in male urine that correlated with female behavior. It turned out that these substances are derivatives of mouse pheromone 6-hydroxy-6-methyl-3-heptanone. The amplitude of peaks corresponding to this pheromone correlated with the testosterone level in blood and the weight of preputial glands. The amplitude of peaks increased in males after mating with whom the females turned out to be pregnant. It is important to note that body weight, weight of testes, weight of seminal vesicles, weight of preputial glands, and plasma testosterone level alone are not reliable indicators of male reproductive success. Thus, the content of the pheromone 6-hydroxy-6-methyl-3-heptanone in the urine of males can serve as a good predictor of the quality of the male as a sexual partner for female CD-1 mice

ИЗУЧЕНИЕ ДИНАМИКИ ОПУХОЛЕВОГО КРОВОТОКА ДЛЯ ОЦЕНКИ РАННЕГО ОТВЕТА РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ НА НЕОАДЪЮВАНТНУЮ ХИМИОТЕРАПИЮ

Background. Over the past 20 years, there has been a change in approaches to the treatment of breast cancer, in particular, a significant increase in the role of drug therapy. Breast cancer response to neoadjuvant chemotherapy is currently considered as a surrogate biomarker, which allows evaluation of the clinical course and prognosis of the disease. To solve this problem, it is necessary to assess the functional and metabolic changes in tumor tissue during treatment. Doppler ultrasound is a non-invasive, affordable, and low-cost imaging technique that can be safely used for repeated measurements.The purpose of the study was to study vascular changes in the tumor by power Doppler ultrasound for the evaluation of the early breast cancer response to neoadjuvant chemotherapy.Material and Methods. From May 2017 to August 2019, 63 patients with breast cancer received neoadjuvant chemotherapy. Changes in the tumor blood flow were assessed before starting the treatment and prior to the second course of neoadjuvant chemotherapy using Doppler scanning. Changes in tumor blood floor after chemotherapy were compared with the pathological tumor response after surgical treatment.Results. In the vast majority of cases (78 %), there was a decrease in the number of tumor vessels after the first cycle of neoadjuvant chemotherapy independent of the grade of pathological response. In 8 cases with increased vascularization after the first cycle of neoadjuvant chemotherapy, histological examination of the removed tumor showed no response / weak response to treatment in the absence of peritumoral inflammation. In 5 cases, a sharp increase in the number of vessels around large areas of intranodular necrosis and peritumoral inflammation was observed. In general, a comparison of changes in tumor vascularization and pathological response revealed a weak, although statistically significant, negative correlation between changes in the tumor blood flow after neoadjuvant chemotherapy and pathological response.Conclusion. It was not possible to establish an unambiguous relationship between the reaction of the vascular bed and the tumor response to the cytostatic effect. An increase in the number of tumor vessels in the absence of peritumoral inflammation was the only situation when changes in tumor blood flow during chemotherapy can be unambiguously interpreted as a predictive criterion for the absence / weak response of the tumor to treatment.Введение. В течение последних 20 лет произошло изменение подходов к лечению рака молочной железы, в частности существенное повышение роли лекарственной терапии. Ответ на неоадъювантную химиотерапию рассматривается в настоящее время как суррогатный биомаркер, который позволяет оценить течение и прогноз заболевания. Для решения данной задачи необходимо проводить оценку функциональных и метаболических изменений опухолевой ткани в процессе лечения. Ультразвуковая допплерография – это неинвазивный, доступный и недорогой метод визуализации, который можно безопасно использовать для повторных измерений. Цель исследования – изучение динамики васкуляризации опухоли ультразвуковым  методом в режиме энергетического допплера для оценки раннего ответа рака молочной железы на неоадъювантную химиотерапию. Материал и методы. Исследование проводилось на базе ФБУЗ ПОМЦ ФМБА России с мая 2017 по август 2019 г. В исследование были включены 63 больных раком молочной железы, которым проводилась неоадъювантная химиотерапия. Оценка кровотока опухоли с использованием допплеровского сканирования проводилась до начала и перед вторым курсом неоадъювантной химиотерапии. Изменения кровоснабжения опухоли на фоне химиотерапии сопоставлялись с патоморфологическим ответом опухоли после оперативного лечения.Результаты. В подавляющем большинстве случаев (78 %) наблюдалось не зависящее от степени лечебного патоморфоза уменьшение количества опухолевых сосудов после первого курса химиотерапии. В 8 случаях повышения васкуляризации после первого  курса неоадъювантной химиотерапии при гистологическом исследовании удаленной опухоли наблюдалось отсутствие ответа/слабый ответ на лечение при отсутствии перитуморального воспаления, в 5 случаях – резкое увеличение количества сосудов вокруг обширных зон интранодулярного некроза и обусловленного им перитуморального воспаления. В целом сопоставление динамики васкуляризации опухоли и  патоморфологического ответа выявило слабую, хотя и статистически значимую отрицательную корреляцию между изменениями кровоснабжения опухоли на фоне химиотерапии и степенью лечебного патоморфоза. Выводы. Не удалось установить однозначной зависимости между реакцией сосудистого русла и ответом опухоли на цитостатическое воздействие. Повышение количества  опухолевых сосудов при отсутствии перитуморального воспаления оказалось  единственной ситуацией, когда изменения опухолевого кровотока на фоне проведения химиотерапии могут быть однозначно интерпретированы как предиктивный критерий отсутствия/слабого ответа опухоли на лечение

Combination of Atrial Fibrillation and Coronary Heart Disease in Patients in Clinical Practice: Comorbidities, Pharmacotherapy and Outcomes (Data from the REСVASA Registries)

Aim. Assess the structure of comorbid conditions, cardiovascular pharmacotherapy and outcomes in patients with atrial fibrillation (AF) and concomitant coronary artery disease (CAD) included in the outpatient and hospital RECVASA registries.Materials and methods. 3169 patients with AF were enrolled in outpatient RECVASA (Ryazan), RECVASA AF-Yaroslavl registries and hospital RECVASA AF (Moscow, Kursk, Tula). 2497 (78.8%) registries of patients with AF had CAD and 703 (28.2%) of them had a previous myocardial infarction (MI).Results. There were 2,497 patients with a combination of AF and CAD (age was 72.2±9.9 years; 43.1% of men; CHA2DS2-VASc – 4.57±1.61 points; HAS-BLED – 1.60±0,75 points), and the group with AF without CAD included 672 patients (age was 66.0±12.3 years; 43.2% of men; CHA2DS2-VASc – 3.26±1.67 points; HAS-BLED – 1,11±0.74 points). Patients with CAD were on average 6.2 years older and had a higher risk of thromboembolic and hemorrhagic complications (p<0.05). 703 patients with a combination of AF and CAD had the previous myocardial infarction (MI; age was 72.3±9.5 years; 55.2% of men; CHA2DS2-VASc – 4.57±1.61; HAS-BLED – 1.65±0.76), and 1794 patients didn't have previous MI (age was 72.2±10.0 years; 38.4% of men; CHA2DS2-VASc – 4.30±1.50; HAS-BLED – 1.58±0.78). The proportion of men was 1.4 times higher among those with the previous MI. Patients with a combination of AF and CAD significantly more often (p <0.0001) than in the absence of CAD received a diagnosis of hypertension (93.8% and 78.6%), chronic heart failure (90.1% and 51.2%), diabetes mellitus (21.4% and 13.8%), chronic kidney disease (24.8% and 17.7%), as well as anemia (7.0% and 3.0%; p=0.001). Patients with and without the previous MI had the only significant difference in the form of a diabetes mellitus higher incidence having the previous MI (27% versus 19.2%, p=0.0008). The frequency of proper cardiovascular pharmacotherapy was insufficient, mainly in the presence of CAD (67.8%) than in its absence (74.5%), especially the prescription of anticoagulants (39.1% and 66.2%; p <0.0001), as well as in the presence of the previous MI (63.3%) than in its absence (74.3%). The presence of CAD and, in particular, the previous MI, was significantly associated with a higher risk of death (risk ratio [RR]=1.58; 95% confidence interval [CI] was 1.33-1.88; p <0.001 and RR=1.59; 95% CI was 1.33-1.90; p <0.001), as well as with a higher risk of developing a combined cardiovascular endpoint (RR=1.88; 95% CI was 1.17-3 , 00; p <0.001 and RR=1.75; 95% CI was 1.44-2.12; p<0.001, respectively).Conclusion. 78.8% of patients from AF registries in 5 regions of Russia were diagnosed with CAD, of which 28.2% had previously suffered myocardial infarction. Patients with a combination of AF and CAD more often than in the absence of CAD had hypertension, chronic heart failure, diabetes, chronic kidney disease and anemia. Patients with the previous MI had higher incidence of diabetes than those without the previous MI. The frequency of proper cardiovascular pharmacotherapy was insufficient, and to a greater extent in the presence of CAD and the previous MI than in their absence. All-cause mortality was recorded in patients with a combination of AF and CAD more often than in the absence of CAD. All-cause mortality and the incidence of nonfatal myocardial infarction were higher in patients with AF and the previous MI than in those without the previous MI. The presence of CAD and, in particular, the previous MI, was significantly associated with a higher risk of death, as well as a higher risk of developing a combined cardiovascular endpoint

Observations of the luminous red nova AT 2021biy in the nearby galaxy NGC 4631

We present an observational study of the luminous red nova (LRN) AT\,2021biy in the nearby galaxy NGC\,4631. The field of the object was routinely imaged during the pre-eruptive stage by synoptic surveys, but the transient was detected only at a few epochs from $\sim 231$\,days before maximum brightness. The LRN outburst was monitored with unprecedented cadence both photometrically and spectroscopically. AT\,2021biy shows a short-duration blue peak, with a bolometric luminosity of $\sim 1.6 \times 10^{41}$\,erg\,s$^{-1}$, followed by the longest plateau among LRNe to date, with a duration of 210\,days. A late-time hump in the light curve was also observed, possibly produced by a shell-shell collision. AT\,2021biy exhibits the typical spectral evolution of LRNe. Early-time spectra are characterised by a blue continuum and prominent H emission lines. Then, the continuum becomes redder, resembling that of a K-type star with a forest of metal absorption lines during the plateau phase. Finally, late-time spectra show a very red continuum ($T_{\mathrm{BB}} \approx 2050$ K) with molecular features (e.g., TiO) resembling those of M-type stars. Spectropolarimetric analysis indicates that AT\,2021biy has local dust properties similar to those of V838\,Mon in the Milky Way Galaxy. Inspection of archival {\it Hubble Space Telescope} data taken on 2003 August 3 reveals a $\sim 20$\,\msun\ progenitor candidate with log\,$(L/{\rm L}_{\odot}) = 5.0$\,dex and $T_{\rm{eff}} = 5900$\,K at solar metallicity. The above luminosity and colour match those of a luminous yellow supergiant. Most likely, this source is a close binary, with a 17--24\,\msun\ primary component.Comment: 21 pages, 14 figures. Accepted by Astronomy and Astrophysic

Patients with a Combination of Atrial Fibrillation and Chronic Heart Failure in Clinical Practice: Comorbidities, Drug Treatment and Outcomes

Aim. To assess in clinical practice the structure of multimorbidity, cardiovascular pharmacotherapy and outcomes in patients with a combination of atrial fibrillation (AF) and chronic heart failure (CHF) based on prospective registries of patients with cardiovascular diseases (CVD).Materials and Methods. The data of 3795 patients with atrial fibrillation (AF) were analyzed within the registries RECVASA (Ryazan), RECVASA FP (Moscow, Kursk, Tula, Yaroslavl), REGION-PO and REGION-LD (Ryazan), REGION-Moscow, REGATA (Ryazan). The comparison groups consisted of 3016 (79.5%) patients with AF in combination with CHF and 779 (29.5%) patients with AF without CHF. The duration of prospective observation is from 2 to 6 years.Results. Patients with a combination of AF and CHF (n=3016, age was 72.0±10.3 years; 41.8% of men) compared with patients with AF without CHF (n=779, age was 70.3±12.0 years; 43.5% of men) had a higher risk of thromboembolic complications (CHA2DS2-VASc – 4.68±1.59 and 3.10±1.50; p<0.001) and hemorrhagic complications (HAS-BLED – 1.59±0.77 and 1.33±0.76; p<0.05). Patients with a combination of AF and CHF significantly more often (p<0.001) than in the absence of CHF were diagnosed with arterial hypertension (93.9% and 83.8%), coronary heart disease (87.9% and 53,5%), myocardial infarction (28.4% and 14.0%), diabetes mellitus (22.4% and 7.7%), chronic kidney disease (24.8% and 16.2%), as well as respiratory diseases (20.1% and 15.3%; p=0.002). Patients with AF in the presence of CHF, compared with patients without CHF, were more often diagnosed with a permanent form of arrhythmia (49.3% and 32.9%; p<0.001) and less often paroxysmal (22.5% and 46.2%; p<0.001) form  of  arrhythmia.  Ejection  fraction  ≤40%  (9.3%  and  1.2%;  p<0.001),  heart  rate  ≥90/min  (23.7% and 19.3%; p=0.008) and blood pressure ≥140/90 mm Hg (59.9% and 52.2%; p<0.001) were recorded with AF in the presence of CHF more often than in the absence of CHF. The frequency of proper cardiovascular pharmacotherapy was higher, albeit insufficient, in the presence of CHF (64.9%) than in the absence of it (56.1%), but anticoagulants were prescribed less frequently when AF and CHF were combined (38.8% and  49, 0%; p<0.001). The frequency of unreasonable prescription of antiplatelet agents instead of anticoagulants was 52.5% and 33.3% (p<0.001) in the combination of AF, CHF and coronary heart disease, as well as in the combination of AF with coronary heart disease but without CHF. Patients with AF and CHF during the observation period compared with those without CHF had higher mortality from all causes (37.6% and 30.3%; p=0.001), the frequency of non-fatal cerebral stroke (8.2% and 5.4%; p=0.032) and myocardial infarction (4.7% and 2.5%; p=0.036), hospitalizations for CVD (22.8% and 15.5%; p<0.001).Conclusion. Patients with a combination of AF and CHF, compared with the group of patients with AF without CHF, were older, had a higher risk of thromboembolic and hemorrhagic complications, they were more often diagnosed with other concomitant cardiovascular and chronic noncardiac diseases, decreased left ventricular ejection fraction, tachysystole, failure to achieve the target blood pressure level in the presence of arterial hypertension. The frequency of prescribing proper cardiovascular pharmacotherapy was higher, albeit insufficient, in the presence of CHF, while the frequency of prescribing anticoagulants was less. The  incidence of mortality from all causes, the development of non-fatal myocardial infarction   and cerebral stroke, as well as the incidence of hospitalizations for CVDs were higher in AF associated with CHF

Modern Trends of Organic Chemistry in Russian Universities

© 2018, Pleiades Publishing, Ltd. This review is devoted to the scientific achievements of the departments of organic chemistry in higher schools of Russia within the past decade