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Increasing evidence suggests an association between atopic dermatitis, the most chronic inflammatory disease of the skin, and autism spectrum disorders, which are a group of neurodevelopmental diseases. Inflammation and immune dysregulation associated with genetic and environmental factors seem to characterize the pathophysiological mechanisms of both conditions. We conducted a literature review of the PubMed database aimed at identifying the clinical features and alleged risk factors that could be used in clinical practice to predict the onset of ASD and/or AD or worsen their prognosis in the context of comorbidities.

Vitamin C is a water-soluble vitamin introduced through the diet with anti-inflammatory, immunoregulatory, and antioxidant activities. Today, this vitamin is integrated into the treatment of many inflammatory pathologies. However, there is increasing evidence of possible use in treating autoimmune and neoplastic diseases. We reviewed the literature to delve deeper into the rationale for using vitamin C in treating this type of pathology. There is much evidence in the literature regarding the beneficial effects of vitamin C supplementation for treating autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA) and neoplasms, particularly hematological neoplastic diseases. Vitamin C integration regulates the cytokines microenvironment, modulates immune response to autoantigens and cancer cells, and regulates oxidative stress. Moreover, integration therapy has an enhanced effect on chemotherapies, ionizing radiation, and target therapy used in treating hematological neoplasm. In the future, integrative therapy will have an increasingly important role in preventing pathologies and as an adjuvant to standard treatments.

Lung cancer (LC) is one of the most prevalent cancers in both men and women and today is still characterized by high mortality and lethality. Several biomarkers have been identified for evaluating the prognosis of non-small cell lung cancer (NSCLC) patients and selecting the most effective therapeutic strategy for these patients. The introduction of innovative targeted therapies and immunotherapy with immune checkpoint inhibitors (ICIs) for the treatment of NSCLC both in advanced stages and, more recently, also in early stages, has revolutionized and significantly improved the therapeutic scenario for these patients. Promising evidence has also been shown by analyzing both micro-RNAs (miRNAs) and the lung/gut microbiota. MiRNAs belong to the large family of non-coding RNAs and play a role in the modulation of several key mechanisms in cells such as proliferation, differentiation, inflammation, and apoptosis. On the other hand, the microbiota (a group of several microorganisms found in human orgasms such as the gut and lungs and mainly composed by bacteria) plays a key role in the modulation of inflammation and, in particular, in the immune response. Some data have shown that the microbiota and the related microbiome can modulate miRNAs expression and vice versa by regulating several intracellular signaling pathways that are known to play a role in the pathogenesis of lung cancer. This evidence suggests that this axis is key to predicting the prognosis and effectiveness of ICIs in NSCLC treatment and could represent a new target in the treatment of NSCLC. In this review, we highlight the most recent evidence and data regarding the role of both miRNAs and the lung/gut microbiome in the prediction of prognosis and response to ICI treatment, focusing on the link between miRNAs and the microbiome. A new potential interaction based on the underlying modulated intracellular signaling pathways is also shown.

Immunosenescence is a complex multifactorial phenomenon consisting of wide-ranging remodeling of the immune system during the life span, resulting in an age-related qualitative-quantitative decline of immune cells and cytokines. A growing body of evidence in the international literature is highlighting the etiopathogenetic role of skin immunosenescence in the onset of various dermatologic conditions. Skin immunosenescence also serves as an interesting watershed for the onset of system-wide conditions in the context of allergic inflammation. Moreover, in recent years, an increasingly emerging and fascinating etiopathogenetic parallelism has been observed between some mechanisms of immunosenescence, both at cutaneous and systemic sites. This would help to explain the occurrence of apparently unconnected comorbidities. Throughout our review, we aim to shed light on emerging immunosenescent mechanisms shared between dermatologic disorders and other organ-specific diseases in the context of a more extensive discussion on the etiopathogenetic role of skin immunosenescence. A promising future perspective would be to focus on better understanding the mutual influence between skin and host immunity, as well as the influence of high inter-individual variability on immunosenescence/inflammaging. This can lead to a more comprehensive "immunobiographic" definition of each individual., Competing Interests: The authors declare no conflict of interest.

Cardiac amyloidosis is an uncommon restrictive cardiomyopathy featuring an unregulated amyloid protein deposition that impairs organic function. Early cardiac amyloidosis diagnosis is generally delayed by indistinguishable clinical findings of more frequent hypertrophic diseases. Furthermore, amyloidosis is divided into various groups, according to a generally accepted taxonomy, based on the proteins that make up the amyloid deposits; a careful differentiation between the various forms of amyloidosis is necessary to undertake an adequate therapeutic treatment. Thus, cardiac amyloidosis is thought to be underdiagnosed, which delays necessary therapeutic procedures, diminishing quality of life and impairing clinical prognosis. The diagnostic work-up for cardiac amyloidosis begins with the identification of clinical features, electrocardiographic and imaging findings suggestive or compatible with cardiac amyloidosis, and often requires the histological demonstration of amyloid deposition. One approach to overcome the difficulty of an early diagnosis is the use of automated diagnostic algorithms. Machine learning enables the automatic extraction of salient information from "raw data" without the need for pre-processing methods based on the a priori knowledge of the human operator. This review attempts to assess the various diagnostic approaches and artificial intelligence computational techniques in the detection of cardiac amyloidosis.

Primary and secondary immunodeficiencies cause an alteration in the immune response which can increase the rate of infectious diseases and worsened prognoses. They can also alter the immune response, thus, making the infection even worse. Curcumin is the most biologically active component of the turmeric root and appears to be an antimicrobial agent. Curcumin cooperates with various cells such as macrophages, dendritic cells, B, T, and natural killer cells to modify the body's defence capacity. Curcumin also inhibits inflammatory responses by suppressing different metabolic pathways, reduces the production of inflammatory cytokines, and increases the expression of anti-inflammatory cytokines. Curcumin may also affect oxidative stress and the non-coding genetic material. This review analyses the relationships between immunodeficiency and the onset of infectious diseases and discusses the effects of curcumin and its derivatives on the immune response. In addition, we analyse some of the preclinical and clinical studies that support its possible use in prophylaxis or in the treatment of infectious diseases. Lastly, we examine how nanotechnologies can enhance the clinical use of curcumin.

High-mobility Group Box 1 (HMGB1) is a nuclear protein that plays a key role in acute and chronic inflammation. It has already been studied in several diseases, among them melanoma. Indeed, HMGB1 is closely associated with cell survival and proliferation and may be directly involved in tumor cell metastasis development thanks to its ability to promote cell migration. This research aims to assess the role of this molecule in the pathogenesis of human melanoma and its potential therapeutic role. The research has been conducted on the PubMed database, and the resulting articles are sorted by year of publication, showing an increasing interest in the last five years. The results showed that HMGB1 plays a crucial role in the pathogenesis of skin cancer, prognosis, and therapeutical response to therapy. Traditional therapies target this molecule indirectly, but future perspectives could include the development of new target therapy against HMGB1, thus adding a new approach to the therapy, which has often shown primary and secondary resistance. This could add a new therapy arm which has to be prolonged and specific for each patient.

Acne Vulgaris (AV) and Hidradenitis suppurativa (HS) are common chronic inflammatory skin conditions that affect the follicular units that often coexist or are involved in differential diagnoses. Inflammation in both these diseases may result from shared pathways, which may partially explain their frequent coexistence. MicroRNAs (miRNAs) are a class of endogenous, short, non-protein coding, gene-silencing or promoting RNAs that may promote various inflammatory diseases. This narrative review investigates the current knowledge regarding miRNAs and their link to AV and HS. The aim is to examine the role of these molecules in the pathogenesis of AV and HS and to identify possible common miRNAs that could explain the similar characteristics of these two diseases. Five miRNA (miR-155 miR-223-, miR-21, and miRNA-146a) levels were found to be altered in both HS and AV. These miRNAs are related to pathogenetic aspects common to both pathologies, such as the regulation of the innate immune response, regulation of the Th1/Th17 axis, and fibrosis processes that induce scar formation. This review provides a starting point for further studies aimed at investigating the role of miRNAs in AV and HS for their possible use as diagnostic-therapeutic targets.

Vitamin D (VD) is essential for bone homeostasis, but it is also involved in pleiotropic effects on various organs and tissues. In adults, VD deficiency can cause or exacerbate osteoporosis and induce osteomalacia. However, every tissue and cell in the body has a VD receptor, including the brain, heart, stomach, pancreas, skin, gonads, and immune cells, and a deficiency may modify the function of these organs. Thus, the wide-ranging actions of VD help to explain why a reduction in VD amount has been correlated with numerous chronic diseases. In fact, VD deficiency increases the risk of osteoporosis and several other diseases and complications characterized by impaired bone metabolisms, such as autoimmune diseases, inflammatory bowel diseases, allergy, endocrinological diseases, hematological malignancies, and bone marrow transplantation. This review aims to investigate the link between VD deficiency, osteoporosis, and its concomitant diseases. Further epidemiological and mechanistic studies are necessary in order to ascertain the real role of hypovitaminosis in causing the reported diseases; however, adequate vitamin supplementation and restoration of metabolic normality could be useful for better management of these pathologies.

Vitamin D is a steroid hormone that is essential for bone mineral metabolism and it has several other effects in the body, including anti-cancer actions. Vitamin D causes a reduction in cell growth by interrupting the cell cycle. Moreover, the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, exerts various effects via its interaction with the vitamin D receptor on the innate and adaptive immune system, which could be relevant in the onset of tumors. Multiple myeloma is a treatable but incurable malignancy characterized by the growth of clonal plasma cells in protective niches in the bone marrow. In patients affected by multiple myeloma, vitamin D deficiency is commonly correlated with an advanced stage of the disease, greater risk of progression, the development of pathological fractures, and a worse prognosis. Changes in the vitamin D receptor often contribute to the occurrence and progress of deficiencies, which can be overcome by supplementation with vitamin D or analogues. However, in spite of the findings available in the literature, there is no clear standard of care and clinical practice varies. Further research is needed to better understand how vitamin D influences outcomes in patients with monoclonal gammopathies.

Hundreds of trillions of bacteria are present in the human body in a mutually beneficial symbiotic relationship with the host. A stable dynamic equilibrium exists in healthy individuals between the microbiota, host organism, and environment. Imbalances of the intestinal microbiota contribute to the determinism of various diseases. Recent research suggests that the microbiota is also involved in the regulation of the bone metabolism, and its alteration may induce osteoporosis. Due to modern molecular biotechnology, various mechanisms regulating the relationship between bone and microbiota are emerging. Understanding the role of microbiota imbalances in the development of osteoporosis is essential for the development of potential osteoporosis prevention and treatment strategies through microbiota targeting. A relevant complementary mechanism could be also constituted by the permanent relationships occurring between microbiota and microRNAs (miRNAs). miRNAs are a set of small non-coding RNAs able to regulate gene expression. In this review, we recapitulate the physiological and pathological meanings of the microbiota on osteoporosis onset by governing miRNA production. An improved comprehension of the relations between microbiota and miRNAs could furnish novel markers for the identification and monitoring of osteoporosis, and this appears to be an encouraging method for antagomir-guided tactics as therapeutic agents.

Autism spectrum disorders (ASDs) constitute a set of heterogeneous neurodevelopmental conditions, characterized by a wide genetic variability that has led to hypothesize a polygenic origin. The metabolic profiles of patients with ASD suggest a possible implication of mitochondrial pathways. Although different physiological and biochemical studies reported deficits in mitochondrial oxidative phosphorylation in subjects with ASD, the role of mitochondrial DNA variations has remained relatively unexplored. In this review, we report and discuss very recent evidence to demonstrate the key role of mitochondrial disorders in the development of ASD.

Systemic sclerosis (SSc) is a rare chronic autoimmune disease associated with significant morbidity and mortality. Two main subsets of SSc are recognized: (i) diffuse cutaneous SSc with rapidly progressive fibrosis of the skin, lungs, and other internal organs; and (ii) limited cutaneous SSc, which is dominated by vascular manifestations, with skin and organ fibrosis generally limited and slowly progressing. In spite of intense investigation, both etiology and pathogenesis of SSc are still unknown. Genetic and environmental factors, as well as abnormalities of immune functions, are strongly suggested for etiology, while microvascular abnormalities, immune system activation, and oxidative stress are suggested for the pathogenesis. Recently, it has been found that a multitude of mediators and cytokines are implicated in the fibrotic processes observed in SSc. Among these, a central role could be exerted by "alarmins", endogenous and constitutively expressed proteins/peptides that function as an intercellular signal defense. This review describes, in a detailed manner, the role of alarmins in the pathogenesis of scleroderma.

Interleukin (IL)-33 is a chromatin-related nuclear interleukin that is a component of IL-1 family. IL-33 production augments the course of inflammation after cell damage or death. It is discharged into the extracellular space. IL-33 is regarded as an "alarmin" able to stimulate several effectors of the immune system, regulating numerous immune responses comprising cancer immune reactions. IL-33 has been demonstrated to influence tumorigenesis. However, as far as this cytokine is concerned, we are faced with what has sometimes been defined as the IL-33 paradox. Several studies have demonstrated a relevant role of IL-33 to numerous malignancies, where it may have pro- and-less frequently-antitumorigenic actions. In the field of hematological malignancies, the role of IL-33 seems even more complex. Although we can affirm the existence of a negative role of IL-33 in Chronic myelogenos leukemia (CML) and in lymphoproliferative diseases and a positive role in pathologies such as Acute myeloid leukemia (AML), the action of IL-33 seems to be multiple and sometimes contradictory within the same pathology. In the future, we will have to learn to govern the negative aspects of activating the IL-33/ST2 axis and exploit the positive ones.