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Topic Review
Sublethal Cell Death Signaling
An important role of cell death pathways is to protect tissues and minimize disease by limiting the transference of potentially oncogenic mutations to daughter clones. However, there is increasing evidence demonstrating that activation of sublethal cell death signaling pathways, in particular apoptotic signaling, in the absence of direct DNA damaging stimuli, can promote genomic instability in cells that fail to die. This may increase the risk of the formation of subsequent neoplasms. Apoptosis-mediated mutagenesis occurs indirectly via sublethal activation of caspases and apoptotic nucleases (specifically CAD). On the other hand, cells surviving sublethal necroptotic signaling did not acquire mutations, most likely due to caspase-independent pathways, although the possibility of mutagenesis under conditions of oxidative stress are still elusive. It may therefore be possible for necroptosis-inducing anti-cancer drugs to be less likely than apoptosis-inducing or DNA damaging drugs to trigger therapy-related cancers.
  • 1.3K
  • 12 Jul 2021
Topic Review
Hyperthermia
Hyperthermia is one of the severe acute adverse effects that can be caused by the ingestion of recreational drugs, such as methcathinones. The effect of hyperthermia on neurotoxicity is currently not known. The primary aim of our study was therefore to investigate the effects of hyperthermia (40.5 °C) on the neurotoxicity of methcathinone (MC), 4-chloromethcathinone (4-CMC), and 4-methylmethcathinone (4-MMC) in SH-SY5Y cells. We found that 4-CMC and 4-MMC were cytotoxic (decrease in cellular ATP and plasma membrane damage) under both hyper- (40.5 °C) and normothermic conditions (37 °C), whereby cells were more sensitive to the toxicants at 40.5 °C. 4-CMC and 4-MMC impaired the function of the mitochondrial electron transport chain and increased mitochondrial formation of reactive oxygen species (ROS) in SH-SY5Y cells, which were accentuated under hyperthermic conditions. Hyperthermia was associated with a rapid expression of the 70 kilodalton heat shock protein (Hsp70), which partially prevented cell death after 6 h of exposure to the toxicants. After 24 h of exposure, autophagy was stimulated by the toxicants and by hyperthermia but could only partially prevent cell death. In conclusion, hyperthermic conditions increased the neurotoxic properties of methcathinones despite the stimulation of protective mechanisms. These findings may be important for the understanding of the mechanisms and clinical consequences of the neurotoxicity associated with these compounds.
  • 1.3K
  • 29 Oct 2020
Topic Review
MiR-615
miR-615, a miRNA highly conserved across eutherian mammals. It is involved not only during embryogenesis in the regulation of growth and development, for instance during osteogenesis and angiogenesis, but also in the regulation of cell growth and the proliferation and migration of cells, acting as a tumor suppressor or tumor promoter. It, therefore, serves as a biomarker for several types of cancer and recently has also been found to be involved in reparative processes and neural repair.
  • 1.3K
  • 27 Oct 2020
Topic Review
Human Neuroblastoma Cell
Neuroblastoma is one of the most common childhood solid tumors and develops from neural stem cells that normally comprise the embryonic structure termed the neural crest. Human neuroblastoma cell lines have special properties as they exhibit cell growth and are induced to become mature neurons by drugs such as retinoid.
  • 1.3K
  • 21 Oct 2021
Topic Review
Lipid Metabolism in Glioblastoma
Glioblastoma (GBM) is the most lethal primary brain tumor. With limited therapeutic options, novel therapies are desperately needed. Recent studies have shown that GBM acquires large amounts of lipids for rapid growth through activation of sterol regulatory element-binding protein 1 (SREBP-1), a master transcription factor that regulates fatty acid and cholesterol synthesis, and cholesterol uptake. Interestingly, GBM cells divert substantial quantities of lipids into lipid droplets (LDs), a specific storage organelle for neutral lipids, to prevent lipotoxicity by increasing the expression of diacylglycerol acyltransferase 1 (DGAT1) and sterol-O-acyltransferase 1 (SOAT1), which convert excess fatty acids and cholesterol to triacylglycerol and cholesteryl esters, respectively. 
  • 1.3K
  • 16 Aug 2022
Topic Review
Tregs in IBD
Inflammatory bowel disease (IBD) is a complex inflammatory chronic and pathological condition that includes Crohn’s disease (CD) and Ulcerative colitis (UC). CD primarily affects the small and large intestine whereas the prime targets for UC are colon and rectum. Immune sentinel subsets of CD4+ T cells such as Th (T helper cells)-1, Th2, Th17, and regulatory T cells (Tregs) play a crucial role in the pathogenesis of IBD. Immunological balance between effector Th cells and Trges is essential for maintaining immune-homeostasis. Immunoregulatory Trges are characterized by the expression of transcription factor Forkhead box P3 (Foxp3), and surface marker CD25, and are functionally immunosuppressive & important for immune tolerance. Therapeutic arrangement based on Tregs is important to address the systemic inflammatory and autoimmune diseases such as IBD and rheumatoid arthritis.
  • 1.3K
  • 11 Aug 2021
Topic Review
Age-Related Alterations at Neuromuscular Junction
With advancing aging, a decline in physical abilities occurs, leading to reduced mobility and loss of independence. Although many factors contribute to the physio-pathological effects of aging, an important event seems to be related to the compromised integrity of the neuromuscular system, which connects the brain and skeletal muscles via motoneurons and the neuromuscular junctions (NMJs). NMJs undergo severe functional, morphological, and molecular alterations during aging and ultimately degenerate. The effect of this decline is an inexorable decrease in skeletal muscle mass and strength, a condition generally known as sarcopenia. Moreover, several studies have highlighted how the age-related alteration of reactive oxygen species (ROS) homeostasis can contribute to changes in the neuromuscular junction morphology and stability, leading to the reduction in fiber number and innervation. Increasing evidence supports the involvement of epigenetic modifications in age-dependent alterations of the NMJ. In particular, DNA methylation, histone modifications, and miRNA-dependent gene expression represent the major epigenetic mechanisms that play a crucial role in NMJ remodeling. It is established that environmental and lifestyle factors, such as physical exercise and nutrition that are susceptible to change during aging, can modulate epigenetic phenomena and attenuate the age-related NMJs changes.
  • 1.3K
  • 15 Jun 2021
Topic Review
Amyloid Precursor Protein
Amyloid precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. Its primary function is not known, though it has been implicated as a regulator of synapse formation, neural plasticity, antimicrobial activity , and iron export. APP is best known as the precursor molecule whose proteolysis generates amyloid beta (Aβ), a polypeptide containing 37 to 49 amino acid residues, whose amyloid fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients.
  • 1.3K
  • 25 Nov 2022
Topic Review
Vasculogenic Mimicry in Breast Cancer
In solid tumors, vasculogenic mimicry (VM) is the formation of vascular structures by cancer cells, allowing to generate a channel-network able to transport blood and tumor cells. While angiogenesis is undertaken by endothelial cells, VM is assumed by cancer cells. Besides the participation of VM in tumor neovascularization, the clinical relevance of this process resides in its ability to favor metastasis and to drive resistance to antiangiogenic therapy. VM occurs in many tumor types, including breast cancer, where it has been associated with a more malignant phenotype, such as triple-negative and HER2-positive tumors. The latter may be explained by known drivers of VM, like hypoxia, TGFB, TWIST1, EPHA2, VEGF, matrix metalloproteinases, and other tumor microenvironment-derived factors, which altogether induce the transformation of tumor cells to a mesenchymal phenotype with a high expression rate of stemness markers.
  • 1.3K
  • 29 Mar 2022
Topic Review
Viral Infections in HNC
Head and neck cancers (HNC) occur in the upper aerodigestive tract and are among the most common cancers. The etiology of HNC is complex, involving many factors, including excessive tobacco and alcohol consumption. Over the last two decades, oncogenic viruses have also been recognized as an important cause of HNC. Major etiological agents of nasopharynx carcinoma and oropharyngeal carcinoma include Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), both of which are able to interfere with cell cycle control. Additionally, the association of hepatitis C and hepatitis B infection was observed in oral cavity, oropharyngeal, laryngeal, and nasopharyngeal cancers. Overall prognoses depend on anatomic site, stage, and viral status. Current treatment options, including radiotherapy, chemotherapy, targeted therapies and immunotherapies, are distributed in order to improve overall patient prognosis and survival rates. However, the interplay between viral genome sequences and the health, disease, geography, and ethnicity of the host are crucial for understanding the role of viruses and for development of potential personalized treatment and prevention strategies.
  • 1.3K
  • 22 Sep 2021
Topic Review
PPAR Alpha
Peroxisome proliferator-activated receptor α is a potent regulator of systemic and cellular metabolism and energy homeostasis, but it also suppresses various inflammatory reactions.
  • 1.3K
  • 19 Oct 2021
Topic Review
Filaggrin in Atopic Dermatitis
The discovery in 2006 that loss-of-function mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris and can predispose to atopic dermatitis (AD) galvanized the dermatology research community and shed new light on a skin protein that was first identified in 1981. However, although outstanding work has uncovered several key functions of filaggrin in epidermal homeostasis, a comprehensive understanding of how filaggrin deficiency contributes to AD is still incomplete, including details of the upstream factors that lead to the reduced amounts of filaggrin, regardless of genotype.
  • 1.3K
  • 16 May 2022
Topic Review
PBK/TOPK: A Therapeutic Target
T-lymphokine-activated killer cell-originated protein kinase (TOPK), also known as PDZ-binding kinase (PBK), was a member of the MEK3/6-related MAPKK family. As a mitotic serine/threonine protein kinase, accumulating evidence supported its role in mitosis and cell-cycle progression of mitotically active cells, especially proliferative malignant cells. PBK/TOPK was confirmed to be associated with the development, progression, and metastasis of malignancies, which made it a potential therapeutic target in cancer therapy. Further, it was also demonstrated to play crucial roles in ischemic injury and involve in protection against ischemia. This protective effect of PBK/TOPK in the context of ischemia challeged the development of PBK/TOPK inhibitors in anti-tumor therapy, and more research was required to further explore its role and underlying mechanisms to translate its application to clinical studies.  
  • 1.3K
  • 20 Mar 2021
Topic Review
Diet in Stem and Cancer Stem Cells
Diet and lifestyle factors greatly affect health and susceptibility to diseases, including cancer. Stem cells’ functions, including their ability to divide asymmetrically, set the rules for tissue homeostasis, contribute to health maintenance, and represent the entry point of cancer occurrence. Stem cell properties result from the complex integration of intrinsic, extrinsic, and systemic factors. In this context, diet-induced metabolic changes can have a profound impact on stem cell fate determination, lineage specification and differentiation.
  • 1.3K
  • 01 Aug 2022
Topic Review
Cilia Distal Domain
Eukaryotic cilia are microtubule-based organelles that protrude from the cell surface to fulfill sensory and motility functions. Their basic structure consists of an axoneme templated by a centriole/basal body. Striking differences in ciliary ultra-structures can be found at the ciliary base, the axoneme and the tip, not only throughout the eukaryotic tree of life, but within a single organism. Defects in cilia biogenesis and function are at the origin of human ciliopathies. This structural/functional diversity and its relationship with the etiology of these diseases is poorly understood. Some of the important events in cilia function occur at their distal domain, including cilia assembly/disassembly, IFT (intraflagellar transport) complexes’ remodeling, and signal detection/transduction. How axonemal microtubules end at this domain varies with distinct cilia types, originating different tip architectures. Additionally, they show a high degree of dynamic behavior and are able to respond to different stimuli. The existence of microtubule-capping structures (caps) in certain types of cilia contributes to this diversity. 
  • 1.3K
  • 20 Sep 2023
Topic Review
Connexins in Cancer
The expression, localization, and function of connexins, the protein subunits that comprise gap junctions, are often altered in cancer. In addition to cell–cell coupling through gap junction channels, connexins also form hemichannels that allow communication between the cell and the extracellular space and perform non-junctional intracellular activities. Historically, connexins have been considered tumor suppressors; however, they can also serve tumor-promoting functions in some contexts. Here, we review the literature surrounding connexins in cancer cells in terms of specific connexin functions and propose that connexins function upstream of most, if not all, of the hallmarks of cancer. The development of advanced connexin targeting approaches remains an opportunity for the field to further interrogate the role of connexins in cancer phenotypes, particularly through the use of in vivo models. More specific modulators of connexin function will both help elucidate the functions of connexins in cancer and advance connexin-specific therapies in the clinic.
  • 1.3K
  • 24 Dec 2020
Topic Review
Cellular Protein Trafficking in Low-Temperature Response Pathway
Over the years, although substantial progress has been made in understanding low-temperature response mechanisms in plants, the research is more focused on aerial parts of the plants rather than on the root or whole plant, and more efforts have been made in identifying and testing the major regulators of this pathway preferably in the model organism rather than in crop plants. For the low-temperature stress response mechanism, ICE-CBF regulatory pathway turned out to be the solely established pathway, and historically most of the low-temperature research is focused on this single pathway instead of exploring other alternative regulators.
  • 1.3K
  • 24 Apr 2022
Topic Review
Brown Adipose Tissue Architecture and Thermogenic Function
The body of mammals harbors two distinct types of adipose tissue: While cells within the white adipose tissue (WAT) store surplus energy as lipids, brown adipose tissue (BAT) is nowadays recognized as the main tissue for transforming chemical energy into heat. This process, referred to as ‘non-shivering thermogenesis’, is facilitated by the uncoupling of the electron transport across mitochondrial membranes from ATP production. BAT-dependent thermogenesis acts as a safeguarding mechanism under reduced ambient temperature but also plays a critical role in metabolic and energy homeostasis in health and disease. 
  • 1.3K
  • 19 Dec 2022
Topic Review
Calcium in Apoptosis and Cancer
Calcium (Ca2+) is a major second messenger in cells and is essential for the fate and survival of all higher organisms. Different Ca2+ channels, pumps, or exchangers regulate variations in the duration and levels of intracellular Ca2+, which may be transient or sustained. These changes are then decoded by an elaborate toolkit of Ca2+-sensors, which translate Ca2+ signal to intracellular operational cell machinery, thereby regulating numerous Ca2+-dependent physiological processes. Alterations to Ca2+ homoeostasis and signaling are often deleterious and are associated with certain pathological states, including cancer. Altered Ca2+ transmission has been implicated in a variety of processes fundamental for the uncontrolled proliferation and invasiveness of tumor cells and other processes important for cancer progression, such as the development of resistance to cancer therapies.
  • 1.3K
  • 22 Sep 2021
Topic Review
Corneal Confocal Microscopy Imaging
In vivo corneal confocal microscopy (IVCM) is a non-invasive ophthalmic imaging technique that provides images of the cornea at the cellular level. The observation of the corneal cells, both normal and inflammatory, and the possibility of quantification of the corneal nerve density with manual or automated tools, makes IVCM have a significant potential to improve the diagnosis and prognosis in several systemic and corneal conditions.
  • 1.3K
  • 04 Jan 2023
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