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Neurons in the central nervous system release extracellular vesicles (EVs) and exosomes in response to synaptic activity to regulate physiological processes at target neurons. The intercellular transfer of proteins, mRNAs, lipids or metabolites through EVs potentially modulates the structure and function of neurons and circuits. Whereas the biogenesis of EVs, their release from donor cells, and their molecular composition have been studied extensively, the critical factors and mechanisms regulating EV interactions with target cells are incompletely understood. Here, we identified tetraspanin 15 (Tspan15) as a component of tumor susceptibility gene 101 protein (TSG101)‐ and CD81‐positive EV fractions. Tspan15 fluorescent fusion proteins were released from donor cells and interacted with target cells together with the exosomal marker CD63. EVs collected from wildtype cortical neurons (WT‐EVs) underwent similar association with target neurons derived from either wildtype (+/+) or Tspan15 knockout (−/−) mice. In contrast, target cell interactions of EVs collected from Tspan15 (−/−) cortical donor neurons (KO‐EVs) were significantly impaired, as compared to WT‐EVs. Our data suggest that Tspan15 is dispensable at target neuron plasma membranes, but is required at the EV surface to promote EV docking at target neurons. [ABSTRACT FROM AUTHOR]

Abstract Neurons in the central nervous system release extracellular vesicles (EVs) and exosomes in response to synaptic activity to regulate physiological processes at target neurons. The intercellular transfer of proteins, mRNAs, lipids or metabolites through EVs potentially modulates the structure and function of neurons and circuits. Whereas the biogenesis of EVs, their release from donor cells, and their molecular composition have been studied extensively, the critical factors and mechanisms regulating EV interactions with target cells are incompletely understood. Here, we identified tetraspanin 15 (Tspan15) as a component of tumor susceptibility gene 101 protein (TSG101)‐ and CD81‐positive EV fractions. Tspan15 fluorescent fusion proteins were released from donor cells and interacted with target cells together with the exosomal marker CD63. EVs collected from wildtype cortical neurons (WT‐EVs) underwent similar association with target neurons derived from either wildtype (+/+) or Tspan15 knockout (−/−) mice. In contrast, target cell interactions of EVs collected from Tspan15 (−/−) cortical donor neurons (KO‐EVs) were significantly impaired, as compared to WT‐EVs. Our data suggest that Tspan15 is dispensable at target neuron plasma membranes, but is required at the EV surface to promote EV docking at target neurons.

The horizon of immunotherapy using CAR-T cells is continuously extending to treat solid tumors beyond the success in the treatment of liquid tumors. Precise in-vitro evaluations of CAR-T cells for their phenotypes, quantity and quality of activation in various tumor microenvironments including different antigen densities, and the resulting effector functions are critical for the successful development of CAR-T therapies and safe translation to clinics. Unfortunately, the development of methods and tools to accommodate these needs have been lagging behind. Here, we developed a novel biomaterial platform, acellular artificial target particles (aaTPs) against CAR-T cells, using magnetic microbeads that are already widely employed in the manufacturing of T cell products. By devising a simple and standardized procedure, we precisely controlled the antigen surface densities presented on the aaTPs for a wide range. By co-incubation of aaTPs with CAR-T cells followed by flow cytometry and cytokine assays, we quantitatively determined the antigen-specific and dose-dependent activation of anti-HER2 CAR-T cells. We also demonstrated that the aaTP can serve as a clean target cell in in-vitro assays to prove the proposed mechanism of action of a next-generation CAR-T product. Overall, the simple, inexpensive, modular and precisely controllable synthetic nature of aaTPs enables the development of clean and standardized in-vitro assays for CAR-T cells, which provides critical advantages over the conventional assays using target cell lines. The design of aaTPs can be extended to include other tumor antigens and relevant surface molecules of physiological target cells. Thus, the aaTP platform has great potential as a standardized tool for the development and evaluation of both conventional and new CAR-T products in the context of approval from regulatory agencies and clinical translation. [ABSTRACT FROM AUTHOR]

Molecular endoscopy in inflammatory bowel disease (IBD) has made the translation from preclinical studies to clinical trials. The so far performed in vivo studies, using fluorescent antibodies, have addressed areas of heightened clinical interest with unmet needs. These include the distribution of targeted therapies within the mucosa, which could elucidate the most fitting dosing for the individual patient, the mode of action of currently used treatments, and subsequently also the prediction of therapeutic response. Altogether, molecular endoscopy might enable us to base individualized therapeutic decisions on preceded in vivo molecular analysis to optimize treatment in IBD., Competing Interests: Disclosure R. Atreya has served as a speaker, or consultant, or received research grants from AbbVie, Abivax, AstraZeneca, Bristol-Myers Squibb, Celltrion Healthcare, Galapagos, Johnson&Johnson, Lilly, MSD, Pfizer, and Takeda Pharma. DFG-SFB/TRR241 Project No. C02 and IBDome, CRU5024 B04 are funded by the German Research Council (DFG). Further supported by the FIBROTARGET project. The FIBROTARGET project has received funding from the European Union’s Horizon Europe Research & Innovation program under grant agreement no. 101080523. Funded by the European Union. Views and opinions expressed are those of the author(s) only and do not necessarily reflect those of the European Union or European Health and Digital Executive Agency (HADEA). Neither the European Union nor the granting authority can be held responsible for them. T. Rath has received speaker fees from Olympus Medical, PENTAX Medical, Mauna Kea Technologies, Medtronic, Takeda, Galapagos, Falk, Janssen, AbbVie, Repha, Medical Tribune, and Lilly. M F. Neurath has served as advisor or speaker for Pentax, Roche Pharma, Takeda Pharma, Pfizer, MSD, PPM, Janssen, Gilead, Dr Falk Pharma, Boehringer Ingelheim, Amgen, and AbbVie., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Copyright of Croatian Nursing Journal is the property of University of Applied Health Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

NK (Natural killer) cells are a special population of peripheral blood lymphocytes that kill virus-infected cells as well as tumor cells. For testing NK cell function, the classic gold standard assay has been used for a long time, determining the activity from target tumor cells using radioactive chromium in cell cultures for 4h. In this study two hematological cell lines K562 and MDS where used and target and results showed different sensitivity to killing by NK cells separated from healthy volunteers. Results have been shown that MDS release significantly more radioactive chromium indicating higher degree of necrosis during cell culture. In addition, K562 cell line is better target for NK killing in all different E:T ratio in comparison to MDS cell line previously described. Based on this, it is suggested that K562 cells be continues used in the future as better target for investigation NK killing. [Display omitted] • Two hematological cell lines K562 and MDS were used to test sensitivity to NK activity. • The results show that both cells equally bind radioactive 51 Cr. • MDS cells show a much higher release of radioactive 51Cr. • NK activity is much higher towards K562 cells than MDS cells. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Medical Equipment Journal is the property of Chinese Medical Equipment Journal Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Genetic lineage tracing in cell type-specific mouse models of T-cell acute lymphoblastic leukemia (T-ALL) have revealed that tumor cell identity is imposed by expression of the oncogene Lim Domain Only 2 (LMO2), rather than by the target cell phenotype. This approach allowed to identify that secondary genomic alterations, like Notch1 mutations, appeared late and only took place within the thymus during T-ALL development. These concepts are therefore critical for the development of modern therapies aimed at curing T-ALL.

Metal coordination of bioorganic compounds from both natural and synthetic products is not only gaining recognition in drug design and medicinal inorganic chemistry research, also they are being considered in the improvement of the bioactivity of drugs. What is done in this paper is a review of recent advances in the study of coordination-driven drug delivery, i.e., metal-based drugs (MBDs). The role of some late first row transition metal ions namely Fe, Cu and Zn in the biological activities of metallodrugs such as antimalarials and antimicrobials are highlighted. It was revealed that the interaction between these bio-essential transition metal ions and the organic drugs could enhance the diagnostic and therapeutic potentials of such formed drugs. This is because such interactions were proved to have improved the stability, bioavailability and cell delivery functions of the metallodrugs. Emphasizing on the challenge of metal ions toxicity, the researchers concluded on the need for the development of MBDs to combat drug resistant parasites without causing injury to normal cells. This would be of significance in addressing the concern World Health Organisation of ameliorating the increasing mortality rate in developing countries. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cell, a kind of lymphocyte cells, plays an important role in attacking infectious, immature, and cancer cell. Its function could be modulated by food bioactive compounds. This experiment was conducted to investigate the effects of ginger root bioactive compounds such as oleoresin, gingerol, and shogaol on cytolitic response of NK cell in vitro. Lymphocyte cells were isolated by centrifugation on ficoll-hypaque density (1,77 ?0,001 g/ml) method. Leukemic cells line K-562 as target cells(TC) labelled by [3H]-timidin, together with lymphocyte as effector cell (EC) were cultured in two ratio levels of EC : TC equal to 1:50 and 1:100), and two culture conditions, for 4 hours, respectively. Paraquate dichloride (1,1-dimethyl-4,4-bipyridilium dichloride) 3 mM was used to induce stress oxidative circumstance. Cytolytic capacity of NK cells was determined by percentage of TC lysed by NK cells, in normal and oxidative stress conditions. Statistical analysis showed that the effects of ginger bioactive compounds on cytolytic response of NK cell depended on the culture conditions, as shown by cultures in the presence of oleoresin, and gingerol, but not shogaol. In the lymphocyte culture without stress oxidative, oleoresin, gingerol and shogaol compounds increased significantly cytolytic response of NK cells cultured at a ratio of TC : EC equal to 1:50, with the highest increament of 65 % at oleoresin concentration of 50 ?g/ml. However, in culture at a ratio of TC : EC equals to 1:100, only oleoresin at a concentration of 50 ?g/ml increased significantly cytolytic response of NK cells with the highest increament of 8 %. Shogaol did not affect significantly NK cells cytolytic response. Under stress oxidative conditions, shogaol increased significantly cytolytic response of NK cells cultured at a ratio of TC:EC equal to 1:50, but the highest increament of 56 % , was by oleoresin at concentration of 50 ?g/ml. Meanwhile, oleoresin and gingerol did not increased significantly cytolytic response of NK cells. At a culture- ratio of TC: EC equal to 1:100, gingerol increased significantly cytolytic response of NK cells of 21 % at a concentration of 50 ?g/ml. However, oleoresin did not increased significantly cytolytic response of NK cells. In contrast, shogaol decreased significantly cytolytic response of NK cell with the highest decreament of 16 % at 200 ?g/ml. These findings verified that ginger root bioactive compounds increased cytolityc response of NK cells in destroying cancer cells, at certain conditions and concentrations, especially at low concentrations.

Background: In the Retic channel of DxH 800 (Beckman Coulter), the red blood cells (RBCs) resistant to hemoglobin clearing are counted as unghosted cells (UGCs). The aim of this study was to evaluate that the UGC is a surrogate marker for both the detection and counting of target cells. Methods: In total, 1181 samples including 22 from iron deficiency anemia (IDA) patients, 95 from jaundice, 2 from sickle cell anemia, 3 from thalassemia, 1 cord blood, and 269 from normal controls were analyzed. Slides were prepared from all samples except normal controls and target cells were counted for correlation analysis of target cell counts to UGCs. Results: The normal control samples showed 0.01% (0%-0.01%) UGCs, and the reference range was set at ≤0.02%. The IDA samples showed 0.015% (0.01%-0.03%) UGC count and 0.05% (0%-0.2%) target cell count. The jaundice samples showed 0.98% (0.1%-5.36%) UGC count, and 1.4% (0.1%-7.0%) target cell count. The two sickle cell anemia samples showed 0.41% and 3.74% UGC counts and 0.4% and 11.5% target cell counts. A cord blood sample showed 0.01% UGCs and 0% target cells. The three thalassemia samples showed 0.01%, 1.99%, and 7.82% UGC counts and 0%, 1.4%, and 15.5% target cell counts. The samples showing poikilocytosis other than target cells showed normal UGC count (≤0.02%). The positive predictive value of UGCs was 58.2% (124/213) and the negative predictive value was 96.8% (674/696). The UGC counts were well correlated to the manual target cell counts (r=0.944, p=0.000). Conclusions: This study demonstrates for the first time in the literature that a hematological parameter obtained automatically every time a reticulocyte counting is performed can be used to both screen for the presence of target cells and reliably quantify them. [ABSTRACT FROM AUTHOR]

Abstract: Currently, little is known on the cellular pathogenesis of equine arteritis virus (EAV). The purpose of the present study was to identify the target cells in ponies experimentally inoculated with EAV 08P178 (EU, clade-1). EAV-target organs (respiratory tissues with associated lymphoid tissues and large intestines), collected at 3 and 7 days post inoculation (dpi) and with virus titers≥105.0 TCID50/g, were processed with double immunofluorescence staining for the simultaneous detection of EAV N-protein and one of the following cell markers: CD172a (myeloid cells), CD3 (T lymphocytes), IgM (B lymphocytes) and von Willebrand factor (endothelial cells). In the different analyzed organs, 31–58% and 47–63% of the EAV-positive cells were mononuclear leukocytes (mainly CD172a+ followed by CD3+) at 3 and 7 dpi, respectively. EAV-positive endothelial cells were not detected in 3.200 large blood vessels (≥3 endothelial cells/vessel cross section). However, in terminal capillaries (1–2 endothelial cells/vessel cross section) of the different organs, 15–51% of the endothelial cells were EAV-positive. In conclusion, the present study demonstrates that EAV 08P178 (i) has a main tropism for CD172a+ and CD3+ mononuclear leukocytes and (ii) infects a large number of endothelial cells in terminal capillaries. EAV 08P178 infection in capillaries is most probably the cause of an increased vascular permeability leading to leakage of fluid (edema-serous exudate) but not to severe vasculitis and hemorrhages. [Copyright &y& Elsevier]

Abstract: Tuberculosis (TB) remains one of the most worrying infectious diseases affecting public health around the world; 8.7 million new TB cases were reported in 2011. The search for an Mycobacterium tuberculosis H37Rv protein sequence which is functionally important in host-pathogen interaction has been proposed for developing a new vaccine which will allow efficient and safe control of the spread of this disease. The present study thus reports the results obtained for the Rv1268c protein described in the M. tuberculosis H37Rv genome as a hypothetical unknown, probably secreted, protein based on a highly robust, specific, sensitive and functional approach to the search for potential epitopes to be included in an anti-tuberculosis vaccine. Rv1268c presence was determined by immunoblotting after obtaining polyclonal sera against mycobacterial total sonicate or subcellular fractions. Such sera were used in electron immunomicroscopy (EIM) for confirming protein localisation on the M. tuberculosis envelop by recognising colloidal gold-labelled immunoglobulin. Screening assays revealed the presence of two sequences having high binding activity: one binding A549 alveolar epithelial cells (141TGMAALEQYLGSGHAVIVSI160) and other binding U937 monocyte-derived macrophages (21AVALGLASPADAAAGTMYGD40). Such sequences’ ability to inhibit mycobacterial entry during in vitro assays was analysed. The structure of synthetic peptides binding to target cells was also determined, bearing in mind the structure–function relationship. These results, together with those obtained for other proteins, have been involved in selecting peptides which might be included in a subunit-based anti-tuberculosis vaccine. [Copyright &y& Elsevier]

Abstract: A gas target system has been developed for nuclear scattering experiments with a highly dispersive spectrometer at small scattering angles including 0°. The system is equipped with a gas cell that has a wide beam window of 44mm in width and 14mm in height. The size is sufficient to pass a dispersed beam, which is essential for high energy-resolution measurement. A gas handling system allows target gas that is often limited in quantity, to be collected for reuse. Typical areal density is 1mg/cm2 for 20Ne or 36Ar gas. The target can be operated either at room temperature or at the liquid nitrogen temperature. The gas target has been employed in a proton inelastic-scattering experiment at 295MeV with the Grand Raiden spectrometer at the Research Center for Nuclear Physics. A good energy resolution of 20keV (FWHM) has been achieved at scattering angles of 0–4.5°. [Copyright &y& Elsevier]

Apoptotic cell death has been considered an underlying mechanism in acute lung injury. To evaluate the evidence of this process, apoptosis rate was determined in effector cells (alveolar macrophages, neutrophils) and target cells (tracheobronchial and alveolar epithelial cells) of the respiratory compartment upon exposure to hypoxia and endotoxin stimulation in vitro. Cells were exposed to 5% oxygen or incubated with lipopolysaccharide (LPS) for 4, 8 and 24 h, and activity of caspase-3, -8 and -9 was determined. Caspase-3 of alveolar macrophages was increased at all three time-points upon LPS stimulation, while hypoxia did not affect apoptosis rate at early time-points. In neutrophils, apoptosis was decreased in an early phase of hypoxia at 4 h. However, enhanced expression of caspase-3 activity was seen at 8 and 24 h. In the presence of LPS a decreased apoptosis rate was observed at 8 h compared to controls, while it was increased at 24 h. Tracheobronchial as well as alveolar epithelial cells experienced an enhanced caspase-3 activity upon LPS stimulation with no change of apoptosis rate under hypoxia. While increased apoptosis rate is triggered through an intrinsic and extrinsic pathway in alveolar macrophages, intrinsic signalling is activated in tracheobronchial epithelial cells. The exact pathway pattern in neutrophils and alveolar epithelial cells could not be determined. These data clearly demonstrate that upon injury each cell type experiences its own apoptosis pattern. Further experiments need to be performed to determine the functional role of these apoptotic processes in acute lung injury. [ABSTRACT FROM AUTHOR]

Abstract: Human leukocyte antigen–G (HLA-G) is a nonclassical tolerogenic molecule that can be expressed either as membrane bound (HLA-G1) or secreted (HLA-G5) isoforms. Upregulation of HLA-G1 or HLA-G5 expression by tumor cells constitutes an efficient way to escape from antitumoral immune responses. The inhibitory role of HLA-G1 on NK cell cytotoxicity is well characterized; however, that of the HLA-G5 isoform secreted by tumor is poorly understood. Our results indicate that the HLA-G5 isoform secreted by M8 melanoma cells is able to protect them from natural killer leukemia cell line (NKL) cytotoxicity. Analysis of NKL/M8-HLA-G5 conjugates by confocal microscopy demonstrates that the inhibition of NKL cytotoxic activity resulted from an impairment of NKL actin reorganization and perforin granules polarization toward M8-HLA-G5 target cell. This study also indicates that HLA-G5 soluble isoform remains evenly distributed in the cytoplasm of M8-HLA-G5 conjugated to NKL cells, suggesting that HLA-G5 does not require to polarize toward effector cell to induce efficient inhibition. These results highlight the inhibitory mechanisms mediated through HLA-G5 leading to tumor escape from NK cell cytotoxicity. [Copyright &y& Elsevier]

Abstract: Porcine circovirus type 2 (PCV2) is detected in high amounts within the characteristic microscopic lesions of postweaning multisystemic wasting syndrome (PMWS) affected pigs. In spite of recent advances on disease pathogenesis, the precise cell types that support viral replication are still a major issue of scientific discussion. In this study, a new methodology to detect cell types that support PCV2 replication was designed. For this purpose, two in situ hybridisation (ISH) methods were developed and applied on tissues of PMWS naturally affected pigs using two probes designed from the ORF1 sequence of the virus. While the complementary probe (CP) detected ssDNA, ORF1 mRNA and replicative form (RF) of PCV2, the RF probe (RFP) exclusively hybridised with the RF of the virus, thus, only labelling cells where PCV2 replication is taking place. Both probes demonstrated to be specific and equally sensitive by an in vitro Southern blot hybridisation assay. ISH labelling with the CP was extensive in lymphoid tissues and of variable amount in other non-lymphoid tissues. With this probe, mainly macrophage-like cells were labelled but also other cell types such as hepatocytes and other epithelial cells. Tissues in which RFP labelling was found more frequently were lung, inguinal and mesenteric lymph nodes, tonsil and liver. Labelling with the RFP was always nuclear, and found in the same cell types as with the CP, although in a relatively low proportion of them; labelling of macrophage-like cells was infrequent. Therefore, the results indicate that at least a certain proportion of macrophages may support PCV2 replication, but main cells where PCV2 replicates are of epithelial/endothelial origin. In summary, the present study permitted the study of cell types that support PCV2 replication by the use of ISH on formalin-fixed, paraffin-embedded tissues of PMWS affected pigs. [Copyright &y& Elsevier]

Abstract: The utility of adenovirus serotype 5 (Ad5)-based vectors for gene therapy applications would be improved by cell-specific targeting. However, strategies to redirect Ad5 vectors to alternate cellular receptors via replacement of the capsid fiber protein have often resulted in structurally unstable vectors. In view of this, we hypothesized that the selection of modified adenoviruses during their rescue and propagation would be a straightforward approach that guarantees the generation of functional, targeted vectors. Based on our first generation fiber-fibritin molecule, several new chimeric fibers containing variable amounts of fibritin and the Ad5 fiber shaft were analyzed via a new scheme for Ad vector selection. Our selected chimera, composed of the entire Ad5 fiber shaft fused to the 12th coiled-coil segment of fibritin, is capable of efficient capsid incorporation and ligand display. Moreover, transduction by the resultant vector is independent of the expression of the native Ad5 receptor. The incorporation of the Fc-binding domain of Staphylococcus aureus protein A at the carboxy terminus of this chimeric fiber facilitates targeting of the vector to a variety of cellular receptors by means of coupling with monoclonal antibodies. In addition, we have concluded that Ad5 vectors incorporating individual targeting ligands require individual optimization of the fiber-fibritin chimera, which may be accomplished by selecting the optimal fiber-fibritin variant at the stage of rescue of the virus in cells of interest, as described herein. [Copyright &y& Elsevier]

Consider n cells, of which some are target cells, and suppose that each cell has a weight. The cells are killed in a sequential manner, with each currently live cell being the next one killed with a probability proportional to its weight. We study the distribution of the number of cells that are alive at the moment when all the target cells have been killed. [ABSTRACT FROM AUTHOR]

The primary target cell of human papillomaviruses (HPVs) is an unsettled issue. Recent studies have suggested that the hair follicle is an important candidate as the reservoir of certain HPV types. However, little is known about the cells which serve as the target or the reservoir of HPVs in nonhairy palmoplantar skin.To investigate whether the eccrine sweat gland, the only skin appendage in nonhairy palmoplantar skin, also serves as the target or the reservoir of HPVs.HPV 63-induced warts were employed in this study, because the virus induces tiny warty lesions of a punctuate appearance in the plantar skin and shows peculiar intracytoplasmic inclusion bodies as a diagnostic histopathological marker of infection: this seemed to provide a useful model for the present study. Serial sections were obtained from the entire body of each biopsy specimen and were investigated histologically, immunohistochemically and using DNA–DNAin situhybridization (ISH) for the histological localization of HPV 63 infection.On microscopy, HPV 63 histopathological changes were seen closely associated with eccrine ducts. Using ISH, HPV 63 DNA was detected not only in keratinocytes resident around acrosyringia but also in the uppermost portion of the eccrine dermal duct. A few keratinocytes harbouring HPV 63 DNA were also identified in acrosyringeal areas in the normal plantar skin adjacent to the wart lesions.On the basis of our results, it seems likely that HPV 63 targets keratinocytes resident in or around the eccrine ducts in the plantar skin. The results may also suggest that not only hair follicles but also eccrine ducts serve as reservoirs for certain HPV types, including HPV 63, especially in the nonhairy plantar skin. [ABSTRACT FROM AUTHOR]

Superparamagnetic iron oxide nanoparticles have been used for many years as magnetic resonance imaging contrast agents or in drug delivery applications. Tissue and cell-specific drug targeting by these nanoparticles can be achieved by employing nanoparticle coatings or carrier-drug conjugates that contain a ligand recognized by a receptor on the target cell. In this study, superparamagnetic iron oxide nanoparticles with specific shape and size have been prepared and coupled to insulin for their targeting to cell expressed surface receptors and thereby preventing the endocytosis. The influence of these nanoparticles on human fibroblasts is studied using various techniques to observe cell-nanoparticle interaction that includes light, scanning, and transmission electron microscopy studies. The derivatization of the nanoparticle surface with insulin-induced alterations in cell behavior that were distinct from the underivatized nanoparticles suggests that cell response can be directed via specifically engineered particle surfaces. The results from cell culture studies showed that the uncoated particles were internalized by the fibroblasts due to endocytosis, which resulted in disruption of the cell membrane. In contradiction, insulin-coated nanoparticles attached to the cell membrane, most likely to the cell-expressed surface receptors, and were not endocytosed. The presence of insulin on the surface of the nanoparticles caused an apparent increase in cell proliferation and viability. One major problem with uncoated nanoparticles has been the endocytosis of particles leading to irreversible entry. These results provide a route to prevent this problem. The derivatized nanoparticles show high affinity for cell membrane and opens up new opportunities for magnetic cell separation and recovery that may be of crucial interest for the development of cellular therapies. [ABSTRACT FROM PUBLISHER]

Myelopeptides (MPs) are low-molecular-weight immunoregulatory peptides of bone marrow origin. The peculiarities of their immunoregulatory effects are demonstrated with two of the six synthesized MPs, MP-1 (Phe-Leu-Gly-Phe-Pro-Thr) and MP-2 (Leu-Val-Val-Tyr-Pro-Trp). It is shown that MP action is directed to the damaged links of immunity. MP-1 enhances a decreased level of antibody production in cyclophosphamide (Cy)-treated mice, but does not influence the antibody formation in normal animals. MP-2 inhibits the tumor growth more in a tumor-bearing organism as the tumor size gets larger, insofar as MP-2 antitumor effect is concerned, by its ability to recover functional activity of T lymphocytes suppressed by tumor products. Selective immunocorrective effects of MPs are based on ligand–receptor interactions. Using FITC-labeled MP-1 and [3H]-labeled MP-2, specific binding of these peptides with appropriate cell populations is shown. The cytofluorimetric analysis revealed a target cell for MP-1—CD4+ T lymphocyte (T helper). The data obtained suggest that MPs are endogenic immunoregulators which participate in the maintenance of immune homeostasis. [Copyright &y& Elsevier]

Stimulation of Natural Killer (NK) cells with cytokines, target cell interaction, or antibody mediated activation of receptors on the NK cell surface enables the dissection of specific signaling intermediates in different activation pathways. NK cell activation status is commonly measured by production of interferon gamma (IFNγ) and expression of the degranulation marker LAMP-1 (CD107a). Cytotoxic potency can also be assessed by the production of perforin, granzymes, and tumor necrosis factor alpha (TNFα). NK cell receptor mediated activation by antibodies requires crosslinking of the receptor-specific antibodies; thus, in vitro activation assays are performed by binding antibodies to cell culture plates. All parameters can be measured by flow cytometry., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Copyright of Blut: Zeitschrift für die Gesamte Blutforschung is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)