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Topic Review
MOB in Cytokinesis, Cell Architecture and Tissue Homeostasis
The Monopolar spindle One Binder protein (MOB) family proteins are constituted by highly conserved eukaryote kinase signal adaptors that are often essential both for cell and organism survival. Historically, MOB family proteins have been described as kinase activators participating in Hippo and Mitotic Exit Network/Septation Initiation Network (MEN/SIN) signaling pathways that have central roles in regulating cytokinesis, cell polarity, cell proliferation and cell fate to control organ growth and regeneration. In metazoans, MOB proteins act as central signal adaptors of the core kinase module MST1/2, LATS1/2, and NDR1/2 kinases that phosphorylate the YAP/TAZ transcriptional co-activators, effectors of the Hippo signaling pathway. MOBs have been shown to also have non-kinase partners and to be involved in cilia biology, indicating that its activity and regulation is more diverse than expected.
  • 717
  • 18 Sep 2023
Topic Review
Epicardial Cell Heterogeneity during Cardiogenesis and Heart Regeneration
The outermost layer of the heart, the epicardium, is an essential cell population that contributes, through epithelial-to-mesenchymal transition (EMT), to the formation of different cell types and provides paracrine signals to the developing heart. Despite its quiescent state during adulthood, the adult epicardium reactivates and recapitulates many aspects of embryonic cardiogenesis in response to cardiac injury, thereby supporting cardiac tissue remodeling. Thus, the epicardium has been considered a crucial source of cell progenitors that offers an important contribution to cardiac development and injured hearts. 
  • 717
  • 12 Oct 2023
Topic Review
Mechanism of Action of circRNAs in Cancer Cells
The ever-increasing number of cancer cases and persistently high mortality underlines the urgent need to acquire new perspectives for developing innovative therapeutic approaches. As the research on protein-coding genes brought significant yet only incremental progress in the development of anticancer therapy, much attention is now devoted to understanding the role of non-coding RNAs (ncRNAs) in various types of cancer. The ncRNAs recognized previously as “dark matter” are, in fact, key players in shaping cancer development. Moreover, breakthrough discoveries concerning the role of a new group of ncRNAs, circular RNAs, have evidenced their high importance in many diseases, including malignancies. 
  • 716
  • 17 Feb 2023
Topic Review
Precision Oncology Beyond Genomics
Cancer is a multifactorial disease with increasing incidence. There are more than 100 different cancer types, defined by location, cell of origin, and genomic alterations that influence oncogenesis and therapeutic response. This heterogeneity between tumors of different patients and also the heterogeneity within the same patient’s tumor pose an enormous challenge to cancer treatment.
  • 715
  • 06 May 2021
Topic Review
Role of Neurotrophin Signaling in CNS Homeostasis
Neurotrophins (NTs), also known as neurotrophic factors, are proteins involved in many important functions in the central nervous system (CNS), such as survival, synaptic plasticity, apoptosis, differentiation, and growth. The current knowledge of NTs includes the nerve growth factor (NGF), neurotrophin 3 (NT-3), NT-4, NT-5, and brain-derived neurotrophic factor (BDNF). These NTs are commonly known to be synthesized by CNS cells. However, other cell types, including immune system cells, can produce NTs and express their receptors on the cell surface. These proteins also play a vital role in regulating immune functions, promoting the survival of different immune cells such as monocytes and lymphocytes and influencing cytokine expression. NTs significantly contribute to healthy CNS development and maintenance. Furthermore, most mechanisms mediated by NTs signaling have essential physiological effects which perdure through most animal lifecycles. In consequence, alterations in neurotrophic signaling can have substantial ramifications, especially during embryonic development.
  • 715
  • 31 May 2022
Topic Review
Flavones in Hypertensive Disease
Hypertension is the leading remediable risk factor for cardiovascular morbidity and mortality in the United States. Excess dietary salt consumption, which is a catalyst of hypertension, initiates an inflammatory cascade via activation of antigen-presenting cells (APCs). This pro-inflammatory response is driven primarily by sodium ions (Na+) transporting into APCs by the epithelial sodium channel (ENaC) and subsequent NADPH oxidase activation, leading to high levels of oxidative stress. Flavonoids, a natural phenolic compound, have these therapeutic benefits and can potentially serve as anti-hypertensives. Flavones are a type of flavonoid that have increased anti-inflammatory effects that may allow them to act as therapeutic agents for hypertension, including diosmetin, which is able to induce significant arterial vasodilation in several different animal models.
  • 714
  • 02 Nov 2023
Topic Review
TRIM Proteins Family
TRIM (TRIpartite Motif-containing) proteins family is one of the largest groups of E3 ubiquitin ligases. Among them, interest in TRIM8 has greatly increased in recent years. TRIM8 functions are not limited to ubiquitination, and it has a role either as an oncogene or as a tumor suppressor gene, acting as a “double-edged weapon”. This is linked to its involvement in the selective regulation of three pivotal cellular signaling pathways: the p53 tumor suppressor, NF-κB and JAK-STAT pathways.
  • 713
  • 29 Mar 2021
Topic Review
Extracellular Vesicles in Normal Pregnancy
Extracellular vesicles (EVs) are small vesicles ranging from 20–200 nm to 10 μm in diameter that are discharged and taken in by many different types of cells. Depending on the nature and quantity of their content—which generally includes proteins, lipids as well as microRNAs (miRNAs), messenger-RNA (mRNA), and DNA—these particles can bring about functional modifications in the receiving cells. During pregnancy, placenta and/or fetal-derived EVs have recently been isolated, eliciting interest in discovering their clinical significance. 
  • 713
  • 26 Apr 2021
Topic Review
Mitochondrial Metabolism and Dynamics in Prostate Cancer
Prostate cancer (PCa) is the second leading cause of cancer deaths among men in Western countries. Mitochondria, the “powerhouse” of cells, undergo distinctive metabolic and structural dynamics in different types of cancer. PCa cells experience peculiar metabolic changes during their progression from normal epithelial cells to early-stage and, progressively, to late-stage cancer cells.
  • 712
  • 08 Mar 2023
Topic Review
Desmosomal Genes and Arrhythmogenic Cardiomyopathy
Cardiomyopathies (CMPs) represent a significant healthcare burden and are a major cause of heart failure leading to premature death. Several CMPs are now recognized to have a strong genetic basis, including arrhythmogenic cardiomyopathy (ACM), which predisposes patients to arrhythmic episodes. 
  • 711
  • 19 Oct 2023
Topic Review
Genetics of Aging Plasticity
Biological aging is characterized by irreversible cell cycle blockade, a decreased capacity for tissue regeneration, and an increased risk of age-related diseases and mortality. A variety of genetic and epigenetic factors regulate aging, including the abnormal expression of aging-related genes, increased DNA methylation levels, altered histone modifications, and unbalanced protein translation homeostasis. The epitranscriptome is also closely associated with aging. Aging is regulated by both genetic and epigenetic factors, with significant variability, heterogeneity, and plasticity. Understanding the complex genetic mechanisms of aging will aid the identification of aging-related markers, which may in turn aid the development of effective interventions against this process.
  • 710
  • 04 May 2023
Topic Review
Role of TAM Receptors in Bone Remodeling
The TAM (TYRO3, MERTK, and AXL) family of receptor tyrosine kinases are pleiotropic regulators of adult tissue homeostasis maintaining organ integrity and self-renewal. Disruption of their homeostatic balance fosters pathological conditions like autoinflammatory or degenerative diseases including rheumatoid arthritis, lupus erythematodes, or liver fibrosis. Moreover, TAM receptors exhibit prominent cell-transforming properties, promoting tumor progression, metastasis, and therapy resistance in various cancer entities. Emerging evidence shows that TAM receptors are involved in bone homeostasis by regulating osteoblastic bone formation and osteoclastic bone resorption. Therefore, TAM receptors emerge as new key players of the regulatory cytokine network of osteoblasts and osteoclasts and represent accessible targets for pharmacologic therapy for a broad set of different bone diseases, including primary and metastatic bone tumors, rheumatoid arthritis, or osteoporosis.
  • 710
  • 10 Jan 2024
Topic Review
Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria
The precise function of CERKL, a Retinitis Pigmentosa (RP) causative gene, is not yet fully understood. There is evidence that CERKL is involved in the regulation of autophagy, stress granule generation and mitochondrial dynamics, and it is considered a resilience gene that protects retinal cells from oxidative stress. Mutations in most RP genes affect photoreceptors, but retinal pigment epithelium (RPE) cells may be also affected. Upon oxidative stress conditions, CERKL knockdown causes RPE mitochondrial fragmentation and respiratory metabolism alterations, whereas CERKL overexpression protects mitochondria of RPE cells. Particular retinal phenotypic traits observed in patients carrying CERKL mutations may reflect a combination of photoreceptor and RPE alterations.
  • 710
  • 31 Dec 2021
Topic Review
Targeting Strategies against Radioresistant Tumors
A radiosensitizer is a drug that makes cancer cells more sensitive to radiation therapy. These compounds apparently promote the scavenging of free radicals produced by radiation damage on the molecular level. Radiation therapy generally affects DNA; mainly, it leads to DNA DSBs. Therefore, many radiosensitizing agents have been formulated to target the clinically developed DNA DSB repair pathways. Other agents instead target different pathways, e.g., DNA-PKcs, ATM, and ATR signaling cascades. More than seven PARP inhibitors, for example, are currently being developed considering their role in DNA repair, especially for tumors with DNA repair defects, such as BRCA mutation, because of their synthetic lethality.
  • 709
  • 16 Sep 2022
Topic Review
The Communication of Senescence-Associated Secretory Phenotype
Cellular senescence is a complex cell state that can occur during physiological ageing or after exposure to stress signals, regardless of age. It is a dynamic process that continuously evolves in a context-dependent manner. Senescent cells interact with their microenvironment by producing a heterogenous and plastic secretome referred to as the senescence-associated secretory phenotype (SASP). Hence, understanding the cross-talk between SASP and the microenvironment can be challenging due to the complexity of signal exchanges.
  • 709
  • 14 Jul 2023
Topic Review
Elongational Stresses and Cells
Shear often attributed as being the main source of cell deformation/damage in devices like prosthetic heart valves and artificial organs. Less well understood and studied are extensional stresses which are often found in such devices, in bioreactors, and in normal blood circulation. Several microfluidic channels utilizing hyperbolic, abrupt, or tapered constrictions and cross-flow geometries, have been used to isolate the effects of extensional flow. Under such flow cell deformations, erythrocytes, leukocytes, and a variety of other cell types have been examined. Results suggest that extensional stresses cause larger deformation than shear stresses of the same magnitude. This has further implications in assessing cell injury from mechanical forces in artificial organs and bioreactors. The cells’ greater sensitivity to extensional stress has found utility in mechanophenotyping devices, which have been successfully used to identify pathologies that affect cell deformability. Further application outside of biology includes disrupting cells for increased food product stability and harvesting macromolecules for biofuel. 
  • 708
  • 08 Oct 2021
Topic Review
The Microenvironment of the Pathogenesis of Cardiac Hypertrophy
Pathological cardiac hypertrophy is a key risk factor for the development of heart failure and predisposes individuals to cardiac arrhythmia and sudden death. While physiological cardiac hypertrophy is adaptive, hypertrophy resulting from conditions comprising hypertension, aortic stenosis, or genetic mutations, such as hypertrophic cardiomyopathy, is maladaptive. Prolonged cardiovascular stress causes cardiomyocytes and non-myocardial cells to enter an activated state releasing numerous pro-hypertrophic, pro-fibrotic, and pro-inflammatory mediators such as vasoactive hormones, growth factors, and cytokines, i.e., commencing signaling events that collectively cause cardiac hypertrophy. Fibrotic remodeling is mediated by cardiac fibroblasts as the central players, but also endothelial cells and resident and infiltrating immune cells enhance these processes. Many of these hypertrophic mediators are now being integrated into computational models that provide system-level insights and will help to translate our knowledge into new pharmacological targets. 
  • 708
  • 14 Jul 2023
Topic Review
Two-Pore Channels and Ca2+ Homeostasis in Immune Cells
Two-pore channels (TPCs) are ligand-gated cation-selective ion channels that are preserved in plant and animal cells. In the latter, TPCs are located in membranes of acidic organelles, such as endosomes, lysosomes, and endolysosomes. Mast cells, along with basophil granulocytes, play an essential role in anaphylaxis and allergic reactions by releasing inflammatory mediators. Signaling in mast cells is mainly regulated via the release of Ca2+ from the endoplasmic reticulum as well as from acidic compartments, such as endolysosomes. For the crosstalk of these organelles TPCs seem essential. Allergic reactions and anaphylaxis were previously shown to be associated with the endolysosomal two-pore channel TPC1. The release of histamine, controlled by intracellular Ca2+ signals, was increased upon genetic or pharmacologic TPC1 inhibition. Conversely, stimulation of TPC channel activity by one of its endogenous ligands, namely nicotinic adenine dinucleotide phosphate (NAADP) or phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), were found to trigger the release of Ca2+ from the endolysosomes; thereby improving the effect of TPC1 on regulated mast cell degranulation. 
  • 708
  • 16 May 2022
Topic Review
Mir-137
In molecular biology, miR-137 (or microRNA-137) is a short non-coding RNA molecule that functions to regulate the expression levels of other genes by various mechanisms. miR-137 is located on human chromosome 1p22 and has been implicated to act as a tumor suppressor in several cancer types including colorectal cancer, squamous cell carcinoma and melanoma via cell cycle control. Recent genome-wide association studies (GWAS) have provided evidence to suggest that single nucleotide polymorphisms in the vicinity of the MIR137 gene are statistically associated with schizophrenia and other psychiatric disorders. miR-137 is shown to regulate neural stem cell proliferation and differentiation in mouse embryonic stem cells, and neuronal maturation, including regulation of dendrite length, branch points, end points, and spine density in mouse adult hippocampal neuroprogenitor-derived and mouse fetal hippocampus neurons. Decreased spine density has also been observed in the dorsolateral cortex of patients with schizophrenia. miR-137 belongs to the miR-137 clan (a clan is group of two or more RNA families that have arisen from a single evolutionary origin, as derived from their related structure and function). The miR-137 clan contains two members: miR-137 and miR-234; the total number of RNA domains in the clan is 112.
  • 707
  • 01 Dec 2022
Topic Review
Exercise Regulates Microglial Activation by Increasing Anti-Inflammatory Factors
Exercise impacts our body at multiple levels, including the central nervous system (CNS). In responding to exercise-related stress (e.g., hypoxia, heat, free radicals, etc.) and injuries, the body launches multiple endogenous protective and repair systems by altering gene expression and releasing a range of factors that prepare the body for the next challenge. Accumulating evidence indicates that exercise can enhance brain function and attenuate neurodegeneration. Besides improving neuroplasticity by altering the synaptic structure and function in various brain regions, exercise also modulates multiple systems that are known to regulate neuroinflammation and glial activation. Activated microglia and several pro-inflammatory cytokines play active roles in the pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. 
  • 707
  • 17 Jul 2023
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