IL-33 immunohistochemical pattern of expression in neoplastic and nonneoplastic peripheral lung tissues of stage 1 o 2 lung adenocarcinoma.

IL-33 is a multifaceted cytokine, plays a pivotal role in various biological processes, making it a subject of extensive research and intrigue in the field of immunology. This cytokine acts as a key regulator, effectively putting the brakes on proinflammatory nuclear factor-kappa B (NF-κB), thereby modulating chromatin compaction by promoting nucleosome-to-nucleosome interactions. IL-33's influence extends to the realm of innate and acquired immunity through its binding to the membrane-bound ST2 molecule (ST2L) of the IL-33R complex, which is expressed on various immune cells, such as Th2 cells, mast cells, natural killer cells, myeloid cells, and dendritic cells. IL-33's role in inflammation is far from one-dimensional, as it has been found to have a dual role in inflammatory disorders. In the quest to understand the origins of IL-33, immunohistochemical examination of lung tissue samples from patients with adenocarcinoma could shed light on its presence in bronchial epithelial and vascular endothelial cells, in lung tissue cancerous lesions. For this reason, we conducted a pilot study about the immunohistochemical expression of IL-33 in surgical specimens of stage 1 o 2 lung adenocarcinoma received after lung resection surgery.Our results demonstrated that patients had nuclear IL-33 immunopositivity in the alveolar pneumocytes of the normal lung tissue at the periphery of lung adenocarcinoma specimen. Note the evident negativity of the neoplastic adenocarcinoma cells. Other data showed IL-33 nuclear immunoexpression in endothelial cells of intratumoral vascular structures.This finding could indicate that IL-33 might be involved in regulating blood vessel formation and maintenance within the tumor, which is a critical factor in tumor growth and progression.The presence of IL-33 in normal lung tissue and intratumoral vascular structures may be related to its physiological functions in these contexts, while its absence in neoplastic adenocarcinoma cells could indicate a potential loss of regulatory control, which might have implications for the development and progression of the tumor.

Polyphenols from Mediterranean Plants: Biological Activities for Skin Photoprotection in Atopic Dermatitis, Psoriasis, and Chronic Urticaria.

Polyphenols are a diverse class of natural compounds that are widely distributed in various fruits, vegetables, and herbs. They possess antioxidant and anti-inflammatory properties and bring benefits in the prevention and treatment of various diseases. Studies suggested that polyphenols may improve cardiovascular health and may have neuroprotective effects. The Mediterranean region is a vast area. Although the territory encompasses a wide variety of cultures and dietary patterns, there are some commonalities in terms of the plant-based foods and their polyphenol content. Such polyphenols have been studied for their potential photoprotective effects on the skin. We focused on nutraceutical effects of Mediterranean plants in skin photoprotection in atopic dermatitis, psoriasis, and chronic urticaria. Results highlight the importance of exploring natural compounds for therapeutic purposes. The wide variety of polyphenols found in different foods and plants allows for a diverse range of pharmacological effects. The Mediterranean diet, rich in polyphenol-containing foods, is associated with a lower incidence of various chronic diseases, including dermatological conditions. While more research is needed to fully understand the mechanisms of action and optimal dosing of polyphenols, there is initial evidence to support their potential use as adjunctive therapy for atopic dermatitis, psoriasis, and chronic urticaria.

Multiparametric Evaluation of Geriatric Patients Admitted to Intermediate Care: Impact on Geriatric Rehabilitation.

Optimizing the functional status of patients of any age is a major global public health goal. Rehabilitation is a process in which a person with disabilities is accompanied to achieve the best possible physical, functional, social, intellectual, and relational outcomes. The Intermediate Care Unit within the O.U. of Geriatrics and Gerontology of the San Martino Hospital in Genoa is focused on the treatment and motor reactivation of patients with geriatric pathologies. The objective of this study was to identify which factor, among the characteristics related to the patient and those identified by the geriatric evaluation, had the greatest impact on rehabilitation outcomes. Our findings revealed significant correlations between the Barthel Index delta, the 4AT Screening Test, and the number of drugs taken. This association highlights the potential benefits of medication management in enhancing the overall well-being and functional abilities of frail older adults, despite the literature suggesting that polypharmacotherapy is associated with a reduction in functional status and an increase in mortality. These findings underscore the significance of a multidimensional geriatric assessment. Refining and optimising these multidisciplinary approaches is the objective of a more effective geriatric rehabilitation strategy.

The role of High-mobility group box-1 and Psoriasin in multiple myeloma: Analysis of a population affected by monoclonal gammopathies and review of the literature.

Multiple myeloma (MM) is a plasma cells neoplasm which is often preceded by a preneoplastic condition called monoclonal gammopathy of unknown significance (MGUS). A protein called High-mobility group box-1 (HMGB-1) controls transcription and genomic stability. Both pro- and anti-tumor properties of HMGB1 have been described during tumor growth. The S100 protein family includes a protein known as psoriasin. Poorer prognosis and survival were linked to higher psoriasin expression in cancer patients. The goal of the current investigation was to compare the plasma levels of HMGB-1 and psoriasin in patients with MM and MGUS significance, as well as in a group of healthy controls. According to our research, patients with MGUS have higher HMGHB-1 concentrations than healthy controls (846.7 ± 287.6 pg/ml vs. 176.9 ± 204.8 pg/ml for controls, p < 0.001). Similarly, we found a huge difference in HMGB-1 levels for MM patients with respect to controls (928.0 ± 551.4 pg/ml vs. 176.9 ± 204.8 pg/ml; p = 0.001). No difference was found as for the Psoriasin levels in the three groups considered. Additionally, we tried to evaluate the knowledge already present in the literature about putative mechanisms of action for these molecules in the onset and development of these disorders.

Age-Related Diseases and Foods Generating Chlorinative Stress.

BACKGROUND: Aging is a slow and inexorable process affecting all life beings and is characterised by age-related worsening in adaptation to external changes. Several factors contribute to such a process, and oxidative stress due to external damages is one key player. Of particular interest is the oxidative stress generated from halogen compounds such as chloride. Hypochlorus acid is produced starting from MPO's interaction with hydrogen peroxide. We focused on the oxidation of tyrosine residues by HOCl, which leads as a result to the formation of 3-chlorotyrosine (3-ClTyr). This molecule, due to its stability, is considered a marker for MPO activity. RESULTS: We collected data from literature research articles evaluating chlorinative stress and the effects of 3-ClTyr on chronic diseases linked to aging. As diseases are not the only source of 3-ClTyr in people, we also focused on other origins of chlorinative stress, such as food intake. DISCUSSION: Oxidation and halogenation are caused by infectious diseases and by pathologies characterised by inflammation. Moreover, diet could negatively or positively influence chlorinative stress. Comparing 3-ClTyr levels in the oldest and youngest old with age-related diseases and comparing data between different geographic areas with different pesticide rules could be the next challenge.

Bioactive natural products in donkey and camel milk: a perspective review.

Mammalian milk has numerous components that exhibit chemical and functional activities. They support human homeostasis. Immunoglobulins, peptides with antibacterial and antimicrobial activities, carbohydrates, lipids, and minor molecules have positive effects on health. Beyond the nutritional values of milk, milk-borne biologically active compounds such as proteins and other minor constituents exhibit essential physiological and biochemical functions. Human milk guarantees a healthy development and improves immunity. It is hypoallergenic. Sometimes, it is necessary to substitute this food with other milk for different reasons. Cow, sheep, goat, camel and donkey milk are natural alternatives. We evaluated the different compounds within donkey and camel milk analysing their biomolecular characteristics and potential benefits for human health. Camel and donkey milk bioactive products could be good candidates for controlling several diseases and excellent substitutes in the case of milk protein allergies in infants. However, more research should be conducted to further evaluate their nutraceutical potential.

Neuro-Inflammaging and Psychopathological Distress.

Inflammaging is a low degree of chronic and systemic tissue inflammation associated with aging, and is intimately linked to pro-inflammatory mediators. These substances are involved in the pathogenesis of chronic inflammatory diseases and related psychopathological symptoms. When inflammation and aging affect the brain, we use the term neuro-inflammaging. In this review, we focused on the neuro-inflammatory process typical of advanced ages and the related psychopathological symptoms, with particular attention to understanding the immune-pathogenetic mechanisms involved and the potential use of immunomodulatory drugs in the control of clinical psychological signs. Inflammation and CNS were demonstrated being intimately linked in the neuro-inflammatory loop. IL-1, IL-6, TNF-a, COX and PGE are only partially responsible. BBB permeability and the consequent oxidative stress resulting from tissue damage make the rest. Some authors elaborated the "theory of cytokine-induced depression". Inflammation has a crucial role in the onset symptoms of psychopathological diseases as it is capable of altering the metabolism of biogenic monoamines involved in their pathogenesis. In recent years, NSAIDs as an adjunct therapy in the treatment of relevant psychopathological disorders associated with chronic inflammatory conditions demonstrated their efficacy. Additionally, novel molecules have been studied, such as adalimumab, infliximab, and etanercept showing antidepressant and anxiolytic promising results. However, we are only at the beginning of a new era characterized by the use of biological drugs for the treatment of inflammatory and autoimmune diseases, and this paper aims to stimulate future studies in such a direction.

Epigenetic Crosstalk between Malignant Plasma Cells and the Tumour Microenvironment in Multiple Myeloma.

In multiple myeloma, cells of the bone marrow microenvironment have a relevant responsibility in promoting the growth, survival, and drug resistance of multiple myeloma plasma cells. In addition to the well-recognized role of genetic lesions, microenvironmental cells also present deregulated epigenetic systems. However, the effect of epigenetic changes in reshaping the tumour microenvironment is still not well identified. An assortment of epigenetic regulators, comprising histone methyltransferases, histone acetyltransferases, and lysine demethylases, are altered in bone marrow microenvironmental cells in multiple myeloma subjects participating in disease progression and prognosis. Aberrant epigenetics affect numerous processes correlated with the tumour microenvironment, such as angiogenesis, bone homeostasis, and extracellular matrix remodelling. This review focuses on the interplay between epigenetic alterations of the tumour milieu and neoplastic cells, trying to decipher the crosstalk between these cells. We also evaluate the possibility of intervening specifically in modified signalling or counterbalancing epigenetic mechanisms.

Harnessing Unconventional T Cells and Innate Lymphoid Cells to Prevent and Treat Hematological Malignancies: Prospects for New Immunotherapy.

Unconventional T cells and innate lymphoid cells (ILCs) make up a heterogeneous set of cells that characteristically show prompt responses toward specific antigens. Unconventional T cells recognize non-peptide antigens, which are bound and presented by diverse non-polymorphic antigen-presenting molecules and comprise γδ T cells, MR1-restricted mucosal-associated invariant T cells (MAITs), and natural killer T cells (NKTs). On the other hand, ILCs lack antigen-specific receptors and act as the innate counterpart to the T lymphocytes found in the adaptive immune response. The alteration of unconventional T cells and ILCs in frequency and functionality is correlated with the onset of several autoimmune diseases, allergy, inflammation, and tumor. However, depending on the physio-pathological framework, unconventional T cells may exhibit either protective or pathogenic activity in a range of neoplastic diseases. Nonetheless, experimental models and clinical studies have displayed that some unconventional T cells are potential therapeutic targets, as well as prognostic and diagnostic markers. In fact, cell-mediated immune response in tumors has become the focus in immunotherapy against neoplastic disease. This review concentrates on the present knowledge concerning the function of unconventional T cell sets in the antitumor immune response in hematological malignancies, such as acute and chronic leukemia, multiple myeloma, and lymphoproliferative disorders. Moreover, we discuss the possibility that modulating the activity of unconventional T cells could be useful in the treatment of hematological neoplasms, in the prevention of specific conditions (such as graft versus host disease), and in the formulation of an effective anticancer vaccine therapy. The exact knowledge of the role of these cells could represent the prerequisite for the creation of a new form of immunotherapy for hematological neoplasms.

Exosome-Mediated Therapeutic Strategies for Management of Solid and Hematological Malignancies.

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.

Advanced glycation end-products and advanced oxidation protein products in schizophrenia.

Schizophrenia pathophysiology is still not well understood. Genetic factors involving biochemical systems are key players and oxidative stress takes part to the development and worsening of SZ. Oxidative stress led to the permanent production of oxidation products such as advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs). These proteins interact with their receptor amplifying ROS production and pro-inflammatory cytokines sustaining a permanent loop. We tested plasma levels of AGEs and AOPPs in 30 SZ patients. Their levels were statistically higher than controls confirming their involvement in mental disorders. Antioxidant nutraceuticals and a healthy lifestyle could diminish oxidative stress and ameliorate SZ symptoms.

Modulation of Cellular Redox Parameters for Improving Therapeutic Responses in Multiple Myeloma.

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.

Specialized Intercellular Communications via Tunnelling Nanotubes in Acute and Chronic Leukemia.

Effectual cell-to-cell communication is essential to the development and differentiation of organisms, the preservation of tissue tasks, and the synchronization of their different physiological actions, but also to the proliferation and metastasis of tumor cells. Tunneling nanotubes (TNTs) are membrane-enclosed tubular connections between cells that carry a multiplicity of cellular loads, such as exosomes, non-coding RNAs, mitochondria, and proteins, and they have been identified as the main participants in healthy and tumoral cell communication. TNTs have been described in numerous tumors in in vitro, ex vivo, and in vivo models favoring the onset and progression of tumors. Tumor cells utilize TNT-like membranous channels to transfer information between themselves or with the tumoral milieu. As a result, tumor cells attain novel capabilities, such as the increased capacity of metastasis, metabolic plasticity, angiogenic aptitude, and chemoresistance, promoting tumor severity. Here, we review the morphological and operational characteristics of TNTs and their influence on hematologic malignancies' progression and resistance to therapies, focusing on acute and chronic myeloid and acute lymphoid leukemia. Finally, we examine the prospects and challenges for TNTs as a therapeutic approach for hematologic diseases by examining the development of efficient and safe drugs targeting TNTs.

IL-33 genetics and epigenetics in immune-related diseases.

Interleukin-33 (IL-33) is a 30KDa protein, which belongs to the Interleukin-1 cytokine family. It is a crucial regulator of innate and adaptive immune responses. This interleukin is additionally involved in the inflammatory reaction versus helminthic infections. Interleukin 33 acts on group 2 innate lymphoid cells and mast cells macrophages, dendritic cells and CD4 + Th2 cells eliciting a type 2 immune response. Moreover, the cytokine can activate the ST2 of Tregs, demonstrating its ability to downregulate inflammation. IL-33 has also an intracellular function by regulating transcription. The active IL-33 doesn't have a signal peptide, so it's not released across a normal secretory pathway; the interleukin is released when the cells are damages and acts like an "alarmin". Its influence on immune activation could be slightly adjusted via fine epigenetic interactions involving cascade pathways and immune genes. Due to the diverse data emerged from different experimental research, we decided span literature to clarify, as much as possible, how IL-33 is influenced by and influence gene expression. The authors reported how its balance is influenced, according to the tissue considered. Fundamental for immune-related diseases, IL-33 has a key role in controlling inflammation. The understanding of the cytokine switch will be fundamental in a near future in order to block or activate some immune pathways. In fact, we could control interleukins effects not only by monoclonal antibodies but also by using siRNA or miRNAs for silencing or expressing key genes.

Therapies with Antioxidant Potential in Psoriasis, Vitiligo, and Lichen Planus.

Oxidative stress plays an important pathogenetic role in many chronic inflammatory diseases, including those of dermatological interest. In particular, regarding psoriasis, vitiligo, and lichen planus, excess reactive oxygen species and a decline in endogenous antioxidant systems are observed. In this regard, treatments with antioxidant properties could be appropriate therapeutic options. To date, clinical trials in dermatology on these treatments are limited. We reviewed the available studies on the efficacy of antioxidant therapies in psoriasis, vitiligo, and lichen planus. The role of herbal derivatives, vitamins, and trace elements was analyzed. The antioxidant properties of conventional therapies were also evaluated. Data from the literature suggest that antioxidants might be useful, but available studies on this topic are limited, heterogeneous, not completely standardized, and on small populations. Furthermore, in most cases, antioxidants alone are unable to induce significant clinical changes, except perhaps in mild forms, and must be used in conjunction with standard drug treatments to achieve measurable results. Further studies need to be conducted, considering larger populations and using internationally validated scales, in order to compare the results and clinical efficacy.

A spotlight on lime: a review about adverse reactions and clinical manifestations due to Citrus aurantiifolia.

Lime (Citrus aurantiifolia) is a plant belonging to the family of Rutaceae and to the genus Citrus. The fruit is widely used in the United States, Mexico, Southeast Asia, Latin America, but is increasingly widespread all over the world. It is used as a fresh fruit, in the preparation of foods, sweets and drinks and its oils are used in the cosmetic and pharmaceutical industry. The main adverse reactions to lime seem to be represented by contact dermatitis, allergic and phototoxic type. In the context of allergic forms, several allergens have been identified in the citrus family, the main one being limonene, but no noteworthy cross-reactivity has been identified. However, a case of fruit protein contact dermatitis has been described, showing sensitization to other fruits, such as kiwi, avocado, pineapple and apple. There are several molecules responsible for phototoxic reactions and mainly belonging to the coumarin and furocoumarins families. Reactions related to ingesting the fruit or inhaling pollen from the tree appear to be rare, as there are no known cases reported in the literature. The increasing diffusion of lime in Europe must pay attention to possible adverse reactions due to contact with this fruit, which seem destined to increase in future years. Further importance must be placed on patch tests and on the possibility of using alternative extracts to classic fragrance mixes.

IL-31, itch and hematological malignancies.

Pruritus is one of the most common symptoms experienced by neoplastic patients. The pathogenesis of neoplastic itch is complex and multifactorial and could be due to an unbalanced production of humoral mediators by altered immune effector cells. IL-31 is a pro-inflammatory cytokine produced by CD4 + T helper cells. The aim of this review was to evaluate the role of this Th2 cytokine and its receptor IL-31RA, in the onset of neoplastic pruritus. We analysed scientific literature looking for the most relevant original articles linking IL-31to itch in oncologic diseases. Interleukin-31 seems to be a main itch mediator in several hematologic disease such as Cutaneous T cells lymphomas. In these patients IL-31 was positively linked to itch level, and IL-31 matched with disease stage. IL-31 seems to play an important role in the signalling pathway involved in pruritus, but it is also suggested to play a proinflammatory and immunomodulatory role which could play a part in the progression of the neoplastic disease. Further studies will be fundamental in facing pruritus in oncologic patients, since this problem compromise their quality of life worsening an already critic picture.

Alarmins, COVID-19 and comorbidities.

The coronavirus SARS-CoV-2, the aetiological agent of COVID-19 disease, is representing a worldwide threat for the medical community and the society at large so that it is being defined as "the twenty-first-century disease". Often associated with a severe cytokine storm, leading to more severe cases, it is mandatory to block such occurrence early in the disease course, to prevent the patients from having more severe, sometimes fatal, outcomes. In this framework, early detection of "danger signals", possibly represented by alarmins, can represent one of the most promising strategies to effectively tailor the disease and to better understand the underlying mechanisms eventually leading to death or severe consequences. In light of such considerations, the present article aims at evaluating the role of alarmins in patients affected by COVID-19 disease and the relationship of such compounds with the most commonly reported comorbidities. The conducted researches demonstrated yet poor literature on this specific topic, however preliminarily confirming a role for danger signals in the amplification of the inflammatory reaction associated with SARS-CoV-2 infection. As such, a number of chronic conditions, including metabolic syndrome, gastrointestinal and respiratory diseases, in turn, associated with higher levels of alarmins, both foster the infection and predispose to a worse prognosis. According to these preliminary data, prompt detection of high levels of alarmins in patients with COVID-19 and co-morbidities could suggest an immediate intense anti-inflammatory treatment.Key messageAlarmins have a role in the amplification of the inflammatory reaction associated with SARS-CoV-2 infectiona prompt detection of high levels of alarmins in patients with COVID-19 could suggest an immediate intense anti-inflammatory treatment.

IL-33 in Mental Disorders.

Mental disorders are common in the general population; every year about 25% of the total European population is affected by a mental condition. The prevalence of psychiatric disorders might be underestimated. Emerging evidence highlights the role of immune response as a key factor in MDs. Immunological biomarkers seem to be related to illness progression and to treatment effectiveness; several studies suggest strong associations among IL-6, TNFa, S100b, IL 1b, and PCR with affective or schizophrenic disorders. The purpose of this review is to examine and to understand the possible link between mental disorders and interleukin 33 to clarify the role of this axis in the immune system. We found 13 research papers that evaluated interleukin 33 or interleukin 31 levels in subjects affected by mental disorders. Eight studies investigated cytokines in affective disorders. Three studies measured levels of IL-33 in schizophrenia and two studies focused on patients affected by autism spectrum disorders. Alterations in brain structure and neurodevelopmental outcome are affected by multiple levels of organization. Disorders of the autoimmune response, and of the IL-33/31 axis, may therefore be one of the factors involved in this process. These results support the evidence that alarmins, particularly the IL-33/31 axis, need more consideration among researchers and practitioners.

Nutraceuticals against Oxidative Stress in Autoimmune Disorders.

Antioxidant mechanisms are constituted of enzymes, endogenous, and non-enzymatic, exogenous, which have the role of counterbalancing oxidative stress. Intake of these compounds occurs in the diet. Vegetables, plants, and fruits contain a wide range of alkaloids, polyphenols, and terpenoids which are called "phytochemicals". Most of these substances are responsible for the positive properties of fruits and vegetables, which are an essential part of a healthy life with roles in ameliorating chronic illnesses and favoring longevity. Nutraceuticals are substances contained in a food or fragment of it influencing health with positive effects on health helping in precenting or treating disorders. We conducted a review illustrating the principal applications of nutraceuticals in autoimmune disorders. Literature reported several studies about exogenous dietary antioxidant supplementation in diverse autoimmune diseases such as rheumatoid arthritis, lupus, diabetes, and multiple sclerosis. In these pathologies, promising results were obtained in some cases. Positive outcomes were generally associated with a reduction of oxidative stress parameters and a boost to antioxidant systems, and sometimes with anti-inflammatory effects. The administration of exogenous substances through food derivates or dietary supplements following scientific standardization was demonstrated to be effective. Further bias-free and extended studies should be conducted that include ever-increasing oxidative stress biomarkers.