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Topic Review
Biological Roles of circRNAs
Circular RNAs (circRNAs) comprise a large class of endogenous non-coding RNA with covalently closed loops and have independent functions as linear transcripts transcribed from identical genes. circRNAs are generated by a “back-splicing” process regulated by regulatory elements in cis and associating proteins in trans. Many studies have shown that circRNAs play important roles in multiple processes, including splicing, transcription, chromatin modification, miRNA sponges, and protein decoys. circRNAs are highly stable because of their closed ring structure, which prevents them from degradation by exonucleases, and are more abundant in terminally differentiated cells, such as brains.
  • 848
  • 12 Aug 2022
Topic Review
Dendritic Cell Tumor Vaccination
Despite significant recent improvements in the field of immunotherapy, cancer remains a heavy burden on patients and healthcare systems. In recent years, immunotherapies have led to remarkable strides in treating certain cancers. However, despite the success of checkpoint inhibitors and the advent of cellular therapies, novel strategies need to be explored to (1) improve treatment in patients where these approaches fail and (2) make such treatments widely and financially accessible. Vaccines based on tumor antigens (Ag) have emerged as an innovative strategy with the potential to address these areas. Here, we review the fundamental aspects relevant for the development of cancer vaccines and the critical role of dendritic cells (DCs) in this process. We first offer a general overview of DC biology and routes of Ag presentation eliciting effective T cell-mediated immune responses. We then present new therapeutic avenues specifically targeting Fc gamma receptors (FcγR) as a means to deliver antigen selectively to DCs and its effects on T-cell activation. We present an overview of the mechanistic aspects of FcγR-mediated DC targeting, as well as potential tumor vaccination strategies based on preclinical and translational studies. In particular, we highlight recent developments in the field of recombinant immune complex-like large molecules and their potential for DC-mediated tumor vaccination in the clinic. These findings go beyond cancer research and may be of relevance for other disease areas that could benefit from FcγR-targeted antigen delivery, such as autoimmunity and infectious diseases.
  • 847
  • 29 Apr 2021
Topic Review
Extracellular Traps in Disease/Protection
The first formal description of the microbicidal activity of extracellular traps (ETs) containing DNA occurred in neutrophils in 2004. Since then, ETs have been identified in different populations of cells involved in both innate and adaptive immune responses. Much of the knowledge has been obtained from in vitro or ex vivo studies; however, in vivo evaluations in experimental models and human biological materials have corroborated some of the results obtained. Two types of ETs have been described—suicidal and vital ETs, with or without the death of the producer cell. The studies showed that the same cell type may have more than one ETs formation mechanism and that different cells may have similar ETs formation mechanisms. ETs can act by controlling or promoting the mechanisms involved in the development and evolution of various infectious and non-infectious diseases, such as autoimmune, cardiovascular, thrombotic, and neoplastic diseases, among others.
  • 845
  • 09 Aug 2021
Topic Review
Mesenchymal Stem Cells in Infectious Diseases
Mesenchymal stem cells (MSCs) are attractive in various fields of regenerative medicine due to their therapeutic potential and complex unique properties. Basic stem cell research and the global COVID-19 pandemic have given impetus to the development of cell therapy for infectious diseases. 
  • 845
  • 22 Nov 2022
Topic Review
Mitochondria in Health and Disease
Mitochondrial alterations have been implicated in a wide range of diseases, such as neurodegenerative disorders, metabolic disorders, and cancer. 
  • 845
  • 29 May 2023
Topic Review
The H+ Transporter SLC4A11
Solute-linked cotransporter, SLC4A11, a member of the bicarbonate transporter family, is an electrogenic H+ transporter activated by NH3 and alkaline pH. Although SLC4A11 does not transport bicarbonate, it shares many properties with other members of the SLC4 family. SLC4A11 mutations can lead to corneal endothelial dystrophy and hearing deficits that are recapitulated in SLC4A11 knock-out mice. SLC4A11, at the inner mitochondrial membrane, facilitates glutamine catabolism and suppresses the production of mitochondrial superoxide by providing ammonia-sensitive H+ uncoupling that reduces glutamine-driven mitochondrial membrane potential hyperpolarization. Mitochondrial oxidative stress in SLC4A11 KO also triggers dysfunctional autophagy and lysosomes, as well as ER stress. SLC4A11 expression is induced by oxidative stress through the transcription factor NRF2, the master regulator of antioxidant genes.
  • 842
  • 25 Jan 2022
Topic Review
ZEB1 in Cornea
ZEB1 is an important transcription factor for epithelial to mesenchymal transition (EMT) and in the regulation of cell differentiation and transformation. In the cornea, ZEB1 presents in all three layers: the epithelium, the stroma and the endothelium. Mutations of ZEB1 have been linked to multiple corneal genetic defects, particularly to the corneal dystrophies including keratoconus (KD), Fuchs endothelial corneal dystrophy (FECD), and posterior polymorphous corneal dystrophy (PPCD).
  • 841
  • 22 Apr 2021
Topic Review
Mesenchymal Stem Cells and Inflammaging
Rapid growth of the geriatric population has been made possible with advancements in pharmaceutical and health sciences. Hence, age-associated diseases are becoming more common. Aging encompasses deterioration of the immune system, known as immunosenescence. Dysregulation of the immune cell production, differentiation, and functioning lead to a chronic subclinical inflammatory state termed inflammaging. The hallmarks of the aging immune system are decreased naïve cells, increased memory cells, and increased serum levels of pro-inflammatory cytokines. Mesenchymal stem cell (MSC) transplantation is a promising solution to halt immunosenescence as the cells have excellent immunomodulatory functions and low immunogenicity.
  • 841
  • 08 Jun 2021
Topic Review
Astrocytes and Tissue Engineering
Astrocytes are key cells in the central nervous system. They are involved in many functions under physiological and pathological conditions. Primary cultures of astrocytes represent an important object for basic and translational neuroscience research, especially for in vitro cell models. Astrocyte cultures for functional cell models are most commonly isolated from rodent brains, because they are easily accessible and grow rapidly. Tissue engineering and biomaterial development represent a promising alternative to animal testing and provide an ideal opportunity to develop and test various biomaterials as scaffolds for purposes such as cell ingrowth and tissue repair.
  • 841
  • 13 Jul 2021
Topic Review
Colon Cancer Stem Cells
Cancer stem cells (CSCs) are a small subpopulation of cells within tumors with properties, such as self-renewal, differentiation, and tumorigenicity. CSCs have been proposed as a plausible therapeutic target as they are responsible for tumor recurrence, metastasis, and conventional therapy resistance. Selectively targeting CSCs is a promising strategy to eliminate the propagation of tumor cells and impair overall tumor development.
  • 840
  • 09 May 2023
Topic Review
IL-6 Cytokines and EMP
Epithelial–mesenchymal plasticity (EMP) plays critical physiological roles during embryonic development, postnatal growth and epithelial homeostasis, but it is also involved in a number of pathological conditions, including wound repair, fibrosis, inflammation and cancer. EMP has been intimately linked with most, if not all, of the steps during cancer development and progression (e.g., migration, invasion, immune escape, drug resistance and metastatic dissemination). Cytokines from the interleukin 6 (IL-6) family play fundamental roles in mediating tumour-promoting inflammation within the tumour microenvironment. In general, IL-6 cytokines activate EMP processes, fostering the acquisition of mesenchymal features in cancer cells. Here, we will summarise all the relevant literature related to all members of the IL-6 family and EMP.
  • 838
  • 29 Mar 2022
Topic Review
Telomere-Binding Protein
Telomere-binding proteins (also known as TERF, TRBF, TRF) function to bind telomeric DNA in various species. In particular, telomere-binding protein refers to TTAGGG repeat binding factor-1 (TRF1) and TTAGGG repeat binding factor-2 (TRF2). Telomere sequences in humans are composed of TTAGGG sequences which provide protection and replication of chromosome ends to prevent degradation. Telomere-binding proteins can generate a T-loop to protect chromosome ends. TRFs are double-stranded proteins which are known to induce bending, looping, and pairing of DNA which aids in the formation of T-loops. They directly bind to TTAGGG repeat sequence in the DNA. There are also subtelomeric regions present for regulation. However, in humans, there are six subunits forming a complex known as shelterin.
  • 837
  • 16 Nov 2022
Topic Review
Potential Therapeutic Targets on SARS-CoV-2
Coronavirus disease 19 (COVID-19) is caused by an enveloped, positive-sense, single-stranded RNA virus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the realm Riboviria, order Nidovirales, family Coronaviridae, genus Betacoronavirus and the species Severe acute respiratory syndrome-related coronavirus. This viral disease is characterized by a myriad of varying symptoms, such as pyrexia, cough, hemoptysis, dyspnoea, diarrhea, muscle soreness, dysosmia, lymphopenia and dysgeusia amongst others. The virus mainly infects humans, various other mammals, avian species and some other companion livestock. SARS-CoV-2 cellular entry is primarily accomplished by molecular interaction between the virus’s spike (S) protein and the host cell surface receptor, angiotensin-converting enzyme 2 (ACE2), although other host cell-associated receptors/factors, such as neuropilin 1 (NRP-1) and neuropilin 2 (NRP-2), C-type lectin receptors (CLRs), as well as proteases such as TMPRSS2 (transmembrane serine protease 2) and furin, might also play a crucial role in infection, tropism, pathogenesis and clinical outcome.
  • 836
  • 15 Oct 2021
Topic Review
Kinase Inhibition in Hematologic Neoplasms
Protein kinases (PK) are signaling regulators involved in various cellular functions including metabolism, cell cycle regulation, survival, and differentiation. Tumor dependence of continuous proliferative signals mediated through protein kinases overexpression instigated increased strategies of kinase inhibition in the oncologic practice over the last couple decades.
  • 836
  • 14 Oct 2021
Topic Review
Arabidopsis HY2 NaCl Signaling during Seed Germination
PΦB is an open-chain tetrapyrrole chromophore, a critical synthetase for phytochromes to function as a light receptor to regulate plant growth and development. Arabidopsis HY2 encodes a key synthase of PΦB, which is a ferredoxin-dependent biliverdin reductase that catalyzes the reduction in the A-ring 2,3,31,32-diene system to produce an ethylidene group for assembly with apophytochromes.
  • 836
  • 03 Dec 2021
Topic Review
Nanoparticles in Pediatric Brain Tumors' Cancer Stem Cells
Primary malignant brain tumors are the most common solid neoplasm in childhood. Despite recent advances, many children affected by aggressive or metastatic brain tumors still present poor prognosis, therefore the development of more effective therapies is urgent. Cancer stem cells (CSCs) have been discovered and isolated in both pediatric and adult patients with brain tumors (e.g., medulloblastoma, gliomas and ependymoma). CSCs are a small clonal population of cancer cells responsible for brain tumor initiation, maintenance and progression, displaying resistance to conventional anticancer therapies. CSCs are characterized by a specific repertoire of surface markers and intracellular specific pathways. These unique features of CSCs biology offer the opportunity to build therapeutic approaches to specifically target these cells in the complex tumor bulk.
  • 836
  • 15 Mar 2023
Topic Review
Exosomes in Bone Sarcomas
Bone sarcomas are rare cancers which often present with metastatic disease and are still associated with poor survival rates. Studies in the last decade have identified that exosomes, a type of extracellular vesicle released by cells, play an important role in tumour progression and dissemination. Through the transfer of their cargo (RNAs, proteins, and lipids) across cells, they are involved in cellular cross-talk and can induce changes in cellular behaviour. Exosomes have been shown to be important in metastasis organotropism, induction of angiogenesis and vascular permeability, the education of cells towards a pro-metastatic phenotype or the interaction between stromal and tumour cells. Due to the importance exosomes have in disease progression and the high incidence of metastasis in bone sarcomas, recent studies have evaluated the implications of these extracellular vesicles in bone sarcomas.
  • 836
  • 17 May 2021
Topic Review
Detection of Sepsis in Platelets
The incidence of sepsis varies depending on the hospital studied, being higher in those dealing with more clinically severe patients, such as cancer hospitals.
  • 835
  • 09 Dec 2021
Topic Review
Intrinsic Mechanisms of Hippocampal Neural Stem Cell Aging
Since Joseph Altman's groundbreaking research revealing neurogenesis in the adult rat hippocampus, the field has witnessed an exponential growth in publications. Researchers know that the adult hippocampus harbors a pool of adult neural stem cells (NSCs) driving life-long neurogenesis and plasticity. Aging significantly influences NSC functions, leading to a diminished capacity for generating new neurons and contributing to the gradual deterioration of hippocampus-related cognitive functions. Although the mechanisms underlying this age-related decline are only partially understood, factors such as increased NSC quiescence, altered differentiation patterns and NSC exhaustion have been linked to it.
  • 835
  • 30 Nov 2023
Topic Review
Axon Initial Segment and Neurodegenerative Diseases
Brain channelopathies are a group of neurological disorders that result from genetic mutations affecting ion channels in the brain. Ion channels are specialized proteins that play a crucial role in the electrical activity of nerve cells by controlling the flow of ions such as sodium, potassium, and calcium. When these channels are not functioning properly, they can cause a wide range of neurological symptoms such as seizures, movement disorders, and cognitive impairment. In this context, the axon initial segment (AIS) is the site of action potential initiation in most neurons. This region is characterized by a high density of voltage-gated sodium channels (VGSCs), which are responsible for the rapid depolarization that occurs when the neuron is stimulated. The AIS is also enriched in other ion channels, such as potassium channels, that play a role in shaping the action potential waveform and determining the firing frequency of the neuron. In addition to ion channels, the AIS contains a complex cytoskeletal structure that helps to anchor the channels in place and regulate their function. 
  • 834
  • 06 May 2023
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