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Topic Review
Mechano-Immunomodulation in Space
The gravity environment in space is termed “microgravity” (μG) and is defined as approximately 10−6 of Earth’s surface gravity (G), as there is never truly a complete absence of gravity. The effects of μG on various cell types have been documented in bone, cartilage, and endothelial cells, to name a few, and immune cells are no exception. Among the various microgravity-induced side effects, a compromised or altered immune response can have serious consequences and jeopardize the survival of humans in space.
  • 992
  • 28 Oct 2021
Topic Review
Psoriasis and Its Clinical Implications
Psoriasis is the result of uncontrolled keratinocyte proliferation, and its pathogenesis involves the dysregulation of the immune system. The interplay among cytokines released by dendritic, Th1, Th2, and Th17 cells leads to the phenotypical manifestations seen in psoriasis. Biological therapies target the cytokine-mediated pathogenesis of psoriasis and have improved patient quality of life.
  • 990
  • 05 May 2022
Topic Review
Acute-on-Chronic Liver Failure
Acute-on-chronic liver failure (ACLF) is a complex syndrome that develops in patients with cirrhosis and is characterized by acute decompensation, organ failure(s) and high short-term mortality. ACLF frequently occurs in close temporal relationship to a precipitating event, such as acute alcoholic, drug-induced or viral hepatitis or bacterial infection and, in cases without precipitating events, probably related to intestinal translocation of bacterial products. Dysbalanced immune function is central to its pathogenesis and outcome with an initial excessive systemic inflammatory response that drives organ failure and mortality. This hyperinflammatory state ultimately impairs the host defensive mechanisms of immune cells, rendering ACLF patients immunocompromised and more vulnerable to secondary infections, and therefore to higher organ dysfunction and mortality. (Draft for you)
  • 989
  • 24 Dec 2020
Topic Review
Immunotherapy with Checkpoint-Inhibitors for HCC
Immune checkpoint inhibitors (ICIs) are beginning to show promise in the clinical management of hepatocellular carcinoma (HCC). Most recently, the anti-programmed death protein-1 (PD-1) agent atezolizumab combined with bevacizumab demonstrated superiority to sorafenib in a Phase 3 randomised clinical trial in the frontline setting. Other ongoing trials of immunotherapy for HCC are exploring different drug combinations, such as a double checkpoint blockade with PD-1 and anti-Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) agents or with tyrosine kinase inhibitors. Moreover, ICIs are being tested in the adjuvant and neoadjuvant settings trying to resolve long-time unmet needs in HCC. The results of the ongoing trials will be critical to understanding the extent of the therapeutic role of ICIs in the complex and multifaceted clinical scenario of HCC. Still, there are some critical points which need further attention to clarify the best use of ICIs in HCC patients. For instance, the actual eligibility rate of patients in the real-life scenario, the prompt identification and correct management of immune-mediated adverse events, the identification of biomarkers predicting response or resistance, and strategies to prevent the tumour escape from ICI effect.  Deatail review paper about the current therapeutic scenario of immune checkpoint inhibitors (in particular nivolumab, ipilimumab, atezolizumab, pembrolizumab, durvalumab) for the treatment of hepatocellular carcinoma. The first part of this review is dedicated to the concluded and ongoing clinical trials. The second part deals with the hot topics in the field of immunotherapy borrowing concepts from other cancers and adapting them to the specific scenario of hepatocellular carcinoma.
  • 987
  • 25 Oct 2020
Topic Review
Tumor Immune Microenvironment in ccRCC
Clear cell renal cell carcinoma (ccRCC) is a type of kidney cancer that arises from the cells lining the tubes of the kidney. The tumor immune microenvironment (TIME) of ccRCC is a complex interplay of various immune cells, cytokines, and signaling pathways. One of the critical features of the ccRCC TIME is the presence of infiltrating immune cells, including T cells, B cells, natural killer cells, dendritic cells, and myeloid-derived suppressor cells. The complex interplay between the immune system and the tumor in ccRCC has important implications for developing new treatment strategies. Immunotherapy, which aims to activate the immune system to recognize and eliminate tumor cells, has shown promise in the treatment of ccRCC, and several immune-based therapies have been approved for clinical use.
  • 987
  • 08 May 2023
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.
  • 986
  • 18 Dec 2020
Topic Review
Liver-Associated Injuries in COVID-19 Patients
The global outbreak of COVID-19 possesses serious challenges and adverse impacts for patients with progression of chronic liver disease and has become a major threat to public health. COVID-19 patients have a high risk of lung injury and multiorgan dysfunction that remains a major challenge to hepatology. COVID-19 patients and those with liver injury exhibit clinical manifestations, including elevation in ALT, AST, GGT, bilirubin, TNF-α, and IL-6 and reduction in the levels of CD4 and CD8. Liver injury in COVID-19 patients is induced through multiple factors, including a direct attack of SARS-CoV-2 on liver hepatocytes, hypoxia reperfusion dysfunction, cytokine release syndrome, drug-induced hepatotoxicity caused by lopinavir and ritonavir, immune-mediated inflammation, renin-angiotensin system, and coagulopathy. Cellular and molecular mechanisms underlying liver dysfunction are not fully understood in severe COVID-19 attacks. High mortality and the development of chronic liver diseases such as cirrhosis, alcoholic liver disease, autoimmune hepatitis, nonalcoholic fatty liver disease, and hepatocellular carcinoma are also associated with patients with liver damage. COVID-19 patients with preexisting or developing liver disease should be managed. They often need hospitalization and medication, especially in conjunction with liver transplants. 
  • 986
  • 13 Jan 2023
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). 
  • 985
  • 23 Nov 2020
Topic Review
Innate Immune Receptor Stimulation
Immunometabolism is a relatively new field of research that aims at understanding interconnections between the immune system and cellular metabolism. This is now well-documented for innate immune cells of the myeloid lineage such as macrophages and myeloid dendritic cells (DCs) when they engage their differentiation or activation programs. Several studies have shown that stimulation of DCs or macrophages by the binding of pathogen-associated molecular patterns (PAMPs) to pattern recognition receptors (PRRs) leads to increased glycolytic activity and rewiring of central carbon metabolism. These metabolic modulations are essential to support and settle immunological functions by providing energy and immunoregulatory metabolites. As the understanding of molecular mechanisms progressed, significant differences between cell types and species have also been discovered. Pathways leading to the regulation of central carbon metabolism in macrophages and DCs by PRR signaling and consequences on cellular functions are reviewed here.
  • 982
  • 08 Feb 2021
Topic Review
Liver Resident Memory T Cells
Immunological memory is fundamental to maintain immunity against re-invading pathogens. It is the basis for prolonged protection induced by vaccines and can be mediated by humoral or cellular responses - the latter largely mediated by T cells. Memory T cells belong to different subsets with specialized functions and distributions within the body. They can be broadly separated into circulating memory cells, which pace the entire body through the lymphatics and blood, and tissue-resident memory T (TRM) cells, which are constrained to peripheral tissues. Retained in the tissues where they form, TRM cells provide a frontline defense against reinfection. Here, we review this population of cells with specific attention to the liver, where TRM cells have been found to protect against infections, in particular those by Plasmodium species that cause malaria.
  • 982
  • 13 Dec 2020
Topic Review
Immunomodulatory Properties of Bioactive Products
Bioactive products have an effect on the molecular and biochemical functions of a living organism, causing a physiological response of the given tissue. Such a products are biologically active. Depending on the active component and amount, the effects of such products can be positive or negative. Bioactive products can be food ingredients or dietary supplements, and while they are not required for survival, they are responsible for changes in the body’s health.
  • 980
  • 24 Mar 2022
Topic Review
Autoimmune and Autoinflammatory Diseases in Chronic Urticaria
Chronic spontaneous urticaria (CSU) is defined as the almost daily occurrence of widespread wheals, angioedema, or both, for more than 6 weeks. It affects 1–2% of the general population, with a higher prevalence in female patients, and is more frequent patients over 20 years of age. More than half of all cases of chronic idiopathic urticaria are thought to occur due to an autoimmune mechanism, specifically the production of autoantibodies against the high-affinity immunoglobulin E (IgE) receptor (FcεRI). The quality of life in these patients is often greatly compromised, also due to the onset of comorbidities represented by other autoimmune diseases, such as thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, celiac disease, and type 1 diabetes, among others.
  • 980
  • 10 Feb 2023
Topic Review
Natural Killer Cells and Radiotherapy
Natural Killer (NK) cells are innate immune cells with the unique ability to recognize and kill virus-infected and cancer cells without prior immune sensitization. Radiotherapy is an anti-cancer strategy based on the administration of ionizing radiation, which induces DNA damage and cell death, and that is currently included in more than 50% of all anti-cancer treatments. Radiotherapy was found to directly impair NK cell viability and activity in a dose-dependent manner while modulating tumor cell sensitivity to NK cell-mediated cytotoxicity and the TME, potentially both promoting and impairing NK cell function, depending on dose and tumor heterogeneity, suggesting that combining radiotherapy with strategies to maintain NK cell viability and activity could be beneficial.
  • 978
  • 10 Mar 2021
Topic Review
Regulatory T Cell-Derived Extracellular Vesicles in Human Diseases
Regulatory T (Treg) cells play crucial roles in maintaining immune self-tolerance and immune homeostasis, and closely associated with many human diseases. Treg cells-derived extracellular vesicles (Treg-EVs) have been demonstrated as a novel cell-contact independent inhibitory mechanism of Treg cells. Treg-EVs contain many specific biological molecules, which are delivered to target cells and modulate immune responses by inhibiting T cell proliferation, inducing T cell apoptosis, and changing the cytokine expression profiles of target cells. The abnormal quantity or function of Treg-EVs is associated with several types of human diseases or conditions, such as transplant rejection, inflammatory diseases, autoimmune diseases, and cancers. Treg-EVs are promising novel potential targets for disease diagnosis, therapy, and drug transport. Moreover, Treg-EVs possess distinct advantages over Treg cell-based immunotherapies. 
  • 976
  • 29 Nov 2022
Topic Review
SARS-CoV-2 Dysregulates Neutrophil Degranulation and Reduces Lymphocyte Counts
SARS-CoV-2, the virus that causes COVID-19, has given rise to one of the largest pandemics, affecting millions worldwide. High neutrophil-to-lymphocyte ratios have been identified as an important correlate to poor recovery rates in severe COVID-19 patients. However, the mechanisms underlying this clinical outcome and the reasons for its correlation to poor prognosis are unclear. Furthermore, the mechanisms involved in healthy neutrophils acquiring a SARS-CoV-2-mediated detrimental role are yet to be fully understood. 
  • 975
  • 14 Mar 2022
Topic Review
Epithelial-Mesenchymal Transition Phenotype and Immune System
Carcinoma cells that undergo an epithelial-mesenchymal transition (EMT) and display a predominantly mesenchymal phenotype (hereafter EMT tumor cells) are associated with immune exclusion and immune deviation in the tumor microenvironment (TME). A large body of evidence has shown that EMT tumor cells and immune cells can reciprocally influence each other, with EMT cells promoting immune exclusion and deviation and immune cells promoting, under certain circumstances, the induction of EMT in tumor cells. This cross-talk between EMT tumor cells and immune cells can occur both between EMT tumor cells and cells of either the native or adaptive immune system.
  • 974
  • 22 Apr 2022
Topic Review
Mast Cells in Unconventional Immunotherapy
Mast cells are long-lived, granular, myeloid-derived leukocytes that have significant protective and repair functions in tissues. Mast cells sense disruptions in the local microenvironment and are first responders to physical, chemical and biological insults. When activated, mast cells release growth factors, proteases, chemotactic proteins and cytokines thereby mobilizing and amplifying the reactions of the innate and adaptive immune system. Mast cells are therefore significant regulators of homeostatic functions and may be essential in microenvironmental changes during pathogen invasion and disease. During infection by helminths, bacteria and viruses, mast cells release antimicrobial factors to facilitate pathogen expulsion and eradication. Mast cell-derived proteases and growth factors protect tissues from insect/snake bites and exposure to ultraviolet radiation. Finally, mast cells release mediators that promote wound healing in the inflammatory, proliferative and remodelling stages. Since mast cells have such a powerful repertoire of functions, targeting mast cells may be an effective new strategy for immunotherapy of disease and design of novel vaccine adjuvants.
  • 973
  • 22 Apr 2021
Topic Review
IgG N-glycan Signatures as Diagnostic and Prognostic Biomarkers
IgG N-glycans are an emerging source of disease-specific biomarkers. The continued development of glycomic databases and the evolution of glyco-analytic methods have resulted in increased throughput, resolution, and sensitivity. IgG N-glycans promote adaptive immune responses through antibody-dependent cellular cytotoxicity (ADCC) and complement activation to combat infection or cancer and promote autoimmunity. In addition to the functional assays, researchers are examining the ability of protein-specific glycosylation to serve as biomarkers of disease. 
  • 973
  • 28 Mar 2023
Topic Review
Renal Cell Carcinoma
Renal cell carcinoma (RCC) is a malignant tumor associated with various tumor microenvironments (TMEs).
  • 971
  • 22 Sep 2021
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.
  • 970
  • 29 Apr 2021
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