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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. The majority of MSC-sourced bioactive factors are contained within MSC-derived exosomes (MSC-Exos), nano-sized extracellular vesicles which, due to their nanosize dimension and lipid envelope, easily by pass all biological barriers in the body and deliver their cargo directly into the target immune cells. MSC-Exos contain a variety of bioactive proteins (growth factors, immunoregulatory molecules, cytokines, and chemokines) lipids, and microRNAs (miRNAs) which affect viability, proliferation, phenotype, and function of eye-infiltrated immune cells. Accordingly, MSC-Exos may modulate the progression of inflammatory eye diseases, including DED. Therefore, in this review article, we summarized the current knowledge regarding molecular and cellular mechanisms which were responsible for trophic, anti-inflammatory, immunoregulatory, and regenerative properties of MSC-Exos in the treatment of severe DED. For this purpose, an extensive literature review was carried out in February 2024 across several databases (Medline, Embase, and Google Scholar), from 2000 to the present. Eligible studies delineated molecular and cellular mechanisms responsible for the MSC-Exos–based modulation of immune cell–driven eye inflammation in DED, and their findings were analyzed in this review. Results obtained in these studies demonstrated beneficial effects of MSC-Exos in the treatment of severe DED, paving the way for their future clinical use in ophthalmology.

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. However, prolonged immunosuppression could increase the susceptibility to severe bacterial, viral, or fungal pneumonia in lung-transplant recipients. Therefore, there is an urgent need for new therapeutic agents that can effectively reduce lung inflammation and fibrosis without compromising the protective immune response in patients with severe lung fibrosis. Results obtained in recently published studies demonstrated that mesenchymal stem/stromal cell-derived microRNAs (MSC-miRNAs) could attenuate detrimental immune response in injured lungs and prevent progression of lung fibrosis. Through the post-transcriptional regulation of target mRNA, MSC-miRNAs modulate protein synthesis and affect viability, proliferation, and cytokine production in AECs, fibroblasts, and lung-infiltrated immune cells. In order to delineate molecular mechanisms responsible for beneficial effects of MSC-miRNAs in the treatment of lung fibrosis, in this review article, we summarized current knowledge related to anti-fibrotic and anti-inflammatory pathways elicited in immune cells, AECs, and myofibroblasts by MSC-miRNAs.

Dry eye disease (DED) is a common multifactorial disorder characterized by a deficiency in the quality and/or quantity of tear fluid. Tear hyperosmolarity, the dysfunction of ion channel proteins, and eye inflammation are primarily responsible for the development and progression of DED. Alterations in the structure and/or function of ion channel receptors (transient receptor potential ankyrin 1 (TRPA1), transient receptor potential melastatin 8 (TRPM8), transient receptor potential vanilloid 1 and 4 (TRPV1 and TRPV4)), and consequent hyperosmolarity of the tears represent the initial step in the development and progression of DED. Hyperosmolarity triggers the activation of ion channel-dependent signaling pathways in corneal epithelial cells and eye-infiltrated immune cells, leading to the activation of transcriptional factors that enhance the expression of genes regulating inflammatory cytokine production, resulting in a potent inflammatory response in the eyes of DED patients. A persistent and untreated detrimental immune response further modifies the structure and function of ion channel proteins, perpetuating tear hyperosmolarity and exacerbating DED symptoms. Accordingly, suppressing immune cell-driven eye inflammation and alleviating tear hyperosmolarity through the modulation of ion channels in DED patients holds promise for developing new therapeutic strategies. Here, we summarize current knowledge about the molecular mechanisms responsible for the inflammation-induced modification of ion channels leading to tear hyperosmolarity and immune cell dysfunction in DED patients. We also emphasize the therapeutic potential of the newly designed immunomodulatory and hypo-osmotic solution d-MAPPS™ Hypo-Osmotic Ophthalmic Solution, which can activate TRPV4 in corneal epithelial cells, stabilize the tear film, enhance natural cytokine communication, and suppress detrimental immune responses, an important novel approach for DED treatment.

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. Methods: An extensive research in the literature was implemented in order to elucidate the role of MSCs in the attenuation of tear hyperosmolarity and eye inflammation in patients suffering from DED. Results: Findings obtained in preclinical and pilot clinical studies demonstrated that MSCs reduced tear hyperomsolaity-induced pathological changes and suppressed immune cell-driven eye inflammation. Additionally, MSC-based therapy managed to successfully address the most severe DED-related conditions and complications. Conclusions: MSCs should be considered as potentially new therapeutic agents for the treatment of severe DED.

Smoke derived from combustible cigarettes (CCs) contains numerous harmful chemicals that can impair the viability, proliferation, and activation of immune cells, affecting the progression of chronic inflammatory diseases. In order to avoid the detrimental effects of cigarette smoking, many CC users have replaced CCs with heated tobacco products (HTPs). Due to different methods of tobacco processing, CC-sourced smoke and HTP-derived aerosols contain different chemical constituents. With the exception of nicotine, HTP-sourced aerosols contain significantly lower amounts of harmful constituents than CC-derived smoke. Since HTP-dependent effects on immune-cell-driven inflammation are still unknown, herein we used flow cytometry analysis, intracellular staining, and an enzyme-linked immunosorbent assay to determine the impact of CCs and HTPs on systemic inflammatory response in patients suffering from ulcerative colitis (UC), diabetes mellitus (DM), and chronic obstructive pulmonary disease (COPD). Both CCs and HTPs significantly modulated cytokine production in circulating immune cells, affecting the systemic inflammatory response in COPD, DM, and UC patients. Compared to CCs, HTPs had weaker capacity to induce the synthesis of inflammatory cytokines (IFN-γ, IL-1β, IL-5, IL-6, IL-12, IL-23, IL-17, TNF-α), but more efficiently induced the production of immunosuppressive IL-10 and IL-35. Additionally, HTPs significantly enhanced the synthesis of pro-fibrotic TGF-β. The continuous use of CCs and HTPs aggravated immune-cell-driven systemic inflammation in COPD and DM patients, but not in UC patients, suggesting that the immunomodulatory effects of CC-derived smoke and HTP-sourced aerosols are disease-specific, and need to be determined for specific immune-cell-driven inflammatory diseases.

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. Accordingly, there is a need for targeted, personalized therapy that could address the underlying detrimental immune response while minimizing side effects. Results obtained in a large number of recently published studies have demonstrated the therapeutic efficacy of mesenchymal stem cells (MSCs) in the treatment of severe pSS. MSCs, in a juxtacrine and paracrine manner, suppressed the generation of inflammatory Th1 and Th17 lymphocytes, induced the expansion of immunosuppressive cells, impaired the cross-talk between auto-reactive T and B cells, and prevented the synthesis and secretion of auto-antibodies. Additionally, MSC-derived growth and trophic factors promoted survival and prevented apoptosis of injured cells in inflamed lacrimal and salivary glands, thereby enhancing their repair and regeneration. In this review article, we summarized current knowledge about the molecular mechanisms that are responsible for the beneficial effects of MSCs in the suppression of immune cell-driven injury of exocrine glands and vital organs, paving the way for a better understanding of their therapeutic potential in the targeted therapy of severe pSS. [ABSTRACT FROM AUTHOR]

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. Methods: An extensive research in the literature was implemented in order to elucidate the role of MSCs in the attenuation of tear hyperosmolarity and eye inflammation in patients suffering from DED. Results: Findings obtained in preclinical and pilot clinical studies demonstrated that MSCs reduced tear hyperomsolaity-induced pathological changes and suppressed immune cell-driven eye inflammation. Additionally, MSC-based therapy managed to successfully address the most severe DED-related conditions and complications. Conclusions: MSCs should be considered as potentially new therapeutic agents for the treatment of severe DED. [ABSTRACT FROM AUTHOR]

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 (DMENDS), CCs (DMCC) or were non‐smokers (DMAIR), 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. Both CCs and ENDS aggravated MLD‐STZ‐induced DM. Pancreatic injury and inflammation were more severe in CC‐exposed than in ENDS‐exposed diabetic mice. CCs promoted activation of NLRP3 inflammasome, enhanced production of inflammatory cytokines in neutrophils, macrophages and remarkably improved antigen presenting capacity of dendritic cells which resulted in the expansion of TNF‐α, IFN‐γ and IL‐17‐producing Th1 and Th17 lymphocytes, NK and NKT cells. Compared to CCs, ENDS more intensively promoted expansion of FoxP3‐expressing, IL‐10‐producing NK and NKT cells and triggered less intense systemic inflammatory response in diabetic animals. Similar findings were observed in DM patients. The highest numbers of inflammatory, TNF‐α and IL‐1β‐producing neutrophils and monocytes, TNF‐α and IFN‐γ‐producing T lymphocytes, NK and NKT cells were determined in the blood of DMCC patients, while total number of immunosuppressive, TGF‐β‐producing CD3 + CD4 + T cells was the highest in the blood of DMENDS patients. In conclusion, although both CC and ENDS aggravate on‐going inflammation in DM, ENDS have weaker capacity to induce production of inflammatory cytokines in immune cells than CCs. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a common multifactorial disorder characterized by a deficiency in the quality and/or quantity of tear fluid. Tear hyperosmolarity, the dysfunction of ion channel proteins, and eye inflammation are primarily responsible for the development and progression of DED. Alterations in the structure and/or function of ion channel receptors (transient receptor potential ankyrin 1 (TRPA1), transient receptor potential melastatin 8 (TRPM8), transient receptor potential vanilloid 1 and 4 (TRPV1 and TRPV4)), and consequent hyperosmolarity of the tears represent the initial step in the development and progression of DED. Hyperosmolarity triggers the activation of ion channel-dependent signaling pathways in corneal epithelial cells and eye-infiltrated immune cells, leading to the activation of transcriptional factors that enhance the expression of genes regulating inflammatory cytokine production, resulting in a potent inflammatory response in the eyes of DED patients. A persistent and untreated detrimental immune response further modifies the structure and function of ion channel proteins, perpetuating tear hyperosmolarity and exacerbating DED symptoms. Accordingly, suppressing immune cell-driven eye inflammation and alleviating tear hyperosmolarity through the modulation of ion channels in DED patients holds promise for developing new therapeutic strategies. Here, we summarize current knowledge about the molecular mechanisms responsible for the inflammation-induced modification of ion channels leading to tear hyperosmolarity and immune cell dysfunction in DED patients. We also emphasize the therapeutic potential of the newly designed immunomodulatory and hypo-osmotic solution d-MAPPS™ Hypo-Osmotic Ophthalmic Solution, which can activate TRPV4 in corneal epithelial cells, stabilize the tear film, enhance natural cytokine communication, and suppress detrimental immune responses, an important novel approach for DED treatment. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a multifactorial disorder of the lacrimal system and ocular surface, characterized by a deficiency in the quality and/or quantity of the tear fluid. The multifactorial nature of DED encompasses a number of interconnected underlying pathologies, including loss of homeostasis, instability and hyperosmolarity of the tears, and the induction and propagation of detrimental inflammatory responses in the eyes, which finally results in the development of neurosensory dysfunction and visual disruption. Dryness, grittiness, scratchiness, discomfort, inflammation, burning, watering, ocular fatigue, pain, and decreased functional visual acuity are common symptoms of DED. Eye dysfunction drastically attenuates patients’ quality of life. Accordingly, a better understanding of the pathogenic processes that regulate the development and progression of DED is crucially important for the establishment of new and more effective DED-related treatment approaches, which would significantly improve the quality of life of DED patients. Since the process of osmoregulation, which guards the ocular surface epithelia and maintains normal vision, is affected when the osmolarity of the tears is greater than that of the epithelial cells, tear hyperosmolarity (THO) is considered an initial, important step in the development, progression, and aggravation of DED. In order to delineate the role of THO in the pathogenesis of DED, in this review article, we summarize current knowledge related to the molecular mechanisms responsible for the development of THO-induced pathological changes in the eyes of DED patients, and we briefly discuss the therapeutic potential of hypo-osmotic eye drops in DED treatment.

Abstract 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. Human bronchial epithelial cells (NCI-H292) were exposed to cigarette whole smoke and vapor phase and to aerosol from ENDS. We also assessed the inflammatory cytokines interleukin-6 and interleukin-8 and the remodeling mediator matrix metalloproteinase-1. We replicated cell viability results and confirmed that almost 80% of cytotoxic effects are due to volatile compounds in the vapor phase of smoke. Our findings substantiated the reduced cytotoxic effects of ENDS aerosol. However, our data on inflammatory and remodeling activity triggered by smoke differed significantly from those in the original reports. Taken together, independent data from multiple laboratories clearly demonstrated the reduced toxicity of ENDS products compared to cigarettes.

Smoke derived from combustible cigarettes (CCs) contains numerous harmful chemicals that can impair the viability, proliferation, and activation of immune cells, affecting the progression of chronic inflammatory diseases. In order to avoid the detrimental effects of cigarette smoking, many CC users have replaced CCs with heated tobacco products (HTPs). Due to different methods of tobacco processing, CC-sourced smoke and HTP-derived aerosols contain different chemical constituents. With the exception of nicotine, HTP-sourced aerosols contain significantly lower amounts of harmful constituents than CC-derived smoke. Since HTP-dependent effects on immune-cell-driven inflammation are still unknown, herein we used flow cytometry analysis, intracellular staining, and an enzyme-linked immunosorbent assay to determine the impact of CCs and HTPs on systemic inflammatory response in patients suffering from ulcerative colitis (UC), diabetes mellitus (DM), and chronic obstructive pulmonary disease (COPD). Both CCs and HTPs significantly modulated cytokine production in circulating immune cells, affecting the systemic inflammatory response in COPD, DM, and UC patients. Compared to CCs, HTPs had weaker capacity to induce the synthesis of inflammatory cytokines (IFN-γ, IL-1β, IL-5, IL-6, IL-12, IL-23, IL-17, TNF-α), but more efficiently induced the production of immunosuppressive IL-10 and IL-35. Additionally, HTPs significantly enhanced the synthesis of pro-fibrotic TGF-β. The continuous use of CCs and HTPs aggravated immune-cell-driven systemic inflammation in COPD and DM patients, but not in UC patients, suggesting that the immunomodulatory effects of CC-derived smoke and HTP-sourced aerosols are disease-specific, and need to be determined for specific immune-cell-driven inflammatory diseases. [ABSTRACT FROM AUTHOR]

Due to their potent immunoregulatory and angio-modulatory properties, mesenchymal stem cells (MSCs) and their exosomes (MSC-Exos) have emerged as potential game-changers in regenerative ophthalmology, particularly for the personalized treatment of inflammatory diseases. MSCs suppress detrimental immune responses in the eyes and alleviate ongoing inflammation in ocular tissues by modulating the phenotype and function of all immune cells that play pathogenic roles in the development and progression of inflammatory eye diseases. MSC-Exos, due to their nano-sized dimension and lipid envelope, easily bypass all barriers in the eyes and deliver MSC-sourced bioactive compounds directly to target cells. Although MSCs and their exosomes offer a novel approach to treating immune cell-driven eye diseases, further research is needed to optimize their therapeutic efficacy. A significant number of experimental studies is currently focused on the delineation of intracellular targets, which crucially contribute to the immunosuppressive and anti-inflammatory effects of MSCs and MSC-Exos. The activation of NLRP3 inflammasome induces programmed cell death of epithelial cells, induces the generation of inflammatory phenotypes in eye-infiltrated immune cells, and enhances the expression of adhesion molecules on ECs facilitating the recruitment of circulating leukocytes in injured and inflamed eyes. In this review article, we summarize current knowledge about signaling pathways that are responsible for NLRP3 inflammasome-driven intraocular inflammation and we emphasize molecular mechanisms that regulate MSC-based modulation of NLRP3-driven signaling in eye-infiltrated immune cells, providing evidence that NLRP3 inflammasome should be considered a potentially new therapeutic target for MSCs and MSC-Exo-based treatment of inflammatory eye diseases.

Despite the improvements in pharmacological and surgical treatments, cardiovascular diseases (CVDs) are the number one cause of death worldwide. During the last two decades, the search for new therapies has been revolutionized with the growing knowledge of stem cell biology. Due to their huge differentiation capacity and paracrine effects, mesenchymal stem cells (MSCs) are a promising tool for the treatment of CVDs. The encouraging outcomes of preclinical studies using MSCs as a treatment for diseased myocardium have set the scene for worldwide clinical trials. In this review, we overview either complete or ongoing clinical trials using MSCs for the therapy of CVDs. In particular, we analyze the biological properties of MSCs, elucidate recent clinical findings and clinical trial phases of investigation, highlight clinical therapeutic effects of MSCs, and discuss challenges towards the clinical use of these cells in the therapy of CVDs.

Cisplatin (cis-diamminedichloroplatinum II) is a widely used chemotherapeutic agent. However, efficacy and clinical utility of this drug is significantly limited by severe side effects such as nephrotoxicity which develops due to renal accumulation and biotransformation in proximal tubular epithelial cells. Cisplatin-induced nephrotoxicity can be manifested as acute kidney injury (AKI), or as different types of tubulopathies, salt wasting, loss of urinary concentrating ability, and magnesium wasting. The attenuation of cisplatin-caused AKI is currently accomplished by hydration, magnesium supplementation or mannitol-induced forced diuresis. However, mannitol treatment causes over-diuresis and consequent dehydration, indicating an urgent need for the clinical use of newly designed, safe and efficacious renoprotective drug, as an additive therapy for high dose cisplatin-treated patients. Accordingly, we emphasized current knowledge regarding molecular mechanisms responsible for cisplatin-caused nephrotoxicity and we described in detail the main clinical manifestations of cisplatin-induced renal dysfunction in order to pave the way for the design of new therapeutic approaches that can minimize detrimental effects of cisplatin in the kidneys. Having in mind that most of cisplatin-induced cytotoxic effects against renal cells are, at the same time, involved in anti-tumor activity of cisplatin, new nephroprotective therapeutic strategies have to prevent renal injury and inflammation without affecting cisplatin-induced toxicity against malignant cells. [ABSTRACT FROM AUTHOR]

Breast cancer is considered refractory to immunotherapy. Accordingly, there is an urgent need for the therapeutic use of new immunostimulatory agents which would enhance antitumor immune response against breast cancer cells. “Derived Multiple Allogeneic Protein Paracrine Signaling (d-MAPPS)” is a biological product whose activity is based on chemokines and cytokines that modulate homing and phenotype of immune cells. d-MAPPS contains high concentration of dendritic cell (DC) and T cell-attracting chemokine CXCL16 and potent T cell-activating cytokine IL-27 which enhance DC:T cell cross-talk in inflamed tissues. Herewith, we used 4T1 murine model of breast cancer to analyze d-MAPPS-dependent enhancement of T cell-driven antitumor immunity. 4T1+d-MAPPS-treated mice showed delayed mammary tumor appearance compared to 4T1+saline-treated animals. d-MAPPS significantly reduced tumor weight and volume and improved survival of 4T1-treated mice. Significantly increased concentration of CXCL16, IL-27, IFN-γ, and IL-17 and decreased concentration of immunosuppressive TGF-β and IL-10 were measured in serum samples and tumor tissues of 4T1+d-MAPPS-treated mice. d-MAPPS enhanced production of IL-12 and increased expression of MHC class II and costimulatory molecules on tumor-infiltrated DC, significantly improving their antigen-presenting properties. d-MAPPS in CXCL16-dependent manner promoted recruitment of antitumorigenic IFN-γ/IL-17-producing CD4+Th1/Th17 cells and in IL-27-dependent manner induced expansion of tumoricidal CD178+granzyme B-expressing CD8+CTLs and inhibited generation of tolerogenic DC, IL-10, and TGF-β-producing FoxP3-expressing T regulatory cells. In summing up, d-MAPPS, in CXL16- and IL-27-dependent manner, enhanced T cell-driven antitumor immune response and suppressed breast cancer growth in experimental 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. ENDS induced less severe immune response than CCs. Serum concentrations of inflammatory cytokines were significantly lower in the samples of ENDS-exposed mice. Compared to CCs, ENDS recruited lower number of circulating leukocytes in injured lungs and had less capacity to induce CD14/TLR2-dependent activation of NLRP3 inflammasome in lung-infiltrated neutrophils and macrophages. ENDS-primed dendritic cells had reduced capacity for the generation of Th1 and Th17 cell-driven lung inflammation. Accordingly, extensive immune cell-driven lung injury resulted in severe respiratory dysfunction in CCs-exposed mice, while ENDS caused moderate respiratory dysfunction in experimental animals. Conclusions Continuous exposition to either CCs or ENDS induced immune cell-driven lung damage in mice. ENDS triggered immune response, which was less potent than inflammatory response elicited by CCs and, therefore, caused less severe lung injury and inflammation. Implications This is the first study that compared the effects of CCs and ENDS on lung-infiltrated immune cells. Although both CCs and ENDS elicited systemic inflammatory response, immune cell-driven lung injury and inflammation were less severe in ENDS-exposed than in CC-exposed animals. Continuous exposition to ENDS-sourced aerosols was less harmful for respiratory function of experimental animals than CC-derived smoke. [ABSTRACT FROM AUTHOR]

Abstract Background Cisplatin (cis-diamminedichloroplatinum II, CDDP) is one of the most effective chemotherapeutic agents. However, its clinical use is limited due to the severe side effects, including nephrotoxicity and acute kidney injury (AKI) which develop due to renal accumulation and biotransformation of CDDP. The alleviation or prevention of CDDP-caused nephrotoxicity is currently accomplished by hydration, magnesium supplementation or mannitol-induced forced diuresis which is considered for high-dose CDDP-treated patients. However, mannitol treatment causes over-diuresis and consequent dehydration in CDDP-treated patients, indicating an urgent need for the clinical use of safe and efficacious renoprotective drug as an additive therapy for high dose CDDP-treated patients. Main body In this review article we describe in detail signaling pathways involved in CDDP-induced apoptosis of renal tubular cells, oxidative stress and inflammatory response in injured kidneys in order to pave the way for the design of new therapeutic approaches that can minimize CDDP-induced nephrotoxicity. Most of these molecular pathways are, at the same time, crucially involved in cytotoxic activity of CDDP against tumor cells and potential alterations in their function might mitigate CDDP-induced anti-tumor effects. Conclusion Despite the fact that many molecules were designated as potential therapeutic targets for renoprotection against CDDP, modulation of CDDP-induced nephrotoxicity still represents a balance on the knife edge between renoprotection and tumor toxicity.

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. However, prolonged immunosuppression could increase the susceptibility to severe bacterial, viral, or fungal pneumonia in lung-transplant recipients. Therefore, there is an urgent need for new therapeutic agents that can effectively reduce lung inflammation and fibrosis without compromising the protective immune response in patients with severe lung fibrosis. Results obtained in recently published studies demonstrated that mesenchymal stem/stromal cell-derived microRNAs (MSC-miRNAs) could attenuate detrimental immune response in injured lungs and prevent progression of lung fibrosis. Through the post-transcriptional regulation of target mRNA, MSC-miRNAs modulate protein synthesis and affect viability, proliferation, and cytokine production in AECs, fibroblasts, and lung-infiltrated immune cells. In order to delineate molecular mechanisms responsible for beneficial effects of MSC-miRNAs in the treatment of lung fibrosis, in this review article, we summarized current knowledge related to anti-fibrotic and anti-inflammatory pathways elicited in immune cells, AECs, and myofibroblasts by MSC-miRNAs. [ABSTRACT FROM AUTHOR]