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Topic Review
HIV Lifecycle
The theory of immune regulation involves a homeostatic balance between T-helper 1 (Th1) and T-helper 2 (Th2) responses. The Th1 and Th2 theories were introduced in 1986 as a result of studies in mice, whereby T-helper cell subsets were found to direct different immune response pathways. Subsequently, this hypothesis was extended to human immunity, with Th1 cells mediating cellular immunity to fight intracellular pathogens, while Th2 cells mediated humoral immunity to fight extracellular pathogens. Several disease conditions were later found to tilt the balance between Th1 and Th2 immune response pathways, including HIV infection, but the exact mechanism for the shift from Th1 to Th2 cells was poorly understood. 
  • 852
  • 22 Jan 2024
Topic Review
Mechanisms of Immunotoxicity
The immune system orchestrates the body’s main defense against invading biologic agents including but not limited to bacteria, viruses, chemicals, and foreign tissues. Lymphocytes, neutrophils, macrophages, eosinophils, and basophils are the main players. These cells are produced at an increased rate during childhood, where such a blood draw in a child would reveal an average number of 3000/mm3 compared to 4500–11,000/mm3 in adults, and the development of the human immune system begins in the fetal period and reaches its maximum capacity around puberty.
  • 851
  • 04 Aug 2021
Topic Review
Protein Tyrosine Phosphatase Non-Receptor 2 in the Immunity
PTPN2 (protein tyrosine phosphatase non-receptor 2), also called TCPTP (T cell protein tyrosine phosphatase), is a member of the PTP family signaling proteins. Phosphotyrosine-based signaling of this non-transmembrane protein is essential for regulating cell growth, development, differentiation, survival, and migration. 
  • 849
  • 08 Sep 2022
Topic Review
Trypanosoma cruzi Infection; liver involvement
Currently, in Chagas disease, hepatomegaly is cited in most papers published which either study acutely infected patients or experimental models, and we know that the Trypanosoma cruzi can infect multiple cell types in the liver, especially Kupffer cells and dendritic cells. Moreover, liver damage is more pronounced in cases of oral infection, which is mainly found in the Amazon region. However, the importance of liver involvement, including the hepatic immune response, in disease progression does not receive much attention.
  • 843
  • 03 Sep 2021
Topic Review
Glucocorticoid Receptor Activity
Glucocorticoids (GCs) represent a well-known class of lipophilic steroid hormones biosynthesised, with a circadian rhythm, by the adrenal glands in humans and by the inter-renal tissue in teleost fish (e.g., zebrafish).
  • 843
  • 23 Dec 2021
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.  
  • 842
  • 19 Jun 2020
Topic Review
Immunomodulatory Activity of Antimicrobial Peptides
Antimicrobial peptides (AMPs) in humans are represented by three main families: defensins, cathelicidins, histatins. Defensins, depending on the type of disulfide bond arrangement, are divided into alpha- and beta-defensins. Alpha- and beta-defensins are constitutively produced by neutrophils, lymphocytes, and epithelial cells of the skin and mucous membranes.
  • 842
  • 18 Mar 2022
Topic Review
Glucocorticoid Receptor and Its Importance in (Patho)physiology
The glucocorticoid receptor (GR) is a very versatile protein that comes in several forms, interacts with many proteins and has multiple functions. Numerous therapies are based on GRs’ actions but the occurrence of side effects and reduced responses to glucocorticoids have motivated scientists to study GRs in great detail. The notion that GRs can perform functions as a monomeric protein, but also as a homodimer has raised questions about the underlying mechanisms, structural aspects of dimerization, influencing factors and biological functions
  • 842
  • 15 Mar 2022
Topic Review
From Stem Cells to Immune Cells Populations
Although stem cells have been considered promising for the treatment of degenerative diseases by ‘seeding’ them into damaged tissues, it has recently been observed that the regenerative capacity of stem cells is influenced and regulated by the local immune response and in particular by macrophages, which constitute a central component of the damage response and are the coordinators of tissue repair and regeneration. Among the panoply of immune cells involved in the response to both acute and chronic wounds, recent discoveries have highlighted novel and often unexpected roles for certain types of immune cells in promoting a permissive local environment for effective cell replacement and restoration of tissue integrity. Some studies have shown that the control of inflammation is crucial in regenerative therapies: To be effective, regenerative therapies must block and control inflammation to allow tissue regeneration by resident stem cells. Indeed, the presence of inflammation inhibits the regenerative action of tissue-resident mesenchymal stem cells (MSCs). Recent papers suggest that an innovative regenerative strategy could be to polarize macrophages from the M1 inflammatory state to the M2 anti-inflammatory state utilizing immune cells. These reviews conclude that next-generation regenerative therapies need an immune-centric approach instead of the use of stem cells. Thus, depending on the tissue or organ targeted, regenerative strategies could be developed to stimulate macrophage polarization or to recruit subpopulations of pro-healing macrophages. Already, it has been observed  that the regeneration of myocardial tissue after ischemia was induced by macrophages that regulate resident stem cells and promote regeneration, suggesting that targeting macrophages could be a new strategy to improve infarct healing and repair. The regenerative and stem-cell-controlling capacity of macrophages has also recently been demonstrated in bone tissue: mesenchymal stem cells act through a paracrine and immune-modulatory and non-differentiative mechanism and the microenvironment and immune system regulate the activity of MSCs regardless of the tissue from which they originate. Based on the role played by several types of macrophages and lymphocytes in the wound-healing response, it is tempting to hypothesize that interventions that reduce the M1 macrophage phenotype and promote M2 may represent a new therapy to induce tissue regeneration.
  • 841
  • 28 Feb 2022
Topic Review
Respiratory Viral Infection and Epithelial Immunity in Asthma
Viral respiratory tract infections are associated with asthma development and exacerbation in children and adults. In the course of immune responses to viruses, airway epithelial cells are the initial platform of innate immunity against viral invasion. Patients with severe asthma are more vulnerable than those with mild to moderate asthma to viral infections.
  • 841
  • 10 Oct 2022
Topic Review
Innate Immunity and COVID-19 Vaccines
The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to almost seven million deaths worldwide. SARS-CoV-2 causes infection through respiratory transmission and can occur either without any symptoms or with clinical manifestations which can be mild, severe or, in some cases, even fatal. Innate immunity provides the initial defense against the virus by sensing pathogen-associated molecular patterns and triggering signaling pathways that activate the antiviral and inflammatory responses, which limit viral replication and help the identification and removal of infected cells. 
  • 840
  • 23 Feb 2024
Topic Review
Peripheral Blood-Based Biomarkers
As cancer immunotherapy using immune checkpoint inhibitors (ICIs) is rapidly evolving in clinical practice, it is necessary to identify biomarkers that will allow the selection of cancer patients who will benefit most or least from ICIs and to longitudinally monitor patients’ immune responses during treatment. Various peripheral blood-based immune biomarkers are being identified with recent advances in high-throughput multiplexed analytical technologies. The identification of these biomarkers, which can be easily detected in blood samples using non-invasive and repeatable methods, will contribute to overcoming the limitations of previously used tissue-based biomarkers. Here, we discuss the potential of circulating immune cells, soluble immune and inflammatory molecules, circulating tumor cells and DNA, exosomes, and the blood-based tumor mutational burden, as biomarkers for the prediction of immune responses and clinical benefit from ICI treatment in patients with advanced cancer. 
  • 839
  • 29 Mar 2022
Topic Review
Zoonotic Visceral Leishmaniasis: Blood Macrophages and Kupffer Cells
Leishmania infantum is a parasite that causes zoonotic visceral leishmaniasis, a disease that affects humans, wild and domestic animals, mainly domestic dogs. Macrophages are cells of the immune system, existing in the peripheral blood and associated with different tissues in the mammal body, having the task to protect against microbiological threats. Interestingly, Leishmania can manipulate the macrophages into a non-active ghost-like state, allowing the parasite to stay in the host. The liver, which is a vital organ and a target for the parasite, has a resident population of macrophages designated as Kupfer cells. Therefore, a better understanding of the immune mechanisms exhibited by the macrophages when facing Leishmania parasite is needed to improve control strategies.
  • 836
  • 13 Jan 2022
Topic Review
Oncolytic Virotherapy in Solid Tumors
Oncolytic virotherapy (OVT) is a promising approach in cancer immunotherapy. Oncolytic viruses (OVs) could be applied in cancer immunotherapy without in-depth knowledge of tumor antigens.
  • 834
  • 20 Apr 2021
Topic Review
Mass Spectrometry-Based Proteomics
Omics technologies provide the tools required to investigate DNA, RNA, proteins, and other molecular determinants. These technologies include genomics, transcriptomics, proteomics, and metabolomics. However, proteomics is one of the main approaches to studying allergic disorders’ pathophysiology. Proteins are used to indicate normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Proteomics studies the complete set of proteins present in a live organism at a specific time or condition, including expression, structure, functions, interactions, and modifications, which are crucial for early disease diagnosis, prognosis, and monitoring of disease development.
  • 833
  • 26 May 2022
Topic Review
Pyroptosis in Inflammasome-Related Disorders
Inflammasomes are multiprotein complexes orchestrating intracellular recognition of endogenous and exogenous stimuli, cellular homeostasis, and cell death. Upon sensing of certain stimuli, inflammasomes typically activate inflammatory caspases that promote the production and release of the proinflammatory cytokines IL-1β, IL-1α, and IL-18 and induce a type of inflammatory cell death known as “pyroptosis”. Pyroptosis is an important form of regulated cell death executed by gasdermin proteins, which is largely different from apoptosis and necrosis. Recently, several signaling pathways driving pyroptotic cell death, including canonical and noncanonical inflammasome activation, as well as caspase-3-dependent pathways, have been reported. While much evidence exists that pyroptosis is involved in the development of several inflammatory diseases, its contribution to inflammasome-related disorders (IRDs) has not been fully clarified. 
  • 833
  • 21 Sep 2022
Topic Review
NOD2 in Alzheimer’s Diseases
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by a progressive decline in cognitive function, including memory loss, language difficulties, and changes in behavior. Researchers have demonstrated the potential of Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) receptor agonists in AD treatment. These agonists facilitate the conversation of pro-inflammatory monocytes into patrolling monocytes, leading to the efficient clearance of amyloid-β (Aβ) in the AD-affected cerebrovascular system. This approach surpasses the efficacy of targeting Aβ formation, marking a significant shift in therapeutic strategies. 
  • 831
  • 07 Jul 2023
Topic Review
Doublecortin-Like Kinase 1
Microtubule-associated doublecortin-like kinase 1 (DCLK1) is an accepted marker of tuft cells (TCs) and several kinds of cancer stem cells (CSCs), and emerging evidence suggests that DCLK1-positive TCs participate in the initiation and formation of inflammation-associated cancer. DCLK1-expressing CSCs regulate multiple biological processes in cancer, enhance resistance to host anti-tumor immunity, promote resistance to therapy, and are associated with metastasis. 
  • 829
  • 05 Jan 2021
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. 
  • 825
  • 26 Dec 2020
Topic Review
Cannabinoid Type-2 Receptor Agonist
JWH133, a selective, full functional agonist of the CB2 receptor, has been extensively studied for its potent anti-inflammatory, antiviral, and immunomodulatory properties. JWH133 modulates numerous signaling pathways and inhibits inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostanoids, and eicosanoids.
  • 825
  • 25 Oct 2021
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