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Topic Review
Mediterranean-Type Diets for Asthma and Atopy
The basis of the MedDi model is the diet of the people of the island of Crete in the early 1950s; it is characterized by a high plant/animal food ratio, and, compared with other populations, it is linked with a markedly low prevalence of chronic diseases, including cardiovascular disease (CVD), breast cancer, colorectal cancer, diabetes mellitus (DM), obesity, asthma, erectile dysfunction, depression and cognitive decline, and with a high life expectancy.
  • 1.2K
  • 19 May 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. 
  • 1.2K
  • 15 Nov 2023
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.
  • 1.2K
  • 01 Jun 2021
Topic Review
Ezrin, VASO-Active Intestinal Peptide and COVID-19
SARS-CoV-2 infection inhibits interferon expression, while hyper-activating innate-immune signalling and expression of pro-inflammatory cytokines. SARS-CoV-2 proteins: Spike, M and nsp6, nsp12 and nsp13 inhibit IFR3-mediated Type-1-interferon defence, but hyper-activate intracellular signalling, which leads to dysfunctional expression of pro-inflammatory cytokines, particularly IL-1β IL-6, IL-8, and TNFα. Ezrin, a sub-membrane adaptor-protein, organises multi-protein-complexes such as ezrin+NHERF1+NHE+CFTR, which control the density and location of ACE2 receptor expression on the luminal surface of airway-epithelial-cells, as well as determining susceptibility to SARS-CoV-2 infection. This protein complex is vital for lung-surfactant production for efficient gas-exchange. Ezrin also forms multi-protein-complexes that regulate signalling kinases; Ras, PKC, PI3K, and PKA. m-RAGE is a pattern-recognition-receptor of the innate immune system that is triggered by AGEs, which are chemically modified proteins common in the elderly and obese. Vasoactive Intestinal Peptide (VIP) is a 28-amino acid peptide released by intrinsic neurons in the human airways. 
  • 1.2K
  • 22 Apr 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.
  • 1.2K
  • 30 Oct 2020
Topic Review
The Viral Agents of BRDC
Bovine respiratory disease complex (BRDC) is a multifactorial disease of cattle which presents as bacterial and viral pneumonia. The causative agents of BRDC work in synergy to suppress the host immune response and increase the colonisation of the lower respiratory tracts by pathogenic bacteria. Environmental stress and/or viral infection predispose cattle to secondary bacterial infections via suppression of key innate and adaptive immune mechanisms. This allows bacteria to descend the respiratory tract unchallenged. BRDC is the costliest disease among feedlot cattle, and whilst vaccines exist for individual pathogens, there is still a lack of evidence for the efficacy of these vaccines and uncertainty surrounding the optimum timing of delivery. 
  • 1.2K
  • 14 Apr 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
Rheumatic Manifestations for ICIs
Immune checkpoint inhibitors (ICI) are monoclonal antibodies that activate the immune system aiming at enhancing antitumor immunity.  Their clinical efficacy is well documented but the side effects associated with their use are still under investigation.  These drugs cause several immune related adverse events (ir-AE) some of which stand within the field of Rheumatology.  Herein, we performed a literature review in an effort to evaluate all publicly available clinical data regarding rheumatic manifestations associated with ICI.  The most common musculoskeletal ir-AEs are inflammatory arthritis, polymyalgia rheumatica and myositis.  Non musculoskeletal rheumatic manifestations are less frequent with the most prominent being sicca, vasculitides and sarcoidosis.  Cases of systemic lupus erythematosus or scleroderma are extremely rare.  The majority of musculoskeletal ir-AE are of mild/moderate severity and can be managed with steroids with no need for ICI discontinuation.  In severe cases, more intense immunosuppressive therapy and permanent ICI discontinuation may be employed.  Oncologists should periodically screen patients receiving ICI for new onset inflammatory musculoskeletal complaints and seek a rheumatology consultation in cases of persisting symptoms.
  • 1.2K
  • 28 Oct 2020
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. 
  • 1.2K
  • 21 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. 
  • 1.2K
  • 17 Feb 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
Vaccines, Microbiota and Immunonutrition
Vaccination represents one of the most crucial achievements in the history of medicine, a turning point in the fight against infectious diseases. A key factor in modulating the immune system, both in its adaptive and innate components, is the microbiota. While microbiota can be modulated in different ways (i.e., antibiotics, probiotics, prebiotics), an effective and somewhat obvious mechanism is via nutrition. The science of nutrients and their therapeutic application is called immunonutrition, and it is increasingly being considered in several conditions.
  • 1.2K
  • 08 Mar 2022
Topic Review
Germinal Centers in Rheumatoid Arthritis
Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, affecting approximately 1% of the general population. To alleviate symptoms and ameliorate joint damage, chronic use of immunosuppressives is needed. However, these treatments are only partially effective and may lead to unwanted side effects. Therefore, a more profound understanding of the pathophysiology might lead to more effective therapies, or better still, a cure.  The presence of autoantibodies in RA indicates that B-cells might have a pivotal role in the disease. This concept is further supported by the fact that a diverse antibody response to various arthritis related epitopes is associated with arthritis development. In this context, attention has focused in recent years on the role of Germinal Centers (GCs) in RA. Since GCs act as the main anatomic location of somatic hypermutations, and thus contribute to the diversity and specificity of (auto) antibodies, it has been speculated that defects in germinal center reactions might be crucial in the initiation and maintenance of auto-immune events.
  • 1.2K
  • 27 Oct 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].
  • 1.2K
  • 27 Oct 2020
Topic Review
The Formyl Peptide Receptors
The formyl peptide receptors, abbreviated as formyl peptide receptors (FPRs) in humans, are pattern recognition receptors (PRRs) with central roles in host defense and inflammation.
  • 1.2K
  • 15 Dec 2022
Topic Review
The Adaptor Protein p66Shc
p66Shc is an adaptor protein with anti-mitogenic, anti-chemotactic, pro-apoptotic and pro-oxidant activities.  Neoplastic B cells from chronic lymphocytic leukemia (CLL) patients  have a profound deficiency in the expression of p66Shc which results in leukemic cell resistance to apoptosis and in an altered balance between homing and egress receptors that control B cell homing to and residency into the pro-survival lymphoid niche. Ablation of the gene encoding p66Shc in the Eμ-TCL1 mouse model of human CLL worsens disease presentation  by promoting leukemic cell invasiveness, providing in vivo evidence of the pathogenic role of the p66Shc defect in CLL pathogenesis. Here we briefly summarize the functions of p66Shc in lymphocytes, focalizing on the mechanisms exploited by p66Shc to control B cell trafficking and the abnormalities in this process caused by p66Shc deficiency in CLL. 
  • 1.1K
  • 12 Nov 2020
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. 
  • 1.1K
  • 08 Aug 2022
Topic Review
Adaptive Immune-Response to Tick-Borne Hemoparasites
Interactions between tick-borne pathogenic hemoparasites and different host effector mechanisms of T- and/or B cell-mediated adaptive immunity, involved in the late and long-lasting protective immune response. 
  • 1.1K
  • 02 Dec 2020
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.  
  • 1.1K
  • 02 Feb 2021
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. 
  • 1.1K
  • 26 Jul 2022
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