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Topic Review
Pathogens, Diagnosis and Treatment of Chronic Granulomatous Disease
Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in the phagocytic function of the innate immune system owing to mutations in genes encoding the five subunits of the nicotinamide adenine dinucleotide phosphatase (NADPH) oxidase enzyme complex. The most common microorganisms observed in the patients with CGD are Staphylococcus aureus, Aspergillus spp., Candida spp., Nocardia spp., Burkholderia spp., Serratia spp., and Salmonella spp. Antibacterial prophylaxis with trimethoprim-sulfamethoxazole, antifungal prophylaxis usually with itraconazole, and interferon gamma immunotherapy have been successfully used in reducing infection in CGD. Haematopoietic stem cell transplantation (HCT) have been successfully proven to be the treatment of choice in patients with CGD.
  • 345
  • 07 Oct 2023
Topic Review
Synergism of Radiotherapy, PARP Inhibition, and Immune-Checkpoint Blockade
Radiotherapy and, more recently, PARP inhibitors (PARPis) and immune-checkpoint inhibitors represent effective tools in cancer therapy. Radiotherapy exerts its effects not only by damaging DNA and inducing tumor cell death, but also stimulating anti-tumor immune responses. PARPis are known to exert their therapeutic effects by inhibiting DNA repair, and they may be used in combination with radiotherapy. Both radiotherapy and PARPis modulate inflammatory signals and stimulate type I IFN (IFN-I)-dependent immune activation. However, they can also support the development of an immunosuppressive tumor environment and upregulate PD-L1 expression on tumor cells. When provided as monotherapy, immune-checkpoint inhibitors (mainly antibodies to CTLA-4 and the PD-1/PD-L1 axis) result particularly effective only in immunogenic tumors. Combinations of immunotherapy with therapies that favor priming of the immune response to tumor-associated antigens are, therefore, suitable strategies. The widely explored association of radiotherapy and immunotherapy has confirmed this benefit for several cancers. Association with PARPis has also been investigated in clinical trials. Immunotherapy counteracts the immunosuppressive effects of radiotherapy and/or PARPis and synergies with their immunological effects, promoting and unleashing immune responses toward primary and metastatic lesions (abscopal effect). 
  • 344
  • 22 Feb 2023
Topic Review
Metal-Based Nanoparticles for Cancer Metalloimmunotherapy
Metalloimmunotherapy offers a new form of cancer immunotherapy that utilizes the inherent immunomodulatory features of metal ions to enhance anticancer immune responses. Their versatile functionalities for a multitude of direct and indirect anticancer activities together with their inherent biocompatibility suggest that metal ions can help overcome the current issues associated with cancer immunotherapy. However, metal ions exhibit poor drug-like properties due to their intrinsic physicochemical profiles that impede in vivo pharmacological performance, thus necessitating an effective pharmaceutical formulation strategy to improve their in vivo behavior. Metal-based nanoparticles provide a promising platform technology for reshaping metal ions into more drug-like formulations with nano-enabled engineering approaches. 
  • 341
  • 01 Aug 2023
Topic Review
The Mechanisms of cGAS-STING Pathway-Induced Apoptosis
The cGAS–STING signaling axis can be activated by cytosolic DNA, including both non-self DNA and self DNA. This axis is used by the innate immune system to monitor invading pathogens and/or damage. Increasing evidence has suggested that the cGAS-STING pathway not only facilitates inflammatory responses and the production of type I interferons (IFN), but also activates other cellular processes, such as apoptosis.
  • 339
  • 23 Apr 2023
Topic Review
DSS-Induced Colitis in Brief
Dextran Sulfate Sodium (DSS)-induced colitis is a widely used experimental model for studying inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). This research delves into the intricacies of DSS-induced colitis, exploring its mechanisms, key features, and relevance in IBD research. 
  • 339
  • 08 Oct 2023
Topic Review
Heme Interactions
Heme (Fe2+-protoporphyrin IX) is a pigment of life, and as a prosthetic group in several hemoproteins, it contributes to diverse critical cellular processes. Direct interactions of extracellular heme with alternative pathway complement components (APCCs) may be implicated molecularly in diverse conditions at sites of abnormal cell damage and vascular injury. 
  • 335
  • 29 Jun 2023
Topic Review
Immunogenic Cell Death by Radiation
Ionizing radiation (IR) is used to treat 50% of cancers. While the cytotoxic effects related to DNA damage with IR have been known since the early 20th century, the role of the immune system in the treatment response is still yet to be fully determined. IR can induce immunogenic cell death (ICD), which activates innate and adaptive immunity against the cancer.
  • 333
  • 06 May 2023
Topic Review
Nanoparticle-Mediated Nucleic Acid Delivery Systems for Immunotherapy
Successful clinical results of immunotherapeutic approaches for cancer treatment were led by antibodies targeting immune checkpoints, and many have advanced through clinical trials and obtained FDA approval. A major opportunity remains for the development of nucleic acid technology for cancer immunotherapy in the form of cancer vaccines, adoptive T-cell therapies, and gene regulation. However, these therapeutic approaches face many challenges related to their delivery to target cells, including their in vivo decay, the limited uptake by target cells, the requirements for nuclear penetration (in some cases), and the damage caused to healthy cells. These barriers can be avoided and resolved by utilizing advanced smart nanocarriers (e.g., lipids, polymers, spherical nucleic acids, metallic nanoparticles) that enable the efficient and selective delivery of nucleic acids to the target cells and/or tissues.
  • 333
  • 28 Jun 2023
Topic Review
Organophosphate-Pesticide-Mediated Immune Response Modulation
Organophosphate pesticides (OPs) have greatly facilitated food production worldwide, and their use is not limited to agriculture and the control of pests and disease vectors. However, these substances can directly affect the immune response of non-target organisms. In this sense, exposure to OPs can have negative effects on innate and adaptive immunity, promoting deregulation in humoral and cellular processes such as phagocytosis, cytokine expression, antibody production, cell proliferation, and differentiation, which are crucial mechanisms for host defense against external agents. It found that there is an important gap in the study of non-target organisms, examples of which are echinoderms and chondrichthyans. It is therefore important to increase the number of studies on other species directly or indirectly affected by Ops, to assess the degree of impact at the individual level and how this affects higher levels, such as populations and ecosystems.
  • 329
  • 15 May 2023
Topic Review
Teleostei Innate Immune System
The innate immune system is the first line of defense in multicellular organisms. Danio rerio is widely considered a promising model for IIS-related research, with the most amount of scRNAseq data available among Teleostei.
  • 327
  • 29 Dec 2023
Topic Review
SARS-CoV-2 Specific T Cell Epitopes
The COVID-19 pandemic has caused extensive loss of lives and economic hardship. In response, infectious disease experts and vaccine developers promptly responded by bringing forth candidate vaccines, some of which have been listed in the World Health Organization’s Emergency Use Listing.  Differences in the human leukocyte antigen (HLA) in variation of the T cell epitopes of SARS-CoV-2 genetic mutations left room for improvement of the vaccines.
  • 326
  • 11 Oct 2022
Topic Review
Damage-Associated Molecular Patterns in Psoriasis
Psoriasis is a chronic skin disorder that involves both innate and adaptive immune responses in its pathogenesis. Local tissue damage is a hallmark feature of psoriasis and other autoimmune diseases. In psoriasis, damage-associated molecular patterns (DAMPs) released by damaged local tissue act as danger signals and trigger inflammatory responses by recruiting and activating immune cells. They also stimulate the release of pro-inflammatory cytokines and chemokines, which exacerbate the inflammatory response and contribute to disease progression. DAMPs have a dual function. On the one hand, they can regulate cell homeostasis and maintain cell function when present within cells. On the other hand, they can also act as endogenous molecules of cell death or injury and amplify the signal of inflammation through various cell receptors upon release. This leads to the activation of immune cells and the secretion of a large number of inflammatory factors. DAMPs not only play a pro-inflammatory role in acute inflammation, such as sepsis, acute liver injury, or acute pancreatitis, but they also mediate immunity in chronic immune diseases such as rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease.
  • 326
  • 23 Jan 2024
Topic Review
Monoclonal Antibodies
The development of severe multidrug-resistant bacterial infections has recently intensified because of the COVID-19 pandemic. According to the guidelines issued by the World Health Organization (WHO), routine antibiotic administration is not recommended for patients with supposed or confirmed mild SARS-CoV-2 infection or pneumonia, unless bacterial infection is clinically suspected.
  • 325
  • 19 Feb 2024
Topic Review
Intravenous Immunoglobulin in Kawasaki Disease
Kawasaki disease (KD) is an acute vasculitis of childhood that affects the medium vessels with a special predilection to the involvement of coronary arteries. The major morbidity of this disease is due to coronary artery aneurysm, which occurs in about 25–30% of untreated cases. Intravenous immunoglobulin (IVIg) has consistently been shown to reduce the risk of CAAs to less than 5%. However, the mechanism of immunomodulation remains unclear. Several studies on the role of IVIg in the modulation of toll-like receptor pathways, autophagy, and apoptosis of the mononuclear phagocytic system, neutrophil extracellular trap, and dendritic cell modulation suggest a modulatory effect on the innate immune system. Similarly, certain studies have shown its effect on T-cell differentiation, cytokine release, and regulatory T-cell function.
  • 324
  • 14 Aug 2023
Topic Review
Adaptive Immunity in Older People
Vaccination is the best strategy to prevent this fact, but older people present a less efficient response, as their immune system is weaker due mainly to a phenomenon known as immunosenescence. The adaptive immune system is constituted by two types of lymphocytes, T and B cells, and the function and fitness of these cell populations are affected during ageing.
  • 323
  • 08 Sep 2022
Topic Review
Intracellular Antibodies for Drugs and Drug Discovery
The application of antibodies in cells was first shown in the early 1990s, and subsequently, the field of intracellular antibodies has expanded to encompass antibody fragments and their use in target validation and as engineered molecules that can be fused to moieties (referred to as warheads) to replace the Fc effector region of a whole immunoglobulin to elicit intracellular responses, such as cell death pathways or protein degradation. These various forms of intracellular antibodies have largely been used as research tools to investigate function within cells by perturbing protein activity. New applications of such molecules are on the horizon, namely their use as drugs per se and as templates for small-molecule drug discovery. The former is a potential new pharmacology that could harness the power and flexibility of molecular biology to generate new classes of drugs (herein referred to as macrodrugs when used in the context of disease control). Delivery of engineered intracellular antibodies, and other antigen-binding macromolecules formats, into cells to produce a therapeutic effect could be applied to any therapeutic area where regulation, degradation or other kinds of manipulation of target proteins can produce a therapeutic effect.
  • 323
  • 13 Jul 2023
Topic Review
Immune Checkpoint Proteins, Metabolism and CAR T-Cell Migration
Adoptive transfer of T cells genetically engineered to express chimeric antigen receptors (CAR) has demonstrated striking efficacy for the treatment of several B-cell malignancies. CAR are synthetic receptors that consist of an MHC-independent antigen binding domain usually derived from a tumor-specific monoclonal antibody fused to an intracellular signaling region, composed of the CD3ζ chain and costimulatory molecules from CD28 and 4-1BB. As of September 2021, five CAR T products have been approved by the Food and Drug Administration (FDA) in the United States, targeting leukemia, lymphoma, and multiple myeloma.
  • 322
  • 22 Jun 2022
Topic Review
Antimicrobial Peptides in the Nervous System
Antimicrobial peptides (AMPs) are short, mainly positively charged, amphipathic molecules. AMPs are important effectors of the immune response in insects with a broad spectrum of antibacterial, antifungal, and antiparasitic activity. In addition to these well-known roles, AMPs exhibit many other, often unobvious, functions in the host.
  • 322
  • 31 Mar 2023
Topic Review
Alcohol-Induced Liver Injury in Brief
Alcoholic liver disease (ALD) is a global health concern, representing a spectrum of liver disorders resulting from chronic alcohol consumption. To decipher the intricate mechanisms underlying ALD and develop effective therapies, researchers have turned to experimental models. Among these, the alcohol-induced liver injury model, accomplished through chronic alcohol administration to animals, has been pivotal in elucidating key pathophysiological aspects of ALD. This research navigates through the methodologies employed to induce liver injury, highlights the diverse pathological features observed, explores the underlying mechanisms, and discusses the model's relevance in advancing our understanding of ALD. Additionally, it delves into the multifaceted applications of this model in the quest for novel therapeutic strategies to combat ALD.
  • 318
  • 08 Oct 2023
Topic Review
Role of Macrophage lncRNAs in Mediating Inflammatory Processes
Long noncoding RNAs (lncRNAs) are molecules >200 bases in length without protein-coding functions implicated in signal transduction and gene expression regulation via interaction with proteins or RNAs, exhibiting various functions. The expression of lncRNAs has been detected in many cell types, including macrophages, a type of immune cell involved in acute and chronic inflammation, removal of dead or damaged cells, and tissue repair. Increasing evidence indicates that lncRNAs play essential roles in macrophage functions and disease development.
  • 317
  • 17 Aug 2023
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