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Topic Review
Muramyl Peptides of Bacterial Origin
Muramyl peptides (MPs) are part of the peptidoglycan that forms the backbone of the cell walls of bacteria—both Gram-positive and Gram-negative. MPs are formed during the degradation of bacteria and are pathogen-associated molecular patterns (PAMPs) that are recognized by innate immune receptors.
  • 1.6K
  • 02 Aug 2022
Topic Review
Th17/Treg Imbalance in Lung Inflammatory Diseases
Regulatory T cells (Tregs) and T helper 17 cells (Th17) are two CD4+ T cell subsets with antagonist effects. Th17 cells promote inflammation, whereas Tregs are crucial in maintaining immune homeostasis. Th17 cells and Treg cells are the foremost players in several inflammatory diseases.
  • 1.6K
  • 03 Apr 2023
Topic Review
Immunotherapy-Based Treatment Strategy for Autoimmune Type 1 Diabetes
Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β-cells by their own immune system, resulting in lifelong insulin deficiency. Continuous exogenous insulin replacement therapy is the current standard of care for T1D. Transplantation of primary pancreatic islets or the entire pancreas is a viable remedy for managing patients with autoimmune T1D. However, this strategy is not feasible due to several obstacles, including a scarcity of donors, islet cells, and poor vascular engraftment of islets post-transplantation, as well as the need for prolonged immune suppression. 
  • 1.6K
  • 18 Feb 2022
Topic Review
A Novel Innate Immune Regulatory Player: LncRNAs
Long non-coding RNAs (lncRNAs) represent crucial transcriptional and post-transcriptional gene regulators during antimicrobial responses in the host innate immune system. Studies have shown that lncRNAs are expressed in a highly tissue- and cell-specific- manner and are involved in the differentiation and function of innate immune cells, as well as inflammatory and antiviral processes, through versatile molecular mechanisms. These lncRNAs function via the interactions with DNA, RNA, or protein in either cis or trans pattern, relying on their specific sequences or their transcriptions and processing. The dysregulation of lncRNA function is associated with various human non-infectious diseases, such as inflammatory bowel disease, cardiovascular diseases, and diabetes mellitus. Here, we provide an overview of the regulation and mechanisms of lncRNA function in the development and differentiation of innate immune cells, and during the activation or repression of innate immune responses. These elucidations might be beneficial for the development of therapeutic strategies targeting inflammatory and innate immune-mediated diseases.
  • 1.6K
  • 09 Oct 2021
Topic Review
Neutrophil Extracellular Traps and Human Disease
The first description of a new form of neutrophil cell death distinct from that of apoptosis or necrosis was discovered in 2004 and coined neutrophil extracellular traps “(NETs)” or “NETosis”. Different stimuli for NET formation, and pathways that drive neutrophils to commit to NETosis have been elucidated in the years that followed. Critical enzymes required for NET formation have been discovered and targeted therapeutically. It has become clear that although this mechanism is thought to enhance host defense by ensnaring bacteria within large webs of DNA to increase bactericidal killing capacity, it is also injurious to innocent bystander tissue. Proteases and enzymes released from NETs injure epithelial and endothelial cells, perpetuating inflammation. In the context of autoimmunity, NETs release over 70 well-known autoantigens. NETs are associated with pathology in multiple diseases: lung diseases, vasculitis, autoimmune kidney diseases, atherosclerosis, rheumatoid arthritis, cancer, and psoriasis. Defining these pathways that drive NET release will provide insight into mechanisms of pathological insult and provide potential therapeutic targets.
  • 1.6K
  • 25 Apr 2022
Topic Review
P53
While viewed as the “guardian of the genome”, the importance of the tumor suppressor p53 protein has increasingly gained ever more recognition in modulating additional modes of action related to cell death. Slowly but surely, its importance has evolved from a mutated genetic locus heavily implicated in a wide array of cancer types to modulating lysosomal-mediated cell death either directly or indirectly through the transcriptional regulation of the key signal transduction pathway intermediates involved in this. Taken with its ability to directly modulate mitochondrial outer-membrane permeabilization (and cell death) collectively highlights the complex role that this protein undertakes at the molecular level
  • 1.6K
  • 07 Dec 2020
Topic Review
AP-1 Transcription Factors in Cancer
Immune check point blockade therapy has revolutionized the standard of cancer treatment and is credited with producing remarkable tumor remissions and increase in overall survival. This unprecedented clinical success however is feasible for a limited number of cancer patients due to resistance occurring before or during a course of immunotherapy, which is often associated with activation of oncogenic signaling pathways, co-inhibitory checkpoints upregulation or expansion of immunosuppressive regulatory T-cells (Tregs) in the tumor microenviroment (TME). Targeted therapy aiming to inactivate a signaling pathway such as the Mitogen Activated Protein Kinases (MAPKs) has recently received a lot of attention due to emerging data from preclinical studies indicating synergy with immune checkpoint blockade therapy. The dimeric transcription factor complex Activator Protein-1 (AP-1) is a group of proteins involved in a wide array of cell processes and a critical regulator of nuclear gene expression during T-cell activation. It is also one of the downstream targets of the MAPK signaling cascade.
  • 1.6K
  • 09 Sep 2021
Topic Review
Machine Learning in T- and B-Cell Epitope Prediction
An antigenic determinant (AD) is a portion of an antigen molecule known as an epitope that is recognized by the human immune system, specifically by antibodies or T and B cells. Recognition of epitopes is considered important in EBPV design to contain pandemics, epidemics, and endemics due to the outbreak of infectious diseases. To design an effective and viable EBPV against different strains of a pathogen, it is important to identify the putative T- and B-cell epitopes. Using the wet-lab experimental approach to identify these epitopes is time-consuming and costly because the experimental screening of a vast number of potential epitope candidates is required. Fortunately, various available machine learning (ML)-based prediction methods have reduced the burden related to the epitope mapping process by decreasing the potential epitope candidate list for experimental trials. Moreover, these methods are also cost-effective, scalable, and fast. 
  • 1.6K
  • 16 Feb 2022
Topic Review
The Effects of Dietary on Tumor Metabolism
The remodeled cancer cell metabolism affects the tumor microenvironment and promotes an immunosuppressive state by changing the levels of macro- and micronutrients and by releasing hormones and cytokines that recruit immunosuppressive immune cells. Novel dietary interventions such as amino acid restriction and periodic fasting mimicking diets can prevent or dampen the formation of an immunosuppressive microenvironment by acting systemically on the release of hormones and growth factors, inhibiting the release of proinflammatory cytokines, and remodeling the tumor vasculature and extracellular matrix.
  • 1.6K
  • 10 Aug 2023
Topic Review
Cocktail Anti-Tick Vaccines
Cocktail vaccines are a combination of at least two anti-tick vaccines. The concept of anti-tick vaccines was first demonstrated in 1939 [1], after which numerous antigens were identified [2-6]. However, until now, Bm86- based vaccines (Gavac TM in Cuba and TickGARD PLUSTM in Australia) are the only commercialized tick vaccines and are the most successful under field conditions [7-8]. Consequently, Willadsen [9], proposed that a combination of tick-antigens could enhance the efficacy of anti-tick vaccines. Additionally, this could broaden the vaccine protection- spectrum: (A) against multiple tick species (B) against tick-borne pathogens. Similar to single anti-tick vaccines [10-12], when ingested, antibodies induced against the cocktail vaccine-antigen constituents can traverse the gut epithelium, through the hemolymph to react against the corresponding tissue proteins, hence interfering with physiological functions of the proteins.
  • 1.6K
  • 01 Nov 2020
Topic Review
Peripheral Responses to Pain
Pain can be induced by tissue injuries, diseases and infections. The interactions between the peripheral nervous system (PNS) and immune system are primary actions in pain sensitizations. In response to stimuli, nociceptors release various mediators from their terminals that potently activate and recruit immune cells, whereas infiltrated immune cells further promote sensitization of nociceptors and the transition from acute to chronic pain by producing cytokines, chemokines, lipid mediators and growth factors. Immune cells not only play roles in pain production but also contribute to PNS repair and pain resolution by secreting anti-inflammatory or analgesic effectors. 
  • 1.6K
  • 12 Mar 2021
Topic Review
Unrecognizable Memory Phenotype CD8+ T-cells
Virtual memory T (TVM) cells are a recently described population of conventional CD8+ T cells that, in spite of their antigen inexperience, express markers of T cell activation. TVM cells exhibit rapid responsiveness to both antigen-specific and innate stimuli in youth but acquire intrinsic antigen-specific response defects in the elderly.
  • 1.6K
  • 09 Dec 2020
Topic Review
Orthodontically Induced Inflammatory Root Resorption
Orthodontically induced inflammatory root resorption (OIIRR) is considered an undesired and inevitable complication induced by orthodontic forces. This inflammatory mechanism is regulated by immune cells that precede orthodontic tooth movement (OTM) and can influence the severity of OIIRR. OIIRR occurs on almost all tooth roots exposed to orthodontic forces.
  • 1.5K
  • 20 Oct 2022
Topic Review
Thrombospondin-1 in the Tumor Microenvironment
The identification of thrombospondin-1 as an angiogenesis inhibitor in 1990 prompted interest in its role in cancer biology and potential as a therapeutic target. Decreased thrombospondin-1 mRNA and protein expression are associated with progression in several cancers, while expression by nonmalignant cells in the tumor microenvironment and circulating levels in cancer patients can be elevated. THBS1 is not a tumor suppressor gene, but the regulation of its expression in malignant cells by oncogenes and tumor suppressor genes mediates some of their effects on carcinogenesis, tumor progression, and metastasis. In addition to regulating angiogenesis and perfusion of the tumor vasculature, thrombospondin-1 limits antitumor immunity by CD47-dependent regulation of innate and adaptive immune cells. Conversely, thrombospondin-1 is a component of particles released by immune cells that mediate tumor cell killing. Thrombospondin-1 differentially regulates the sensitivity of malignant and nonmalignant cells to genotoxic stress caused by radiotherapy and chemotherapy. 
  • 1.5K
  • 23 Jun 2021
Topic Review
Proteases and Mucus
Proteases are enzymes that catalyse the hydrolysis of peptide bonds within proteins, facilitating their cleavage; this hydrolysis can either activate, inactivate, or modulate the activity of the target protein.
  • 1.5K
  • 04 Jun 2021
Topic Review
Molecular Characterization of LAG-3
Lymphocyte activation gene 3 (LAG-3) is a cell surface inhibitory receptor with multiple biological activities over T cell activation and effector functions. LAG-3 plays a regulatory role in immunity and emerged some time ago as an inhibitory immune checkpoint molecule comparable to PD-1 and CTLA-4 and a potential target for enhancing anti-cancer immune responses. LAG-3 is the third inhibitory receptor to be exploited in human anti-cancer immunotherapies, and it is considered a potential next-generation cancer immunotherapy target in human therapy, right next to PD-1 and CTLA-4. Unlike PD-1 and CTLA-4, the exact mechanisms of action of LAG-3 and its relationship with other immune checkpoint molecules remain poorly understood. This is partly caused by the presence of non-conventional signaling motifs in its intracellular domain that are different from other conventional immunoregulatory signaling motifs but with similar inhibitory activities.
  • 1.5K
  • 25 Jun 2021
Topic Review
Reactive Species on Innate Immunity
The role of reactive species RS (of oxygen ROS, nitrogen RNS and halogen RHS) on innate immunity is examined. The importance of these species in innate immunity was first recognized in phagocytes that underwent a “respiratory burst” after activation. The anion superoxide •O2− and hydrogen peroxide H2O2 are detrimental to the microbial population. NADPH oxidase NOx, as an •O2− producer is essential for microbial destruction, and patients lacking this functional oxidase are more susceptible to microbial infections. Reactive nitrogen species RNS (the most important are nitric oxide radical -•NO, peroxynitrite ONOO— and its derivatives), are also harmful to microorganisms, including bacteria, viruses, and parasites. Hypochlorous acid HOCl and hypothiocyanous acid HOSCN synthesized through the enzyme myeloperoxidase MPO, which catalyzes the reaction between H2O2 and Cl− or SCN−, are important inorganic bactericidal molecules, effective against a wide range of microbes. 
  • 1.5K
  • 26 Oct 2022
Topic Review
Effects of Particulate Matter on Inflammation and Thrombosis
Ambient air pollution has become a common problem worldwide. Exposure to pollutant particles causes many health conditions, having a particular impact on pulmonary and cardiovascular disease. Increased understanding of the pathological processes related to these conditions may facilitate the prevention of the adverse impact of air pollution on our physical health. 
  • 1.5K
  • 04 Aug 2022
Topic Review
Macrophage Migration Inhibitory Factor in Renal Inflammation
Renal inflammation is an initial pathological process during progressive renal injury regardless of the initial cause. Macrophage migration inhibitory factor (MIF) is a truly proinflammatory stress mediator that is highly expressed in a variety of both inflammatory cells and intrinsic kidney cells. MIF is released from the diseased kidney immediately upon stimulation to trigger renal inflammation by activating macrophages and T cells, and promoting the production of proinflammatory cytokines, chemokines, and stress molecules via signaling pathways involving the CD74/CD44 and chemokine receptors CXCR2, CXCR4, and CXCR7 signaling. In addition, MIF can function as a stress molecule to counter-regulate the immunosuppressive effect of glucocorticoid in renal inflammation. Given the critical position of MIF in the upstream inflammatory cascade, the regulatory role and molecular mechanisms of MIF in kidney diseases will be focused on.
  • 1.5K
  • 29 Jun 2022
Topic Review
Main Potential Cytokine Targets in Psoriasis
Psoriasis is an autoimmune disease mediated by disturbed T cells and other immune cells, and is defined by deep-red, well-demarcated skin lesions. Using biologics to target specific immune components, such as upregulated cytokines secreted by activated immune cells, is the most advanced therapy for psoriasis to date.
  • 1.5K
  • 28 Feb 2022
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