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Topic Review
Mitogen-Activated Protein Kinases
Influenza A viral (IAV) infections are common, yet persistent as one of the major contributors towards respiratory viral diseases. With the complete eradication of IAVs seemingly impossible, IAV infections are of major public health concern globally as evident by the need for constant surveillance and vaccine renewals. This entry focuses on the innate immune response against influenza infections and in particular, the roles of mitogen-activated protein kinases (MAPKs) in this response. We first detailed the conventional methods of pathogen recognition of influenza viruses by pathogen recognition receptors (PRRs), leading to the activation of pathways involved in the anti-viral response. Predominantly, we have highlighted the roles that MAPKs (ERK, p38 and JNK) play in the activation of Type I Interferons (IFNs) and pro-inflammatory cytokines to resolve IAV infections. Taking a step further, we also looked at how highly pathogenic influenza A viruses (HPIAVs), as well as aberrant and dysfunctional signalling of the MAPK pathways may lead to a hyperactive immune response that is unwarranted, leading to the progression into acute lung injuries and acute respiratory distress syndrome (ARDS) from a simple infection. Taken together, we hope that this entry may shed some light on the important roles that MAPKs play in the innate immune response towards IAV infections, and to provide important considerations when tackling this global challenge.
  • 1.3K
  • 26 Oct 2020
Topic Review
Cryptococcus
Cryptococcosis is a disease caused by the pathogenic fungi Cryptococcus neoformans and Cryptococcus gattii, both environmental fungi that cause severe pneumonia and may even lead to cryptococcal meningoencephalitis. Although C. neoformans affects more fragile individuals, such as immunocompromised hosts through opportunistic infections, C. gattii causes a serious indiscriminate primary infection in immunocompetent individuals. Typically seen in tropical and subtropical environments, C. gattii has increased its endemic area, largely due to climatic factors that favor contagion in warmer climates. It is important to point out that not only C. gattii, but the Cryptococcus species complex produces a polysaccharidic capsule with immunomodulatory properties, enabling the pathogenic species of Cryptococccus to subvert the host immune response during the establishment of cryptococcosis, facilitating its dissemination in the infected organism. C. gattii causes a more severe and difficult-to-treat infection, with few antifungals eliciting an effective response during chronic treatment. 
  • 1.3K
  • 26 Jul 2022
Topic Review
cfDNA Analysis
Degraded DNA fragments released into the blood or other fluids are known as cfDNA. Its first detection dates back to 1948 in patients with systemic lupus erythematosus.
  • 1.3K
  • 20 Jun 2023
Topic Review
PD-1 and Its Ligands in Allergy
Programmed cell death 1 (PD-1) and its ligands PD-L1 and PD-L2 are receptors that act in co-stimulatory and coinhibitory immune responses. Signaling the PD-1/PD-L1 or PD-L2 pathway is essential to regulate the inflammatory responses to infections, autoimmunity, and allergies, and it has been extensively studied in cancer.
  • 1.3K
  • 13 Jun 2022
Topic Review
Fungal Beta-Glucans
The importance of a well-functioning and balanced immune system has become more apparent in recent decades. Various elements have however not yet been uncovered as shown, for example, in the uncertainty on immune system responses to COVID-19. Fungal beta-glucans are bioactive molecules with immunomodulating properties.
  • 1.3K
  • 01 Jun 2021
Topic Review
NK Cell-Based Immunotherapy in Colorectal Cancer
Human Natural Killer (NK) cells are all round players in immunity thanks to their powerful and immediate response against transformed cells and the ability to modulate the subsequent adaptive immune response. 
  • 1.3K
  • 08 Aug 2022
Topic Review
Autophagy
Hepatitis C virus induces autophagy and temporally regulates the autophagic flux to support its replication. It uses autophagic membranes as a platform for its RNA replication, autophagic vacuoles to support its morphogenesis and autophagy to suppress host innate immune responses.  
  • 1.3K
  • 02 Feb 2021
Topic Review
Complement–Sphingolipid System in COVID-19 and Gaucher Diseases
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced disease (COVID-19) and Gaucher disease (GD) exhibit upregulation of complement 5a (C5a) and its C5aR1 receptor, and excess synthesis of glycosphingolipids that lead to increased infiltration and activation of innate and adaptive immune cells, resulting in massive generation of pro-inflammatory cytokines, chemokines and growth factors. This C5a–C5aR1–glycosphingolipid pathway- induced pro-inflammatory environment causes the tissue damage in COVID-19 and GD. Strikingly, pharmaceutically targeting the C5a–C5aR1 axis or the glycosphingolipid synthesis pathway led to a reduction in glycosphingolipid synthesis and innate and adaptive immune inflammation, and protection from the tissue destruction in both COVID-19 and GD. 
  • 1.3K
  • 29 Nov 2022
Topic Review
Interleukin-18
Interleukin (IL)-18 was originally discovered as a factor that enhanced IFN-γ production from anti-CD3-stimulated Th1 cells, especially in the presence of IL-12. Upon stimulation with Ag plus IL-12, naïve T cells develop into IL-18 receptor (IL-18R) expressing Th1 cells, which increase IFN-γ production in response to IL-18 stimulation. 
  • 1.3K
  • 21 Jan 2022
Topic Review
MRNA-Based Vaccines
The mRNA-based vaccine approach is a promising alternative to traditional vaccines due to its ability for prompt development, high potency, and potential for secure administration and low-cost production.
  • 1.3K
  • 02 Apr 2021
Topic Review
Delta133p53 Isoforms of Human TP53
The TP53 gene is a critical tumor suppressor and key determinant of cell fate which regulates numerous cellular functions including DNA repair, cell cycle arrest, cellular senescence, apoptosis, autophagy and metabolism. The delta133p53 isoforms are critical regulators of these biological processes in human physiology and diseases such as cancer.  
  • 1.2K
  • 28 Sep 2021
Topic Review
Still’s Disease and Kawasaki Disease
Still’s disease and Kawasaki disease (KD) today belong to the group of cytokine storm syndromes, a pathophysiological set related to excessive activation of the innate immune response. 
  • 1.2K
  • 30 Jul 2021
Topic Review
Neutrophil Extracellular Traps in Cancer Therapy Resistance
Neutrophils and their products are increasingly recognized to have a key influence on cancer progression and response to therapy. Their involvement has been shown in nearly every aspect of cancer pathophysiology with growing evidence now supporting their role in resistance to a variety of cancer therapies. Recently, the role of neutrophils in cancer progression and therapy resistance has been further complicated with the discovery of neutrophil extracellular traps (NETs). NETs are web-like structures of chromatin decorated with a variety of microbicidal proteins. They are released by neutrophils in a process called NETosis. NET-dependent mechanisms of cancer pathology are beginning to be appreciated, particularly with respect to tumor response to chemo-, immuno-, and radiation therapy. 
  • 1.2K
  • 26 Apr 2022
Topic Review
Porphyromonas gingivalis during Periodontitis Pathogenesis
Periodontitis is a non-communicable chronic inflammatory disease characterized by the progressive and irreversible breakdown of the soft periodontal tissues and resorption of teeth-supporting alveolar bone. The etiology of periodontitis involves dysbiotic shifts in the diversity of microbial communities inhabiting the subgingival crevice, which is dominated by anaerobic Gram-negative bacteria, including Porphyromonas gingivalis. Indeed, P. gingivalis is a keystone pathogen with a repertoire of attributes that allow it to colonize periodontal tissues and influence the metabolism, growth rate, and virulence of other periodontal bacteria. The pathogenic potential of P. gingivalis has been traditionally analyzed using classical biochemical and molecular approaches.
  • 1.2K
  • 31 Jan 2023
Topic Review
ZIKA Virus and Male Infertility
Zika virus (ZIKV) has been reported by several groups as an important virus causing pathological damage in the male reproductive tract. ZIKV can infect and persist in testicular somatic and germ cells, as well as spermatozoa, leading to cell death and testicular atrophy. ZIKV has also been detected in semen samples from ZIKV-infected patients. This has huge implications for human reproduction. Global scientific efforts are being applied to understand the mechanisms related to arboviruses persistency, pathogenesis, and host cellular response to suggest a potential target to develop robust antiviral therapeutics and vaccines. Here, we discuss the cellular modulation of the immunologic and physiologic properties of the male reproductive tract environment caused by arboviruses infection, focusing on ZIKV. We also present an overview of the current vaccine effects and therapeutic targets against ZIKV infection that may impact the testis and male fertility.
  • 1.2K
  • 01 Nov 2020
Topic Review
TNF’s Pathway in CD
Crohn’s disease (CD) is a chronic disorder characterized by full thickness patchy inflammation of the gastrointestinal tract. The pathogenesis is multifactorial and involves defective innate immune responses, microbiome alterations, and dysregulated activation of the acquired component of mucosal immunity. One of the molecular mediators that is involved at different levels in the initiation and progression of intestinal inflammation characteristic of CD is tumor necrosis factor (TNF).
  • 1.2K
  • 15 Oct 2021
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. 
  • 1.2K
  • 17 Feb 2021
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.
  • 1.2K
  • 30 Oct 2020
Topic Review
Saliva-Assisted Transmission
Saliva-assisted transmission (SAT) is defined as the property of tick saliva to enhance the transmission and establishment of tick-borne pathogens. Tick saliva contains multiple biomolecules that act to repress host immune responses, hemostasis, inflammation, and itchiness. These molecules can be exploited by tick-borne pathogens by increasing their expression or directly binding. The focus of this entry is in defining the mechanism that tick-borne pathogens use to subvert tick salivary secretions in their advantage.
  • 1.2K
  • 03 Mar 2021
Topic Review
Lyotropic Liquid Crystals for Efficient Intestinal Lymphatic Targeting
Lyotropic liquid crystals (LLCs) are liquids that have crystalline structures. LLCs as drug delivery systems that can deliver hydrophobic, hydrophilic, and amphiphilic agents. Due to their unique phases and structures, LLCs can protect both small molecules and biologics from the gastrointestinal tract’s harsh environment, thus making LLCs attractive as carriers for oral drug delivery.
  • 1.2K
  • 30 Nov 2023
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