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Topic Review
Pluripotent Organ-Specific Pericytes in Growth and Maturation
Cells fitting the description of Mesenchymal Stem/Signaling Cells (MSC) have been isolated from a large number of adult tissues. The original characteristics of MSC as defined by Caplan’s group were adherence to plastic, expression of a subset of cell surface antigens, and the cells could be induced in vitro to differentiate towards different cell lineages, including chondrocytes, bone cells, and adipocytes. It has been noted that MSC from most tissues or fluids are very heterogeneous, and some sources appear to have unique features, including unique lectin-binding phenotypes. Interestingly, MSC from bone marrow appear to preferentially respond to osteogenic stimuli, while MSC from synovium respond well to chondrogenic stimuli. Thus, different locations may reflect the needs of different environments.
  • 615
  • 25 May 2022
Topic Review
Nod-Like Receptor Pyrin Containing Protein 3 Inflammasome
Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, whose pathophysiology has been linked to the neuroinflammatory process. The increased activity of the Nod-like receptor pyrin containing protein 3 (NLRP3) inflammasome, an intracellular multiprotein complex, is intrinsically implicated in neuroinflammation by promoting the maturation and release of proinflammatory cytokines such as interleukin (IL)-1β and IL-18.
  • 615
  • 04 Jan 2023
Topic Review
Endoplasmic Reticulum Stress and Cancer
Unfolded protein response (UPR) is an adaptive response which is used for re-establishing protein homeostasis, and it is triggered by endoplasmic reticulum (ER) stress. Specific ER proteins mediate UPR activation, after dissociation from chaperone Glucose-Regulated Protein 78 (GRP78). UPR can decrease ER stress, producing an ER adaptive response, block UPR if ER homeostasis is restored, or regulate apoptosis. 
  • 614
  • 13 Feb 2023
Topic Review
Human Liver Mesenchymal Stem Cells
Mesenchymal stem cells (MSCs) can be isolated from the majority of human tissues and easily maintained in culture. Cells derived from different sources have closely resemblant, but not identical phenotypes, gene expression patterns, and differentiation profiles. Unique features of human liver MSCs include expression of the hepatocyte-specific genes and predisposition to differentiate into the hepatocytes. This makes liver MSCs an attractive starting material for the manufacturing of human hepatocytes, which are in short supply in basic research, drug testing, and cell therapy. 
  • 614
  • 03 Jul 2023
Topic Review
MicroRNA-21 Regulates Stemness in PDAC
Pancreatic ductal adenocarcinoma (PDAC) is the most common and aggressive type of pancreatic cancer (PCa) with a low survival rate. microRNAs (miRs) are endogenous, non-coding RNAs that moderate numerous biological processes. miRs have been associated with the chemoresistance and metastasis of PDAC and the presence of a subpopulation of highly plastic “stem”-like cells within the tumor, known as cancer stem cells (CSCs).
  • 613
  • 19 Apr 2022
Topic Review
Connexins in Tumor Microenvironment Initiation and Maintenance
Connexins are proteins which comprise gap junctions in cells. These junctions can directly connect neighboring cells and the cell interior with the extracellular microenvironment and thus they act as tissue integrators. In addition, connexins perform a variety of non-channel functions. Alterations in connexin regulation can lead to unfavorable shifts in the tissue adhesive context thus eradicating the constraints of the normal tissue microenvironment, triggering (or enhancing) cancerogenesis and further tumor progression.
  • 613
  • 04 May 2023
Topic Review
cAMP-Related Macromolecular Complexes Regulating CFTR Opening
Cystic fibrosis (CF) is the rare genetic disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). These molecules, known as CFTR modulators, have led to unprecedented improvements in the lung function and quality of life of most CF patients. However, the efficacy of these drugs is still suboptimal, and the clinical response is highly variable even among individuals bearing the same mutation. Furthermore, not all patients carrying rare CFTR mutations are eligible for CFTR modulator therapies, indicating the need for alternative and/or add-on therapeutic approaches. Because the second messenger 3′,5′-cyclic adenosine monophosphate (cAMP) represents the primary trigger for CFTR activation and a major regulator of different steps of the life cycle of the channel, there is growing interest in devising ways to fine-tune the cAMP signaling pathway for therapeutic purposes.
  • 613
  • 07 Jul 2023
Topic Review
Heterochromatin and Nuclear Phenotypes of T. infestans
Triatoma infestans (Klug), the most important vector of Chagas disease, is a hemipteran insect belonging to the Triatominae subfamily of the Reduviidae family and one of the 84 species of the Triatomini tribe.
  • 612
  • 07 Oct 2023
Topic Review
Age-Related Alternative Splicing
Alternative splicing changes are closely linked to aging, though it remains unclear if they are drivers or effects. As organisms age, splicing patterns change, varying gene isoform levels and functions. These changes may contribute to aging alterations rather than just reflect declining RNA quality control. Three main splicing types—intron retention, cassette exons, and cryptic exons—play key roles in age-related complexity. These events modify protein domains and increase nonsense-mediated decay, shifting protein isoform levels and functions. This may potentially drive aging or serve as a biomarker. Fluctuations in splicing factor expression also occur with aging. Somatic mutations in splicing genes can also promote aging and age-related disease. 
  • 612
  • 29 Dec 2023
Topic Review
Plasticity of Human RPE Cells
The retina is a specialized light-sensitive tissue in the eye of mammals and humans that provides visual perception, and is actively studied at the cellular, molecular and genetic levels. Photoreceptor cells located in its outer part perform the function of converting light (phototransduction) into neurochemical signals, which are processed in the neurons of the retina and the brain and ultimately form our vision. Functional support for retinal neurons is provided by retinal pigment epithelium cells (RPE cells). The retinal pigment epithelium (RPE) is a single-row layer of pigmented, hexagonal, normally non-proliferating cells located between the choroid and the photoreceptor cells of the retina. The RPE performs many diverse functions to support the retina, including the transepithelial transport of substances, the phagocytosis of photoreceptor outer segments, and a number of processes in the visual cycle, as well as participation in the blood–retinal barrier and secretion of growth factors. The RPE plays an important role in regulating the redox homeostasis of retinal photoreceptors. A few cells have been isolated from the human RPE, which, according to strict clonal analysis and other stem cell criteria (self-renewal and the production of differential progeny), were classified as adult RPE stem cells (RPESCs). The number of  mammalian RPESCs was determined in vitro experiments, from which it became clear that  to 2% of cells are capable of proliferation, self-renewal, and the expression of specific genes characterizing stem cells. Depending on microenvironmental conditions, RPESCs can remain quiescent in a stemness state or exhibit multipotent differentiation. RPESCs can produce RPE cells and are capable of generating different types of photoreceptors and nerve cells, or mesenchymal cells.
  • 612
  • 15 Mar 2024
Topic Review
Primary Stressors in Osteoarthritis Pathogenesis
Osteoarthritis (OA) is characterized by the degradation of joint cartilage tissue, chronic local inflammation, and bone remodeling, which result in joint pain, stiffness, swelling, and restricted motion. Aging phenotypes are considered a manifestation of accumulated cellular damage and defective repair. This is particularly apparent in the primary cell type of the articular joint, the articular chondrocytes. Articular chondrocytes are constantly facing the challenge of stressors, including mechanical overloading, oxidation, DNA damage, proteostatic stress, and metabolic imbalance.
  • 611
  • 04 May 2023
Topic Review
GATNNCDA
Circular RNAs (circRNAs) are a new class of endogenous non-coding RNAs with covalent closed loop structure. Researchers have revealed that circRNAs play an important role in human diseases. As experimental identification of interactions between circRNA and disease is time-consuming and expensive, effective computational methods are an urgent need for predicting potential circRNA–disease associations. In this study, we proposed a novel computational method named GATNNCDA, which combines Graph Attention Network (GAT) and multi-layer neural network (NN) to infer disease-related circRNAs. Specially, GATNNCDA first integrates disease semantic similarity, circRNA functional similarity and the respective Gaussian Interaction Profile (GIP) kernel similarities. The integrated similarities are used as initial node features, and then GAT is applied for further feature extraction in the heterogeneous circRNA–disease graph. Finally, the NN-based classifier is introduced for prediction. The results of fivefold cross validation demonstrated that GATNNCDA achieved an average AUC of 0.9613 and AUPR of 0.9433 on the CircR2Disease dataset, and outperformed other state-of-the-art methods.
  • 609
  • 20 Aug 2021
Topic Review
Roles of Histone Deacetylase 6 in Physiological Processes
Histone deacetylase 6 (HDAC6), by deacetylation of multiple substrates and association with interacting proteins, regulates many physiological processes that are involved in cancer development and invasiveness such as cell proliferation, apoptosis, motility, epithelial to mesenchymal transition, and angiogenesis. Due to its ability to remove misfolded proteins, induce autophagy, and regulate unfolded protein response, HDAC6 plays a protective role in responses to stress and enables tumor cell survival. 
  • 609
  • 24 Jan 2024
Topic Review
Long Non-Coding RNAs in Gliomas
Glioma progression refers to the development and growth of glioma tumors in the brain. Glioma progression is a complex and multifactorial process involving various genetic, molecular, and cellular changes. The prognosis and survival rates for gliomas differ between adults and pediatrics. Overall, pediatric gliomas tend to have better prognoses compared to gliomas in adults. This is partly due to the prevalence of low-grade tumors in children, which generally have better outcomes than high-grade tumors such as glioblastoma. However, certain pediatric gliomas, such as DIPG, have particularly poor prognoses. The mechanism of glioma progression involves a complex interplay of genetic, molecular, cellular, and microenvironmental factors. Generally, glioma progression is driven by the accumulation of genetic mutations.
  • 608
  • 27 Jun 2023
Topic Review
Macrophage lncRNA in Lung Cancer
Ever since RNA sequencing of whole genomes and transcriptomes became available, numerous RNA transcripts without having the classic function of encoding proteins have been discovered. Long non-coding RNAs (lncRNAs) with a length greater than 200 nucleotides were considered as “junk” in the beginning, but it has increasingly become clear that lncRNAs have crucial roles in regulating a variety of cellular mechanisms and are often deregulated in several diseases, such as cancer. Lung cancer is the leading cause of cancer-related deaths and has a survival rate of less than 10%. Immune cells infiltrating the tumor microenvironment (TME) have been shown to have a great effect on tumor development with macrophages being the major cell type within the TME. Macrophages can inherit an inflammatory M1 or an anti-inflammatory M2 phenotype. Tumor-associated macrophages, which are predominantly polarized to M2, favor tumor growth, angiogenesis, and metastasis.
  • 607
  • 29 Sep 2021
Topic Review
EV-Mediated Intercellular Interactions in Stem Cell and Plasticity
In multicellular organisms, interactions between cells and intercellular communications form the very basis of the organism’s survival, the functioning of its systems, the maintenance of homeostasis and adequate response to the environment. The accumulated experimental data point to the particular importance of intercellular communications in determining the fate of cells, as well as their differentiation and plasticity. For a long time, it was believed that the properties and behavior of cells were primarily governed by the interactions of secreted or membrane-bound ligands with corresponding receptors, as well as direct intercellular adhesion contacts. 
  • 607
  • 07 Apr 2023
Topic Review
Advantages of Drosophila Model in Polyploid Cell Investigation
Polyploid cells are frequently observed in advanced cancer, particularly after standard cancer treatment such as anticancer drugs and radiation therapy. This suggests that polyploid cells lurking in a cancer tissue possess a superior ability to withstand environmental stress, making them more likely to survive anticancer therapies. The polyploid cells in cancer tissues, commonly termed polyploid giant cancer cells (PGCCs), but also referred to as blastomere-like cancer cells, osteoclast-like cancer cells, pleomorphic cancer cells, large cancer stem cells, and polyaneuploid cancer cells (PACCs), are thought to play an important role in tumor progression. 
  • 607
  • 17 Jan 2024
Topic Review
Image-Based Annotation of Chemogenomic Libraries for Phenotypic Screening
Phenotypical screening is a widely used approach in drug discovery for the identification of small molecules with cellular activities. However, functional annotation of identified hits often poses a challenge. The development of small molecules with narrow or exclusive target selectivity such as chemical probes and chemogenomic (CG) libraries, greatly diminishes this challenge, but non-specific effects caused by compound toxicity or interference with basic cellular functions still pose a problem to associate phenotypic readouts with molecular targets. Hence, each compound should ideally be comprehensively characterized regarding its effects on general cell functions. Here, the researchers report an optimized live-cell multiplexed assay that classifies cells based on nuclear morphology, presenting an excellent indicator for cellular responses such as early apoptosis and necrosis. This basic readout, in combination with the detection of other general cell damaging activities of small molecules such as changes in cytoskeletal morphology, cell cycle and mitochondrial health, provides a comprehensive time-dependent characterization of the effect of small molecules on cellular health in a single experiment. The developed high-content assay offers multi-dimensional comprehensive characterization that can be used to delineate generic effects regarding cell functions and cell viability, allowing an assessment of compound suitability for subsequent detailed phenotypic and mechanistic studies.
  • 606
  • 15 Apr 2022
Topic Review
Regulation of m6A Modification in GSCs and Tumorigenesis
Glioblastoma is the most common and most lethal primary malignant brain tumor. N6-methyladenosine (m6A) is one of widespread and abundant internal messenger RNA (mRNA) modification found in eukaryotes. Accumulated evidence demonstrates that m6A modification is aberrantly activated in human cancers and is critical for tumorigenesis and metastasis. m6A modification is also strongly involved in key signaling pathways and is associated with prognosis in glioblastoma. Here, the researchers briefly outline the functions of m6A and its regulatory proteins, including m6A writers, erasers, and readers on the fate of RNA. The researchers also summarize the latest breakthroughs in this field, describe the underlying molecular mechanisms that contribute to the tumorigenesis and progression, and highlight the inhibitors targeting the factors in m6A modification in glioblastoma. Further studies focusing on the specific pathways of m6A modification could help identify biomarkers and therapeutic targets that might prevent and treat glioblastoma.
  • 606
  • 06 May 2022
Topic Review
Role of p53 in Nanoparticle-Based Therapy for Cancer
p53 is arguably one of the most important tumor suppressor genes in humans. Due to the paramount importance of p53 in the onset of cell cycle arrest and apoptosis, the p53 gene is found either silenced or mutated in the vast majority of cancers. Furthermore, activated wild-type p53 exhibits a strong bystander effect, thereby activating apoptosis in surrounding cells without being physically present there. For these reasons, p53-targeted therapy that is designed to restore the function of wild-type p53 in cancer cells seems to be a very appealing therapeutic approach. Systemic delivery of p53-coding DNA or RNA using nanoparticles proved to be feasible both in vitro and in vivo. 
  • 604
  • 22 Dec 2023
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