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Topic Review
Iron Absorption and Regulation Mechanisms
Iron deficiency remains one of the main nutritional disorders worldwide and low iron intake and/or bioavailability are currently the major causes of anemia. To fight this public health problem, the scientific challenge is to find an iron form with sufficient bioavailability to increase its levels in humans through food fortification. In turn, biofortification appears as a comparatively advantageous and bearable strategy for the delivery of vitamins and other micronutrients for people without access to a healthy and diverse diet. This approach relies on plant breeding, transgenic techniques, or agronomic practices to obtain a final food product with a higher iron content. It is also known that certain food constituents are able to favor or inhibit iron absorption. The management of these compounds can thus successfully improve the absorption of dietary iron and, ultimately, contribute to fight this disorder present all over the world. This review describes the main causes/manifestations of iron-deficiency anemia, forms of disease prevention and treatment, and the importance of a balanced and preventive diet. A special focus was given to innovative food fortification and biofortification procedures used to improve the iron content in staple food crops. 
  • 615
  • 13 Nov 2021
Topic Review
DIHS/DRESS
Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe type of adverse drug eruption associated with multiorgan involvement and the reactivation of human herpesvirus 6, which arises after prolonged exposure to a limited number of drugs. Severe complications, some of which are related to cytomegalovirus reactivation, can be fatal. DIHS/DRESS is distinct from other drug reactions, as it involves herpes virus reactivation and can lead to the subsequent development of autoimmune diseases. The current consensus on the pathogenesis of DIHS/DRESS is that it occurs as a result of complex interactions between several herpesviruses and comprehensive immune responses, including drug-specific immune responses and antiviral immune responses. Although our understanding of the pathophysiology of DIHS/DRESS has evolved considerably over the last decade, the precise pathomechanisms of this complex disease remain largely unknown. This entry describes the clinical features of DIHS/DRESS, including the associated complications and sequelae.
  • 614
  • 18 May 2021
Topic Review
Mediterranean-Type Diets for Asthma and Atopy
The basis of the MedDi model is the diet of the people of the island of Crete in the early 1950s; it is characterized by a high plant/animal food ratio, and, compared with other populations, it is linked with a markedly low prevalence of chronic diseases, including cardiovascular disease (CVD), breast cancer, colorectal cancer, diabetes mellitus (DM), obesity, asthma, erectile dysfunction, depression and cognitive decline, and with a high life expectancy.
  • 614
  • 19 May 2022
Topic Review
Oncolytic Viruses and ICI
Immuno-oncology (IO) has been an active area of oncology research. Following US FDA approval of the first immune checkpoint inhibitor (ICI), ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody), in 2011, and of the first oncolytic virus, Imlygic (talimogene laherparepvec), in 2015, there has been renewed interest in IO. In the past decade, ICIs have changed the treatment paradigm for many cancers by enabling better therapeutic control, resuming immune surveillance, suppressing tumor immunosuppression, and restoring antitumor immune function. However, ICI therapies are effective only in a small subset of patients and show limited therapeutic potential due to their inability to demonstrate efficacy in "cold" or unresponsive tumor microenvironments (TMEs). Relatedly, oncolytic viruses (OVs) have been shown to induce antitumor immune responses, augment the efficacy of existing cancer treatments, and reform unresponsive TME to turn "cold" tumors "hot," increasing their susceptibility to checkpoint blockade immunotherapies. For this reason, OVs serve as ideal complements to ICIs, and multiple preclinical studies and clinical trials are demonstrating their combined therapeutic efficacy. 
  • 612
  • 26 Dec 2020
Topic Review
Role of Selenium in Viral Infections
Viral infections have afflicted human health and despite great advancements in scientific knowledge and technologies, continue to affect our society today. The current coronavirus (COVID-19) pandemic has put a spotlight on the need to review the evidence on the impact of nutritional strategies to maintain a healthy immune system, particularly in instances where there are limited therapeutic treatments. Selenium, an essential trace element in humans, has a long history of lowering the occurrence and severity of viral infections. Much of the benefits derived from selenium are due to its incorporation into selenocysteine, an important component of proteins known as selenoproteins. Viral infections are associated with an increase in reactive oxygen species and may result in oxidative stress. Studies suggest that selenium deficiency alters immune response and viral infection by increasing oxidative stress and the rate of mutations in the viral genome, leading to an increase in pathogenicity and damage to the host. 
  • 612
  • 19 Jan 2022
Topic Review
Yeast β-Glucan with Immune-Modulatory Properties
β-glucans are a large class of complex polysaccharides with bioactive properties, including immune modulation. Natural sources of these compounds include yeast, oats, barley, mushrooms, and algae. Yeast is abundant in various processes, including fermentation, and they are often discarded as waste products. The production of biomolecules from waste resources is a growing trend worldwide with novel waste resources being constantly identified. Yeast-derived β-glucans may assist the host’s defence against infections by influencing neutrophil and macrophage inflammatory and antibacterial activities. β-glucans were long regarded as an essential anti-cancer therapy and were licensed in Japan as immune-adjuvant therapy for cancer in 1980 and new mechanisms of action of these molecules are constantly emerging.
  • 612
  • 01 Jun 2022
Topic Review
Efficacy of Vaccines
Vaccination is one of the most effective medical procedures with a significant impact on quality of life. The elderly and the immune-suppressed people are at risk to develop side effects or not respond. Elderly people present an altered immune response, known as immunosenescence. Immunosenescence involves mainly the adaptive immune system, with a reduced ability to respond to new antigens, accumulation of memory T cells and the constant presence of low-grade inflammation, known as inflammaging. Many alterations of adaptive immunity system have been observed and are probably central in the development of immunosenescence and possibly in the deficient response to vaccines in the elderly population. In this review, we discuss the role of immunosenescence as the result of alterations in the function of all the branches of the human immune response, which causes a defect in the normal homeostasis of the immune system, resulting probably in a major susceptibility of infections and a poorer response to vaccinations.
  • 611
  • 27 Nov 2020
Topic Review
Vaccination under COVID-19 Pandemic
The current COVID-19 pandemic, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has raised significant economic, social, and psychological concerns. The rapid spread of the virus, coupled with the absence of vaccines and antiviral treatments for SARS-CoV-2, has galvanized a major global endeavor to develop effective vaccines. Within a matter of just a few months of the initial outbreak, research teams worldwide, adopting a range of different strategies, embarked on a quest to develop effective vaccine that could be effectively used to suppress this virulent pathogen. 
  • 611
  • 08 Feb 2021
Topic Review
Porphyromonas gingivalis during Periodontitis Pathogenesis
Periodontitis is a non-communicable chronic inflammatory disease characterized by the progressive and irreversible breakdown of the soft periodontal tissues and resorption of teeth-supporting alveolar bone. The etiology of periodontitis involves dysbiotic shifts in the diversity of microbial communities inhabiting the subgingival crevice, which is dominated by anaerobic Gram-negative bacteria, including Porphyromonas gingivalis. Indeed, P. gingivalis is a keystone pathogen with a repertoire of attributes that allow it to colonize periodontal tissues and influence the metabolism, growth rate, and virulence of other periodontal bacteria. The pathogenic potential of P. gingivalis has been traditionally analyzed using classical biochemical and molecular approaches.
  • 611
  • 31 Jan 2023
Topic Review
Inflammasomes in Teleosts
Pattern recognition receptors (PRRs) play a crucial role in inducing inflammatory responses; they recognize pathogen-associated molecular patterns, damage-associated molecular patterns, and environmental factors. 
  • 610
  • 04 Jun 2021
Topic Review
The Innate Immune System in Cardiovascular Diseases
Innate immune cells are the early responders to infection and tissue damage. They play a critical role in the initiation and resolution of inflammation in response to insult as well as tissue repair. Following ischemic or non-ischemic cardiac injury, a strong inflammatory response plays a critical role in the removal of cell debris and tissue remodeling. However, persistent inflammation could be detrimental to the heart. Studies suggest that cardiac inflammation and tissue repair needs to be tightly regulated such that the timely resolution of the inflammation may prevent adverse cardiac damage. This involves the recognition of damage; activation and release of soluble mediators such as cytokines, chemokines, and proteases; and immune cells such as monocytes, macrophages, and neutrophils. This is important in the context of doxorubicin-induced cardiotoxicity as well. Doxorubicin (Dox) is an effective chemotherapy against multiple cancers but at the cost of cardiotoxicity. The innate immune system has emerged as a contributor to exacerbate the disease.
  • 609
  • 30 Nov 2022
Topic Review
Extracellular Cystatin F and CTLs
Cystatin F is a protein inhibitor of cysteine cathepsins that is found intracellularly in the lysosomal/endosomal pathway as well as extracellularly. The extracellular cystatin F can be internalised into bystander cells and can affect cysteine cathepsin activity in recipient cells. In cytotoxic lymphocytes, extracellular cystatin F after internalisation decreases their cytotoxicity by affecting the activation of granzymes, effector molecules of the perforin/granzyme pathway.
  • 607
  • 18 Dec 2020
Topic Review
Telomerase Reverse Transcriptase in Cell Death Regulation
Telomerase is constitutively expressed in stem cells, including progenitor cells of skin, intestine and hematopoietic niches. It is temporarily induced in a number of proliferating cells, for example, in lymphocytes upon stimulation. Telomerase reverse transcriptase (TERT), a core part of telomerase, is considered as an intriguing link between multiple signaling pathways.
  • 607
  • 19 Apr 2023
Topic Review
HSP70-Mediated NLRP3 Inflammasome Suppression
Acute kidney injury (AKI) is the sudden loss of renal function, usually due to ischemia, nephrotoxic agents, or urinary tract obstructions. Although AKI is a relatively common condition, especially in hospitalized and chronically ill patients, treatments remain largely supportive, despite mortality associated with this condition being as high as 20%. Hence, there is growing interest in developing regenerative therapies for AKI that can repair renal injury as well as prevent its progression to chronic kidney disease. AKI is associated with both systemic and intrarenal inflammation, which is believed to be a key component underlying its pathophysiology. Although inflammation in the acute phase can facilitate tissue repair following injury, disruption of this process can lead to persistent inflammation, causing tissue damage and fibrosis. Many molecular mediators of inflammation have been identified in AKI, which include the NLRP3 inflammasome, toll-like receptors (TLRs), and various secreted cytokines that promote neutrophil- and monocyte-mediated inflammatory responses. Indeed, blockade of innate immune receptors seems to confer protection against AKI in several preclinical studies.   In a recent study conducted by Ullah et al., the authors demonstrated the effect of combination therapy with pulsed focused ultrasound (pFUS) and mesenchymal stem cell derived extracellular vesicles (MSC-derived EVs) in a mouse model of cisplatin-induced AKI.  Here we evaluated their ability to suppress AKI-related inflammation by downregulation of HSP70, which in turn reduced the formation of the NLRP3 inflammasome, resulting in the attenuation of the pro-inflammatory environment characteristic of AKI. The authors validated this effect using in vitro knockdown studies which also suggested that HSP70 is a positive regulator of the NLRP3 inflammasome.  
  • 606
  • 19 Jun 2020
Topic Review
Metabolic Control of Tumor Myeloid Cells
In tumors, myeloid cells, including tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), represent a predominant immune population with significant heterogeneity. 
  • 606
  • 08 Dec 2021
Topic Review
B-Cell Lymphoma
The term B-cell lymphoma encompasses different neoplasms characterised by an abnormal proliferation of lymphoid cells at various stages of differentiation. B-cell lymphoma develops more frequently in older adults and immunocompromised individuals and includes both Hodgkin’s lymphomas (HLs) and most B-cell non-Hodgkin lymphomas (B-NHLs).
  • 606
  • 01 Feb 2021
Topic Review
Vaccines in Ovarian Cancer
Ovarian cancer remains the deadliest of all gynecologic malignancies. Our expanding knowledge of ovarian cancer immunology has allowed the development of therapies that generate systemic anti-tumor immune responses. Current immunotherapeutic strategies include immune checkpoint blockade, cellular therapies, and cancer vaccines. Vaccine-based therapies are designed to induce both adaptive and innate immune responses directed against ovarian cancer associated antigens. Tumor-specific effector cells, in particular cytotoxic T cells, are activated to recognize and eliminate ovarian cancer cells. Vaccines for ovarian cancer have been studied in various clinical trials over the last three decades. Despite evidence of vaccine-induced humoral and cellular immune responses, the majority of vaccines have not shown significant anti-tumor efficacy. Recently, improved vaccine development using dendritic cells or synthetic platforms for antigen presentation have shown promising clinical benefits in patients with ovarian cancer. 
  • 605
  • 06 Aug 2021
Topic Review
Bispecific Antibodies for IFN-β Delivery to ErbB2+ Tumors
The main aim of this work was to create a full-length bispecific antibody (BsAb) as a vehicle for the targeted delivery of interferon-beta (IFN-β) to ErbB2+ tumor cells in the form of non-covalent complex of BsAb and IFN-β. Such a construct is a CrossMab-type BsAb, consisting of an ErbB2-recognizing trastuzumab moiety, a part of chimeric antibody to IFN-β, and human IgG1 Fc domain carrying knob-into-hole amino acid substitutions necessary for the proper assembly of bispecific molecules. The IFN-β- recognizing arm of BsAb not only forms a complex with the cytokine but neutralizes its activity, thus providing a mechanism to avoid the side effects of the systemic action of IFN-β by blocking IFN-β Interaction with cell receptors in the process of cytokine delivery to tumor sites. Enzyme sandwich immunoassay confirmed the ability of BsAb to bind to human IFN-β comparable to that of the parental chimeric mAb.
  • 603
  • 29 Mar 2022
Topic Review
Antiphospholipid Syndrome
Antiphospholipid Syndrome (APS) is an autoimmune disease characterized by arterial and/or venous thrombosis and/or pregnancy morbidity, associated with circulating antiphospholipid antibodies (aPL). 
  • 602
  • 23 Nov 2020
Topic Review
Nutritional Factors in RA
Rheumatoid arthritis (RA) is the most prevalent systemic autoimmune inflammatory disease affecting approximately 1% of the adult population worldwide.
  • 602
  • 29 Apr 2021
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