scholarly journals IMMUNE CELLS AS A POTENTIAL THERAPEUTIC AGENT IN THE TREATMENT OF DEPRESSION

2021 ◽  
Vol 23 (4) ◽  
pp. 699-704
Author(s):  
E. V. Markova ◽  
M. A. Knyazheva
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Functional Activity ◽  
Depressive Disorders ◽  
Negative Impact ◽  
Critical Role ◽  
Brain Structures ◽  
Biologically Active ◽  
Health Concern

The immune and neuroendocrine systems play a critical role in maintaining a dynamic homeostasis in normal conditions and at mental maladaptation. Psycho- and immunopathology closely interrelated: pathological changes in the functioning of both systems occur simultaneously and are interdependent. Depression, as a mental disorder, is a major public health concern. The estimations are showing rise of the depression’s incidence in the future. However, currently used therapy of depression doesn’t provide a complete cure. It is known that a violation of neuroimmune interaction is an essential link in the pathogenesis of the disease, having a negative impact on its course, making the clinical picture worse, reducing effectiveness of the therapy, therefore, it’s urgent to search for a new treatment approaches. There are a sufficient amount data on the immune cells and their biologically active products leading role in the pathogenesis of depression. The unidirectional effect of most psychoactive substances on the central nervous system and the immune system confirms intersystem mutual regulation and allows considering the immune cells as model objects for influencing the intersystem functional relationship; so, cells immunotherapy can be the method of choice in the treatment of depressive disorders. We first demonstrated the possibility of animal’s behavior directed regulation by the transplantation of immune cells with definite functional characteristics, including those with functional activity modulated extracorporeally by a psychoactive substance. Based on the previous results we investigated the effect of the in vitro caffeine- treated immune cells on the behavior and immune phenotypes in depressive-like singeneic recipients. Transplantation of caffeine-treated splenocytes from depressive-like donors has been shown to induce depressive-like behavior editing in syngeneic recipients, which was manifested in anhedonia decrease, stimulation of exploratory behavior in the Open Field test and motor activity in the Porsolt forced swimming test. Recipient’s behavioral changes were registered on the background of decreased brain pro- inflammatory cytokines (TNFα, IL-1β, IL-6, IFNγ) and IL-10 increased in some pathogenetically significant for depressive-like state brain structures (hippocampus, hypothalamus, frontal cortex, striatum), which indicates a decrease in neuroinflammation. It was also detected recipient’s immune system functional activity modulation. The cytokines-mediated mechanisms of depressive-like behavior editing by the in vitro caffeine- modulated immune cells are discussed. 

scholarly journals AGGRESSIVE BEHAVIOR CORRECTION BY THE TRANSPLANTATION OF IN VITRO MODULATED IMMUNE CELLS

2021 ◽  
Vol 23 (4) ◽  
pp. 693-698
Author(s):  
E. V. Markova ◽  
E. V. Serenko ◽  
M. A. Knyazheva
Keyword(s):  
Aggressive Behavior ◽  
Immune Cells ◽  
Depressive Disorders ◽  
Brain Structures ◽  
Psychoactive Substances ◽  
Pathogenetic Mechanisms ◽  
Sensory Contact ◽  
Sensory Contact Model ◽  
Mutual Regulation

Aggression is a serious biomedical problem associated with a high percentage of patients and a lack of selective corrective agents. The most frequent increase in aggressiveness occurs in patients with depressive disorders, schizophrenia, reactive psychoses and adjustment disorders, which are known to be characterized by immunological dysfunction. Antipsychotics are widely used in the correction of psychomotor agitation; the antipsychotic effect of these drugs is manifested in the achievement of a sedative effect. However, like other psychoactive substances, they have a number of side effects that limit their long-term use and determines the need to search for new approaches to the correction of affective disorders. Experimental modeling of aggression is one of the main approaches for studying its pathogenetic mechanisms and searching for new effective therapeutic agents for the treatment. The study of the aggression pathogenetic mechanisms and the search for approaches to therapy within the framework of neuroimmune interaction is currently extremely promising. Currently, there is a large number of clinical and experimental data indicating interrelated changes in the functional activity of the nervous and immune systems during aggression. The leading links in the pathogenetic mechanism of aggression is the violation of the production and mutual regulation of cytokines, neurotransmitters, neuropeptides, growth factors, hormones, the effects of which are mediated by the cellular elements of the immune system. Given the immune cells essential role in the pathogenesis of aggression and the psychoactive substances unidirectional effect on the immune and nervous cells, make it possible to consider immune cells as model objects for influencing the intersystem functional relationship in order to edit the aggressive phenotype. The aim of the study was to investigate the effect of in vitro neuroleptic-modulated immune cells transplantation on behavioral phenotype and brain cytokines in aggressive syngeneic recipients. Aggressive behavior was formed in active male mice (CBA × C57Bl/6) F1 as a result of the experience of 20- fold victories in inter-male confrontations (distant sensory contact model). Aggressive mice splenocytes were treated in vitro with chlorpromazine and intravenously injected to syngeneic aggressive recipients. It has been demonstrated that modulated in vitro by chlorpromazine splenocytes of aggressive mice after transplantation edit the syngeneic aggressive recipient’s behavior against the background of a decrease in cytokines IL-1β, IL-2, IL-6, IFNγ and an increase in IL-4 in pathogenetically significant for aggression brain structures. The mechanisms of the aggressive behavior correcting effect of modulated immune cells are discussed. 

Physical plasma and leukocytes – immune or reactive?

2018 ◽  
Vol 400 (1) ◽  
pp. 63-75 ◽  
Author(s):  
Sander Bekeschus ◽  
Christian Seebauer ◽  
Kristian Wende ◽  
Anke Schmidt
Keyword(s):  
Wound Healing ◽  
Immune System ◽  
Plasma Treatment ◽  
Immune Cells ◽  
The Body ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Physical Plasma

AbstractLeukocytes are professionals in recognizing and removing pathogenic or unwanted material. They are present in virtually all tissues, and highly motile to enter or leave specific sites throughout the body. Less than a decade ago, physical plasmas entered the field of medicine to deliver their delicate mix of reactive species and other physical agents for mainly dermatological or oncological therapy. Plasma treatment thus affects leukocytes via direct or indirect means: immune cells are either present in tissues during treatment, or infiltrate or exfiltrate plasma-treated areas. The immune system is crucial for human health and resolution of many types of diseases. It is therefore vital to study the response of leukocytes after plasma treatmentin vitroandin vivo. This review gathers together the major themes in the plasma treatment of innate and adaptive immune cells, and puts these into the context of wound healing and oncology, the two major topics in plasma medicine.

scholarly journals The immunoregulation of mesenchymal stem cells plays a critical role in improving the prognosis of liver transplantation

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Chenxia Hu ◽  
Lanjuan Li
Keyword(s):  
Liver Transplantation ◽  
Natural Killer ◽  
Immune Cells ◽  
Adaptive Systems ◽  
Critical Role ◽  
Arterial System ◽  
Cell Mediated Immunity ◽  
Adaptive Immune Cells

AbstractThe liver is supplied by a dual blood supply, including the portal venous system and the hepatic arterial system; thus, the liver organ is exposed to multiple gut microbial products, metabolic products, and toxins; is sensitive to extraneous pathogens; and can develop liver failure, liver cirrhosis and hepatocellular carcinoma (HCC) after short-term or long-term injury. Although liver transplantation (LT) serves as the only effective treatment for patients with end-stage liver diseases, it is not very popular because of the complications and low survival rates. Although the liver is generally termed an immune and tolerogenic organ with adaptive systems consisting of humoral immunity and cell-mediated immunity, a high rejection rate is still the main complication in patients with LT. Growing evidence has shown that mesenchymal stromal cell (MSC) transplantation could serve as an effective immunomodulatory strategy to induce tolerance in various immune-related disorders. MSCs are reported to inhibit the immune response from innate immune cells, including macrophages, dendritic cells (DCs), natural killer cells (NK cells), and natural killer T (NKT) cells, and that from adaptive immune cells, including T cells, B cells and other liver-specific immune cells, for the generation of a tolerogenic microenvironment. In this review, we summarized the relationship between LT and immunoregulation, and we focused on how to improve the effects of MSC transplantation to improve the prognosis of LT. Only after exhaustive clarification of the potential immunoregulatory mechanisms of MSCs in vitro and in vivo can we implement MSC protocols in routine clinical practice to improve LT outcome.

scholarly journals Mitoxantrone-Loaded Nanoparticles for Magnetically Controlled Tumor Therapy–Induction of Tumor Cell Death, Release of Danger Signals and Activation of Immune Cells

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 923
Author(s):  
Teresa Ratschker ◽  
Laura Egenberger ◽  
Magdalena Alev ◽  
Lisa Zschiesche ◽  
Julia Band ◽  
...  
Keyword(s):  
Cell Death ◽  
Immune System ◽  
Immune Cells ◽  
Checkpoint Inhibitors ◽  
Tumor Therapy ◽  
Superparamagnetic Iron Oxide ◽  
Dependent Manner ◽  
Tumor Cell Death ◽  
Immune Therapies

Stimulating the patient’s immune system represents a promising therapeutic strategy to fight cancer. However, low immunogenicity of the tumor cells within an immune suppressive milieu often leads to weak anti-tumor immune responses. Additionally, the immune system may be impaired by accompanying aggressive chemotherapies. We show that mitoxantrone, bound to superparamagnetic iron oxide nanoparticles (SPIONs) as the transport system, can be magnetically accumulated in adherent HT-29 colon carcinoma cells, thereby inducing the same cell death phenotype as its soluble counterpart, a chemotherapeutic agent and prototypic inductor of immunogenic cell death. The nanoparticle-loaded drug induces cell cycle stop, apoptosis and secondary necrosis in a dose- and time-dependent manner comparable to the free drug. Cell death was accompanied by the release of interleukin-8 and damage-associated molecular patterns (DAMPs) such as HSP70 and ATP, which fostered chemotactic migration of monocytes and maturation of dendritic cells. We furthermore ensured absence of endotoxin contaminations and compatibility with erythrocytes and platelets and investigated the influence on plasma coagulation in vitro. Summarizing, with magnetic enrichment, mitoxantrone can be accumulated at the desired place, sparing healthy peripheral cells and tissues, such as immune cells. Conserving immune competence in cancer patients in the future might allow combined therapeutic approaches with immune therapies (e.g., checkpoint inhibitors).

scholarly journals MicroRNA-Enriched Exosomes from Different Sources of Mesenchymal Stem Cells Can Differentially Modulate Functions of Immune Cells and Neurogenesis

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 69
Author(s):  
Naina Soni ◽  
Suchi Gupta ◽  
Surender Rawat ◽  
Vishnu Krishnakumar ◽  
Sujata Mohanty ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Expression Profile ◽  
Immune Cells ◽  
Biologically Active ◽  
Rna Seq ◽  
Adult Mesenchymal Stem Cells ◽  
Neutrophil Survival ◽  
Different Sources

Adult Mesenchymal stem cells-derived exosomes carry several biologically active molecules that play prominent roles in controlling disease manifestations. The content of these exosomes, their functions, and effect on the immune cells may differ depending on their tissue sources. Therefore, in this study, we purified the exosomes from three different sources and, using the RNA-Seq approach, highly abundant microRNAs were identified and compared between exosomes and parental cells. The effects of exosomes on different immune cells were studied in vitro by incubating exosomes with PBMC and neutrophils and assessing their functions. The expression levels of several miRNAs varied within the different MSCs and exosomes. Additionally, the expression profile of most of the miRNAs was not similar to that of their respective sources. Exosomes isolated from different sources had different abilities to induce the process of neurogenesis and angiogenesis. Moreover, these exosomes demonstrated their varying effect on PBMC proliferation, neutrophil survival, and NET formation, highlighting their versatility and broad interaction with immune cells. The knowledge gained from this study will improve our understanding of the miRNA landscape of exosomes from hMSCs and provide a resource for further improving our understanding of exosome cargo and their interaction with immune cells.

scholarly journals Neuroprotective Effect of HIF Prolyl Hydroxylase Inhibition in an In Vitro Hypoxia Model

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 662 ◽  
Author(s):  
Maria Savyuk ◽  
Mikhail Krivonosov ◽  
Tatiana Mishchenko ◽  
Irina Gazaryan ◽  
Mikhail Ivanchenko ◽  
...  
Keyword(s):  
Cell Viability ◽  
Functional Activity ◽  
Neuroprotective Effect ◽  
Network Connectivity ◽  
Prolyl Hydroxylase ◽  
Post Treatment ◽  
Biologically Active ◽  
Treatment Scenario ◽  
Hif Prolyl Hydroxylase

A novel potent analog of the branched tail oxyquinoline group of hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors, neuradapt, has been studied in two treatment regimes in an in vitro hypoxia model on murine primary hippocampal cultures. Neuradapt activates the expression of HIF1 and HIF2 target genes and shows no toxicity up to 20 μM, which is more than an order of magnitude higher than its biologically active concentration. Cell viability, functional activity, and network connectivity between the elements of neuronal networks have been studied using a pairwise correlation analysis of the intracellular calcium fluctuations in the individual cells. An immediate treatment with 1 μM and 15 μM neuradapt right at the onset of hypoxia not only protects from the death, but also maintains the spontaneous calcium activity in nervous cells at the level of the intact cultures. A similar neuroprotective effect in the post-treatment scenario is observed for 15 μM, but not for 1 μM neuradapt. Network connectivity is better preserved with immediate treatment using 1 μM neuradapt than with 15 μM, which is still beneficial. Post-treatment with neuradapt did not restore the network connectivity despite the observation that neuradapt significantly increased cell viability at 1 μM and functional activity at 15 μM. The preservation of cell viability and functional activity makes neuradapt promising for further studies in a post-treatment scenario, since it can be combined with other drugs and treatments restoring the network connectivity of functionally competent cells.

scholarly journals Catechins and Sialic Acid AttenuateHelicobacter pylori-Triggered Epithelial Caspase-1 Activity and EradicateHelicobacter pyloriInfection

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Jyh-Chin Yang ◽  
Hung-Chih Yang ◽  
Chia-Tung Shun ◽  
Teh-Hong Wang ◽  
Chiang-Ting Chien ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Signaling Pathway ◽  
Immune Cells ◽  
Critical Role ◽  
Gastric Epithelium ◽  
Ags Cells ◽  
Caspase 1 ◽  
H Pylori

The inflammasome/caspase-1 signaling pathway in immune cells plays a critical role in bacterial pathogenesis; however, the regulation of this pathway in the gastric epithelium duringHelicobacter pyloriinfection is yet to be elucidated. Here, we investigated the effect of catechins (CAs), sialic acid (SA), or combination of CA and SA (CASA) onH. pylori-induced caspase-1-mediated epithelial damage, as well asH. pyloricolonizationin vitro(AGS cells) andin vivo(BALB/c mice). Our results indicate that the activity of caspase-1 and the expression of its downstream substrate IL-1βwere upregulated inH. pylori-infected AGS cells. In addition, we observed increased oxidative stress, NADPH oxidase gp91phox, CD68, caspase-1/IL-1β, and apoptosis, but decreased autophagy, in the gastric mucosa ofH. pylori-infected mice. We have further demonstrated that treatment with CASA led to synergistic anti-H. pyloriactivity and was more effective than treatment with CA or SA alone. In particular, treatment with CASA for 10 days eradicatedH. pyloriinfection in up to 95% ofH. pylori-infected mice. Taken together, we suggest that the pathogenesis ofH. pyloriinvolves a gastric epithelial inflammasome/caspase-1 signaling pathway, and our results show that CASA was able to attenuate this pathway and effectively eradicateH. pyloriinfection.

Interaction of mouse splenocytes and macrophages with bacterial strains in vitro: the effect of age in the immune response

2016 ◽  
Vol 7 (2) ◽  
pp. 275-287 ◽  
Author(s):  
A.A. Van Beek ◽  
J.A. Hoogerland ◽  
C. Belzer ◽  
P. De Vos ◽  
W.M. De Vos ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Interferon Γ ◽  
Bacterial Strains ◽  
Mouse Splenocytes ◽  
Aged Mice ◽  
Inflammatory Conditions ◽  
Cellular Inflammatory Response

Probiotics influence the immune system, both at the local and systemic level. Recent findings suggest the relation between microbiota and the immune system alters with age. Our objective was to address direct effects of six bacterial strains on immune cells from young and aged mice: Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, Lactococcus lactis MG1363, Bifidobacterium breve ATCC15700, Bifidobacterium infantis ATCC15697, and Akkermansia muciniphila ATCC BAA-835. We used splenocytes and naïve or interferon-γ-stimulated bone marrow-derived macrophages (BMDM) as responder populations. All tested bacterial strains induced phenotypic and cytokine responses in splenocytes and BMDM. Based on magnitude of the cellular inflammatory response and cytokine profiles, two subgroups of bacteria were identified, i.e. L. plantarum and L. casei versus B. breve, B. infantis, and A. muciniphila. The latter group of bacteria induced high levels of cytokines produced under inflammatory conditions, including tumour necrosis factor (TNF), interleukin (IL)-6 and IL-10. Responses to L. lactis showed features of both subgroups. In addition, we compared responses by splenocytes and BMDM derived from young mice to those of aged mice, and found that splenocytes and BMDM derived from aged mice had an increased IL-10 production and dysregulated IL-6 and TNF production compared to young immune cells. Overall, our study shows differential inflammatory responses to distinct bacterial strains, and profound age-dependent effects. These findings, moreover, support the view that immune environment importantly influences bacterial immune effects.

scholarly journals The impact of high hydrostatic pressure (40 MPa and 60 MPa) on the apoptosis rates and functional activity of cryopreserved porcine mesenchymal stem cells

2018 ◽  
Vol 18 (1) ◽  
pp. 69-86
Author(s):  
Joanna Romanek ◽  
Jolanta Opiela ◽  
Zdzisław Smorąg
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hydrostatic Pressure ◽  
Functional Activity ◽  
High Hydrostatic Pressure ◽  
Negative Impact ◽  
Caspase 8 ◽  
Significant Difference ◽  
The Impact

AbstractThe aim of the present study was to examine the influence of two varied high hydrostatic pressure (HHP) values on the apoptosis (assessing caspase-8, survivin, CAD, Bax, BclxL and BclxS) and functional activity (using cocultures with bovine embryos) of porcine mesenchymal stem cells (pBMSCs). pBMSCs were isolated from porcine bone marrow and cultured in vitro. Before cryopreservation and storage in liquid nitrogen, pBMSCs were subjected to HHP values of 40 MPa and 60 MPa for 1 h at 24°C. After thawing, the cells were analysed for caspase-8 activity and protein expression of survivin, CAD, Bax, BclxL and BclxS. To indirectly test the influence of HHP on the functional activity of pBMSCs, in vitro maturated bovine oocytes were fertilized in vitro, and the obtained embryos were cultured under 4 different conditions: 1. monoculture in SOF medium; 2. coculture with pBMSCs in SOF medium; 3. coculture with pBMSCs subjected to 40 MPa HHP in SOF medium and 4. coculture with pBMSCs subjected to 60 MPa HHP in SOF medium. The quality of the developed blastocysts was analysed by TUNEL assay. HHP did not induce apoptosis in pBMSCs, as no significant difference was noted in the expression of any of the analysed apoptosis- related proteins between pBMSCs subjected to HHP (40 MPa or 60 MPa) and control. The highest number of obtained blastocysts was observed when the embryos were cultured in SOF. A highly significant difference (P<0.005) was noted between embryos cultured in SOF and embryos cultured in the presence of pBMSCs subjected to 60 MPa HHP or untreated pBMSCs. A significant difference (P<0.05) was noted between embryos cultured in SOF and embryos cultured in the presence of pBMSCs subjected to 40 MPa HHP. In conclusion, HHP does not induce apoptosis in pBMSCs. The obtained results of the blastocysts cocultured in vitro with pBMSCs (HHP-treated and untreated cells) imply that coculture with pBMSCs has a negative impact on the developmental rates of blastocysts.

scholarly journals In Vitro Effects of Enterococcus Faecalis and Selected Biomolecules on the Motility of Rabbit Spermatozoa

2017 ◽  
Vol 66 (3-4) ◽  
pp. 22-31
Author(s):  
Eva Tvrdá ◽  
Michal Ďuračka ◽  
Marek Halenár ◽  
Attila Kántor
Keyword(s):  
Sperm Motility ◽  
Negative Impact ◽  
Selective Advantage ◽  
Positive Control ◽  
Negative Control ◽  
Biologically Active ◽  
Rapid Decline ◽  
Sperm Analysis ◽  
Rabbit Spermatozoa

SummaryThis study assessed the potential efficiency of selected biologically active substances on the motility behavior of rabbit spermatozoa subjected to in vitro induced E. faecalis contamination. Semen samples were collected from 10 male rabbits and the presence of E. faecalis was confirmed using MALDI-TOF Mass Spectrometry. For the in vitro experiments rabbit spermatozoa were resuspended in the presence of 0,3 McF E. faecalis and different concentrations of selected biomolecules (resveratrol - RES, quercetin - QUE, curcumin - CUR, epicatechin - EPI, isoquercitrin - IZO). Sperm motility was assessed using the computer-aided sperm analysis at 0h, 2h, 4h, 6h and 8h. The presence of E. faecalis significantly decreased the motility (P<0.001) when compared to the untreated Control starting at 2h and maintaining this negative impact throughout the entire in vitro culture. Meanwhile, the motility was significantly higher in the experimental samples subjected to E. faecalis together 5 μmol/L RES (P<0.05), 10 μmol/L QUE (P<0.05) as well as 1 μmol/L (P<0.01) and 10 μmol/L CUR (P<0.05) when compared to the Positive Control (4h). No biomolecule was able to maintain the motion comparable to the Negative Control, and none was effective against the rapid decline of sperm motility caused by the presence of E. faecalis during later stages of the in vitro experiment (6h and 8h). We may conclude that RES, QUE and CUR may provide a selective advantage to spermatozoa in the presence of E. faecalis, particularly during short-term rabbit semen handling.

Sign in / Sign up

Export Citation Format

Share Document