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Topic Review
BET Inhibitors in AIDS Therapy
A critical burden of AIDS therapy is the evasive nature of HIV-1 in face of host immune responses, the so-called “latency.” Recently, a promising approach, the “Shock and Kill” strategy, was proposed to eliminate latently HIV-1-infected cell reservoirs. This therapeutic concept involves two crucial steps: HIV-1 reactivation from its latency stage using a latency-reversing agent (LRA) followed by host immune responses to destroy HIV-1-infected cells in combination with reinforced antiretroviral therapy to kill the progeny virus. Looking at epigenetics of HIV-1 infection, researchers proved that some bromodomains and extra-terminal motif protein inhibitors (BETis) can reactivate HIV-1 from latency. However, to date, only a few BETis have shown HIV-1-reactivating functions, and none of them have yet been approved for clinical trial.  
  • 1.5K
  • 29 Jun 2021
Topic Review
MRNA Encoded Antibodies
The field of mRNA has made significant progress in the last ten years and has emerged as a highly attractive means of encoding and producing any protein of interest in vivo. Through the natural role of mRNA as a transient carrier of genetic information for translation into proteins, in vivo expression of mRNA-encoded antibodies offer many advantages over recombinantly produced antibodies.
  • 1.5K
  • 22 Mar 2021
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.
  • 1.5K
  • 11 Nov 2021
Topic Review
CD146 (MCAM)
CD146 is a cell adhesion molecule expressed on all the vascular tree and belongs to the immunoglobulin superfamily. Two isoforms of CD146 exists, a long isoform expressed at the cell junction and a short isoform located at the apical membrane of the cells. CD146 appears to be critical in regulating vascular permeability, cell-cell cohesion, leukocyte transmigration, and angiogenesis. As a consequence, CD146 is involved in the pathogenesis of various diseases including autoimmune diseases and cancers. Also, CD146 exists in a soluble form generated via the action of matrix metalloproteinases and referred to as soluble CD146 (sCD146). The concentration of sCD146 is quantifiable in the sera and cerebrospinal fluid of healthy individuals. Indeed, any variation in its physiological concentration is associated with certain diseases making it an excellent biomarker for diagnostic purposes.  
  • 1.5K
  • 27 Apr 2021
Topic Review
Types of Lipid-Based Nanocarriers for Vaccine Delivery
Lipid-based vaccine delivery systems such as the conventional liposomes, virosomes, bilosomes, vesosomes, pH-fusogenic liposomes, transferosomes, immuno-liposomes, ethosomes, and lipid nanoparticles have gained a remarkable interest in vaccine delivery due to their ability to render antigens in vesicular structures, that in turn prevents its enzymatic degradation in vivo. The particulate form of lipid-based nanocarriers confers immunostimulatory potential, making them ideal antigen carriers.
  • 1.5K
  • 31 Mar 2023
Topic Review
Amygdala Neuroinflammation and Psychiatric Disorders
Depression and anxiety disorder are the most common mental diseases affecting hundreds of millions of people worldwide. The comorbidity rate of anxiety disorder and depression is very high, with 74% of depressed patients having anxiety symptoms, while 61% of anxious patients have depression symptoms. Stress exposure is widely accepted as a critical contributing factor to psychological and neuropathological disorders. Especially during the COVID-19 pandemic, the high pressure of increasingly demanding work and life has led to a sharp rise in the incidence of mental diseases. Inflammation induces psychological and neuropathological disorders by influencing neuronal excitability, neurotransmitter release, receptor, and transporter expression through peripheral hormones and autonomic responses. A number of animal and human studies have revealed that the amygdala, ventral hippocampus, and medial prefrontal cortex (mPFC) are extensively involved in the occurrence of anxiety, depression, and related behavioral regulation. Among them, the amygdala, one of the kernel brain regions mediating stress-coping located in the deep temporal lobe, is considered the hub center for processing emotionally salient stimuli and implementing appropriate behavioral responses.
  • 1.5K
  • 23 Feb 2023
Topic Review
Dysregulated DNA Methylation
Epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs, are known regulators of gene expression and genomic stability in cell growth, development, and differentiation. Since epigenetic mechanisms can regulate several immune system elements, epigenetic alterations have been found in several autoimmune diseases.
  • 1.5K
  • 08 Dec 2021
Topic Review
Crohn’s Disease
Crohn’s disease is increasing in incidence and prevalence in younger people and is of a particularly aggressive nature. One emerging treatment targets Mycobacterium avium paratuberculosis (MAP), an organism implicated in the causation of Crohn’s disease. This study reviewed a cohort of paediatric patients with active Crohn’s disease treated with Anti-Mycobacterial Antibiotic Therapy (AMAT). Sixteen paediatric patients, the majority of whom had failed conventional immunosuppressive therapy, were treated with AMAT. Endoscopic remission was scored using the Simple Endoscopic Score for Crohn’s Disease and clinical remission was assessed using the Weighted Paediatric Crohn’s Disease Activity Index (wPCDAI). Inflammatory blood markers were also routinely recorded. Patients were followed up clinically and endoscopically during treatment after an average of two months (range 1–6) and 17 months (range 2–49), respectively. A significant reduction in both scores assessing clinical improvement (p < 0.001) and mucosal healing (p < 0.0078) was observed at these timepoints; 47% of patients had achieved clinical remission and 63% endoscopic remission. Haemoglobin and serum inflammatory markers normalised for more than 50% of the cohort by six months of treatment. No adverse effects were reported throughout treatment.
  • 1.5K
  • 10 Dec 2020
Topic Review
Immunosuppressive Cells
Tumor-associated macrophages (TAMs) produce various chemokines and angiogenic factors that promote tumor development, along with other immunosuppressive cells. TAMs generated from monocytes develop into functional, fully activated macrophages, and TAMs obtain various immunosuppressive functions to maintain the tumor microenvironment. The main population of TAMs comprises CD163+ M2 macrophages, and CD163+ TAMs release soluble (s)CD163 and several proinflammatory chemokines as a result of TAM activation to induce an immunosuppressive tumor microenvironment. Since direct blockade of PD1/PD-L1 signaling between tumor cells and tumor-infiltrating T cells is mandatory to induce an anti-immune response by anti-PD1 Abs. Understanding the crosstalk between TAMs and immunosuppressive cells is important for optimizing PD1 Ab-based immunotherapy.
  • 1.5K
  • 03 Aug 2020
Topic Review
NLRC4 Inflammasome
The NLR family apoptosis inhibitory proteins (NAIP)-NLR family caspase-associated recruitment domain-containing protein 4 (NLRC4) inflammasome is important for mounting an immune response against Gram-negative bacteria. NLRC4 is activated through NAIPs sensing type 3 secretion system (T3SS) proteins from Gram-negative bacteria, such as Salmonella Typhimurium. Mutations in NAIPs and NLRC4 are linked to autoinflammatory disorders in humans.
  • 1.5K
  • 16 May 2022
Topic Review
Toll-like Receptor 2 in Pro- and Anti-Inflammatory Processes
While a certain level of inflammation is critical for humans to survive infection and injury, a prolonged inflammatory response can have fatal consequences. Pattern recognition Toll-like receptors (TLRs) are key players in the initiation of an inflammatory process. TLR2 is one of the most studied pattern recognition receptors (PRRs) and is known to form heterodimers with either TLR1, TLR4, TLR6, and TLR10, allowing it to recognize a wide range of pathogens.
  • 1.5K
  • 17 Aug 2023
Topic Review
Type I Interferons
Interferons (IFNs) are a heterogenous group of proteins that can be classified into three families (Type I, II, and III) based on distinct functions and characteristics. The family of human type I IFN is composed of 5 subgroups: IFN-α, -β, -κ, -ε, and -ω, whereas the type II IFN group only contains IFN-γ. Type III IFNs are composed of four IFN-λ proteins.
  • 1.5K
  • 06 Mar 2021
Topic Review
Natural Killer Cells and Cytotoxic T Cells
Natural killer (NK) cells and cytotoxic T (CD8+) cells are two of the most important types of immune cells in our body, protecting it from deadly invaders. While the NK cell is part of the innate immune system, the CD8+ cell is one of the major components of adaptive immunity. Still, these two very different types of cells share the most important function of destroying pathogen-infected and tumorous cells by releasing cytotoxic granules that promote proteolytic cleavage of harmful cells, leading to apoptosis.
  • 1.5K
  • 08 Feb 2024
Topic Review
NLRP3 and Preeclampsia
Preeclampsia (PE) is a specific syndrome of human pregnancy, being one of the main causes of maternal death. Persistent inflammation in the endothelium stimulates the secretion of several inflammatory mediators, activating different signaling patterns. One of these mechanisms is related to NLRP3 activation, initiated by high levels of danger signals such as cholesterol, urate, and glucose, producing IL-1, IL-18, and cell death by pyroptosis. Furthermore, reactive oxygen species (ROS), act as an intermediate to activate NLRP3, contributing to subsequent inflammatory cascades and cell damage. Moreover, increased production of ROS may elevate nitric oxide (NO) catabolism and consequently decrease NO bioavailability. NO has many roles in immune responses, including the regulation of signaling cascades. At the site of inflammation, vascular endothelium is crucial in the regulation of systemic inflammation with important implications for homeostasis.
  • 1.5K
  • 19 Nov 2021
Topic Review
Yeast β-Glucans as Fish Immunomodulators
Administration of immunostimulants in fish is a preventive method to combat infections. A wide variety of these biological molecules exist, among which one of the yeast wall compounds stands out for its different biological activities. The β-glucan that forms the structural part of yeast is capable of generating immune activity in fish by cell receptor recognition. The most frequently used β-glucans for the study of mechanisms of action are those of commercial origin, with doses recommended by the manufacturer. Nevertheless, their immune activity is inefficient in some fish species, and increasing the dose may show adverse effects, including immunosuppression. Conversely, experimental β-glucans from other yeast species show different activities, such as antibacterial, antioxidant, healing, and stress tolerance properties.
  • 1.4K
  • 23 Sep 2022
Topic Review
NF-κB Signaling and Virus Infection
The nuclear factor κB (NF-κB) family are the master transcription factors that control cell proliferation, apoptosis, the expression of interferons and proinflammatory factors, and viral infection. During viral infection, host innate immune system senses viral products, such as viral nucleic acids, to activate innate defense pathways, including the NF-κB signaling axis, thereby inhibiting viral infection. In these NF-κB signaling pathways, diverse types of ubiquitination have been shown to participate in different steps of the signal cascades. Recent advances find that viruses also modulate the ubiquitination in NF-κB signaling pathways to activate viral gene expression or inhibit host NF-κB activation and inflammation, thereby facilitating viral infection. Understanding the role of ubiquitination in NF-κB signaling during viral infection will advance our knowledge of regulatory mechanisms of NF-κB signaling and pave the avenue for potential antiviral therapeutics. 
  • 1.4K
  • 07 Apr 2021
Topic Review
Open MHC Class I Conformers
Open MHC-I conformers are mature fully glycosylated plasma membrane molecules (HLA-A, HLA-B, HLA-C, HLA-E, HLA-G, HLA-E, and CD1d in humans; H-2D, H-2L, and H-2K in mice) that have dissociated from the β2m light chain and the peptide. Given the flexibility and mobility of the α1 domain of the heavy chain, the open MHC-I conformers are free to interact with any nearby complementary amino acid sequences or peptides in a covalent and a non-covalent manner. Open MHC-I conformers are functional cis-trans structures capable of establishing physical cis-associations with themselves (i.e., homodimers), with other surface receptors (i.e., heterodimers), and shed into the extracellular milieu (i.e., soluble open conformers). In turn, the open conformers and the homodimers trans-interact with several receptors expressed by lymphomyeloid cells. Overall, the open MHC-I conformers impact cellular physiology and clinical and biomedical settings, including autoimmune responses, tumor escape, graft rejection, and neuronal development and cognition. 
  • 1.4K
  • 27 Oct 2021
Topic Review
Sarcoidosis: Clinical Manifestations
Sarcoidosis is a multi-system disease of unknown etiology characterized by the formation of granulomas in various organs. It affects people of all ethnic backgrounds and occurs at any time of life but is more frequent in African Americans, Scandinavians and in adults between 30 and 50 years of age. Sarcoidosis can affect any organ with a frequency varying according to ethnicity, sex and age.
  • 1.4K
  • 20 Apr 2021
Topic Review
Cx43-Mediated Signaling
The immunological synapse (IS) is an intercellular communication platform, organized at the contact site of two adjacent cells, where at least one is an immune cell. Functional IS formation is fundamental for the modulation of the most relevant immune system activities, such as T cell activation by antigen presenting cells. Extensive evidence suggests that connexins, in particular connexin-43 (Cx43) hemichannels and/or gap junctions (GJ), regulate signaling events in different types of IS. Although the underlying mechanisms are not fully understood, the current evidence suggests that Cx43 channels could act as facilitators for calcium ions, cyclic adenosine monophosphate, and/or adenosine triphosphate uptake and/or release at the interface of interacting cells. These second messengers have relevant roles in the IS signaling during dendritic cell (DC)-mediated T and NK cell activation, regulatory T cell-mediated immune suppression, and cytotoxic T lymphocyte or NK cell-mediated target tumor cell killing.
  • 1.4K
  • 09 Nov 2020
Topic Review
Role of Macrophages in Tendon-Bone Healing
Tendon-bone healing comprises three stages: the inflammatory stage, the repair stage, and the remodeling stage. Macrophages appear in substantial populations in the early stages of tendon-bone healing and persist throughout the healing process, regulating cell proliferation, differentiation, and extracellular matrix formation by secreting various inflammatory factors and growth factors. The importance of macrophages in tendon-bone healing has been progressively emphasized in recent years, and the processes by which they affect tendon-bone healing have gradually been uncovered.
  • 1.4K
  • 28 Nov 2022
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