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Topic Review
Gene Conversion amongst Alu SINE
The process of non-allelic gene conversion acts on homologous sequences during recombination, replacing parts of one with the other to make them uniform. Such concerted evolution is best described as paralogous ribosomal RNA gene unification that serves to preserve the essential house-keeping functions of the converted genes. Transposed elements (TE), especially Alu short interspersed elements (SINE) that have more than a million copies in primate genomes, are a significant source of homologous units and a verified target of gene conversion. The consequences of such a recombination-based process are diverse, including multiplications of functional TE internal binding domains and, for evolutionists, confusing divergent annotations of orthologous transposable elements in related species. 
  • 787
  • 24 Jun 2021
Topic Review
Necroptosis in Brief
Necroptosis is a recently discovered form of programmed cell death that has gained significant attention in scientific and medical research. This review provides a comprehensive exploration of necroptosis, covering its molecular mechanisms and regulatory pathways. Key components like receptor-interacting protein kinases (RIPK1 and RIPK3) and mixed lineage kinase domain-like (MLKL) are discussed in detail, along with their roles in necroptotic cell death. The research also highlights the physiological functions of necroptosis in development, tissue maintenance, and immune response, as well as its involvement in diseases such as neurodegenerative disorders, inflammatory conditions, and cancer. Additionally, it touches on potential therapeutic interventions and the future outlook of necroptosis research.
  • 786
  • 18 Sep 2023
Topic Review
T Cell-Based Therapies of HCC
The scope of therapeutic options for the treatment of hepatocellular carcinoma (HCC) has recently been expanded by immunotherapeutic regimens. T cell-based therapies, especially in combination with other treatments have achieved far better outcomes compared to conventional treatments alone. However, there is an emerging body of evidence that eliciting T cell responses in immunotherapeutic approaches is insufficient for favorable outcomes.
  • 784
  • 29 Mar 2022
Topic Review
Quantitative Super-Resolution Imaging and GPCR Oligomerization Analysis
G-protein coupled receptors (GPCRs) are the largest family of cell surface receptors in eukaryotic cells. These seven-transmembrane receptors have influence in physiological events such as cell to cell communication, immune responses, nerve transmission and even hunger and sleep regulation. The role of GPCRs in diseases such as rheumatoid arthritis, heart disease, cancer, obesity, and neurodegenerative disorders accentuates the need to investigate this family of receptors further. More than a third of all drugs approved by the FDA target GPCRs but often such drugs have a variety of poorly understood mechanisms, as a recent example surrounding opioid receptor agonists illustrates.
  • 784
  • 15 Nov 2021
Topic Review
Critical Functions of PHB2
The prohibitin (PHB) gene was initially found to be antiproliferative and able to inhibit the initiation of DNA synthesis in rat liver in 1989. The human homologue (later to be known as PHB1) was then identified, cloned, and mapped to the human chromosome 17q21. In 1994, another member of prohibitin, PHB2, was discovered on chromosome 12p13 when two proteins were found to associate with the IgM antigen receptor of B lymphocytes.
  • 784
  • 04 May 2023
Topic Review
Iron Metabolism and Mechanisms of Ferroptosis
Ferroptosis is a newly discovered iron-dependent form of regulated cell death driven by phospholipid peroxidation and associated with processes including iron overload, lipid peroxidation, and dysfunction of cellular antioxidant systems. Ferroptosis is found to be closely related to many diseases, including cancer at every stage. Epithelial–mesenchymal transition (EMT) in malignant tumors that originate from epithelia promotes cancer-cell migration, invasion, and metastasis by disrupting cell–cell and cell–cell matrix junctions, cell polarity, etc.
  • 783
  • 31 Jul 2023
Topic Review
Iron, Ferroptosis, and Head and Neck Cancer
Ferroptosis is an iron-dependent regulatory form of cell death characterized by the accumulation of intracellular reactive oxygen species and lipid peroxidation. It plays a critical role not only in promoting drug resistance in tumors, but also in shaping therapeutic approaches for various malignancies. 
  • 783
  • 20 Oct 2023
Topic Review
PE_PGRS33 and humoral immune response
PE_PGRS proteins are surface antigens of Mycobacterium tuberculosis (Mtb) and a few other pathogenic mycobacteria. The PE_PGRS33 protein is among the most studied PE_PGRSs. It is known that the PE domain of PE_PGRS33 is required for the protein translocation through the mycobacterial cell wall, where the PGRS domain remains available for interaction with host receptors. Interaction with Toll like receptor 2 (TLR2) promotes secretion of inflammatory chemokines and cytokines, which are key in the immunopathogenesis of tuberculosis (TB). Here, we address key challenges in the development of a TB vaccine and attempt to provide a rationale for the development of new vaccines aimed at fostering a humoral response against Mtb. We show that the PGRS domain of PE_PGRS33 exposes four PGII sandwiches on the outer surface, which we propose to be directly involved through their loops in the interactions with the host receptors and as such are promising targets for a vaccination strategy aimed at inducing a humoral response. 
  • 782
  • 27 Jan 2021
Topic Review
COVID-19: the Immunological Challenges
Although COVID-19 pneumonia is a novel disease that is different from other types of ARDS, severe COVID-19-associated ARDS shares typical ARDS lung pathology such as diffuse alveolar damage and hyaline membrane formation. As Prasanna et al. summarized, the general rationale for low-dose radiation treatment of COVID-19 is its inhibition of the cytokine storm, which promotes pulmonary dysfunction and ultimately ARDS. Inflammation is a dynamic and progressive process that is tightly associated with redox-modulated reactions. When recruited to sites of inflammation, macrophages and neutrophils generate reactive species, including reactive oxygen and nitrogen species (ROS and RNS). With multiple pro-inflammatory cytokines and chemokines being secreted, the latter together with elevated levels of ROS and RNS deteriorate redox homeostasis, and further worsen the disease. During the past two decades, research has revealed that low-dose radiation-mediated homeostasis is associated with enhanced cellular detoxification of ROS by a major antioxidant enzyme (manganese superoxide dismutase, MnSOD) within the mitochondria. This adaptive protection of mitochondrial metabolic functions is thought to provide experimental and theoretical support for using low-dose radiation to limit virus replication. Other antioxidants, including glutathione, were also shown to be increased following exposure to low doses of sparsely ionizing radiation such as X and γ rays. Schaue et al. suggested that it might be difficult and challenging for patients with complicated conditions and advanced age to rebalance redox levels, and low-dose radiation treatment might be of clinical value with its broad suppression of various inflammatory, pro-oxidant pathways at multiple levels.
  • 782
  • 29 Sep 2021
Topic Review
GRP78 Autoantibodies in Immune-Mediated Neurological Diseases
The 78 kDa glucose-regulated protein (GRP78), a member of the 70 kDa heat-shock family of molecular chaperones (HSP70), is essential for the regulation of the unfolded protein response (UPR) resulting from cellular endoplasmic reticulum (ER) stress. During ER stress, GRP78 evades retention mechanisms and is translocated to the cell surface (csGRP78) where it functions as an autoantigen. Autoantibodies to GRP78 appear in prostate, ovarian, gastric, malignant melanoma, and colorectal cancers. They are also found in autoimmune pathologies such as rheumatoid arthritis (RA), neuromyelitis optica (NMO), anti-myelin oligodendrocyte glycoprotein antibody-associated disorder (AMOGAD), Lambert-Eaton myasthenic syndrome (LEMS), multiple sclerosis (MS), neuropsychiatric systemic lupus erythematosus (NPSLE) and type 1 diabetes (T1D). 
  • 782
  • 16 Jun 2022
Topic Review
Furin in Type 2 Diabetes
Post-translational modifications (PTMs) are chemical or enzymatic alterations that occur on proteins after they are synthesized from their corresponding genes. They are essential for protein function and are involved in various biological processes, including protein folding, localization, stability, activity, and interaction with other proteins. Proprotein convertases (PCs) are irreversible post-translational modifiers that have been extensively studied and are considered as key targets for novel therapeutics. They cleave proteins at specific sites causing conformational changes affecting their functions. Furin is considered as a PC model in regulating growth factors and is involved in regulating many pro-proteins. 
  • 781
  • 12 Oct 2023
Topic Review
Piperine’s Dual Mechanisms of Prevention and Destruction ofCancer
Piperine, an active alkaloid with a wide range of therapeutic properties, including antioxidant, anti-inflammatory, and immunomodulatory effects, has garnered attention for its potential in cancer prevention and treatment. Cancer chemoprevention emboldens the use of natural and synthetic biologically active substances to prevent, inhibit, or reverse cancer progression. Chemopreventive agents have been classified into blocking agents and suppressing agents. Blocking agents impede the initiation of tumors. Suppressing agents, on the other hand, act subsequently by suppressing the transformation of initiated cells into preneoplastic and/or neoplastic cells and malignancy. Piperine exhibits a unique duality in its abilities, functioning as both a blocking and a suppressing agent in cancer prevention and therapy. This dual role allows piperine to target multiple pathways and aspects of cancer development and progression, ultimately enhancing the effectiveness of chemoprevention strategies.
  • 781
  • 30 Nov 2023
Topic Review
Red Blood Cells and Their Adhesiveness in Disease
Red blood cells (RBCs) have been implicated in the progression of a wide range of disease states where their roles have been specifically linked to their adhesiveness. Such diseases include, inter alia, atherosclerosis, tumors (in terms of its growth suppression), polycythemia vera, central retinal occlusion and diabetes mellitus.
  • 781
  • 13 Jul 2023
Topic Review
Melanoma and The Ubiquitin Pathway
Ubiquitination is a post-translational modification that plays a crucial role in various cellular biological activities and participates in cancer pathogenesis, including melanoma. 
  • 780
  • 28 Jul 2022
Topic Review
Ethanol on Melanoma Initiation and Progression
Malignant melanoma is an aggressive cancer of the skin and the leading cause of death from skin cancer. One major risk factor linked to melanoma development is exposure to UV radiation. Recent studies have demonstrated that alcohol consumption is positively linked with an increased risk of cancers, including melanoma.
  • 780
  • 25 Oct 2022
Topic Review
mTORC1 Pathway and Autophagy in Platinum-Based Chemotherapeutics Resistance
Cisplatin (cis-diamminedichloroplatinum I) is a platinum-based drug, the mainstay of anticancer treatment for numerous solid tumors. Drug resistance is a serious problem in the treatment with platinum-based drugs. Resistance to cisplatin depends on both the inner adaptive mechanisms of cancer cells and the tumor microenvironment, where hypoxic conditions increase the tolerance of cancer cells to the drug. Among intercellular adaptive factors, the most important are: (1) a reduced drug accumulation due to either a decreased influx or an increased efflux; (2) an increase in DNA repair and changes in DNA damage response (DDR); (3) an alteration of apoptosis; (4) changes in signaling pathways, notably the mammalian target of rapamycin complex 1 (mTORC1) pathway. 
  • 779
  • 11 Aug 2023
Topic Review
Generation of Liver Organoids
The liver represents the most important metabolic organ of the human body. It is evident that an imbalance of liver function can lead to several pathological conditions, known as liver failure. Orthotropic liver transplantation (OLT) is currently the most effective and established treatment for end-stage liver diseases and acute liver failure (ALF). Due to several limitations, stem-cell-based therapies are currently being developed as alternative solutions. Stem cells or progenitor cells derived from various sources have emerged as an alternative source of hepatic regeneration. Therefore, hematopoietic stem cells (HSCs), mesenchymal stromal cells (MSCs), endothelial progenitor cells (EPCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are also known to differentiate into hepatocyte-like cells (HPLCs) and liver progenitor cells (LPCs) that can be used in preclinical or clinical studies of liver disease. Furthermore, these cells have been shown to be effective in the development of liver organoids that can be used for disease modeling, drug testing and regenerative medicine.
  • 778
  • 13 May 2022
Topic Review
Fibrillin-1 Microfibrils in Organismal Physiology
Fibrillin-1 is the major structural component of the 10 nm-diameter microfibrils that confer key physical and mechanical properties to virtually every tissue, alone and together with elastin in the elastic fibers. Mutations in fibrillin-1 cause pleiotropic manifestations in Marfan syndrome (MFS), including dissecting thoracic aortic aneurysms, myocardial dysfunction, progressive bone loss, disproportionate skeletal growth, and the dislocation of the crystalline lens. 
  • 778
  • 15 Jun 2022
Topic Review
(BEN)-Domain Containing Protein 3
(BEN)-Domain containing protein 3 (BEND3) is a transcription factor that plays a critical role in the regulation of gene expression in mammals. While there is limited research on the role of BEND3 as a tumor suppressor or an oncogene and its potential role in cancer therapy is still emerging, several studies suggest that it may be involved in both the processes. Its interaction and regulation with multiple other factors via p21 have already been reported to play a significant role in cancer development, which serves as an indication of its potential role in oncogenesis. Its interaction with chromatin modifiers such as NuRD and NoRC and its role in the recruitment of polycomb repressive complex 2 (PRC2) are some of the additional events indicative of its potential role in cancer development.
  • 776
  • 07 Aug 2023
Topic Review
Breast Cancer Metastasis Studying Tool
During the metastatic process, breast cancer cells must come into contact with the extra-cellular matrix (ECM) at every step. The ECM provides both structural support and biochemical cues, and cell–ECM interactions can lead to changes in drug response. Here, we used fibroblast-derived ECM (FDM) to perform high throughput drug screening of 4T1 breast cancer cells on metastatic organ ECM (lung), and we see that drug response differs from treatment on plastic. The FDMs that we can produce from different organs are abundant in and contains a complex mixture of ECM proteins. We also show differences in ECM composition between the primary site and secondary organ sites. Furthermore, we show that global kinase signalling of 4T1 cells on the ECM is relatively unchanged between organs, while changes in signalling compared to plastic are significant. Our study highlights the importance of context when testing drug response in vitro, showing that consideration of the ECM is critically important. 
  • 775
  • 06 Jul 2021
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