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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.
  • 898
  • 30 Jul 2022
Topic Review
Immune Checkpoint Inhibitors in Melanoma
Despite of melanoma immunogenicity, this tumor develops immune escape mechanisms that stimulate a fast melanoma progression. Such mechanisms include impaired antigen presentation by tumor cells, accumulation of dysfunctional effector T cells and generation of the immunosuppressive TME represented by MDSC, TAN, CAF, TAM, and Treg. Therefore, numerous approaches were developed to reinvigorate the anti-tumor immune response. Recently approved immunotherapies with ICI (anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies) have revolutionized the treatment of melanoma. This treatment significantly increased the survival of melanoma patients and provided a durable control of the disease [26,27,28]. However, the response rates to ICI are still restricted. Thus, further efforts should be undertaken to maximize the efficacy of ICI treatment. This aim could be achieved by improving the selection of patients who might benefit from the ICI therapy, by applying early radiological findings and by measuring predictive markers from tumor and liquid biopsies. Furthermore, the combination of different ICI (such as ipilimumab and nivolumab), their combination with targeting of the immunosuppressive TME or with other anti-cancer therapies could significantly improve the efficacy of tumor immunotherapy. Furthermore, targeting of other immune checkpoints (such as LAG-3, TIM-3, TIGIT) and its combination with approved ICI are currently under investigation.
  • 896
  • 30 Oct 2020
Topic Review
Neutrophils during Arboviral Infections
Arboviruses are known to cause large-scale epidemics in many parts of the world. These arthropod-borne viruses are a large group consisting of viruses from a wide range of families. The ability of their vector to enhance viral pathogenesis and transmission makes the development of treatments against these viruses challenging. Neutrophils are generally the first leukocytes to be recruited to a site of infection, playing a major role in regulating inflammation and, as a result, viral replication and dissemination. However, the underlying mechanisms through which neutrophils control the progression of inflammation and disease remain to be fully understood. In this review, we highlight the major findings from recent years regarding the role of neutrophils during arboviral infections. We discuss the complex nature of neutrophils in mediating not only protection, but also augmenting disease pathology. Better understanding of neutrophil pathways involved in effective protection against arboviral infections can help identify potential targets for therapeutics. 
  • 895
  • 05 Jul 2021
Topic Review
MSCs for Osteoarthritis Treatment
Osteoarthritis (OA) has traditionally been known as a “wear and tear” disease, which is mainly characterized by the degradation of articular cartilage and changes in the subchondral bone. Despite the fact that OA is often thought of as a degenerative disease, the catabolic products of the cartilage matrix often promote inflammation by activating immune cells. Current OA treatment focuses on symptomatic treatment, with a primary focus on pain management, which does not promote cartilage regeneration or attenuate joint inflammation. Since articular cartilage have no ability to regenerate, thus regeneration of the tissue is one of the key targets of modern treatments for OA. Cell-based therapies are among the new therapeutic strategies for OA. Mesenchymal stem cells (MSCs) have been extensively researched as potential therapeutic agents in cell-based therapy of OA due to their ability to differentiate into chondrocytes and their immunomodulatory properties that can facilitate cartilage repair and regeneration.
  • 895
  • 21 Jul 2021
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. 
  • 892
  • 04 Aug 2021
Topic Review
Immunotherapy for Peritoneal Carcinomatosis
Peritoneal carcinomatosis is a challenging condition that affects many cancer patients, and conventional therapies have limited efficacy in treating it. However, recent advances in the field of immunotherapy have shown promise in improving treatment outcomes. One promising approach is immune checkpoint inhibitors, which block proteins that inhibit T-cell activity and promote an anti-tumor immune response. Another approach involves the use of CAR-T cells, which are genetically modified T cells engineered to recognize and target cancer cells expressing specific antigens. In addition, dendritic cells and vaccine-based therapeutics are also designed to stimulate the immune system to recognize and attack cancer cells.
  • 887
  • 15 Jun 2023
Topic Review
Microglia Activation and Noradrenergic System
The nervous system requires immune cells to fight foreign body invasion including the pathogenic infection. This function is accomplished by microglia, which also play many other roles in the central nervous system including elimination of apoptotic cells, synaptic pruning, supporting neuronal survival, clearing debris, etc. Under healthy conditions, cyto-morphologically, microglia possess long thin processes and a small cell body, useful for debris clearance. However, upon exposure to inflammation, it becomes “activated” to function as immune cells of the central nervous system and develop short, thick processes and a larger cell body. They phagocytose the pathogens, release inflammatory mediators, and regulate T-cell activity. A variety of neurotransmitter receptors are expressed on the microglia which facilitate bidirectional communication between neurons and microglia. It has been shown that withdrawal of noradrenaline (NA) is a necessity for generation of rapid eye movement sleep (REMS). It has been proposed that REMS has evolved to maintain NA level in the brain. Further, NA exerts neuromodulatory action on microglia and facilitates immune function of the brain. Thus, REMS modulates immune functions of the brain.
  • 886
  • 29 Dec 2022
Topic Review
APOE and NF-κB in Alzheimer’s Disease
Apolipoprotein E (APOE) has three different isoforms, with APOE4 carriers representing a major risk factor for the development of Alzheimer’s disease (AD). The APOE4 isoform is associated with many pathological mechanisms, such as increased neuroinflammation. The presence of APOE4 can increase neuroinflammation via overactivation of the nuclear factor kappa B (NF-kB) pathway. The NF-kB pathway is a family of transcription factors involved with regulating over 400 genes involved with inflammation. AD is associated with sustained inflammation and an overactivation of the NF-kB pathway. Therefore, targeting the APOE4 isoform and suppressing the NF-kB pathway using anti-inflammatory compounds may result in the development of novel therapeutics for the prevention/treatment of AD.
  • 885
  • 11 Nov 2021
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.
  • 885
  • 09 Jan 2023
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.
  • 883
  • 22 Dec 2020
Topic Review
Tripartite Motif Family
The tripartite motif (TRIM) family comprises at least 80 members in humans, with most having ubiquitin or SUMO E3 ligase activity conferred by their N-terminal RING domain. TRIMs regulate a wide range of processes in ubiquitination- or sumoylation-dependent manners in most cases, and fewer as adaptors. Their roles in the regulation of viral infections, autophagy, cell cycle progression, DNA damage and other stress responses, and carcinogenesis are being increasingly appreciated, and their E3 ligase activities are attractive targets for developing specific immunotherapeutic strategies for immune diseases and cancers.
  • 883
  • 22 Sep 2021
Topic Review
Pre-Clinical Murine Models of Colitis
Crohn’s disease (CD) and ulcerative colitis (UC) are both highly inflammatory diseases of the gastrointestinal tract, collectively known as inflammatory bowel disease (IBD). Although the cause of IBD is still unclear, several experimental IBD murine models have enabled researchers to make great inroads into understanding human IBD pathology. Murine experimental models of human IBD exhibit immune pathological signatures resembling Crohn’s disease (CD) or ulcerative colitis (UC). These models include the chemical-induced trinitrobenzene sulfonic acid (TNBS) model, oxazolone and dextran sulfate sodium (DSS) models, the gene-deficient I-kappa-B kinase gamma (Iκκ-γ) and interleukin(IL)-10 models, and the CD4+ T-cell transfer model. Although most pre-clinical murine models do not fully recapitulate the complexity of human IBD, these models have added to our knowledge about the causes of disease and have provided targets for developing new treatments. 
  • 883
  • 26 Sep 2022
Topic Review
Cyclic Dinucleotide Vaccine Adjuvants
Cyclic dinucleotides(CDNs) are a class of bacterial and mammalian second messengers with potent immunomodulatory and immunostimulatory properties. CDNs mediate a potent systemic as well as a mucosal vaccine response and induces a balanced memory Th1/Th2/Th17 and CD8+ T cell response. CDNs do not cause acute toxicity in mice and have been reported safe in humans from the recent clinical trials (ClinicalTrials.gov: NCT02675439, NCT03010176, NCT03172936, NCT03937141, and NCT0414414). As therapeutic cancer vaccine adjuvants, CDNs induce potent anti-tumor immunity,including cytotoxic T cells and NK cell activation that achieve durable regression in multiple mice models of tumor. In this entry, we review the status of CDN vaccine adjuvant research, including their superior adjuvant activities, in vivo mode of action, and confounding factors that affect their efficacy in humans.
  • 882
  • 02 Nov 2020
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. 
  • 882
  • 12 Oct 2022
Topic Review
Nasal Air Conditioning and SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as with the influenza virus, has been shown to spread more rapidly during winter. Severe coronavirus disease 2019 (COVID-19), which can follow SARS-CoV-2 infection, disproportionately affects older persons and males as well as people living in temperate zone countries with a tropical ancestry. The available data are consistent with optimal warming and humidifying of inspired air by the nose (nasal air conditioning) being essential for minimising SARS-CoV-2 infectivity of the upper respiratory tract (URT)  and, as a consequence, severe COVID-19. 
  • 880
  • 04 Jan 2022
Topic Review
Non-Small Cell Lung Cancer
Lung cancer is divided to Non-Small Cell Lung Cancer (NSCLC) comprising about 85% of lung cancer cases, and small cell lung cancer (15% of lung cancer cases). Non-small cell lung cancer (NSCLC) has several subtypes: a. Adenocarcinoma, b. Squamous cell carcinoma, c. Large cell carcinoma, or d. mixed histology. Treatment of localized NSCLC is surgical resection, stereotactic ablative radiation therapy, or combination of chemotherapy and radiation (chemoradiation). Treatment of advanced / metastatic disease includes targeted therapies, chemotherapy and immunotherapy. 
  • 877
  • 17 Feb 2021
Topic Review
Macrophages as Key Players in Intestinal Fibrogenesis
Intestinal fibrosis is a common complication in inflammatory bowel disease (IBD) without specific treatment. Macrophages are the key actors in inflammatory responses and the wound healing process. By their exceptional ability to integrate diverse stimuli in their surrounding environment, macrophages display a multitude of phenotypes to underpin a broad spectrum of functions, from the initiation to the resolution of inflammation following injury. The hypothesis that distinct macrophage subtypes could be involved in fibrogenesis and wound healing is emerging and could open up new therapeutic perspectives in the treatment of intestinal fibrosis. 
  • 876
  • 11 Mar 2022
Topic Review
Vitamin D, microbiome, and IBD
Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract (GIT), including Crohn’s disease (CD) and ulcerative colitis (UC), which differ in the location and lesion extensions. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e.g., vitamin D hypovitaminosis). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. Vitamin D receptor (VDR) regulates the biological actions of the active VitD (1α,25-dihydroxyvitamin D3), and is involved in the genetic, environmental, immune, and microbial aspects of IBD. VitD deficiency is correlated with disease activity and its administration targeting a concentration of 30 ng/mL may have the potential to reduce disease activity. Moreover, VDR regulates functions of T cells and Paneth cells and modulates release of antimicrobial peptides in gut microbiota-host interactions. Meanwhile, beneficial microbial metabolites, e.g., butyrate, upregulate the VDR signaling.
  • 875
  • 31 Jan 2021
Topic Review
Molecular Mechanisms of Eosinophilic Esophagitis
Eosinophilic esophagitis is a recently recognized allergic-mediated disease with eosinophil-predominant esophagus inflammation. Its pathogenesis is a complicated network of interactions and signaling between epithelial, mesenchymal, and immune cells on molecular and intercellular levels.
  • 872
  • 14 Dec 2021
Topic Review
Immune Checkpoint Inhibitors
There are several forms of Immune checkpoint inhibitors (ICIs) targeting at several checkpoint proteins or receptors including programmed cell death 1 (PD-1), PD-1 ligand (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), B and T cell lymphocyte attenuator (BTLA), V-domain Ig suppressor of T cell activation (VISTA), lymphocyte activation gene 3 (LAG3) and T cell immunoglobulin and mucin domain 3 (TIM-3) [5,6,7,8,9]. ICIs, specifically PD-1, PDL-1 and CTLA-4 inhibitors have been approved for the treatment of a variety of solid tumors, initially beginning with melanoma in 2011. Both PD-1 and CTLA-4 are negative costimulatory molecules that when inhibited enhance T cell activation and the eventual killing of tumor cells [10].ICIs can be used in patients with chemotherapy-resistant tumors through tissue agnostic approval for MSI-H and high mutational burden tumors [14]. ICIs have shown that they are not only efficacious but have superior safety profile as well [15]. Most of the ICIs are well tolerated, however, they have distinct side effects compared to traditional cytotoxic chemotherapies [16,17].
  • 861
  • 27 Oct 2020
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