Estimation of the effect of lithium salts on cytokine production by blood cells in in vitro experiments

Aim. To study the effects of lithium salts on production of cytokines by immunocompetent cells in the whole-blood culture of patients with alcohol dependence and affective disorders.Materials and methods. The study materials were blood samples from 25 patients with alcohol dependence (AD) and 12 patients with bipolar disorder (BD). Blood diluted 1:1 with complete RPMI-1640 medium (Gibco, UK) was added to the wells of the culture plate, then new lithium salts (succinate, fumarate, pyruvate, ascorbate) and a reference salt – lithium carbonate at a final concentration of 1.2 mmol / l per lithium ion – were added. In parallel, control samples without lithium salts were tested; the samples were incubated for a day. The concentration of cytokines (interferon (IFN) γ, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, tumor necrosis factor (TNF) α) was determined in the culture supernatants on the MAGPIX multiplex analyzer (Luminex, USA) (Center for Collective Use “Medical Genomics”, Tomsk NRMC) using the Human Cytokine / Chemokine Magnetic Bead Panel (Merck, Germany).Results. All lithium salts had a unidirectional effect on the production of cytokines by immunocompetent cells (ICC), except for lithium ascorbate and IL-8. The concentrations of cytokines in the supernatants of loaded and control samples (spontaneous production) were comparable, which indicates an absence of stimulating or suppressing effects of salts on the functional activity of ICC under the experimental conditions. The effect of lithium ascorbate as an IL-8 inducer was detected: the production of IL-8 induced by lithium ascorbate was 2.3–2.5 times higher than its spontaneous production.Conclusion. The obtained results, as well as the previously revealed antioxidant and cytoprotective properties of new lithium salts, confirmed that they are promising for development of pharmacological agents with combined action.

INVESTIGATION OF BLOOD MONONUCLEAR CELLS CYTOKINE-PRODUCTION FUNCTION FROM PATIENTS WITH MULTIPLE SCLEROSIS TREATED WITH THE ENDOGENOUS RETROVIRUS HERV-E λ 4-1 CONSERVATIVE REGION SYNTHETIC OLIGOPEPTIDE

Considering to the data of class I human endogenous retrovirus HERV-Е λ 4-1 subgroup association with multiple sclerosis, an autoimmune disease accompanied by neuroinflammation, changes in the neurotransmitters level, progressive neurological dysfunction, as well as the ability of this retrovirus to replicate and to produce proteins with potential immunomodulatory properties, the aim of this work was a comparative study of the blood immune cells cytokine synthesizing function in conventionally healthy individuals and multiple sclerosis patients under the synthetic 17 – amino acid oligopeptide homologous to the hydrophobic transmembrane protein р15Е HERV-Е λ 4-1 conserved region influence. The 40 patients, 17 male persons aged 38.0 (31.0-47.0) years old and 23 female persons aged 39.0 (31.0-50.0) years old with an established diagnosis of multiple sclerosis (G 35, ICD-10), corresponding to the McDonald 2005, modified in 2010 criteria with a continuously progressive disease course and the disease duration of 17.0 (14.0-18.0) years, and 30 conditionally healthy individuals, 12 male persons aged 32.0 (23.0-43.0) years old and 18 female persons aged 36.0 (29.0-46.0) years old were the objects of the study. An open-label, observational, single-center, cohort, controlled, randomized trial was conducted. It was found that the donor’s blood mononuclear cells IL-1β, IL-6, TNFα, IFNγ and IL-2 spontaneous production in culture was stimulated, but that of IL-4 and IL-10 did not change under the retroviral oligopeptide influence. At the same time, the spontaneous and mitogenstimulated production of all studied cytokines did not change under the control oligopeptide influence. The PHA-stimulated donor’s blood mononuclear cells cultivation in presence of the retroviral oligopeptide, as compared to the control one, was accompanied by an increase in the IL-1β, IL-6 and TNFα release into the culture supernatant. The multiple sclerosis patients were characterized by IL-1β, IL-6 and IFNγ higher content in the mitogen-unstimulated blood mononuclear cells culture supernatant, compared with conditionally healthy individuals, as well as by a higher production of IL-6 and IFNγ in response to PHA stimulation. The retroviral oligopeptide, in contrast to the control one, stimulated the IL-1β, IL-6, TNFα and IFNγ spontaneous production without altering that of IL-4 and IL-10 in multiple sclerosis patients. The obtained results indicate that the synthetic oligopeptide homologous to the conserved region of the hydrophobic transmembrane protein p15E HERV-Е λ 4-1 has the pro-inflammatory properties, which is probably the one of human endogenous retrovirus HERV-Е λ 4-1 pathological abilities realization mechanism in multiple sclerosis.

Tumour microenvironment markers in spontaneous and induced incubation of breast cancer biopsies

Aim. To study the spontaneous and stimulated production of cytokines in biopsies of breast cancer (BC) depending on the cancer stage.Materials and methods. An experimental study was carried out with cell cultures of breast cancer biopsies of stages I–II (group 1, n = 15) and III–IV stages (group 2, n = 15). The control consisted of 6 healthy women who underwent mastopexy. We used enzyme immunoassay method to access spontaneous and induced by a complex of polyclonal activators (PA: phytohemagglutinin 4 μg / ml, concanavalin A 4 μg / ml, lipopolysaccharide 2 μg / ml) concentration of TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, MCP-1, TGF-β1. The index of the effect of polyclonal activators (IVPA) on cytokine production (induced production / spontaneous production) was calculated. To compare groups, the Mann-Whitney test and the median test, the chi-square test and the Fisher’s exact test were used.Results. Groups 1 and 2 did not differ in age, histological variant and immunohistochemical type of tumour, predominantly invasive cancer without signs of specificity prevailed. In group 2, a pronounced vascularization was more often observed: in 6 (40%) patients versus 1 (7%) in group 1 (p < 0.05). In both groups, compared with the control, there was a statistically sig-nificant (p < 0.05) increase in spontaneous production of TNF-α by 4.2 and 4.8 times, MCP-1 by 6.7 and 6.3 times, TGF-β1 – 2.2 and 2.5 times, VEGF 11.9 and 14.6 times; GM-CSF 15.6 and 13.4 times, G-CSF 96.8 and 79.5 times, respectively. The concentration of MCP-1 and IFN-γ was higher in group 1 (p < 0.05), VEGF and TGF-β1 – in group 2 (p < 0.05). IVPA in group 2 exceeded similar values in group 1 for G-CSF, VEGF, TGF-β1 (p < 0.05).Conclusion. The production of cytokines (TNF-α, MCP-1, GM-CSF, G-CSF, VEGF, TGF-β1) in breast cancer biopsies is significantly higher than in biopsies of the unchanged mammary gland and depends on the stage of the tumour process.

Variation in quality of maternal input and development of coda stops in English-speaking children in Singapore

This study examines the effects of input quality on early phonological acquisition by investigating whether interadult variation in specific phonetic properties in the input is reflected in the production of their children. We analysed the English coda stop release patterns in the spontaneous speech of fourteen mothers and compared them with the spontaneous production of their preschool children. The analysis revealed a very strong positive input–production relationship; mothers who released coda stops to a lesser degree also had children who tended to not release their stops, and the same was true for mothers who released their stops to a higher degree. The findings suggest that young children are sensitive to acoustic properties that are subphonemic, and these properties are also reflected in their production, showing the importance of considering input quality when investigating child production.

Machine Learning of Motion Statistics Reveals the Kinematic Signature of the Identity of a Person in Sign Language

Sign language (SL) motion contains information about the identity of a signer, as does voice for a speaker or gait for a walker. However, how such information is encoded in the movements of a person remains unclear. In the present study, a machine learning model was trained to extract the motion features allowing for the automatic identification of signers. A motion capture (mocap) system recorded six signers during the spontaneous production of French Sign Language (LSF) discourses. A principal component analysis (PCA) was applied to time-averaged statistics of the mocap data. A linear classifier then managed to identify the signers from a reduced set of principal components (PCs). The performance of the model was not affected when information about the size and shape of the signers were normalized. Posture normalization decreased the performance of the model, which nevertheless remained over five times superior to chance level. These findings demonstrate that the identity of a signer can be characterized by specific statistics of kinematic features, beyond information related to size, shape, and posture. This is a first step toward determining the motion descriptors necessary to account for the human ability to identify signers.

Multilab Direct Replication of Flavell, Beach, and Chinsky (1966): Spontaneous Verbal Rehearsal in a Memory Task as a Function of Age

Work by Flavell, Beach, and Chinsky indicated a change in the spontaneous production of overt verbalization behaviors when comparing young children (age 5) with older children (age 10). Despite the critical role that this evidence of a change in verbalization behaviors plays in modern theories of cognitive development and working memory, there has been only one other published near replication of this work. In this Registered Replication Report, we relied on researchers from 17 labs who contributed their results to a larger and more comprehensive sample of children. We assessed memory performance and the presence or absence of verbalization behaviors of young children at different ages and determined that the original pattern of findings was largely upheld: Older children were more likely to verbalize, and their memory spans improved. We confirmed that 5- and 6-year-old children who verbalized recalled more than children who did not verbalize. However, unlike Flavell et al., substantial proportions of our 5- and 6-year-old samples overtly verbalized at least sometimes during the picture memory task. In addition, continuous increase in overt verbalization from 7 to 10 years old was not consistently evident in our samples. These robust findings should be weighed when considering theories of cognitive development, particularly theories concerning when verbal rehearsal emerges and relations between speech and memory.

Hydrogen Peroxide: A Novel Mechanism of Its Production from Pure Water

The latest cutting-edge research findings published in highly influential journals have greatly advanced our current understanding of hydrogen peroxide (H₂O₂), a notable reactive oxygen species, in chemistry, biology, and medicine. In this context, recent studies by J.K. Lee et al., published in Proc Natl Acad Sci USA, discovered a novel mechanism of spontaneous production of H₂O₂ from pure water in the absence of catalysts or external electric field. This discovery by J.K. Lee et al. has changed our view on the chemical connection between H₂O₂ and H₂O though the biological significance of the discovery remains unknown. REFERENCES Hopkins RZ, Li YR. Essentials of Free Radical Biology and Medicine. Cell Med Press, Raleigh, NC, USA. 2017. Hopkins RZ. Hydrogen peroxide in biology and medicine: an overview. React Oxyg Species (Apex) 2017; 3(7):26–37. doi: https://dx.doi.org/10.20455/ros.2017.809. Bergman P, Parise B, Liseau R, Larsson B, Olofsson H, Menten KM, et al. Detection of interstellar hydrogen peroxide. Astronomy Astrophysics 2011; 531:L8. doi: https://dx.doi.org/10.1051/0004-6361/201117170. Lee JK, Walker KL, Han HS, Kang J, Prinz FB, Waymouth RM, et al. Spontaneous generation of hydrogen peroxide from aqueous microdroplets. Proc Natl Acad Sci USA 2019; 116(39):19294‒8. doi: https://dx.doi.org/10.1073/pnas.1911883116. Lee JK, Han HS, Chaikasetsin S, Marron DP, Waymouth RM, Prinz FB, et al. Condensing water vapor to droplets generates hydrogen peroxide. Proc Natl Acad Sci USA 2020; 117(49):30934‒41. doi: https://dx.doi.org/10.1073/pnas.2020158117.