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Topic Review
Proteoglycan 4 (PRG4)/Lubricin in Gout
Proteoglycan 4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes, released into synovial fluid, and adsorbed on cartilage and synovial surfaces. PRG4′s roles include cartilage boundary lubrication, synovial homeostasis, immunomodulation, and suppression of inflammation. PRG4 supplementation may offer a new therapeutic option for gout.
  • 612
  • 27 Jul 2023
Topic Review
Immunogenic Cell Death Role in Urothelial Cancer Therapy
Bladder cancer is the 13th most common cause of cancer death with the highest lifetime cost for treatment of all cancers. The role of a novel therapeutic approach called immunogenic cell death (ICD) in urothelial cancer of the bladder is clarified.
  • 611
  • 29 Sep 2022
Topic Review
Alternative Splicing in Immunomodulatory Genes
The interaction between the tumor and immune cells within the tumor microenvironment is facilitated by signaling pathways driven by immunomodulatory proteins. Alternative splicing regulates the production of multiple immunomodulatory proteins with diverse functionality from a single mRNA transcript. Splicing factors are pivotal in modulating alternative splicing processes but are also subject to regulation. The dysregulation of alternative splicing may result from splicing factor (SF) abnormal expression levels and mutations in the cis and trans-acting elements and small nuclear RNA (snRNA) molecules. Aberrant splicing may generate abnormal mRNA transcripts encoding isoforms with altered functions that contribute to tumorigenesis or cancer progression.
  • 611
  • 30 Aug 2023
Topic Review
P2RX7
P2RX7 belongs to the family of P2X receptors that are assembled and active when in their trimeric form. Each monomer is composed of two transmembrane domains that are connected by a large extracellular loop, and an N- and C- termini domain located intracellularly. However, unlike other members, P2RX7 has a long intracellular C-terminal domain that structurally distinguishes it from the others and confers its unique biological activities. Even though all seven members of the P2X receptors recognize eATP, they are activated with various affinities that range from 0.5 µM for P2RX3 to over 100 µM for P2RX7. Thus, activation of P2RX7 requires high levels of eATP, levels that are found in the tumor microenvironment (TME) which controls the three main activities of the receptor: cationic exchange, macropore opening and NLRP3 inflammasome activation.
  • 610
  • 09 Jun 2023
Topic Review
Immunotherapy through Non-Small Cell Lung Cancer
The landscape of non-small cell lung cancer has changed dramatically. This is largely due to the introduction of immunotherapy, and in particular, immune checkpoint blockade inhibitors. Anti-PD-1 immunotherapy is now standard treatment for patients with non-small cell lung cancer. However, not all patients respond to immunotherapy, and few patients achieve long-term survival. Moreover, some patients experience adverse effects from the treatment.
  • 607
  • 14 Jun 2023
Topic Review
Cellular Component of the Hepatic Tumor Microenvironment
Organ microenvironments are irrefutable modules enabling the proliferation of cancer cells to organ systems exterior to the primary tumor. The hepatic tumor immune microenvironment constitutes cellular and non-cellular components including a complex mixture of immune cells.
  • 604
  • 12 Jan 2023
Topic Review
Inflammasomes in Inflammatory Diseases
Inflammasomes, a group of multiprotein complexes, are essential in regulating inflammation and immune responses. Several inflammasomes, including nucleotide-binding domain leucine-rich repeat-containing protein 1 (NLRP1), NLRP3, NLRP6, NLRP7, NLRP12, interferon-inducible protein 16 (IFI16), NOD-like receptor family CARD domain-containing protein 4 (NLRC4), absent in melanoma 2 (AIM2), and pyrin, have been studied in various inflammatory diseases. Activating inflammasomes leads to the processing and production of proinflammatory cytokines, such as interleukin (IL)-1β and IL-18. The NLRP3 inflammasome is the most extensively studied and well characterized. Consequently, targeting inflammasomes (particularly NLRP3) with several compounds, including small molecule inhibitors and natural compounds, has been studied as a potential therapeutic strategy. 
  • 604
  • 17 Nov 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.
  • 599
  • 29 Dec 2023
Topic Review
Immunosenescence and Cytomegalovirus
Aging induces numerous physiological alterations, with immunosenescence emerging as a pivotal factor. This phenomenon has attracted both researchers and clinicians, prompting profound questions about its implications for health and disease. Among the contributing factors, one intriguing actor in this complex interplay is human cytomegalovirus (CMV), a member of the herpesvirus family. Latent CMV infection exerts a profound influence on the aging immune system, potentially contributing to age-related diseases.
  • 597
  • 22 Jan 2024
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.
  • 596
  • 13 Jul 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. 
  • 591
  • 29 Jun 2023
Topic Review
Implications of Flaviviruses Immunity on ZIKV Vaccine
The Zika virus (ZIKV) was first isolated from a rhesus macaque in the Zika forest of Uganda in 1947. Isolated cases were reported until 2007, when the first major outbreaks of Zika infection were reported from the Island of Yap in Micronesia and from French Polynesia in 2013. In 2015, ZIKV started to circulate in Latin America, and in 2016, ZIKV was considered by WHO to be a Public Health Emergency of International Concern due to cases of Congenital Zika Syndrome (CZS), a ZIKV-associated complication never observed before. After a peak of cases in 2016, the infection incidence dropped dramatically but still causes concern because of the associated microcephaly cases, especially in regions where the dengue virus (DENV) is endemic and co-circulates with ZIKV. A vaccine could be an important tool to mitigate CZS in endemic countries. However, the immunological relationship between ZIKV and other flaviviruses, especially DENV, and the low numbers of ZIKV infections are potential challenges for developing and testing a vaccine against ZIKV.
  • 590
  • 02 Mar 2022
Topic Review
Targets on Astrocytes for the Treatment of ALS
Astrocytes, the most numerous and giant glial cells in the central nervous system (CNS), possess the unique ability to divide and proliferate throughout life. The cytosol of astrocytes exhibits a distinctive star-shaped morphology, housing a critical structural component known as the glial filament. Comprised of glial fibrillary acidic protein (GFAP), this intermediate filament is essential to the cytoskeleton and serves as a standard marker for astrocytes. Importantly, it is not entirely exclusive to astrocytes but also labels neural stem cells. Apart from organizing the blood–brain barrier (BBB) and supporting, sequestering, and isolating neurons, these cells perform a multitude of vital biological functions. These include the metabolism, synthesis, and secretion of neurotrophic factors, regulation of neurotransmitters and calcium homeostasis, maintenance of mitochondrial function, participation in nervous system and circuit development, and regulation of the immune status of the CNS. However, these functions are partially or wholly lost in reactive astrocytes. Amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by the degeneration of upper and lower motor neurons (MNs), with an average survival of 3–5 years.
  • 589
  • 18 Feb 2024
Topic Review
RKIP Pleiotropic Activities in Cancer and Inflammatory Diseases
Several gene products play pivotal roles in the induction of inflammation and the progression of cancer. The Raf kinase inhibitory protein (RKIP) is a cytosolic protein that exerts pleiotropic activities in such conditions, and thus regulates oncogenesis and immune-mediated diseases through its deregulation.
  • 585
  • 22 Dec 2021
Topic Review
MiR-223 as Diagnostic and Prognostic Markers in Cancer
MicroRNAs (miRNAs) are endogenous small non-coding RNAs that function in the regulation of gene expression and regulate a wide array of biological processes, including carcinogenesis. Several mechanisms are involved in miRNA-associated cancer development, such as amplification or deletion of miRNA genes, abnormal transcriptional control of miRNAs, dysregulated epigenetic changes, and defects in miRNA biogenesis machinery. MiRNA-223 has been found to be a critical miRNA that is involved in a wide range of molecular processes. It is involved in the regulation of inflammatory cytokines, epithelial homeostasis, immune checkpoint signaling pathways, apoptosis, cell cycle, cell proliferation, invasion, and chemosensitivity. Published literature has demonstrated that miRNA-223 expression is associated with cancer development and prevention. Mir-223 functions as either a tumor suppressor or oncogene under certain circumstances, containing multiple targets or specific targets. Hence, miR-223 could be a potential candidate diagnostic biomarker, prognostic biomarker, or therapeutic target of cancer. 
  • 584
  • 28 Feb 2022
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.
  • 582
  • 28 Jun 2023
Topic Review
EV miRNAs Modulate Inflammation
In rheumatoid arthritis (RA), extracellular vesicles (EVs) are associated with both the propagation and attenuation of joint inflammation and destruction. However, the specific EV content responsible for these processes is largely unknown. Investigations into identifying EV content are confounded by the challenges in obtaining high-quality EV preparations from synovial fluid. Implementing a size exclusion chromatography-based method of EV isolation, coupled with small RNA sequencing, we accurately characterised EV miRNAs in synovial fluid obtained from RA patients and investigated the differences between joints with high- and low-grade inflammation. 
  • 579
  • 24 May 2021
Topic Review
Emerging Immunotherapies in Breast Cancer
Immunotherapy is a highly emerging form of breast cancer therapy that enables clinicians to target cancers with specific receptor expression profiles. Two popular immunotherapeutic approaches involve chimeric antigen receptor-T cells (CAR-T) and bispecific antibodies (BsAb). Briefly mentioned in this review as well is the mRNA vaccine technology recently popularized by the COVID-19 vaccine. These forms of immunotherapy can highly select for the tumor target of interest to generate specific tumor lysis. Combining emerging immunotherapeutics with tumor marker discovery sets the stage for highly targeted immunotherapy to be the future of cancer treatments. This review highlights the principles of CAR-T and BsAb therapy, improvements in CAR and BsAb engineering, and recently identified human breast cancer markers in the context of in vitro or in vivo CAR-T or BsAb treatment. 
  • 578
  • 06 Dec 2021
Topic Review
T Cell Immune Checkpoint Molecules in HIV
T cell exhaustion is a condition of cell dysfunction despite antigen engagement, characterized by augmented surface expression of immune checkpoint molecules such as programmed cell death protein 1 (PD-1), which suppress T cell receptor (TCR) signaling and negatively impact the proliferative and effector activities of T cells. T cell function is tightly modulated by cellular glucose metabolism, which produces adequate energy to support a robust reaction when battling pathogen infection. The transition of the T cells from an active to an exhausted state following pathogen persistence involves a drastic change in metabolic activity. The human immunodeficiency virus (HIV) is a human pathogen that attacks the immune system by targeting CD4+ T lymphocytes. HIV infection can result in acquired immunodeficiency syndrome (AIDS), a fatal stage at which the host immune system collapses and becomes vulnerable to many types of opportunistic infections.
  • 578
  • 10 Nov 2022
Topic Review
Immunological Aspects of Long COVID-19
The COVID-19 pandemic has affected the world unprecedentedly, with both positive and negative impacts. COVID-19 significantly impacted the immune system, and understanding the immunological consequences of COVID-19 is essential for developing effective treatment strategies. The immunological aspects of long COVID-19 is a phenomenon where individuals continue to experience a range of symptoms and complications, even after the acute phase of COVID-19 infection has subsided. The immune system responds to the initial infection by producing various immune cells and molecules, including antibodies, T cells, and cytokines. However, in some patients, this immune response becomes dysregulated, leading to chronic inflammation and persistent symptoms. 
  • 578
  • 06 Nov 2023
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