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Исследования гомеостазиса развития от популяциионной биологии развития до концепции здоровья среды.

Журнальные статьи

1. PDF
Alexander A.J.T. et al. Calcium homeostasis plays important roles in the internalization and activities of the small synthetic antifungal peptide PAF26 // Mol. Microbiol.

Fungal diseases are responsible for the deaths of over 1.5 million people worldwide annually. Antifungal peptides represent a useful source of antifungals with novel mechanisms-of-action, and potentially provide new methods of overcoming resistance. Here we investigate the mode-of-action of the small, rationally designed synthetic antifungal peptide PAF26 using the model fungusNeurospora crassa. Here we show that the cell killing activity of PAF26 is dependent on extracellular Ca(2+)and the presence of fully functioning fungal Ca(2+)homeostatic/signaling machinery. In a screen of mutants with deletions in Ca2+-signaling machinery, we identified three mutants more tolerant to PAF26. The Ca(2+)ATPase NCA-2 was found to be involved in the initial interaction of PAF26 with the cell envelope. The vacuolar Ca(2+)channel YVC-1 was shown to be essential for its accumulation and concentration within the vacuolar system. The Ca(2+)channel CCH-1 was found to be required to prevent the translocation of PAF26 across the plasma membrane. In the wild type, Ca(2+)removal from the medium resulted in the peptide remaining trapped in small vesicles as in the Delta yvc-1mutant. It is, therefore, apparent that cell killing by PAF26 is complex and unusually dependent on extracellular Ca(2+)and components of the Ca2+-regulatory machinery.

http://dx.doi.org/10.1111%2Fmmi.14532

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Beaudequin D. et al. Using measures of intrinsic homeostasis and extrinsic modulation to evaluate mental health in adolescents: Preliminary results from the longitudinal adolescent brain study (LABS) // Psychiatry Res. 2020. Vol. 285. P. 112848.

Adolescence is a period when complex interactions occur between mental health risk factors. The Longitudinal Adolescent Brain Study (LABS) commenced in 2018, to monitor environmental and psychosocial factors thought to influence mental health in 500 young people. Participants commence at 12 years of age, via a communitybased recruitment model, and data is collected at 15 time-points over five years. This study examines demographic and psychosocial self-report data from time-point 1, for the first 50 participants. Here we investigate associations between environmental and psychosocial factors, considered as measures of intrinsic homeostasis and extrinsic modulation. Numerous strong correlations were found. Findings indicate that sleep dysfunction and social connectedness were strongly associated external modulators of intrinsic homeostasis in this sample of 12-year old participants. To successfully address the increase in mental health problems in young people, comprehensive evaluation of lifestyle and environmental risk factors is recommended in addition to medicalised approaches. Interventions to promote mental health wellbeing in young adolescents should include a focus on sleep quality and patterns and the positive and negative aspects of social connectedness.

http://dx.doi.org/10.1016%2Fj.psychres.2020.112848

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Bellantuono I. et al. A toolbox for the longitudinal assessment of healthspan in aging mice // Nat. Protoc. 2020. Vol. 15, № 2. P. 540–574.

The number of people aged over 65 is expected to double in the next 30 years. For many, living longer will mean spending more years with the burdens of chronic diseases such as Alzheimer's disease, cardiovascular disease, and diabetes. Although researchers have made rapid progress in developing geroprotective interventions that target mechanisms of aging and delay or prevent the onset of multiple concurrent age-related diseases, a lack of standardized techniques to assess healthspan in preclinical murine studies has resulted in reduced reproducibility and slow progress. To overcome this, major centers in Europe and the United States skilled in healthspan analysis came together to agree on a toolbox of techniques that can be used to consistently assess the healthspan of mice. Here, we describe the agreed toolbox, which contains protocols for echocardiography, novel object recognition, grip strength, rotarod, glucose tolerance test (GTT) and insulin tolerance test (ITT), body composition, and energy expenditure. The protocols can be performed longitudinally in the same mouse over a period of 4-6 weeks to test how candidate geroprotectors affect cardiac, cognitive, neuromuscular, and metabolic health. A series of techniques (echocardiography, novel object recognition, grip strength, rotarod, glucose and insulin tolerance tests, body composition, and energy expenditure) are used to assess the health of mice.

http://dx.doi.org/10.1038%2Fs41596-019-0256-1

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Boulestreau J. et al. Mesenchymal Stem Cell Derived Extracellular Vesicles in Aging // Front. Cell. Dev. Biol. 2020. Vol. 8. P. 107.

Aging is associated with high prevalence of chronic degenerative diseases that take a large part of the increasing burden of morbidities in a growing demographic of elderly people. Aging is a complex process that involves cell autonomous and cell non-autonomous mechanisms where senescence plays an important role. Senescence is characterized by the loss of proliferative potential, resistance to cell death by apoptosis and expression of a senescence-associated secretory phenotype (SASP). SASP includes pro-inflammatory cytokines and chemokines, tissue-damaging proteases, growth factors; all contributing to tissue microenvironment alteration and loss of tissue homeostasis. Emerging evidence suggests that the changes in the number and composition of extracellular vesicles (EVs) released by senescent cells contribute to the adverse effects of senescence in aging. In addition, age-related alterations in mesenchymal stem/stromal cells (MSCs) have been associated to dysregulated functions. The loss of functional stem cells necessary to maintain tissue homeostasis likely directly contributes to aging. In this review, we will focus on the characteristics and role of EVs isolated from senescent MSCs, the potential effect of MSC-derived EVs in aging and discuss their therapeutic potential to improve age-related diseases.

http://dx.doi.org/10.3389%2Ffcell.2020.00107

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De Gaetano A. et al. Impaired Mitochondrial Morphology and Functionality inLonp1(wt/-)Mice // J. Clin. Med. 2020. Vol. 9, № 6. P. 1783.

LONP1 is a nuclear-encoded mitochondrial protease crucial for organelle homeostasis; mutations ofLONP1have been associated with Cerebral, Ocular, Dental, Auricular, and Skeletal anomalies (CODAS) syndrome. To clarify the role of LONP1 in vivo, we generated a mouse model in whichLonp1was ablated. The homozygousLonp(-/-)mouse was not vital, while the heterozygousLonp1(wt/-)showed similar growth rate, weight, length, life-span and histologic features as wild type. Conversely, ultrastructural analysis of heterozygous enterocytes evidenced profound morphological alterations of mitochondria, which appeared increased in number, swollen and larger, with a lower complexity. Embryonic fibroblasts (MEFs) fromLonp1(wt/-)mice showed a reduced expression ofLonp1andTfam, whose expression is regulated by LONP1. Mitochondrial DNA was also reduced, and mitochondria were swollen and larger, albeit at a lesser extent than enterocytes, with a perinuclear distribution. From the functional point of view, mitochondria from heterozygous MEF showed a lower oxygen consumption rate in basal conditions, either in the presence of glucose or galactose, and a reduced expression of mitochondrial complexes than wild type. In conclusion, the presence of one functional copy of theLonp1gene leads to impairment of mitochondrial ultrastructure and functions in vivo.

http://dx.doi.org/10.3390%2Fjcm9061783

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Dobson C.M., Knowles T.P.J., Vendruscolo M. The Amyloid Phenomenon and Its Significance in Biology and Medicine // Cold Spring Harbor Perspect. Biol. 2020. Vol. 12, № 2. P. a033878.

The misfolding of proteins is now recognized to be the origin of a large number of medical disorders. One particularly important group of such disorders is associated with the aggregation of misfolded proteins into amyloid structures, and includes conditions ranging from Alzheimer's and Parkinson's diseases to type II diabetes. Such conditions already affect over 500 million people in the world, a number that is rising rapidly, and at present these disorders cannot be effectively treated or prevented. This review provides an overview of this field of science and discusses recent progress in understanding the nature and properties of the amyloid state, the kinetics and mechanism governing its formation, the origins of its links with disease, and the manner in which its formation may be inhibited or suppressed. This latter topic is of particular importance, both to enhance our knowledge of the maintenance of protein homeostasis in living organisms and also to address the development of transherapeutic strategies through which to combat the loss of homeostasis and the associated onset and progression of disease.

http://dx.doi.org/10.1101%2Fcshperspect.a033878

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Hermann J. et al. Contribution of NAADP to Glutamate-Evoked Changes in Ca(2+)Homeostasis in Mouse Hippocampal Neurons // Front. Cell. Dev. Biol. 2020. Vol. 8. P. 496.

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger that evokes calcium release from intracellular organelles by the engagement of calcium release channels, including members of the Transient Receptor Potential (TRP) family, such as TRPML1, the (structurally) related Two Pore Channel type 1 (TPC1) and TPC2 channels as well as Ryanodine Receptors type 1 (RYR1;Guse, 2012). NAADP evokes calcium release from acidic calcium stores of many cell types (Guse, 2012), and NAADP-sensitive Ca(2+)stores have been described in hippocampal neurons of the rat (Bak et al., 1999;McGuinness et al., 2007). Glutamate triggers Ca2+-mediated neuronal excitotoxicity in inflammation-induced neurodegenerative pathologies such as Multiple Sclerosis (MS;Friese et al., 2014), and when applied extracellularly to neurons glutamate can elevate NAADP levels in these cells. Accordingly, glutamate-evoked Ca(2+)signals from intracellular organelles were inhibited by preventing organelle acidification (Pandey et al., 2009). Analysis of reported RNA sequencing experiments of cultured hippocampal neurons revealed the abundance of Mcoln1 (encoding TRPML1), Tpcn1, and Tpcn2 (encoding TPC1 and TPC2, respectively) as potential NAADP target channels in these cells. Transcripts encoding Ryr1 were not found in contrast to Ryr2 and Ryr3. To study the contribution of NAADP signaling to glutamate-evoked calcium transients in murine hippocampal neurons we used the NAADP antagonists Ned-19 (Naylor et al., 2009) and BZ194 (Dammermann et al., 2009). Our results show that both NAADP antagonists significantly reduce glutamate-evoked calcium transients. In addition to extracellular glutamate application, we studied synchronized calcium oscillations in the cells of the neuronal cultures evoked by addition of the GABA(A)receptor antagonist bicuculline. Pretreatment with Ned-19 (50 mu M) or BZ194 (100 mu M) led to an increase in the frequency of bicuculline-induced calcium oscillations at the cost of calcium transient amplitudes. Interestingly, Ned-19 triggered a rise in intracellular calcium concentrations 25 min after bicuculline stimulation, leading to the question whether NAADP acts as a neuroprotective messenger in hippocampal neurons. Taken together, our results are in agreement with the concept that NAADP signaling significantly contributes to glutamate evoked Ca(2+)rise in hippocampal neurons and to the amplitude and frequency of synchronized Ca(2+)oscillations triggered by spontaneous glutamate release events.

http://dx.doi.org/10.3389%2Ffcell.2020.00496

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Hoshino S. et al. WWP1 knockout in mice exacerbates obesity-related phenotypes in white adipose tissue but improves whole-body glucose metabolism // FEBS Open Bio. 2020. Vol. 10, № 3. P. 306–315.

White adipose tissue (WAT) is important for maintenance of homeostasis, because it stores energy and secretes adipokines. The WAT of obese people demonstrates mitochondrial dysfunction, accompanied by oxidative stress, which leads to insulin resistance. WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) is a member of the HECT-type E3 family of ubiquitin ligases and is associated with several diseases. Recently, we demonstrated that WWP1 is induced specifically in the WAT of obese mice, where it protects against oxidative stress. Here, we investigated the function of WWP1 in WAT of obese mice by analyzing the phenotype of Wwp1 knockout (KO) mice fed a high-fat diet. The levels of oxidative stress markers were higher in obese WAT from Wwp1 KO mice. Moreover, Wwp1 KO mice had lower activity of citrate synthase, a mitochondrial enzyme. We also measured AKT phosphorylation in obese WAT and found lower levels in Wwp1 KO mice. However, plasma insulin level was low and glucose level was unchanged in obese Wwp1 KO mice. Moreover, both glucose tolerance test and insulin tolerance test were improved in obese Wwp1 KO mice. These findings indicate that WWP1 participates in the antioxidative response and mitochondrial function in WAT, but knockdown of WWP1 improves whole-body glucose metabolism.

http://dx.doi.org/10.1002%2F2211-5463.12795

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Jiang Y. et al. Bromide impairs the circadian clock and glycolytic homeostasis via disruption of autophagy in rat H9C2 cardiomyocytes // BMC Mol. Cell Biol. 2020. Vol. 21, № 1. P. 44.

Background Trace elements function as essential cofactors that are involved in various biochemical processes in mammals. Autophagy is vital for nutrient supplement, which is an importantZeitegberfor the circadian homeostasis in heart. Here, we considered the possibility that autophagy, as well as the cardiomyocyte clock and glycolysis are interlinked. Detrimental effects were observed when cardiac system is exposed to bromine containing drugs. This study investigated the effects and mechanisms of bromide on the circadian clock and glycolytic metabolism of H9C2 cardiomyocytes. Results In the present study, bromide does not affect cell viability and apoptosis of H9C2 cardiomyocytes. Bromide dampens the clock and glycolytic (Hk2andPkm2) gene expression rhythmicity in a dose-dependent manner. Additionally, bromide inhibits autophagic process in H9C2 cardiomyocytes. In contrast, rapamycin (an autophagy inducer) dramatically restores the inhibitory effect of NaBr on the mRNA expression levels of clock genes (Bmal1,Cry1andRor alpha) and glycolytic genes (Hk2andPkm2). Conclusions Our results reveal that bromide represses the clock and glycolytic gene expression patterns, partially through inhibition of autophagy.

http://dx.doi.org/10.1186%2Fs12860-020-00289-8

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Kauppinen A., Kaarniranta K., Salminen A. Potential Role of Myeloid-Derived Suppressor Cells (MDSCs) in Age-Related Macular Degeneration (AMD) // Front. Immunol. 2020. Vol. 11. P. 384.

Myeloid cells, such as granulocytes/neutrophils and macrophages, have responsibilities that include pathogen destruction, waste material degradation, or antigen presentation upon inflammation. During persistent stress, myeloid cells can remain partially differentiated and adopt immunosuppressive functions. Myeloid-derived suppressor cells (MDSCs) are primarily beneficial upon restoring homeostasis after inflammation. Because of their ability to suppress adaptive immunity, MDSCs can also ameliorate autoimmune diseases and semi-allogenic responses, e.g., in pregnancy or transplantation. However, immunosuppression is not always desirable. In certain conditions, such as cancer or chronically inflamed tissue, MDSCs prevent restorative immune responses and thereby aggravate disease progression. Age-related macular degeneration (AMD) is the most common disease in Western countries that severely threatens the central vision of aged people. The pathogenesis of this multifactorial disease is not fully elucidated, but inflammation is known to participate in both dry and wet AMD. In this paper, we provide an overview about the potential role of MDSCs in the pathogenesis of AMD.

http://dx.doi.org/10.3389%2Ffimmu.2020.00384

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Lee K.-Y. The solution on enigmas in COVID-19: the protein-homeostasis-system hypothesis // J. Korean Med. Assoc. 2020. Vol. 63, № 7. P. 366–372.

Infectious diseases, including coronavirus disease 2019 (COVID-19), are representative, of which etiology is known in all human diseases. However, many enigmas persist in relation to COVID-19, including different clinical phenotypes and incubation periods across individuals, species-specificity, appearance of cytokine storm and lymphopenia, and the mechanism of damage to organ cells. Current immunological concepts have limitations to explain these unsolved issues. Meanwhile, results of clinical, pathological, and animal studies have suggested that the virus itself is not a direct cause of acute injury to the lung or other organ cells. For better understanding of COVID-19, a presumed immunopathogenesis of COVID-19 is presented under the protein-homeostasis-system hypothesis; every disease, including COVID-19, has associated etiological substances, and the host immune system controls these diverse substances according to the size and biochemical property. These etiological substances, inducing inflammation and subsequent tissue injury, are smaller substances derived from virus-infected cells. Initially acting nonspecific adaptive immune reaction with cytokine imbalance may be responsible for target cell injury. Furthermore, substances from initial target cell injury and secondary bacterial invasion can induce further inflammation if released from local or systemic circulation. COVID-19 patients with pneumonia show hypercytokinemia with lymphocytopenia corresponding to the severity of pneumonia at early stages. Thus, early immune-modulator treatment, including corticosteroids and intravenous immunoglobulin, has an immunological rationale. It could help reduce the morbidity and possibly mortality of older patients with underlying conditions.

http://dx.doi.org/10.5124%2Fjkma.2020.63.7.366

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Ma S. et al. Structural and functional changes of gut microbiota in ovariectomized rats and their correlations with altered bone mass // Aging-US. 2020. Vol. 12, № 11. P. 10736–10753.

As a critical factor involved in the maintenance of physiological homeostasis, the gut microbiota (GM) reportedly plays a key role in bone development. To date, the association between the GM and steroid deficiency-induced osteoporosis remains poorly understood. Forty female Sprague Dawley rats were divided into an ovariectomy (OVX) or control group. We performed 16S rRNA and metagenome sequencing, to compare diversity, taxonomic differences, and functional genes. The GM composition did not change in the control group and the number of operational taxonomic units increased significantly following ovariectomy. Alpha diversity, determined by ACE estimator, CHAO estimator, the Shannon index, and the Simpson index showed an increasing trend after ovariectomy. Samples in the OVX group were well clustered both pre- and post-ovariectomy, as demonstrated by principal coordinate 1 (PC1) and PC2. Functional genes of GM, including those involved in synthesis and metabolism of carbohydrates and nucleotides, microbial structure, and heme, as well as hemin uptake and utilization, increased at the early stage of osteoporosis. We observed that Ruminococcus flavefaciens exhibited the greatest variation in abundance among the GM and this was also associated with osteoclastic indicators and the estrobolome. Specific changes in fecal microbiota are associated with the pathogenesis of steroid deficiency-induced osteoporosis.

http://dx.doi.org/10.18632%2Faging.103290

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Miao Q. et al. Antiatherosclerosis Properties of Total Saponins of Garlic in Rats // Evid.-based Complement Altern. Med. 2020. Vol. 2020. P. 3683659.

Garlic has been proven effective in the prevention and treatment of atherosclerosis (AS), which is widely used as a food and medicine by people in daily life. Garlic saponins are the main active nonsulfur compounds of garlic, which have a variety of pharmacological activities against cardiovascular diseases. In this study, the antiatherosclerosis properties and mechanism of total saponins of garlic (TSG) in rats were explored. The AS animal model was established by a combination of high-fat feeding, intraperitoneal injection of vitamin D-3,D- and ovalbumin-induced inflammation in SD rats. Then, the atherosclerotic rats were gavaged daily by TSG for 4 weeks. Administration of TSG markedly decreased atherosclerotic lesions in the aorta of atherosclerotic rats. TSG restored the serum lipid profile by significantly decreasing the lipid levels and had effective antioxidation by inhibiting the content of malondialdehyde (MDA) and restoring the reduced activity of superoxide dismutase (SOD). Additionally, the ratio of thromboxane B-2 (TXB2) and 6-keto-prostaglandin F-1 alpha (6-keto-PGF(1 alpha)) could be maintained in a relatively stable dynamic balance after administration of TSG to maintain the vascular homeostasis. In summary, TSG had therapeutic effects on AS, which are promising as functional foods or nutraceuticals for the prevention and treatment of AS.

http://dx.doi.org/10.1155%2F2020%2F3683659

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Muhammad A. et al. Spatzle Homolog-Mediated Toll-Like Pathway Regulates Innate Immune Responses to Maintain the Homeostasis of Gut Microbiota in the Red Palm Weevil, Rhynchophorus ferrugineus Olivier (Coleoptera: Dryophthoridae) // Front. Microbiol. 2020. Vol. 11. P. 846.

Spatzle (Spz) is a dimeric ligand that responds to the Gram-positive bacterial or fungal infection by binding Toll receptors to induce the secretion of antimicrobial peptides. However, whether the Toll-like signaling pathway mediates the innate immunity of Rhynchophorus ferrugineus to modulate the homeostasis of gut microbiota has not been determined. In this study, we found that a Spz homolog, RfSpatzle, is a secretory protein comprising a signal peptide and a conservative Spz domain. RT-qPCR analysis revealed that RfSpatzle was significantly induced to be expressed in the fat body and gut by the systemic and oral infection with pathogenic microbes. The expression levels of two antimicrobial peptide genes, RfColeoptericin and RfCecropin, were downregulated significantly by RfSpatzle knockdown, indicating that their secretion is under the regulation of the RfSpatzle-mediated signaling pathway. After being challenged by pathogenic microbes, the cumulative mortality rate of RfSpatzle-silenced individuals was drastically increased as compared to that of the controls. Further analysis indicated that these larvae possessed the diminished antibacterial activity. Moreover, RfSpatzle knockdown altered the relative abundance of gut bacteria at the phylum and family levels. Taken together, these findings suggest that RfSpatzle is involved in RPW immunity to confer protection and maintain the homeostasis of gut microbiota by mediating the production of antimicrobial peptides.

http://dx.doi.org/10.3389%2Ffmicb.2020.00846

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Navarro P. et al. Maternal folic acid supplementation does not counteract the deleterious impact of prenatal exposure to environmental pollutants on lipid homeostasis in male rat descendants // J. Dev. Orig. Health Dis. 2020. Vol. 11, № 4. P. 427–437.

Prenatal exposure to persistent organic pollutants (POPs) has been associated with the development of metabolic syndrome-related diseases in offspring. According to epidemiological studies, father's transmission of environmental effects in addition to mother's can influence offspring health. Moreover, maternal prenatal dietary folic acid (FA) may beneficially impact offspring health. The objective is to investigate whether prenatal FA supplementation can overcome the deleterious effects of prenatal exposure to POPs on lipid homeostasis and inflammation in three generations of male rat descendants through the paternal lineage. Female Sprague-Dawley rats (F0) were exposed to a POPs mixture (or corn oil) +/- FA supplementation for 9 weeks before and during gestation. F1 and F2 males were mated with untreated females. Plasma and hepatic lipids were measured in F1, F2, and F3 males after 12-h fast. Gene expression of inflammatory cytokines was determined by qPCR in epididymal adipose tissue. In F1 males, prenatal POPs exposure increased plasma lipids at 14 weeks old and hepatic lipids at 28 weeks old and prenatal FA supplementation decreased plasma total cholesterol at 14 weeks old. Prenatal POPs exposure decreased plasma triglycerides at 14 weeks old in F2 males. No change was observed in inflammatory markers. Our results show an impact of the paternal lineage on lipid homeostasis in rats up to the F2 male generation. FA supplementation of the F0 diet, regardless of POPs exposure, lowered plasma cholesterol in F1 males but failed to attenuate the deleterious effects of prenatal POPs exposure on plasma and hepatic lipids in F1 males.

http://dx.doi.org/10.1017%2FS2040174419000497

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Rampelli S. et al. Shotgun Metagenomics of Gut Microbiota in Humans with up to Extreme Longevity and the Increasing Role of Xenobiotic Degradation // mSystems. 2020. Vol. 5, № 2. P. e00124-20. 1

The gut microbiome of long-lived people display an increasing abundance of subdominant species, as well as a rearrangement in health-associated bacteria, but less is known about microbiome functions. In order to disentangle the contribution of the gut microbiome to the complex trait of human longevity, we here describe the metagenomic change of the human gut microbiome along with aging in subjects with up to extreme longevity, including centenarians (aged 99 to 104 years) and semisupercentenarians (aged 105 to 109 years), i.e., demographically very uncommon subjects who reach the extreme limit of the human life span. According to our findings, the gut microbiome of centenarians and semisupercentenarians is more suited for xenobiotic degradation and shows a rearrangement in metabolic pathways related to carbohydrate, amino acid, and lipid metabolism. Collectively, our data go beyond the relationship between intestinal bacteria and physiological changes that occur with aging by detailing the shifts in the potential metagenomic functions of the gut microbiome of centenarians and semisupercentenarians as a response to progressive dietary and lifestyle modifications. IMPORTANCE The study of longevity may help us understand how human beings can delay or survive the most frequent age-related diseases and morbidities. In this scenario, the gut microbiome has been proposed as one of the variables to monitor and possibly support healthy aging. Indeed, the disruption of host-gut microbiome homeostasis has been associated with inflammation and intestinal permeability as well as a general decline in bone and cognitive health. Here, we performed a metagenomic assessment of fecal samples from semisupercentenarians, i.e., 105 to 109 years old, in comparison to young adults, the elderly, and centenarians, shedding light on the longest compositional and functional trajectory of the human gut microbiome with aging. In addition to providing a fine taxonomic resolution down to the species level, our study emphasizes the progressive age-related increase in degradation pathways of pervasive xenobiotics in Western societies, possibly as a result of a supportive process within the molecular continuum characterizing aging.

http://dx.doi.org/10.1128%2FmSystems.00124-20

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Rocha M.L.M. et al. Malnourishment during early lactation disrupts the ontogenetic distribution of the CART and alpha-MSH anorexigenic molecules in the arcuate/paraventricular pathway and lateral hypothalamus in male rats // Brain Res. 2020. Vol. 1743. P. 146906. 1.

Developmental malnourishment impacts the energetic metabolism control throughout life. In rat offspring, a 0% protein diet during the first 10 days of lactation results in leptin resistance and in alterations in: feeding behavior, serum leptin and neuropeptide Y (NPY) levels in the hypothalamic arcuate nucleus (ARC)/paraventricular (PVN) pathway. Here, the distributions of alpha-melanocyte stimulating hormone (alpha-MSH) and cocaine and amphetamine regulated transcript (CART), anorexigenic molecules, were immunohistochemically assessed in the ARC, PVN and lateral hypothalamus (LH) nuclei. Rat dams were subjected to one of the following diet protocols from postnatal day (P) 1-10: 1) Protein-free (PFG, 0% protein chow); 2) Pair-fed (UFG, normoprotein chow); 3) Control group (CG, normoprotein chow). PFG, UFG and CG male offspring were analyzed at different time points, from P5 to P180. In the ARC, PFG alpha-MSH and CART were increased from P10 to P45 when compared to CG and UFG. In the PVN, alpha-MSH and CART peaks in PFG animals were delayed from P20 to P30 when compared to CG. In the LH, CART was more intense in PFG animals than in UFG and CG ones by P20, and, by P30, UFG immunostaining became less intense than in CG. In conclusion, aproteic diet altered the ontogenetic distribution of both anorexigenic molecules. In the PVN, the peak was delayed to P30, which coincides with the leptin peak and follows the previously described NPY (orexigenic) peak in this model. The permanent LH CART and alpha-MSH increase may be associated with the previously observed PFG hypophagia.

http://dx.doi.org/10.1016%2Fj.brainres.2020.146906

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Seo G.-Y., Giles D.A., Kronenberg M. The role of innate lymphoid cells in response to microbes at mucosal surfaces // Mucosal mmunol. 2020. Vol. 13, № 3. P. 399–412.

Innate lymphoid cells (ILCs) are a lymphocyte population that is mostly resident at mucosal surfaces. They help to induce an appropriate immune response to the microbiome at homeostasis. In healthy people, the mucosal immune system works symbiotically with organisms that make up the microbiota. ILCs play a critical role in orchestrating this balance, as they can both influence and in turn be influenced by the microbiome. ILCs also are important regulators of the early response to infections by diverse types of pathogenic microbes at mucosal barriers. Their rapid responses initiate inflammatory programs, production of antimicrobial products and repair processes. This review will focus on the role of ILCs in response to the microbiota and to microbial infections of the lung and intestine.

http://dx.doi.org/10.1038%2Fs41385-020-0265-y

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Wright C.B. et al. Chronic Dicer1 deficiency promotes atrophic and neovascular outer retinal pathologies in mice // Proc. Natl. Acad. Sci. U. S. A. 2020. Vol. 117, № 5. P. 2579–2587.

Degeneration of the retinal pigmented epithelium (RPE) and aberrant blood vessel growth in the eye are advanced-stage processes in blinding diseases such as age-related macular degeneration (AMD), which affect hundreds of millions of people worldwide. Loss of the RNase DICER1, an essential factor in micro-RNA biogenesis, is implicated in RPE atrophy. However, the functional implications of DICER1 loss in choroidal and retinal neovascularization are unknown. Here, we report that two independent hypomorphic mouse strains, as well as a separate model of postnatal RPE-specific DICER1 ablation, all presented with spontaneous RPE degeneration and choroidal and retinal neovascularization. DICER1 hypomorphic mice lacking critical inflammasome components or the innate immune adaptor MyD88 developed less severe RPE atrophy and pathological neovascularization. DICER1 abundance was also reduced in retinas of the JR5558 mouse model of spontaneous choroidal neovascularization. Finally, adenoassociated vector-mediated gene delivery of a truncated DICER1 variant (OptiDicer) reduced spontaneous choroidal neovascularization in JR5558 mice. Collectively, these findings significantly expand the repertoire of DICER1 in preserving retinal homeostasis by preventing both RPE degeneration and pathological neovascularization.

http://dx.doi.org/10.1073%2Fpnas.1909761117

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Yu S. et al. Radix et Rhizoma Ginseng chemoprevents both initiation and promotion of cutaneous carcinoma by enhancing cell-mediated immunity and maintaining redox homeostasis // J. Ginseng Res. 2020. Vol. 44, № 4. P. 580–592.

Background: Radix et Rhizoma Ginseng (thereafter called ginseng) has been used as a medicinal herb for thousands of years to maintain people's physical vitality and is also a non-organ-specific cancer preventive and therapeutic traditional medicine in several epidemiologic and preclinical studies. Owing to few toxic side effects and strong enhancement on body immunity, ginseng has admirable application potential and value in cancer chemoprevention. The study aims at investigating the chemopreventive effects of ginseng on cutaneous carcinoma and the underlying mechanisms. Methods: The mouse skin cancer model was induced by 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate. Ultraperformance liquid chromatography/mass spectrometry was used for identifying various ginsenosides, the main active ingredients of ginseng. Comprehensive approaches (including network pharmacology, bioinformatics, and experimental verification) were used to explore the potential targets of ginseng. Results: Ginseng treatment inhibited cutaneous carcinoma in terms of initiation and promotion. The content of Rb1, Rb2, Rc, and Rd ginsenosides was the highest in both mouse blood and skin tissues. Ginseng and its active components well maintained the redox homeostasis and modulated the immune response in the model. Specifically, ginseng treatment inhibited the initiation of skin cancer by enhancing T-cell-mediated immune response through upregulating HSP27 expression and inhibited the promotion of skin cancer by maintaining cellular redox homeostasis through promoting nuclear translocation of Nrf2. Conclusion: According to the study results, ginseng can be potentially used for cutaneous carcinoma as a chemopreventive agent by enhancing cell-mediated immunity and maintaining redox homeostasis with multiple components, targets, and links. (C) 2019 The Korean Society of Ginseng. Publishing services by Elsevier B.V.

http://dx.doi.org/10.1016%2Fj.jgr.2019.05.004

21. 047257
Ворфоломеев С.А. СРАВНИТЕЛЬНАЯ ОЦЕНКА РЕЗУЛЬТАТОВ МОЛЕКУЛЯРНО ГЕНЕТИЧЕСКИХ И ЦИТОГЕНЕТИЧЕСКИХ МЕТОДОВ ОПРЕДЕЛЕНИЯ ГЕНО- ТОКСИЧНОСТИ ФАКТОРОВ СРЕДЫ И ГЕНЕТИЧЕСКОГО ГОМЕОСТАЗА ОРГАНИЗМА ЧЕЛОВЕКА // Актуальная биотехнология. 2019. № 1 (28). С. 16-29.

В настоящее время в окружающую среду попадает значительное число химических соединений, обладающих генотоксической активностью. В связи с этим, представляется актуальным сравнить результаты по оценке повреждений мтДНК, установленных с использованием молекулярно генетических методов и повреждений генома с использованием цитогенетических методов. Решение данной задачи позволит перебросить «мост» между молекулярно- генетическими исследованиями оценки генотоксичности факторов окружающей среды и классическими цитогенетическими методами выявления хромосомных и геномных аберраций, а также оценить чувствительность методов на молекулярно- генетическом и клеточном уровне организации живой материи.

https://www.elibrary.ru/item.asp?id=41403331

22. 039284
Демченко Г.А., Булекбаева Л.Э., Абдрешов С.Н., Нурмаханова Б.А., Осикбаева С.О. ВОДНЫЙ ГОМЕОСТАЗ И СОСТАВ БИОЛОГИЧЕСКИХ ЖИДКОСТЕЙ МОЛОДЫХ И ЗРЕЛЫХ ЖИВОТНЫХ // Международный журнал прикладных и фундаментальных исследований. 2019. № 5. С. 20-25.

Исследовали особенности водного гомеостаза и состав биологических жидкостей у молодых (20-40-дневных) и зрелых (10-12-месячных) крыс линии Wistar. Показано снижение лимфотока, диуреза, обьема плазмы крови интерстициальной жидкости у зрелых животных в сравнении с молодыми. В крови и лимфе несколько увеличилось количество холестерина и триглицеридов, а количество глюкозы снизилось у зрелых животных. Биохимические показатели, такие как ионный состав и др. изучаемых жидкостей, колебался в пределах среднестатистической ошибки. Наблюдалось увеличение лейкоцитов, нейтрофилов, СД-20 лимфоцитов в крови и лимфе и лимфоцитов в лимфе у зрелых животных. Становление механизмов движения лимфы у крыс начинается с рождения до одно-двухмесячного возраста, когда к уже существующим с рождения интралимфатическим и экстралимфатическим факторам движения лимфы присоединяется сформировавщиеся сосудодвигательная иннервация, гладкая мускулатура и появляется собственная сократительная активность гладкомышечных клеток в лимфатических сосудах и узлах, способствующая активному транспорту жидкости из интерстиция в кровеносное русло, что подтверждается полученными нами данными - биохимическим, клеточным, ионным, иммунным показателям крови и лимфы, лимфотоку, диурезу, составу и обьему интерстициальной жидкости, которые соответствовали физиологическим изменениям от молодого организма к зрелому.

https://www.elibrary.ru/item.asp?id=38165671

23. PDF
Доброборский Б.С., Медрес Е.Е. О ГОМЕОСТАЗЕ С ПОЗИЦИИ ТЕРМОДИНАМИКИ БИОЛОГИЧЕСКИХ СИСТЕМ // Инновационная наука. 2020. № 6. С. 28-30.

Проведены теоретические исследования гомеостаза и его роли в функционировании живых организмов как неравновесных термодинамических систем. Установлено, что гомеостаз представляет собой комплекс процессов, направленных на обеспечение оптимального неравновесного термодинамическому состоянию живого организма в зависимости от условий его функционирования.

https://www.elibrary.ru/item.asp?id=42939878

24. 043025
Дружинин В.Г., Буслаев В.Ю., Баранова Е.Д., Начева Л.В. РОЛЬ МИКРОБИОТЫ В ПОДДЕРЖАНИИ ГОМЕОСТАЗА И ИНДУКЦИИ МУТАГЕНЕЗА В СОМАТИЧЕСКИХ КЛЕТКАХ ЧЕЛОВЕКА // Фундаментальная и клиническая медицина. 2018. Т. 3. № 4. С. 83-92.

Бактерии, населяющие наш организм, составляют сложнейшее сообщество микроорганизмов, называемое микробиотой. В связи с этим организм человека следует рассматривать как «мета-организм», имея в виду многообразие эволюционно закрепленных в организме человека бактерий. Развитие современных методов молекулярной биологии позволило накопить достаточное количество фактов влияния микробиоты в поддержании жизнедеятельности организма человека преимущественно через синтез биологически-активных соединений. Вместе с тем в процессе исследования микробиома было установлено, что некоторые бактерии способны к продукции генотоксинов, вызывающих мутации в ДНК клетках организма-хозяина. Негативное влияние некоторых факторов внешней среды приводит к дисбалансу состава микробиоты в конкретных органах, что, в свою очередь, способствует возникновению ряда патологических процессов. Выявляются новые связи состава бактериальной микрофлоры с различными заболеваниями, в том числе со многими формами рака. Целью данного обзора является обобщение основных фактов влияния микробиоты на поддержание нормальных физиологических процессов в организме человека и на развитие различных патологических состояний, вызванных продуктами метаболизма бактерий.

https://www.elibrary.ru/item.asp?id=36689908

25. 005108
Захаров В.М., Минин А.А., Трофимов И.Е. ИССЛЕДОВАНИЕ ГОМЕОСТАЗА РАЗВИТИЯ: ОТ ПОПУЛЯЦИОННОЙ БИОЛОГИИ РАЗВИТИЯ И КОНЦЕПЦИИ ЗДОРОВЬЯ СРЕДЫ ДО КОНЦЕПЦИИ УСТОЙЧИВОГО РАЗВИТИЯ // Онтогенез. 2018. Т. 49. № 1. С. 3-14.

Исследование показателей гомеостаза развития в природных популяциях ведет к определению основ популяционной биологии развития, связанной с оценками природы фенотипического разнообразия, механизмов динамики популяций и микроэволюционных преобразований. Характеристика качества среды на основе оценки состояния популяций по гомеостазу развития определяет основы концепции здоровья среды. Перспективным оказывается приложение представлений о гомеостазе развития и здоровье среды и при исследовании гомеостатических механизмов биологических систем разного уровня, от организма и популяции до сообщества и экосистемы. Это дает новые возможности для понимания механизмов обеспечения устойчивости и их соотношения на разных уровнях, характеристики значимости онтогенетической стабильности. Представления о гомеостазе развития, или гомеорезе, представляются перспективными для разработки эколого-биологических основ устойчивого развития.

https://www.elibrary.ru/item.asp?id=32400520

26. PDF
Казаков В.Н., Казакова Н.В. ГОМЕОСТАЗ. ПОСТОЯНСТВО ВНУТРЕННЕЙ СРЕДЫ ОРГАНИЗМА И ЕГО КОНСТАНТЫ // Архив клинической и экспериментальной медицины. 2019. Т. 28. № 1. С. 78-90.

В статье описана история изучения постоянства внутренней среды организма. Излагается понятие о гомеостазе как фундаментальном состоянии живого организма. Гомеостатические константы - противоречия в терминологии и в существе понятия. Представления о девиации констант. Размеры девиаций. Управление константами гомеостаза. Законы гомеостатической регуляции. Анализ нейрогуморальной модели гомеостаза.

https://www.elibrary.ru/item.asp?id=37078117

27. 00789X
Лаврушкина С.В., Овсянникова Н.Л., Юдина А.С., Стрелкова О.С., Жиронкина О.А., Перепелина К.И., Малашичева А.Б., Киреев И.И. РОЛЬ МЕХАНИЧЕСКИХ СВОЙСТВ ЯДРА В ПОДДЕРЖАНИИ ГОМЕОСТАЗА ТКАНЕЙ // Цитология. 2018. Т. 60. № 11. С. 911-915.

Жесткий скелет, сформированный сетями ламинов типов А и В, отвечает за поддержание формы ядра. Более того, изменение соотношения белков-ламинов в его составе, по-видимому, является ключевым фактором, определяющим механические свойства клеточного ядра, в частности пластичность. В данной работе было рассмотрено влияние компонентного состава ядерной ламины на устойчивость клеток к механическому воздействию и на подвижность клеток. Экспрессия мутантных форм ламина типа А сопровождается изменениями в расстоянии между микродоменами ламинов в составе ядерной оболочки, а также наблюдается ее повышенное «пузырение» относительно клеток дикого типа и клеток, гиперэкспрессирующих ламин типа А. При воздействии осмотического шока отмечается повышенное количество деформированных ядер. Оценка влияния изменения молекулярного состава ядерной ламины за счет повышения (снижения) экспрессии ламина типа А, а также введения прогерина на модели экспериментальной раны показало, что в условиях неограниченного пространства различий нет.

https://www.elibrary.ru/item.asp?id=36613865

28. 042272
Лебедева А.И., Муслимов С.А., Гареев Е.М., Афанасьев С.А., Кондратьева Д.С., Попов С.В. МАКРОФАГИ КАК РЕГУЛЯТОРЫ ГОМЕОСТАЗА МИОКАРДА ПОСЛЕ ЕГО ИШЕМИЧЕСКОГО ПОВРЕЖДЕНИЯ В УСЛОВИЯХ ПРИМЕНЕНИЯ АЛЛОГЕННОГО БИОМАТЕРИАЛА // Бюллетень сибирской медицины. 2020. Т. 19. № 1. С. 67-75.

Макрофаги как клетки-эффекторы играют ключевую роль в инициации воспалительного процесса, предопределяют выраженность постинфарктного кардиосклероза. Популяция этих клеток является гетерогенной и представлена преимущественно М1 и М2 фенотипами. Аллогенный биоматериал аллоплант (БМА) резорбируется макрофагами, продукты резорбции влияют на их способность регулировать клеточные взаимодействия.Цель. Раскрыть особенности постинфарктного заживления миокарда после введения БМА. Оценить динамику изменения численности макрофагов и c-kit+-клеток.Материалы и методы. Экспериментальные исследования были проведены на 100 самцах крыс линии Вистар массой 0,18-0,25 кг. Всем животным была проведена коронароокклюзия верхней трети левой нисходящей коронарной артерии. В опытной группе сразу после стенозирования артерии в ее бассейн интрамиокардиально вводили суспензию, содержащую 12 мг БМА. Использовали гистологические, электронно-микроскопические, иммуногистохимические (CD 68, c-kit, Timp-2), морфометрические и статистические методы исследования...

https://www.elibrary.ru/item.asp?id=42766760

29. 00789X
Марахова И.И., Шатрова А.Н., Виноградова Т.А., Домнина А.П., Земельно В.И., Пуговкина Н.А., Никольский Н. ИОННЫЙ ГОМЕОСТАЗ КУЛЬТИВИРУЕМЫХ МЕЗЕНХИМНЫХ СТВОЛОВЫХ КЛЕТОК ЧЕЛОВЕКА. II.ИЗМЕНЕНИЯ СОДЕРЖАНИЯ КАЛИЯ, СВЯЗАННЫЕ С ВОЗРАСТОМ КЛЕТОЧНОЙ КУЛЬТУРЫ // Цитология. 2018. Т. 60. № 12. С. 976-982.

Проведено исследование ионного гомеостаза мезенхимных стволовых клеток (МСК) человека, размножающихся в культуре в течение длительного времени. Обнаружено, что на ранних пассажах (2-4-й) после разморозки одного и того же клона МСК удельное внутриклеточное содержание калия, рассчитанное на общий клеточный белок, почти на 40 % выше, чем в клетках того же клона, который прошел в культуре не менее 12-15 пассажей. В этих же условиях по мере увеличения возраста МСК удельное внутриклеточное содержание натрия остается практически без изменений. Цитофлуориметрический анализ пролиферации культур МСК разного возраста показал, что снижение внутриклеточного содержания калия коррелирует с накоплением клеток в фазе Gi клеточного цикла и сопутствует замедлению размножения клеток. Опираясь на совокупность данных, полученных при изучении транспорта моновалентных катионов у клеток постоянных линий человека (стволовых и нормальных лимфоцитов), обсуждаются механизмы участия ионов калия в пролиферации клеток. Сделан вывод о том, что изменения удельного внутриклеточного содержания калия в расчете на общий клеточный белок, связанные с запуском или торможением пролиферации клеток, отражают участие ионов калия в регуляции объема клетки. Удельное внутриклеточное содержание калия в расчете на общий клеточный белок является адекватным маркером функционального состояния и пролиферативного статуса стволовых клеток in vitro.

https://www.elibrary.ru/item.asp?id=36712418

30. 006882
Наточин Ю.В. ФИЗИОЛОГИЯ ЧЕЛОВЕКА: ВОДНО-СОЛЕВОЙ ГОМЕОСТАЗ // Физиология человека. 2018. Т. 44. № 3. С. 5-13.

Физиология человека дает интегральное представление о механизмах всего спектра функций в организме человека. Их успешное осуществление возможно в условиях высоко стабилизированной внутренней среды, которая непрерывно воссоздается эффекторными органами под влиянием нервных импульсов, гормонов, инкретинов, аутокоидов. Приведены данные о физико-химических параметрах внутренней среды человека. Обсуждаются новые возможности методов клиренса при участии почек в гомеостатических процессах.

https://www.elibrary.ru/item.asp?id=35060033

31. 000231
Сентюрова Л.Г., Шерышева Ю.В., Неваленная Л.А., Журавлева Г.Ф., Ткачева Н.В. ОСОБЕННОСТИ РЕГУЛЯЦИИ МЕСТНОГО ГОМЕОСТАЗА В СОСУДИСТЫХ СПЛЕТЕНИЯХ ГОЛОВНОГО МОЗГА ПОЗВОНОЧНЫХ // Морфология. 2019. Т. 155. № 2. С. 254.

https://www.elibrary.ru/item.asp?id=38174324

32. 000231
Стадников А.А. ПЕРСПЕКТИВЫ ПРИМЕНЕНИЯ ОКСИТОЦИНА ДЛЯ КОРРЕКЦИИ НАРУШЕННОГО КЛЕТОЧНОГО И ТКАНЕВОГО ГОМЕОСТАЗА // Морфология. 2019. Т. 155. № 2. С. 267.

https://www.elibrary.ru/item.asp?id=38174360

33. 00789X
Шатрова А.Н., Виноградова Т.А., Домнина А.П., Земелько В.И., Пуговкина Н.А., Никольский Н., Марахова И.И. ИОННЫЙ ГОМЕОСТАЗ КУЛЬТИВИРУЕМЫХ МЕЗЕНХИМНЫХ СТВОЛОВЫХ КЛЕТОК ЧЕЛОВЕКА. I. ИЗМЕНЕНИЯ ВНУТРИКЛЕТОЧНОГО СОДЕРЖАНИЯ КАЛИЯ И НАТРИЯ И ПОТОКОВ КАЛИЯ, СВЯЗАННЫЕ С ПЛОТНОСТЬЮ КЛЕТОЧНОЙ КУЛЬТУРЫ // Цитология. 2018. Т. 60. № 12. С. 969-975.

В работе охарактеризованы связанные с ростом культуры изменения содержания калия и натрия и потоков калия через плазматическую мембрану в мезенхимных стволовых клетках (МСК) человека. Показано, что в оптимальных условиях культивирования в процессе роста культуры одного посева удельное внутриклеточное содержание калия, рассчитанное на общий клеточный белок, снижается, в то время как содержание натрия не изменяется. При возрастании плотности культуры снижается ингибируемый уабаином входной поток калия, что свидетельствует о снижении активности Na+,К+-насоса. Установлено, что снижение внутриклеточного содержания калия в растущей культуре МСК человека не является результатом длительного культивирования клеток, оно обусловлено возрастанием плотности клеток в культуре, коррелирует с накоплением клеток в фазе Gi клеточного цикла и свидетельствует о замедлении размножения клеток. Высказывается предположение о том, что связанные с ростом культур изменения внутриклеточного содержания калия отражают участие ионов калия в регуляции объема клетки в процессе прохождении клеточного цикла. Сделан вывод о том, что высокое удельное внутриклеточное содержание калия является маркером функционального состояния и пролиферативного статуса стволовых клеток.

https://www.elibrary.ru/item.asp?id=36712417

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