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The post hoc analysis presented here aimed to address the influence of endogenous vitamin D in the immunological mechanism underlying effective mite allergoid immunotherapy (AIT). Previously, we have shown that in allergic children, after 12 months of this immunoactive treatment, functionally potentiated memory regulatory T cells are identified. Indeed, AIT is the only known treatment that is able to reshape the detrimental immune response against the allergen into a non-noxious one. Besides, VD is widely considered an immunoregulatory molecule that is endogenously produced and exogenously provided by foods and supplements that might interact with the AIT mechanism, thus affecting its outcome. Therefore, a post hoc analysis of the clinical and immunological data from three different cohorts of allergic patients was performed. One cohort (N = 70) was on a standard symptom-controlling pharmacological treatment, while the other two (N = 60 and N = 35) were treated with AIT for 12 months. In the first cohort, a lower mean endogenous VD level (

Antioxidant-rich dietary regimens are considered the best practice to maintain health, control inflammation, and prevent inflammatory diseases. Yet, nutraceuticals as food supplements are self-prescribed and purchasable over the counter by healthy individuals for the purpose of beneficial effects on fitness and aging. Hence, the effectiveness, safety, and correct intake of these compounds need to be better explored. Since redox-modulating activity of these compounds appears to be involved in activation and or suppression of immune cells, the preventive use of nutraceuticals is very attractive even for healthy people. This review focuses on redox- and immunomodulating nutraceuticals in the context of diabetes mellitus (DM). In fact, DM is an illustrative disease of latent and predictable inflammatory pathogenetic processes set out and sustained by oxidative stress. DM has been thoroughly investigated through in vitro and in vivo models. Furthermore, human DM is characterized by uncontrolled levels of glucose, a pivotal factor shaping immune responses. Hence, antioxidant nutraceuticals with multifaced activities, including glucose keeping, are described here. A greater number of such multi-player nutraceuticals might be identified using DM animal models and validated in clinical settings on genetic and environmental high-risk individuals.

Cold atmospheric plasma is an ionized gas produced near room temperature; it generates reactive oxygen species and nitrogen species and induces physical changes, including ultraviolet, radiation, thermal, and electromagnetic effects. Several studies showed that cold atmospheric plasma could effectively provoke death in a huge amount of cell types, including neoplastic cells, via the induction of apoptosis, necrosis, and autophagy. This technique seems able to destroy tumor cells by disturbing their more susceptible redox equilibrium with respect to normal cells, but it is also able to cause immunogenic cell death by enhancing the immune response, to decrease angiogenesis, and to provoke genetic and epigenetics mutations. Solutions activated by cold gas plasma represent a new modality for treatment of less easily reached tumors, or hematological malignancies. Our review reports on accepted knowledge of cold atmospheric plasma’s effect on hematological malignancies, such as acute and chronic myeloid leukemia and multiple myeloma. Although relevant progress was made toward understanding the underlying mechanisms concerning the efficacy of cold atmospheric plasma in hematological tumors, there is a need to determine both guidelines and safety limits that guarantee an absence of long-term side effects.

Industrialization has resulted in a massive increase in garbage output, which is frequently discharged or stored in waterways like rivers and seas. Due to their toxicity, durability, bioaccumulation, and biomagnification, heavy metals (such as mercury, cadmium, and lead) have been identified as strong biological poisons. Their presence in the aquatic environment has the potential to affect water quality parameters and aquatic life in general. Teleosts’ histopathology provides a sensitive indicator of pollutant-induced stress, because their organs have a central role in the transformation of different active chemical compounds in the aquatic environment. In particular, the gills, kidneys, and liver are placed at the center of toxicological studies. The purpose of this study is to examine the morphological changes caused by heavy metals in the kidney and gills of Boops boops, with a focus on melanomacrophages centers (MMCs) and rodlet cells (RCs) as environmental biomarkers, using histological and histochemical stainings (hematoxylin/eosin, Van Gieson trichrome, Periodic Acid Schiff reaction, and Alcian Blue/PAS 2.5), and immunoperoxidase methods. Our findings show an increase of MMCs and RCs linked to higher exposure to heavy metals, confirming the role of these aggregates and cells as reliable biomarkers of potential aquatic environmental changes reflected in fish fauna. The cytological study of RCs and MMCs could be important in gaining a better understanding of the complicated immune systems of teleosts.

Exosomes are small membrane vesicles of endocytic origin containing cytokines, RNAs, growth factors, proteins, lipids, and metabolites. They have been identified as fundamental intercellular communication controllers in several diseases and an enormous volume of data confirmed that exosomes could either sustain or inhibit tumor onset and diffusion in diverse solid and hematological malignancies by paracrine signaling. Thus, exosomes might constitute a promising cell-free tumor treatment alternative. This review focuses on the effects of exosomes in the treatment of tumors, by discussing the most recent and promising data from in vitro and experimental in vivo studies and the few existing clinical trials. Exosomes are extremely promising as transporters of drugs, antagomir, genes, and other therapeutic substances that can be integrated into their core via different procedures. Moreover, exosomes can augment or inhibit non-coding RNAs, change the metabolism of cancer cells, and modify the function of immunologic effectors thus modifying the tumor microenvironment transforming it from pro-tumor to antitumor milieu. Here, we report the development of currently realized exosome modifiers that offer indications for the forthcoming elaboration of other more effective methods capable of enhancing the activity of the exosomes.

Raised oxidative stress and abnormal redox status are typical features of multiple myeloma cells, and the identification of the intimate mechanisms that regulate the relationships between neoplastic cells and redox homeostasis may reveal possible new anti-myeloma therapeutic targets to increase the effectiveness of anti-myeloma drugs synergistically or to eradicate drug-resistant clones while reducing toxicity toward normal cells. An alteration of the oxidative state is not only responsible for the onset of multiple myeloma and its progression, but it also appears essential for the therapeutic response and for developing any chemoresistance. Our review aimed to evaluate the literature’s current data on the effects of oxidative stress on the response to drugs generally employed in the therapy of multiple myeloma, such as proteasome inhibitors, immunomodulators, and autologous transplantation. In the second part of the review, we analyzed the possibility of using other substances, often of natural origin, to modulate the oxidative stress to interfere with the progression of myelomatous disease.

Basophils and mast cells are among the principal inducers of Th2 responses and have a crucial role in allergic and anti-parasitic protective immunity. Basophils can function as antigen-presenting cells that bind antigens on their surface and boost humoral immune responses, inducing Th2 cell differentiation. Their depletion results in lower humoral memory activation and greater infection susceptibility. Basophils seem to have an active role upon immune response to SARS-CoV-2. In fact, a coordinate adaptive immune response to SARS-CoV-2 is magnified by basophils. It has been observed that basophil amount is lower during acute disease with respect to the recovery phase and that the grade of this depletion is an important determinant of the antibody response to the virus. Moreover, mast cells, present in a great quantity in the nasal epithelial and lung cells, participate in the first immune response to SARS-CoV-2. Their activation results in a hyperinflammatory syndrome through the release of inflammatory molecules, participating to the “cytokine storm” and, in a longer period, inducing pulmonary fibrosis. The literature data suggest that basophil counts may be a useful prognostic tool for COVID-19, since their reduction is associated with a worse prognosis. Mast cells, on the other hand, represent a possible therapeutic target for reducing the airway inflammation characteristic of the hyperacute phase of the disease.

Multiple myeloma (MM) is a hematological disease that is still not curable. The bone marrow milieu, with cellular and non-cellular elements, participate in the creation of a pro-tumoral environment enhancing growth and survival of MM plasma cells. Exosomes are vesicles oscillating in dimension between 50 nm and 100 nm in size that can be released by various cells and contribute to the pathogenesis and progression of MM. Exosomes enclose proteins, cytokines, lipids, microRNAs, long noncoding RNAs, and circular RNAs able to regulate interactions between MM plasma cells and adjacent cells. Through exosomes, mesenchymal stem cells confer chemoresistance to MM cells, while myeloma cells promote angiogenesis, influence immune response, cause bone lesions, and have an impact on the outcome of MM patients. In this review, we analyze the role played by exosomes in the progression of monoclonal gammopathies and the effects on the proliferation of neoplastic plasma cells, and discuss the possible employment of exosomes as potential targets for the treatment of MM patients.

Conventional chemotherapy has partial therapeutic effects against hematological malignancies and is correlated with serious side effects and great risk of relapse. Recently, immunotherapeutic drugs have provided encouraging results in the treatment of hematological malignancies. Several immunotherapeutic antibodies and cell therapeutics are in dynamic development such as immune checkpoint blockades and CAR-T treatment. However, numerous problems restrain the therapeutic effectiveness of tumor immunotherapy as an insufficient anti-tumor immune response, the interference of an immune-suppressive bone marrow, or tumoral milieu with the discharge of immunosuppressive components, access of myeloid-derived suppressor cells, monocyte intrusion, macrophage modifications, all factors facilitating the tumor to escape the anti-cancer immune response, finally reducing the efficiency of the immunotherapy. Nanotechnology can be employed to overcome each of these aspects, therefore having the possibility to successfully produce anti-cancer immune responses. Here, we review recent findings on the use of biomaterial-based nanoparticles in hematological malignancies immunotherapy. In the future, a deeper understanding of tumor immunology and of the implications of nanomedicine will allow nanoparticles to revolutionize tumor immunotherapy, and nanomedicine approaches will reveal their great potential for clinical translation.

Background: TiO2 nanoparticles (TiO2 NPs) are the nanomaterial most produced as an ultraviolet (UV) filter. However, TiO2 is a semiconductor and, in nanoparticle size, is a strong photocatalyst, raising concerns about photomutagenesis. Mesoporous silica nanoparticles (MSN) were synthetized incorporating TiO2 NPs (TiO2@MSN) to develop a cosmetic UV filter. The aim of this study was to assess the toxicity of TiO2@MSN, compared with bare MSN and commercial TiO2 NPs, based on several biomarkers. Materials and Methods: Human peripheral blood mononuclear cells (PBMC) were exposed to TiO2@MSN, bare MSN (network) or commercial TiO2 NPs for comparison. Exposed PBMC were characterized for cell viability/apoptosis, reactive oxygen species (ROS), nuclear morphology, and cytokines secretion. Results: All the nanoparticles induced apoptosis, but only TiO2 NPs (alone or assembled into MSN) led to ROS and micronuclei. However, TiO2@MSN showed lower ROS and cytotoxicity with respect to the P25. Exposure to TiO2@MSN induced Th2-skewed and pro-fibrotic responses. Conclusions: Geno-cytotoxicity data indicate that TiO2@MSN are safer than P25 and MSN. Cytokine responses induced by TiO2@MSN are imputable to both the TiO2 NPs and MSN, and, therefore, considered of low immunotoxicological relevance. This analytical assessment might provide hints for NPs modification and deep purification to reduce the risk of health effects in the settings of their large-scale manufacturing and everyday usage by consumers.