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Topic Review
Phytochemicals JAK–STAT for IBD Treatment
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that consists of Crohn’s disease (CD) and ulcerative colitis (UC). Cytokines are thought to be key mediators of inflammation-mediated pathological processes of IBD. These cytokines play a crucial role through the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signaling pathways. Several small molecules inhibiting JAK have been used in clinical trials, and one of them has been approved for IBD treatment. Many anti-inflammatory phytochemicals have been shown to have potential as new drugs for IBD treatment.
  • 1.4K
  • 01 Jun 2021
Topic Review
PD-L1
The gastrointestinal (GI) mucosa is among the most complex systems in the body. It has a diverse commensal microbiome challenged continuously by food and microbial components while delivering essential nutrients and defending against pathogens. For these reasons, regulatory cells and receptors are likely to play a central role in maintaining the gut mucosal homeostasis. Recent lessons from cancer immunotherapy point out the critical role of the B7 negative co-stimulator PD-L1 in mucosal homeostasis. In this entry, we summarize the current knowledge supporting the critical role of PD-L1 in gastrointestinal mucosal tolerance and how abnormalities in its expression and signaling contribute to gut inflammation and cancers. Abnormal expression of PD-L1 and/or the PD-1/PD-L1 signaling pathways have been observed in the pathology of the GI tract. We also discuss the current gap in our knowledge with regards to PD-L1 signaling in the GI tract under homeostasis and pathology. Finally, we summarize the current understanding of how this pathway is currently targeted to develop novel therapeutic approaches.
  • 1.4K
  • 22 Dec 2020
Topic Review
Osteoimmunology in Periodontitis
Periodontitis is one of the most common oral diseases resulting in gingival inflammation and tooth loss. Growing evidence indicates that it results from dysbiosis of the oral microbiome, which interferes with the host immune system, leading to bone destruction. Immune cells activate periodontal ligament cells to express the receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL) and promote osteoclast activity. Osteocytes have active roles in periodontitis progression in the bone matrix. Local proteins are involved in bone regeneration through functional immunological plasticity.
  • 1.4K
  • 02 Jun 2022
Topic Review
Dysregulated Immune Response after Burn Injury
Burn injury induces a complex inflammatory response, both locally and systemically, and is not yet completely unravelled and understood. In order to enable the development of accurate treatment options, it is of paramount importance to fully understand post-burn immunology. Persistent activity of complement, acute phase proteins and pro- and anti-inflammatory mediators, changes in lymphocyte activity, activation of the stress response and infiltration of immune cells have all been related to post-burn local and systemic pathology.
  • 1.4K
  • 08 Feb 2023
Topic Review
Immunosurveillance and Immunoediting
The mechanisms by which immune systems identify and destroy tumors, known as immunosurveillance, have been discussed for decades. However, several factors that lead to tumor persistence and escape from the attack of immune cells in a normal immune system have been found. In the process known as immunoediting, tumors decrease their immunogenicity and evade immunosurveillance. Furthermore, tumors exploit factors such as regulatory T cells, myeloid-derived suppressive cells, and inhibitory cytokines that avoid cytotoxic T cell (CTL) recognition. 
  • 1.4K
  • 13 Feb 2023
Topic Review
Macrophages and Cancer Development
Macrophages are innate immune cells pivotal for tissue homeostasis, removal of superfluous cells, and inflammatory responses to infections. Macrophages also play diverse roles in cancer development, ranging from antitumor activity in early progression stages to, most commonly, tumor-promoting roles in established cancer. Notably, macrophages are highly plastic cells and, depending on the microenvironmental cues in the Tumor Microenvironment (TME), can undergo marked changes in their function. In established cancers, high macrophage infiltration often strongly associates with poor prognosis or tumor progression in many types of solid tumors, including breast, bladder, head and neck, glioma, melanoma, and prostate cancer. Conversely, in colorectal and gastric cancers, high macrophage infiltration correlates with a better prognosis. These apparently opposite effects are likely related to macrophage plasticity and resultant heterogeneity of phenotype and functions in various cancers.
  • 1.4K
  • 14 May 2021
Topic Review
CGAS in Innate Immunity
Cyclic GMP–AMP synthase (cGAS) is the synthase that generates the second messenger cyclic GMP–AMP (cGAMP) upon DNA binding. cGAS was first discovered as the cytosolic DNA sensor that detects DNA exposed in the cytoplasm either from pathogens or cellular damage. Activated cGAS instigates the signaling cascades to activate type I interferon (IFN) expression, critical for host defense and autoimmune diseases. In addition, cGAS plays a role in senescence, DNA repair, apoptosis, and tumorigenesis. Recently, various post-translational modifications (PTMs) of cGAS have been reported, such as phosphorylation, ubiquitination, acetylation, glutamylation, and sumoylation. These PTMs profoundly affect cGAS functions. Thus, here we review the recent reported PTMs of cGAS and how these PTMs regulate cGAS enzymatic activity, DNA binding, and protein stability, and discuss the potential future directions.
  • 1.4K
  • 18 Jan 2021
Topic Review
Fine Regulation during Wound Healing by Mast Cells
Mast cells (MCs) are bone marrow-derived cells capable of secreting many active molecules, ranging from the mediators stored in specific granules, some of which have been known about for several decades (histamine, heparin), to small molecules produced immediately upon stimulation (membrane lipid derivatives, nitric oxide), to a host of constitutively secreted, multifunctional cytokines. With the aid of a wide array of mediators, the activated MCs control the key events of inflammation and therefore participate in the regulation of local immune response. On the basis of the structure, origin, principal subtypes, localization and function of these cells, their involvement in injury repair is therefore to be considered in acute and chronic conditions, respectively.
  • 1.4K
  • 30 Jul 2022
Topic Review
CCl4-Induced Liver Injury in Brief
Carbon tetrachloride (CCl4) has been a cornerstone in experimental liver research for decades, providing valuable insights into hepatotoxicity, liver fibrosis, and potential therapeutic interventions. This research explores the utility of the CCl4-induced liver injury model, encompassing its methods of induction, key pathological features, underlying mechanisms, and applications in drug development. While this model offers essential insights into liver disease, it presents certain limitations that researchers must consider. By providing an in-depth analysis of CCl4-induced liver injury, this research highlights its significance in advancing liver research and our understanding of liver pathology and repair.
  • 1.4K
  • 08 Oct 2023
Topic Review
Anti-Cancer Effects of Atrial Natriuretic Peptides
The atrial natriuretic peptide (ANP), a cardiovascular hormone, plays a pivotal role in the homeostatic control of blood pressure, electrolytes, and water balance and is approved to treat congestive heart failure. In addition, there is a growing realization that ANPs might be related to immune response and tumor growth. The anti-inflammatory and immune-modulatory effects of ANPs in the tissue microenvironment are mediated through autocrine or paracrine mechanisms, which further suppress tumorigenesis. In cancers, ANPs show anti-proliferative effects through several molecular pathways. Furthermore, ANPs attenuate the side effects of cancer therapy. Therefore, ANPs act on several hallmarks of cancer, such as inflammation, angiogenesis, sustained tumor growth, and metastasis. 
  • 1.4K
  • 12 Oct 2022
Topic Review
Immune Landscape in Multiple Myeloma
Multiple myeloma (MM) is a dyscrasia of plasma cells (PCs) characterized by abnormal immunoglobulin (Ig) production. The disease remains incurable due to a multitude of mutations and structural abnormalities in MM cells, coupled with a favorable microenvironment and immune suppression that eventually contribute to the development of drug resistance. The bone marrow microenvironment (BMME) is composed of a cellular component comprising stromal cells, endothelial cells, osteoclasts, osteoblasts, and immune cells, and a non-cellular component made of the extracellular matrix (ECM) and the liquid milieu, which contains cytokines, growth factors, and chemokines. The bone marrow stromal cells (BMSCs) are involved in the adhesion of MM cells, promote the growth, proliferation, invasion, and drug resistance of MM cells, and are also crucial in angiogenesis and the formation of lytic bone lesions. Classical immunophenotyping in combination with advanced immune profiling using single-cell sequencing technologies has enabled immune cell-specific gene expression analysis in MM to further elucidate the roles of specific immune cell fractions from peripheral blood and bone marrow (BM) in myelomagenesis and progression, immune evasion and exhaustion mechanisms, and development of drug resistance and relapse. 
  • 1.4K
  • 15 Nov 2023
Topic Review
Vascular Calcification
A variety of actively regulated processes on cellular and systemic level with various contributing and inhibiting factors can result in vascular calcification (VC). Currently, treatment is limited to management of risk factors including regulation of the calcium-phosphate metabolism. Due to the complex pathophysiology, the mechanisms underlying ectopic calcification are studied in various, distinctly different research models. Beside in vitro models using cells of different origin, ex vivo settings using aortic tissue are available. In addition, various in vivo disease-induced animal models are currently used in research. All of these experimental settings depict (patho)physiologic mechanisms within the vascular calcification process.
  • 1.4K
  • 29 Oct 2020
Topic Review
Insights into Immunogenic Cell Death
Immunogenic cell death (ICD) is a type of regulated cell death (RCD), increasingly studied in recent years, due to its therapeutic implication in several diseases associated with immune system dysfunction. The new and increasingly studied concept of immunogenic cell death (ICD) revealed a previously unknown perspective of the various regulated cell death (RCD) modalities, elucidating their immunogenic properties and rendering obsolete the notion that immune stimulation is solely the outcome of necrosis. A distinct characteristic of ICD is the release of danger-associated molecular patterns (DAMPs) by dying and/or dead cells. These are evolutionary conserved stress signals, recognized primarily by innate immune system receptors. The immunogenicity of DAMPs characterizes ICD, rendering them potential prognostic, diagnostic clinical tools and/or possible therapeutic targets.
  • 1.4K
  • 14 Jul 2022
Topic Review
Correlates of SARS-CoV-2 Vaccine-Induced Protection
Vaccine candidates against COVID-19 have been developed at an unprecedented speed, with more than 200 vaccine candidates currently under investigation. Among those, 20 candidates have entered the clinical Phase 3 to evaluate efficacy, and three have been approved by the European Medicines Agency. The aim of immunization is to act against infection, disease and/or transmission. However, the measurement of vaccine efficacy is challenging, as efficacy trials need to include large cohorts with verum and placebo cohorts. In the future, this will be even more challenging as further vaccine candidates will receive approval, an increasing number of humans will receive vaccinations and incidence might decrease. To evaluate novel and second-generation vaccine candidates, randomized placebo-controlled trials might not be appropriate anymore. Correlates of protection (CoP) could be an important tool to evaluate novel vaccine candidates, but vaccine-induced CoP have not been clearly defined for SARS-CoV-2 vaccines. 
  • 1.4K
  • 04 Aug 2021
Topic Review
The PD-1/PD-L1 Pathway
Binding of the immune checkpoint programmed cell death protein 1 (PD-1) to its ligand programmed death-ligand 1 (PD-L1) downregulates the adaptive immune response. PD-L1 is regularly expressed by antigen presenting cells. During an acute immune response, effector T cells transiently upregulate PD-1. In contrast, chronic immune stimulation leads to continuous expression of PD-1 on effector T cells. The latter also occurs in the tumor microenvironment, where PD-L1 can be expressed by tumor cells. The PD-1/PD-L1 pathway is an excellent example for the clinical application of biomarker research in the context of comparative immuno-oncology. Initial comparator studies on this pathway were mainly conducted on cells and tissues derived from mice and humans. This resulted in the discovery of anti PD-1 or anti-PD-L1 immune checkpoint therapy that is widely applied for the treatment of human cancers. The use of monoclonal antibodies directed against PD-1 or PD-L1 as therapeutic agents restores the anti-cancer immune response. In recent years, investigations on these molecules have been extended to canine cancers and confirm the expression of PD-1 and PD-L1 in several canine tumors. Whether immune checkpoint therapy may be a possible treatment option for those canine cancers remains to be revealed in future clinical trials.
  • 1.4K
  • 02 Dec 2022
Topic Review
Antibodies and T Cells in Viral Infections
The vertebrate immune system functions to eliminate foreign nucleic acids that invade from infectious pathogens and malignant tumors. DNA/RNA motifs characteristic to microbes and cancer cells are recognized as "non-self" by the host innate immune system, represented by pattern-recognition receptors (PRRs), thereby being classified into microbe-associated molecular patterns (MAMPs). MAMPs participate in immune enhancement, which is a host strategy to eliminate invading cells. That is, a variety of PRRs recognize nucleic acid MAMPs. Of the Toll-like receptors (TLRs), TLR3 recognizes RNA double-stranded (ds) motifs such as viral dsRNA. TLR3 is particular in that 1. It is preferentially expressed in endosomes of antigen-presenting dendritic cells (CD141+ DCs), 2. It can be an exclusive target to induce cross-antigen presentation, 3. Several structured RNAs successfully attain endosomal TLR3 in antigen-presenting (CD141+) DCs. Here the researchers summarize the current status of TLR3 adjuvants designed to enter cells without transfection, minimize inflammatory side effects, and provide optimal immune enhancement.
  • 1.4K
  • 09 Jan 2023
Topic Review
Th17 Lymphocytes in Breast Cancer
Th17 cells are the main source of the proinflammatory cytokine IL-17; however, the receptor of this cytokine (IL-17R) is distributed ubiquitously. IL-17 (IL-17A) is a member of the IL-17 cytokine family consisting of IL-17A–F (IL-17E is also known as IL-25) and directly links inflammatory responses and T-cell activation.
  • 1.4K
  • 11 Aug 2022
Topic Review
Inflammation in Neonatal Encephalopathy
Neuroinflammation caused by hypoxia or hypoxic ischemia during the perinatal period contributes to increased risk for neurological deficits and long-term disabilities in children. Inflammation induced by injury results in activation of the resident and peripheral immune cells and production of cytokines.
  • 1.4K
  • 20 Jan 2021
Topic Review
NK Cells in Viral Infections
NK cells are usually defined as immune cells that belong to the innate immune response. They were described as cells capable of killing several tumour cell lines without previous antigen presentation. It was shown then that NK cells lack the TCR and BCR receptors capable of binding specific antigens, and consequently, it was assumed that these cells lack antigen recognition.
  • 1.4K
  • 12 Jan 2022
Topic Review
Specialized Pro-Resolving Lipid Mediators
Resolvins (Rvs), Maresins (MaRs), Protectins (PDs), and Lipoxins (LXs), belong to a large group of molecules known as The Specialized Pro-resolving Lipid Mediators (SPMs). These compounds have been well-characterized since their identification as potent modulators of the immune response and for their effects on inflammation resolution. Furthermore, they have a potential effect on anti-tumor immunity.
  • 1.4K
  • 17 Aug 2023
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