Effects of Mesenchymal Stem Cells on Functions of Chimeric Antigen Receptor-Expressing T Lymphocytes and Natural Killer Cells.

Chimeric antigen receptor (CAR)-engineered immune cells, particularly CAR T lymphocytes and CAR natural killer (NK) cells, have revolutionized cancer immunotherapy. However, their therapeutic efficacy and safety can be influenced by the tumor microenvironment, particularly the presence of mesenchymal stem cells (MSCs). MSCs are immunomodulatory cells which can alter the function of tumor-infiltrated immune cells in both supportive and suppressive ways.

Therapeutic Potential of Mesenchymal Stem Cell-Derived Extracellular Vesicles in the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the gradual loss of dopamine-producing neurons. Oxidative stress, mitochondrial dysfunction, detrimental immune response, and neuroinflammation are mainly responsible for the injury and degeneration of dopaminergic neurons in the brains of patients suffering from PD. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising therapeutic approach for treating PD due to their ability to suppress the activation of inflammatory immune cells and enhance the viability and function of dopamine-producing neurons.

An Interplay Between Pericytes, Mesenchymal Stem Cells, and Immune Cells in the Process of Tissue Regeneration.

Immediately after injury, damaged cells elicit tissue regeneration, a healing process that enables optimal renewal and regrowth of injured tissues. Results obtained in a large number of experimental studies suggested that the cross talk between pericytes, mesenchymal stem cells (MSC), tissue-resident stem cells, and immune cells has a crucially important role in the regeneration of injured tissues. Pericytes, MSCs, and immune cells secrete bioactive factors that influence each other's behavior and function.

Mesenchymal Stem Cell-Sourced Exosomes as Potentially Novel Remedies for Severe Dry Eye Disease.

Severe dry eye disease (DED) is an inflammatory condition characterized by a lack of sufficient moisture or lubrication on the surface of the eye, significantly impacting the quality of life and visual function. Since detrimental immune response is crucially responsible for the development and aggravation of DED, therapeutic agents which modulate phenotype and function of eye-infiltrated inflammatory immune cells could be used for the treatment of severe DED. Due to their potent immunomodulatory properties, mesenchymal stem cells (MSCs) represent potentially new remedies for the treatment of inflammatory eye diseases.

Targeted Therapy for Severe Sjogren's Syndrome: A Focus on Mesenchymal Stem Cells.

Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by the infiltration of lymphocytes on salivary and lacrimal glands, resulting in their dysfunction. Patients suffering from severe pSS have an increased risk of developing multi-organ dysfunction syndrome due to the development of systemic inflammatory response, which results in immune cell-driven injury of the lungs, kidneys, liver, and brain. Therapeutic agents that are used for the treatment of severe pSS encounter various limitations and challenges that can impact their effectiveness.

Molecular Mechanisms Responsible for Mesenchymal Stem Cell-Dependent Attenuation of Tear Hyperosmolarity and Immune Cell-Driven Inflammation in the Eyes of Patients with Dry Eye Disease.

Background: Dry eye disease (DED) is a chronic condition characterized by a decrease in tear production or an increase in tear evaporation, leading to inflammation and damage of the ocular surface. Dysfunction of ion channels, tear hyperosmolarity and immune cell-driven inflammation create a vicious circle responsible for the pathological changes in the eyes of DED patients. Mesenchymal stem cells (MSCs) are adult, rapidly proliferating stem cells that produce a large number of immunoregulatory, angiomodulatory, and growth factors that efficiently reduce tear hyperosmolarity-induced pathological changes, inhibit harmful immune response, and provide trophic support to the injured corneal and conjuctival epithelial cells, goblet cells and acinar cells in lacrimal glands of DED patients.

The Role of MicroRNAs in Mesenchymal Stem Cell-Based Modulation of Pulmonary Fibrosis.

Pulmonary fibrosis is a complex and multifactorial condition that involves a cascade of events, including lung injury, damage of alveolar epithelial cells (AECs), generation of immune cell-driven inflammation, and activation of fibroblasts and their differentiation into myofibroblasts, resulting in the excessive production and deposition of collagen and progressive scarring and fibrosis of the lung tissue. As lung fibrosis advances, the scarring and stiffening of lung tissue can significantly hinder the exchange of oxygen and carbon dioxide, potentially leading to respiratory failure that can be life-threatening. Anti-inflammatory and immunosuppressive drugs are used to slow down the progression of the disease, manage symptoms, and enhance the patient's quality of life.

Effects of combustible cigarettes and electronic nicotine delivery systems on immune cell-driven inflammation: Evidences from diabetic patients and multiple low dose streptozotocin-treated diabetic mice.

Considering detrimental impacts of combustible cigarettes (CCs) on the exacerbation of diabetes mellitus (DM), a significant number of DM patients have substituted CCs with electronic nicotine delivery systems (ENDS). Herewith, we compared CCs and ENDS-dependent modulation of immune cell-driven inflammation in DM patients who used ENDS (DM), CCs (DM) or were non-smokers (DM), paving the way for the better understanding of ENDS-induced biological effects. Multiple low dose streptozotocin (MLD-STZ)-induced mice model of DM was used to support clinical findings.

The Possible Effects of Galectin-3 on Mechanisms of Renal and Hepatocellular Injury Induced by Intravascular Hemolysis.

Intravascular hemolysis is a central feature of congenital and acquired hemolytic anemias, complement disorders, infectious diseases, and toxemias. Massive and/or chronic hemolysis is followed by the induction of inflammation, very often with severe damage of organs, which enhances the morbidity and mortality of hemolytic diseases. Galectin-3 (Gal-3) is a β-galactoside-binding lectin that modulates the functions of many immune cells, thus affecting inflammatory processes.

The Effects of Combustible Cigarettes and Electronic Nicotine Delivery Systems on Immune Cell-Driven Inflammation and Mucosal Healing in Ulcerative Colitis.

Introduction: The effects of combustible cigarettes (CCs) and electronic nicotine delivery systems (ENDS) on immune cell-driven colon inflammation and intestinal healing of patients with ulcerative colitis (UC) are still unknown and, therefore, were examined in this study.

Aims And Methods: Intracellular staining and flow cytometry analysis of immune cells isolated from UC patients who used ENDS (UCENDS), CCs (UCCC) and who were nonsmokers (UCAIR) were performed to elucidate cellular mechanisms which were responsible for CCs and ENDS-dependent modulation of immune response during UC progression. Additionally, dextran sulfate sodium (DSS)-colitis was induced in ENDS/CC/air-exposed mice (DSSENDS/ DSSCC/DSSAIR groups) to support clinical findings.

Effects of combustible cigarettes and heated tobacco products on immune cell-driven inflammation in chronic obstructive respiratory diseases.

Since long-term effects of heated tobacco products (HTP) on the progression of chronic obstructive pulmonary disease (COPD) are unknown, we used COPD mice model to compare immune cell-dependent pathological changes in the lungs of animals which were exposed to HTP or combustible cigarettes (CCs). We also performed intracellular staining and flow cytometry analysis of immune cells which were present in the blood of CCs and HTP users who suffered from immune cell-driven chronic obstructive respiratory diseases. CCs enhanced NLRP3 inflammasome-dependent production of inflammatory cytokines in lung-infiltrated neutrophils and macrophages and increased influx of cytotoxic Th1, Th2, and Th17 lymphocytes in the lungs of COPD mice.

Molecular Mechanisms Responsible for the Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Lung Fibrosis.

Mesenchymal stem cell-derived exosomes (MSC-Exos) are nano-sized extracellular vesicles which contain various MSC-sourced anti-fibrotic, immunoregulatory and angio-modulatory proteins (growth factors, immunoregulatory cytokines, chemokines), lipids, and nucleic acids (messenger RNA and microRNAs). Due to their lipid envelope, MSC-Exos easily by-pass all barriers in the body and deliver their cargo directly in target cells, modulating their viability, proliferation, phenotype and function. The results obtained in recently published experimental studies demonstrated beneficial effects of MSC-Exos in the treatment of lung fibrosis.

Effects of Combustible Cigarettes and Electronic Nicotine Delivery Systems on the Development and Progression of Chronic Lung Inflammation in Mice.

Introduction: Although detrimental effects of combustible cigarettes (CCs) on the progression of lung inflammatory diseases are well known, changes in electronic nicotine delivery systems (ENDS)-exposed lung-infiltrated immune cells are still unrevealed.

Aims And Methods: The analysis of blood gas parameters, descriptive and quantitative histology of lung tissues, determination of serum cytokines, intracellular staining, and flow cytometry analysis of lung-infiltrated immune cells were used to determine the differences in the extent of lung injury and inflammation between mice from experimental (CC and ENDS-exposed animals) and control groups (Air-exposed mice).

Results: Continuous exposition to either CCs or ENDS induced severe systemic inflammatory response, increased activation of NLRP3 inflammasome in neutrophils and macrophages and enhanced dendritic cell-dependent activation of Th1 and Th17 cells in the lungs.

The Role of IL-17 in the Pathogenesis of Oral Squamous Cell Carcinoma.

Elucidating the inflammatory mechanisms underlying formation and progression of oral squamous cell carcinoma (OSCC) is crucial for discovering new targeted therapeutics. The proinflammatory cytokine IL-17 has proven roles in tumor formation, growth, and metastasis. The presence of IL-17 is demonstrated in both in vitro and in vivo models, and in OSCC patients, is mostly accompanied by enhanced proliferation and invasiveness of cancer cells.

The Pivotal Role of Galectin-3 in Viral Infection: A Multifaceted Player in Host-Pathogen Interactions.

Galectin-3 (Gal-3), a beta-galactoside-binding lectin, plays a pivotal role in various cellular processes, including immune responses, inflammation, and cancer progression. This comprehensive review aims to elucidate the multifaceted functions of Gal-3, starting with its crucial involvement in viral entry through facilitating viral attachment and catalyzing internalization. Furthermore, Gal-3 assumes significant roles in modulating immune responses, encompassing the activation and recruitment of immune cells, regulation of immune signaling pathways, and orchestration of cellular processes such as apoptosis and autophagy.

Can Zeolite-Supporting Acridines Boost Their Anticancer Performance?

Acridine and its derivatives (9-chloroacridine and 9-aminoacridine) are investigated here, supported on FAU type zeolite Y, as a delivery system of anticancer agents. FTIR/Raman spectroscopy and electron microscopy revealed successful drug loading on the zeolite surface, while spectrofluorimetry was employed for drug quantification. The effects of the tested compounds on cell viability were evaluated using in vitro methylthiazol-tetrazolium (MTT) colorimetric technique against human colorectal carcinoma (cell line HCT-116) and MRC-5 fibroblasts.

The Expression of IL-1β Correlates with the Expression of Galectin-3 in the Tissue at the Maternal-Fetal Interface during the Term and Preterm Labor.

The inflammatory processes that occur at the maternal−fetal interface are considered one of the factors that are responsible for preterm birth. The pro-inflammatory roles of the Gal-3-induced activation of NLRP3 inflammasome and the consecutive production of IL-1β have been described in several acute and chronic inflammatory diseases, but the role of this inflammatory axis in parturition has not been studied. The aim of this study was to analyze the protein expression of Gal-3, NLRP3, and IL-1β in the decidua, villi, and fetal membranes, and to analyze their mutual correlation and correlation with the clinical parameters of inflammation in preterm birth (PTB) and term birth (TB).

The Pt(-pr-thiosal)2 and BCL1 Leukemia Lymphoma: Antitumor Activity In Vitro and In Vivo.

B cell malignancies are, despite the development of targeted therapy in a certain percentage of the patients still a chronic disease with relapses, requiring multiple lines of therapy. Regimens that include platinum-based drugs provide high response rates in different B cell lymphomas, high-risk chronic lymphocytic leukemia (CLL), and devastating complication of CLL, Richter's syndrome. The aim of this study was to explore the potential antitumor activity of previously synthetized platinum(IV) complex with alkyl derivatives of thyosalicilc acid, PtCl2(-pr-thiosal)2, toward murine BCL1 cells and to delineate possible mechanisms of action.

Comparative assessment of electronic nicotine delivery systems aerosol and cigarette smoke on endothelial cell migration: The Replica Project.

Cigarette smoking is associated with impairment of repair mechanisms necessary for vascular endothelium homeostasis. Reducing the exposure to smoke toxicants may result in the mitigation of the harmful effect on the endothelium and cardiovascular disease development. Previous investigations evaluated in vitro the effect of electronic cigarette (EC) compared with cigarette smoke demonstrating a significant reduction in human umbilical vein endothelial cells (HUVECs) migration inhibition following EC aerosol exposure.

Mitigating toxicity of acetamiprid removal techniques - Fe modified zeolites in focus.

All remediation pathways in aqueous solutions come down to three dominant ones - physical, chemical, and combinations thereof. Materials proposed for adsorption and oxidative degradation can induce positive or negative effects on cells compared to the pollutants themselves. Present research deals with the effects different methods for pesticide remediation have and how they impact cytotoxicity.

CAR T Cell Therapy for Chronic Lymphocytic Leukemia: Successes and Shortcomings.

Chimeric antigen receptor T (CAR T) cell therapy achieved remarkable success in B-cell leukemia and lymphoma which led to its incorporation in treatment protocols for these diseases. CAR T cell therapy for chronic lymphocytic leukemia (CLL) patients showed less success compared to other malignant tumors. In this review, we discuss the published results regarding CAR T cell therapy of CLL, possible mechanisms of failures and expected developments.

Electronic nicotine delivery systems exhibit reduced bronchial epithelial cells toxicity compared to cigarette: the Replica Project.

Electronic nicotine delivery systems (ENDS) may reduce health risks associated with chronic exposure to smoke and their potential benefits have been the matter of intense scientific debate. We aimed to replicate three published studies on cytotoxic and inflammatory effects of cigarette smoke and ENDS aerosol in an independent multi-center ring study. We aimed to establish the reliability of results and the robustness of conclusions by replicating the authors' experimental protocols and further validating them with different techniques.

In vitro and in vivoactivity of series of cationic dinuclearPt(II) complexes.

The antitumour potential of nine dinuclear platinum(II) complexes of the type [{Pt(L)Cl}(μ-X)](where L represents two NH or different bidentantly coordinated diamine ligand - ethylenediamine, en; (±)-1,2-propylenediamine, 1,2-pn; isobutylenediamine, ibn; trans-(±)-1,2-diaminocyclohexane, dach; 1,3-propylenediamine, 1,3-pd; 2,2-dimethyl-1,3-propylenediamine, 2,2-diMe-1,3-pd; (±)-1,3-pentanediamine,1,3-pnd, and X is a bridging pyrazine (pz) or pyridazine (pydz) ligand) were determined by in vitro and in vivo assays using the CT26 cell line and a murine model of heterotopic colon cancer tumour induced in immunocompetent BALB/c mice. This study concludes that complexes Pt1, Pt2 and Pt7 possess significant in vitro cytotoxic activity against mouse colon carcinoma CT26 cells, while all these complexes show moderate apoptotic effect. Complexes Pt1 and Pt7 arrested CT26 cells in G2/M phase of cell cycle, while, evaluated by detection of Ki67 expressing cells, complexes Pt5 and Pt6 exerted the highest antiproliferative effect.

Contrasting Roles of the Galectin-3 in the Schizophrenia Onset, Clinical Presentation, and Somatic Comorbidity.

The role of the Galectin-3 (Gal-3) has already been explored in various somatic diseases, considering its engagement in infection, acute and chronic inflammation, and autoimmunity. Additionally, it has been recognized that Gal-3 is included in neuroinflammation and neurodegeneration, so we presented the possibility for its involvement in neuroprogression in schizophrenia. Gal-3 possibly participates in the early life programming of schizophrenia, also in the specific response to viral infections as a "second hit" later in life, and as a part of a unique systemic somatic dysfunction leading to the specific mental changes.

A new bis-pyrazolylpyridine ruthenium(III) complex as a potential anticancer drug: and activity in murine colon cancer.

We synthesized and characterized the ruthenium(iii) pincer-type complex [RuCl3(H2Lt-Bu] (H2Lt-Bu = 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine, 1) by elemental analysis, IR and UV-Vis spectroscopy, and the mass spectrometry (MS) method ESI Q-TOF. For comparison reasons, we also studied ruthenium(iii) terpyridine complexes of the general formula [Ru(N-N-N)Cl3], where N-N-N = 4'-chloro-terpyridine (Cl-tpy; 2) or 4'-chlorophenyl-terpyridine (Cl-Ph-tpy; 3). A kinetic study of the substitution reactions of 1-3 with biomolecules showed that the rate constants depend on the properties of the spectator ligand and the nature of the entering nucleophile.