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Topic Review
Tumor Necrosis Factor-α
Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine expressed by macrophages, monocytes, and T cells, and its expression is triggered by the immune system in response to pathogens and their products, such as endotoxins. TNF-α plays an important role in host defense by inducing inflammatory reactions such as phagocytes and cytocidal systems activation. TNF-α also plays an important role in bone metabolism and is associated with inflammatory bone diseases. TNF-α binds to two cell surface receptors, the 55kDa TNF receptor-1 (TNFR1) and the 75kDa TNF receptor-2 (TNFR2).
  • 992
  • 11 Mar 2022
Topic Review
Chimeric Antigen Receptor T cells in Multiple Myeloma
Multiple myeloma is a disease of malignant plasma cells and the second most common hematological cancer. This entry describes the history and use of CAR-T cells for the treatment of this disease as well as comment on future approaches.
  • 991
  • 03 Dec 2021
Topic Review
Causality of Vaccine Allergy
Vaccines constitute the most effective medications in public health as they control and prevent the spread of infectious diseases and reduce mortality. Similar to other medications, allergic reactions can occur during vaccination. While most reactions are neither frequent nor serious, anaphylactic reactions are potentially life-threatening allergic reactions that are encountered rarely, but can cause serious complications. The allergic responses caused by vaccines can stem from activation of mast cells via Fcε receptor-1 type I reaction, mediated by the interaction between immunoglobulin E (IgE) antibodies against a particular vaccine, and occur within minutes or up to four hours. 
  • 989
  • 29 Mar 2021
Topic Review
Platelet Biology
Platelets are generated from megakaryocytes in a multi-step process called thrombopoiesis regulated by thrombopoietin. Thrombopoietin stimulates its receptor in megakaryocytes to induce the genesis of pro-platelets via a mechanism activated by low platelet counts. Platelet counts in blood are controlled by the rates of production and removal, involving mechanisms of platelet clearance, activation or ageing. Platelets are the most numerous circulating cell type (≈200,000/µL blood in humans) with an immune function. 
  • 989
  • 14 Feb 2022
Topic Review
Chromogranin A -Derived Peptides as Inflammatory Modulator Molecules
Chromogranin A (CgA) is a glyco-phosphoprotein discovered for the first time in the adrenal medulla but also produced in several cells. CgA can generate different derived antimicrobial peptides (AMPs) influencing numerous physiological processes. CgA-derived peptides modulate inflammation and represent an example of endogenous Multifunctional AMPs (MF-AMPs).
  • 988
  • 21 Oct 2022
Topic Review
Natural Killer T and Natural Killer Cell-Based Immunotherapy
Both natural killer T (NKT) and natural killer (NK) cells are innate cytotoxic lymphoid cells that produce inflammatory cytokines and chemokines, and their role in the innate immune response to tumors and microorganisms has been investigated. Especially, emerging evidence has revealed their status and function in the tumor microenvironment (TME) of tumor cells. As a recent strategy in cancer immunotherapy, the mobilization or restoration of endogenous NKT or NK cells by novel vaccines or therapies has become a focus of research. Several new modalities based on the characteristics of NKT and NK cells, including artificial adjuvant vector cells, chimeric antigen receptor-expressing NK or NKT cell therapy, or their combination with immune checkpoint blockade have been developed. This research examines challenges and future directions for improving these therapies.
  • 988
  • 21 Feb 2023
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).
  • 983
  • 01 Feb 2021
Topic Review
Natural Killer Cells in Immunotherapy
Here, the last pre-clinical and clinical studies published in the last five years where natural killer (NK) cells have been administered as an immunotherapy option for the treatment of cancer patients. Author describe studies administering NK cells alone and in combination with monoclonal antibodies that either promote antibody-dependent cell cytotoxicity or block immune checkpoint receptors. They review the use of genetically modified NK cells including chimeric antigen receptor (CAR)-modified NK cells and other modifications that can enhance the anti-tumor activity of NK cells. Moreover, author describe studies related to the antimicrobial activity of NK cells as we believe they demonstrate important lessons that we can learn and apply to improve the anti-tumor activity of NK cells. All these studies are described with the aim to find tips to improve the success of NK cells as an immunotherapy option in cancer patients.
  • 981
  • 05 Nov 2020
Topic Review
Inflammaging, an Imbalanced Immune Response
Nowadays, new advances in society and health have brought an increased life expectancy. However, at the same time, aging comes with complications that impact the development of autoimmunity, neurodegenerative diseases and cancer. These complications affect the quality of life and impact the public health system. Specifically, with aging, a low-grade chronic sterile systemic inflammation with self-reactivity in the absence of acute infection occurs termed inflammaging. Inflammaging is related to an imbalanced immune response that can be either naturally acquired with aging or accelerated due to external triggers. Different molecules, metabolites and inflammatory forms of cell death are highly involved in these processes. Importantly, adoptive cellular immunotherapy is a modality of treatment for cancer patients that administers ex vivo expanded immune cells in the patient. The manipulation of these cells confers them enhanced proinflammatory properties. A general consequence of proinflammatory events is the development of autoimmune diseases and cancer.
  • 979
  • 11 Oct 2021
Topic Review
Hematopoietic Stem Cells and Metabolic Program
Hematopoietic stem cells (HSCs) in bone marrow continuously supply a large number of blood cells throughout life in collaboration with hematopoietic progenitor cells (HPCs). HSCs and HPCs are thought to regulate and utilize intracellular metabolic programs to obtain metabolites, such as adenosine triphosphate (ATP), which is necessary for various cellular functions. The metabolic programs of tissue stem/progenitor cells and their underlying molecular mechanisms have been elucidated using a variety of metabolic analysis methods.
  • 977
  • 05 Jan 2023
Topic Review
Immunosenescence, Inflammaging, and COVID-19
Aging is characterized by the dynamic remodeling of the immune system designated “immunosenescence,” and is associated with altered hematopoiesis, thymic involution, and lifelong immune stimulation by multitudinous chronic stressors, including the cytomegalovirus (CMV). Such alterations may contribute to a lowered proportion of naïve T-cells and to reduced diversity of the T-cell repertoire. In the peripheral circulation, a shift occurs towards accumulations of T and B-cell populations with memory phenotypes, and to accumulation of putatively senescent and exhausted immune cells. The aging-related accumulations of functionally exhausted memory T lymphocytes, commonly secreting pro-inflammatory cytokines, together with mediators and factors of the innate immune system, are considered to contribute to the low-grade inflammation (inflammaging) often observed in elderly people. These senescent immune cells not only secrete inflammatory mediators, but are also able to negatively modulate their environments. In this review, we give a short summary of the ways that immunosenescence, inflammaging, and CMV infection may cause insufficient immune responses, contribute to the establishment of the hyperinflammatory syndrome and impact the severity of the coronavirus disease 2019 (COVID-19) in elderly people.
  • 976
  • 19 Jan 2022
Topic Review
Caspase-1 Inhibition
The inflammatory protease caspase-1 is associated with the release of cytokines. An excessive number of cytokines (a “cytokine storm”) is a dangerous consequence of COVID-19 infection and has been indicated as being among the causes of death by COVID-19. The anti-inflammatory drug colchicine (which is reported in the literature to be a caspase-1 inhibitor) and the corticosteroid drugs, dexamethasone and methylprednisolone, are among the most effective active compounds for COVID-19 treatment.
  • 976
  • 18 Feb 2022
Topic Review
Macrophages and Wnts in Tissue Injury and Repair
Macrophages, one of the body’s most abundant populations of leukocytes, are mainly derived from the yolk sac during embryogenesis and are found in almost every tissue that plays an essential role during mammalian development. They are specialized phagocytes, large vacuolated cells with abundant cytoplasm containing lysosomal granules. Wnt signaling is a conserved pathway across species. It is involved in various essential tasks by regulating cell differentiation, proliferation, stem cell development, immune cell functions, and tissue repair. Evidence for the Wnt system’s pivotal role is that aberrant alterations of this molecular pathway are involved in multiple human disorders and pathologies, such as congenital abnormalities, autoimmune diseases, and cancer. Wnt and macrophages in the most immunologically active lung, liver, intestine, kidney, heart, and skin are discussed.
  • 975
  • 26 Dec 2022
Topic Review
Regulation of Class Switch Recombination by G4 Structures
Mature B cells notably diversify immunoglobulin (Ig) production through class switch recombination (CSR), allowing the junction of distant “switch” (S) regions. CSR is initiated by activation-induced deaminase (AID), which targets cytosines adequately exposed within single-stranded DNA of transcribed targeted S regions, with a specific affinity for WRCY motifs. In mammalian S regions, abundant G4 (G-quadruplex) DNA on the non-template strand also contributes to the formation of R-loops while the presence of G4 structures within the primary transcripts from S regions participates into recruiting AID. The ability of G4 ligands to modulate the CSR process also underlines the key role of G4 structures in the regulation of CSR.
  • 974
  • 03 Feb 2023
Topic Review
Pancreatic Cancer Treatment
Pancreatic cancer is one of the deadliest cancers worldwide, largely due to its aggressive development. Consequently, treatment options are often palliative, as only one-fifth of patients present with potentially curable tumors. The only available treatment with curative intent is surgery followed by adjuvant chemotherapy. However, even for patients that are eligible for surgery, the 5-year OS remains below 10%.
  • 973
  • 29 Mar 2022
Topic Review
Antigenicity of the Brucella Cell Wall
The members of Brucella spp. as Gram-negative bacteria are characterized by their sandwich-structured cell envelopes composed of the lipopolysaccharide (LPS)-covered bacterial outer membrane and the inner cytoplasmic cell membrane with a thin peptidoglycan layer between them in the periplasmic space.
  • 973
  • 23 May 2023
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. 
  • 971
  • 13 Jan 2023
Topic Review
Hyperuricemia and Gout
Hyperuricemia is a risk factor for gout. It has been well observed that a large proportion of individuals with hyperuricemia have never had a gout flare(s), while some patients with gout can have a normuricemia. This raises a puzzle of the real role of serum uric acid (SUA) in the occurrence of gout flares. As the molecule of uric acid has its dual effects in vivo with antioxidant properties as well as being an inflammatory promoter, it has been placed in a delicate position in balancing metabolisms. Gout seems to be a multifactorial metabolic disease and its pathogenesis should not rely solely on hyperuricemia or monosodium urate (MSU) crystals. 
  • 970
  • 22 Mar 2021
Topic Review
Natural Killer Cell Therapies
The natural killer (NK) cells of the immune system identify and remove stressed, infected, or cancerous cells in the body. This anti-tumor functionality has been harnessed through promising cell-based therapies that involve the isolation, expansion, activation, and delivery of NK cells for the treatment of several cancers.
  • 970
  • 06 Apr 2023
Topic Review
Central Nervous System Delivery of Antibodies
Antibodies, otherwise known as immunoglobulins (Igs), are glycoprotein molecules produced by plasma cells and are mostly found in blood and lymphoid tissues. The primary function of antibodies in vivo is to recognize and neutralize infectious agents, such as pathogenic bacteria and viruses. Antibodies are directed against various antigens and play a pivotal role in the defense mechanism of higher vertebrates and are also involved in autoimmune diseases and allergies.
  • 969
  • 29 Mar 2022
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