Theranostic Platforms Based on Silica and Magnetic Nanoparticles Containing Quinacrine, Chitosan, Fluorophores, and Quantum Dots

In this paper, we describe the synthesis of multilayer nanoparticles as a platform for the diagnosis and treatment of ischemic injuries. The platform is based on magnetite (MNP) and silica (SNP) nanoparticles, while quinacrine is used as an anti-ischemic agent. The synthesis includes the surface modification of nanoparticles with (3-glycidyloxypropyl)trimethoxysilane (GPMS), the immobilization of quinacrine, and the formation of a chitosan coating, which is used to fix the fluorophore indocyanine green (ICG) and colloidal quantum dots AgInS2/ZnS (CQDs), which serve as secondary radiation sources. The potential theranostic platform was studied in laboratory animals.

3-Hydroxyphenylacetic Acid: A Blood Pressure-Reducing Flavonoid Metabolite

Regular intake of polyphenol-rich food has been associated with a wide variety of beneficial health effects, including the prevention of cardiovascular diseases. However, the parent flavonoids have mostly low bioavailability and, hence, their metabolites have been hypothesized to be bioactive. One of these metabolites, 3-hydroxyphenylacetic acid (3-HPAA), formed by the gut microbiota, was previously reported to exert vasorelaxant effects ex vivo. The aim of this study was to shed more light on this effect in vivo, and to elucidate the mechanism of action. 3-HPAA gave rise to a dose-dependent decrease in arterial blood pressure when administered i.v. both as a bolus and infusion to spontaneously hypertensive rats. In contrast, no significant changes in heart rate were observed. In ex vivo experiments, where porcine hearts from a slaughterhouse were used to decrease the need for laboratory animals, 3-HPAA relaxed precontracted porcine coronary artery segments via a mechanism partially dependent on endothelium integrity. This relaxation was significantly impaired after endothelial nitric oxide synthase inhibition. In contrast, the blockade of SKCa or IKCa channels, or muscarinic receptors, did not affect 3-HPAA relaxation. Similarly, no effects of 3-HPAA on cyclooxygenase nor L-type calcium channels were observed. Thus, 3-HPAA decreases blood pressure in vivo via vessel relaxation, and this mechanism might be based on the release of nitric oxide by the endothelial layer.

Frances Power Cobbe

Frances Power Cobbe (b. 1822–d. 1904) was an Anglo-Irish journalist, religious writer, feminist activist, and leading antivivisectionist. She was among the best-known feminist writers and thinkers of her day. She was a prominent spokeswoman for the improvement of Victorian women’s educational and employment opportunities; a witty defender of so-called redundant women; an incisive critic of the Victorian idea of marriage; and a passionate advocate for women’s suffrage and right to bodily integrity. She published essays on these topics in prestigious periodicals and wrote over twenty books on Victorian women, science and medicine, and religious duty, as well as innumerable essays, pamphlets, and tracts for the antivivisection movement. She was a pioneering journalist who wrote the second-leader for the London Echo on the same wide variety of social and cultural topics that animated her highly regarded signed work in the periodical press. She founded two antivivisection societies, the Society for the Protection of Animals Liable to Vivisection (known as the Victoria Street Society) in 1875, and the British Union for the Abolition of Vivisection (BUAV) in 1898. Both societies comprised nationally organized branches that undertook campaigning, demonstrated against institutions that licensed vivisection, and produced and distributed mass publications, many of them by Cobbe herself. She brought her considerable journalistic know-how to her extensive work as leader of these organizations, evident especially in the productivity she was able to sustain over decades of activism and her success at placing essays in leading periodicals. She was instrumental in the passage of the Cruelty to Animals Act (1876), which created a regulatory framework for the use of live animals in scientific research, which she came to see as facilitating abuse rather than protecting animals. She advocated for improved legal protections for laboratory animals until her death. She also wrote carefully to advance the Matrimonial Causes Act (1878), which created new mechanisms for granting child custody and maintenance orders to wives separated from violent husbands, and continued to advocate for women’s autonomy in marriage and as mothers. Based in London for much of her career, Cobbe moved to Wales with her life companion, Mary Lloyd, in 1884 after receiving a substantial legacy from an antivivisectionist supporter. There she continued to write and publish, primarily on her antivivisection causes. She is buried with Lloyd in a double grave at Llanelltydd, Wales, in Lloyd’s family churchyard. Cobbe’s journalism, particularly on domestic violence, was at the center of the scholarship that first brought her writing to the forefront of feminist knowledge in the 1990s. More recently, scholarly frameworks that have reshaped feminist history-making, a revitalized interest in the Victorian Woman Question, and compelling new explorations of LGBTQ identities and life experiences, as well as new approaches to the Victorian periodical and newspaper press, have reframed our understanding of her spirited style and compelling ideas. Scholarship on Cobbe in sexuality studies remains limited, perhaps owing to the scant archival sources. New explorations of LGBTQ2S identities and life experiences may well spur new research into Cobbe’s life and relationships. She is increasingly an integral part of informed understanding of 19th-century feminism, journalism, and reform. Vitally, too, Cobbe’s central role in the antivivisection movement, which had long given her a global popular prominence in animal welfare and rights history, has made her writing and activities of growing academic interest in the field of critical animal studies.

Development of specific immunity in laboratory animals after co-immunization against seasonal influenza and COVID-19

Introduction. In clinical practice, the differential diagnosis of COVID-19 can be challenging during the flu season, entailing serious consequences such as delays in appropriate control measures against the SARS-CoV-2 pandemic. Another problem is posed by co-infection of SARS-CoV-2 and influenza virus (IV), which significantly contributes to the severity of the COVID-19 disease. This study was aimed to explore the cross-impact of co-administration of Russian influenza and COVID-19 vaccines on development of specific immunity in laboratory animals.Materials and methods. The study was conducted on BALB/c mice. The animals were inoculated intramuscularly with the vaccine for COVID-19 prevention (CoviVac) and the vaccine for influenza prevention (Flu-M). The sera from the immunized animals were examined separately. Three IV strains were used in the hemagglutination inhibition assay. Antibodies (Abs) against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay (ELISA). The neutralization test was performed to detect virus neutralizing antibodies against SARS-CoV-2 and IV.Results. Relatively high titers of specific Abs were found in the groups of animals inoculated with one vaccine and with two vaccines concurrently. In the groups of animals inoculated with CoviVac and with two vaccines concurrently, both in the ELISA test and in the neutralization test, the average titers of specific Abs against SARSCoV- 2 did not demonstrate any statistical difference. The group of animals inoculated concurrently with two vaccines demonstrated statistically higher titers of Abs against IV after the second immunization compared to the group of animals inoculated with Flu-M.Discussion. The study has shown that post-vaccination immunity both to IV and to SARS-CoV-2 develops after co-vaccination with two vaccines. The observed enhanced post-vaccination immune response to IV in the coimmunized laboratory animals needs further research.Conclusion. The performed studies suggest the possibility of co-administration of two vaccines to prevent influenza and COVID-19.

Inhibition of Neuronal Necroptosis Mediated by RIPK1 Provides Neuroprotective Effects on Hypoxia and Ischemia In Vitro and In Vivo

Ischemic brain injury is a widespread pathological condition, the main components of which are a deficiency of oxygen and energy substrates. In recent years, a number of new forms of cell death, including necroptosis, have been described. In necroptosis, a cascade of interactions between the kinases RIPK1 and RIPK3 and the MLKL protein leads to the formation of a specialized death complex called the necrosome, which triggers MLKL-mediated destruction of the cell membrane and necroptotic cell death. Necroptosis probably plays an important role in the development of ischemia/reperfusion injury and can be considered as a potential target for finding methods to correct the disruption of neural networks in ischemic damage. In the present study, we demonstrated that blockade of RIPK1 kinase by Necrostatin-1 preserved the viability of cells in primary hippocampal cultures in an in vitro model of glucose deprivation. The effect of RIPK1 blockade on the bioelectrical and metabolic calcium activity of neuron-glial networks in vitro using calcium imaging and multi-electrode arrays was assessed for the first time. RIPK1 blockade was shown to partially preserve both calcium and bioelectric activity of neuron-glial networks under ischemic factors. However, it should be noted that RIPK1 blockade does not preserve the network parameters of the collective calcium dynamics of neuron-glial networks, despite the maintenance of network bioelectrical activity (the number of bursts and the number of spikes in the bursts). To confirm the data obtained in vitro, we studied the effect of RIPK1 blockade on the resistance of small laboratory animals to in vivo modeling of hypoxia and cerebral ischemia. The use of Necrostatin-1 increases the survival rate of C57BL mice in modeling both acute hypobaric hypoxia and ischemic brain damage.

Chinese College Students’ Attitudes towards Animal Welfare

Understanding the attitude of stakeholders towards animals is critical for the development and improvement of animal welfare in a country. College students from veterinary, animal, and life sciences majors represent future key stakeholders that will interact with professionals from animal industries. Therefore, it is critical to understand these college students’ attitudes towards animals and their knowledge about animal welfare. The present survey aimed to investigate Chinese college students’ concerns towards different animal classes (i.e., pets, farm, laboratory, and wild animals) through the animal Sentient and Five Freedoms models. Chinese college students from different majors (i.e., related to animal sciences or not) scored very well in their attitude towards both the animal Sentient and Five Freedoms models, with differences depending on the animal class considered. Pets (dogs and cats) had better consideration for both animal Sentient and Five Freedoms models, followed by wild animals, while farm and laboratory animals were less considered. Veterinary science major students showed the strongest differences in attitudes depending on the animal classes considered compared to other majors. Furthermore, respondents showed better attitude scoring if they currently owned or had owned animals, had participated in animal welfare courses, or in laboratory work that involved animals. When compared to previous studies, our results suggest a general improvement of Chinese college students’ attitudes towards animals.

Immunogenicity of the drug "Live intranasal vaccine for the prevention of pertussis" (GamLPV) with a single use in healthy volunteers

Introduction. A significant increase in the incidence of pertussis in the world, including among adolescents and adults, the prevalence of mild forms of the disease and asymptomatic carrier of bacteria B. pertussis, and the resulting need for mass revaccination of different age groups determine the demand for new vaccines against B. pertussis. In N.F. Gamaleya Federal Research Center for Epidemiology and Microbiology, a live intranasal pertussis vaccine for the prevention of pertussis (GamLPV) has been developed. The GamLPV vaccine underwent preclinical studies that proved its safety and effectiveness in experiments on small laboratory animals and nonhuman monkeys. Safety of vaccine is shown in clinical studies on healthy volunteers.The aim of the study is to assess the immunogenicity of different doses of the drug GamLPV when first used in healthy volunteers.Materials and methods. The study was conducted as randomized placebo-controlled, blind trial with consistent volunteer inclusion and dose escalation. Study ID in clinicaltrials.gov database: NCT03137927 (A Phase I Clinical Study of a GamLPV, a Live Intranasal Bordetella Pertussis Vaccine). The following parameters of humoral and cellular immune responses were assessed in dynamics: levels of specific IgM, IgG and IgA antibodies in blood serum of volunteers and the number of cytokines interleukin-17, tumor necrosis factor-α, interferon-γ produced after specific induction in vitro of blood mononuclears of vaccinated volunteers. Dynamics of attenuated bacteria persistence in nasopharynx of vaccinated volunteers was evaluated.Results. Intranasal vaccination of volunteers with the drug Gam LPV resulted in the formation of a specific humoral (IgG and IgA) and cellular immune response. The dose-dependent nature of immunoglobulin and cytokine production was shown. Attenuated bacteria persisted for a long time in the nose/oropharynx of vaccinated volunteers.Discussion. Good tolerability of all tested doses of the drug justifies the choice for further investigation of a vaccine dose equal to 4 × 109 CFU. At the next stage, the safety and immunogenicity of two-time vaccination of volunteers will be studied.

Dynamics of morphological and immunohistochemical changes in myocardium during hypothyroidism modeling in experiment

An experimental model of hypothyroidism was obtained by thyroidectomy. The operation was carried out on 57 sexually mature male rats weighing 250–300 g. The experiment lasted 45 days. Laboratory animals were removed from the experiment on days 7th, 14th, 21st, 28th, 35th and 45th. As a control, 15 rats were used that were not operated on. For histological examination, pieces of rat myocardium were taken from the left and right ventricles. The pieces were fixed in 10% buffered formalin for 10 days. Histological sections were prepared in a standard manner. Sections were stained with hematoxylin and eosin, picrofuchsin according to van Gieson, toluidine blue, according to Mallory. Results of the study: In the myocardium of rats, hemodynamic disorders, edema, hydropic degeneration of cardiomyocytes, myocytolysis, fragmentation of muscle fibers, colliquation necrosis, compression and atrophy of muscle fibers were found. An immunohistochemical study revealed a decrease in the expression of desmin and sarcomeric actin.

Whey-Adapted versus Natural Cow’s Milk Formulation: Distinctive Feeding Responses and Post-Ingestive c-Fos Expression in Laboratory Mice

The natural 20:80 whey:casein ratio in cow’s milk (CM) for adults and infants is adjusted to reflect the 60:40 ratio of human milk, but the feeding and metabolic consequences of this adjustment have been understudied. In adult human subjects, the 60:40 CM differently affects glucose metabolism and hormone release than the 20:80 CM. In laboratory animals, whey-adapted goat’s milk is consumed in larger quantities. It is unknown whether whey enhancement of CM would have similar consequences on appetite and whether it would affect feeding-relevant brain regulatory mechanisms. In this set of studies utilizing laboratory mice, we found that the 60:40 CM was consumed more avidly than the 20:80 control formulation by animals motivated to eat by energy deprivation and by palatability (in the absence of hunger) and that this hyperphagia stemmed from prolongation of the meal. Furthermore, in two-bottle choice paradigms, whey-adapted CM was preferred against the natural 20:80 milk. The intake of the whey-adapted CM induced neuronal activation (assessed through analysis of c-Fos expression in neurons) in brain sites promoting satiation, but importantly, this activation was less pronounced than after ingestion of the natural 20:80 whey:casein CM. Activation of hypothalamic neurons synthesizing anorexigenic neuropeptide oxytocin (OT) was also less robust after the 60:40 CM intake than after the 20:80 CM. Pharmacological blockade of the OT receptor in mice led to an increase in the consumption only of the 20:80 CM, thus, of the milk that induced greater activation of OT neurons. We conclude that the whey-adapted CM is overconsumed compared to the natural 20:80 CM and that this overconsumption is associated with weakened responsiveness of central networks involved in satiety signalling, including OT.