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Topic Review
Exploiting DNA Replication Stress in Breast Cancer Treatment
Proliferating cells rely on DNA replication to ensure accurate genome duplication. Cancer cells, including breast cancer cells, exhibit elevated replication stress (RS) due to the uncontrolled oncogenic activation, loss of key tumor suppressors, and defects in the DNA repair machinery. This intrinsic vulnerability provides a great opportunity for therapeutic exploitation. An increasing number of drug candidates targeting RS in breast cancer are demonstrating promising efficacy in preclinical and early clinical trials.
  • 1.3K
  • 08 Dec 2022
Topic Review
Protein Kinase D
Protein kinase D (PKD) is a family of serine/threonine protein kinases operating in the signaling network of the second messenger diacylglycerol. PKD belongs to the Calcium/calmodulin-dependent protein kinases superfamily and consists of three isoforms in mammals, notably, PKD1, PKD2 and PKD3. Activated PKD resides in diverse subcellular locations such as cytosol, Golgi apparatus, nucleus, mitochondria to regulate a number of cellular functions.
  • 1.3K
  • 15 Apr 2021
Topic Review
GRP94 in Cancer
Glucose-regulated protein 94 (GRP94) is an endoplasmic reticulum (ER)-resident member of the heat shock protein 90 (HSP90) family. In physiological conditions, it plays a vital role in regulating biological functions, including chaperoning cellular proteins in the ER lumen, maintaining calcium homeostasis, and modulating immune system function. Recently, several reports have shown the functional role and clinical relevance of GRP94 overexpression in the progression and metastasis of several cancers. Therefore, the current review highlights GRP94’s physiological and pathophysiological roles in normal and cancer cells. Additionally, the unmet medical needs of small chemical inhibitors and the current development status of monoclonal antibodies specifically targeting GRP94 will be discussed to emphasize the importance of cell surface GRP94 as an emerging therapeutic target in monoclonal antibody therapy for cancer.
  • 1.3K
  • 11 Oct 2021
Topic Review
Alveolar Epithelial Cells in Pulmonary Fibrosis
An important contributor to the development of idiopathic pulmonary fibrosis (IPF) is the alteration of the intracellular homeostasis of alveolar epithelial cells, which are mainly composed of alveolar type I epithelial cells (AT1), alveolar type II epithelial cells (AT2), as well as abnormal basaloid cells, resulting in aberrant epithelial repair, myofibroblast activation, and increased extracellular matrix deposition to form lung fibrosis
  • 1.3K
  • 27 Feb 2023
Topic Review
Effects of Vitamin D on Satellite Cells
Vitamin D is a micronutrient that plays a role in the homeostasis of various body organs, including skeletal muscle. Skeletal muscle growth and regeneration are critically affected by satellite cells, skeletal muscle stem cells. The discovery of vitamin D receptors on satellite cells supports the role of vitamin D in regulating satellite cell function. In vivo studies have shown the effect of vitamin D on skeletal muscle growth in early life, muscle homeostasis in aging, and skeletal muscle regeneration in conditions of muscle injury or chronic disease.
  • 1.3K
  • 10 Nov 2022
Topic Review
Lipids in Macrophages of Different Tissue Location
Lipid metabolism is the major intracellular mechanism driving a variety of cellular functions such as energy storage, hormone regulation and cell division. Lipids, being a primary component of the cell membrane, play a pivotal role in the survival of macrophages. Lipids are crucial for a variety of macrophage functions including phagocytosis, energy balance and ageing. Lipid-loaded macrophages have recently been emerging as a hallmark for several diseases.
  • 1.3K
  • 12 Jan 2023
Topic Review
Autophagy and Inflammatory Pathways in Macrophages
Autophagy as a conserved bulk degradation and recycling process, performs specific roles in macrophage to regulate innate immune response. This review focuses on the role of autophagy, both as nonselective and selective forms, in the regulation of the inflammatory and phagocytotic functions of macrophages. Specifically, the roles of autophagy in pattern recognition, cytokine release, inflammasome activation, macrophage polarization, LC3-associated phagocytosis, and xenophagy are comprehensively reviewed.
  • 1.3K
  • 30 Nov 2021
Topic Review
Hypoxia in the Cell Cycle
The cell cycle is an important cellular process whereby the cell attempts to replicate its genome in an error-free manner.
  • 1.3K
  • 01 Jul 2021
Topic Review
Current Methodologies for Visualizing ATP in Living Cells
Measuring total ATP levels within cellular compartmental pools in real-time presents a newer and more innovative approach to qualitatively analyzing ATP. Although this method is not precisely quantitative, it can be helpful in determining changes in ATP concentrations in one region of a cell compared to another in a variety of disease states. The overall goal of these assays and imaging methodologies are to evaluate and visualize dynamic ATP trends, such as usage and depletion, between cells and their sub-compartments. However, semi-quantitative evaluation of the relative ATP signal is feasible. The currently developed technologies that utilize this approach to ATP quantification are mainly genetically encoded biosensors. In conjunction with a fluorescent or bioluminescent protein, most of these biosensors harness the folding capabilities of the ϵ subunit of the bacterial ATP synthase subunit. The bacterial ATP synthase protein comprises a β-barrel domain located at the N terminus and an α-helical domain with two α-helices located at the C terminus. Upon ATP binding, the two α-helices interact and refine their conformational structure of the ϵ subunit, leading to fluorescent/bioluminescent illumination, indicating that ATP is present. Overall, this subunit adopts two different conformations: open (ATP-free) or closed (ATP-bound). The uses and applicability of this technology are limitless. 
  • 1.3K
  • 24 Jun 2022
Topic Review
Navigating the ERK1/2 MAPK Cascade
The RAS-ERK pathway is a fundamental signaling cascade crucial for many biological processes including proliferation, cell cycle control, growth, and survival; common across all cell types. Notably, ERK1/2 are implicated in specific processes in a context-dependent manner as in stem cells and pancreatic β-cells. Alterations in the different components of this cascade result in dysregulation of the effector kinases ERK1/2 which communicate with hundreds of substrates. Aberrant activation of the pathway contributes to a range of disorders, including cancer.
  • 1.3K
  • 25 Oct 2023
Topic Review
Human Sirtuins
Sirtuins (SIRTs) are nicotinamide adenine dinucleotide-dependent histone deacetylases that in-corporate complex functions in the mechanisms of cell physiology. Mammals have seven distinct members of the SIRT family (SIRT1-7), which play an important role in a well-maintained net-work of metabolic pathways that control and adapt the cell to the environment, energy availabil-ity and cellular stress. Until recently, very few studies investigated the role of SIRTs in modulating viral infection and progeny. Recent studies have demonstrated that SIRT1 and SIRT2 are promis-ing antiviral targets because of their specific connection to numerous metabolic and regulatory processes affected during infection.
  • 1.3K
  • 01 Mar 2021
Topic Review
Skin Aging and Cellular Senescence
Skin aging is a result of two cumulative and overlaying mechanisms denominated as intrinsic and extrinsic aging. The process of intrinsic or chronological aging affects all tissues and organs of the body, is due to the passage of time, and is influenced by genetic background. However, the skin is continuously exposed to environmental and lifestyle factors such as sunlight, pollution, cigarette smoke, and dietary habits. These factors, collectively denominated the skin exposome, are the major causes of the process of extrinsic skin aging. In addition, cellular senescence and the accumulation of senescent cells in the skin is considered as a hallmark of aging. Senescent cells contribute to the decline of tissue function and lead to age-related changes and pathologies.
  • 1.3K
  • 19 Jul 2022
Topic Review
Alpha-Thalassemia
Alpha-thalassemia (α-thalassemia, α-thalassaemia) is a form of thalassemia involving the genes HBA1 and HBA2. Thalassemias are a group of inherited blood conditions which result in the impaired production of hemoglobin, the molecule that carries oxygen in the blood. Normal hemoglobin consists of two alpha chains and two beta chains; in alpha-thalassemia, there is a quantitative decrease in the amount of alpha chains, resulting in fewer normal hemoglobin molecules. Furthermore, alpha-thalassemia leads to the production of unstable beta globin molecules which cause increased red blood cell destruction. The degree of impairment is based on which clinical phenotype is present (how many genes are affected).
  • 1.3K
  • 31 Oct 2022
Topic Review
Oral and Periodontal Bacteria Microbiota Photobiomodulation
The visible and near-infrared wavelengths can affect bacterial growth. Like in eukaryotic cells also in bacteria, photobiomodulation can affect cellular metabolism, homeostasis, defence to stress, and life-and-death mechanisms. Light-bacteria interaction for microbiota management can represent a supportive medical approach in health and illness patients.
  • 1.3K
  • 11 Feb 2022
Topic Review
MafA Regulation in β-Cells
β-cells are insulin-producing cells in the pancreas that maintain euglycemic conditions. Pancreatic β-cell maturity and function are regulated by a variety of transcription factors that enable the adequate expression of the cellular machinery involved in nutrient sensing and commensurate insulin secretion. One of the key factors in this regulation is MAF bZIP transcription factor A (MafA). MafA expression is decreased in type 2 diabetes, contributing to β-cell dysfunction and disease progression. The molecular biology underlying MafA is complex, with numerous transcriptional and post-translational regulatory nodes. 
  • 1.3K
  • 21 Apr 2022
Topic Review
Mitochondria in Maturation of Cardiomyocytes
Cardiomyocytes obtained from pluripotent stem cells (PSCs)differentiation culture are regarded as immature structurally, electrophysiologically, metabolically, and functionally. Mitochondria are organelles responsible for various cellular functions such as energy metabolism, different catabolic and anabolic processes, calcium fluxes, and various signaling pathways. Cells can respond to cellular needs to increase the mitochondrial mass by mitochondrial biogenesis. On the other hand, cells can also degrade mitochondria through mitophagy. Mitochondria are also dynamic organelles that undergo continuous fusion and fission events. 
  • 1.3K
  • 26 Oct 2021
Topic Review
Extracellular Vesicles in CKD
Over the last few years, preclinical and clinical studies have emphasized the role of extracellular vesicles (EVs) in human diseases. These particles are delimited by a lipid bilayer and are released by almost all cell types and in all organisms. EVs appear to have biological effects in various pathophysiological situations and especially in renal disease. In human organs, EVs can interact with cells and prompt the release of many different molecules, such as proteins, lipids and nucleic acids, that, in turn, regulate various cell signaling pathways. Moreover, EVs are present in the urine and the blood and therefore can be used as potential diagnostic biomarkers in human diseases, such as chronic kidney disease (CKD, also known as chronic renal failure).
  • 1.3K
  • 29 Apr 2021
Topic Review
TMEFF2
Transmembrane protein with an EGF-like and two follistatin-like domains 2 (TMEFF2) is a 374-residue long type-I transmembrane proteoglycan which is proteolytically shed from the cell surface. The protein is involved in a range of functions including metabolism, neuroprotection, apoptosis, embryonic development, onco-suppression and endocrine function. TMEFF2 is methylated in numerous cancers, and an inverse correlation with the stage, response to therapy and survival outcome has been observed. Moreover, TMEFF2 methylation increases with breast, colon and gastric cancer progression. TMEFF2 is methylated early during oncogenesis in breast and colorectal cancer, and the detection of methylated free-circulating TMEFF2 DNA has been suggested as a potential diagnostic tool. The TMEFF2 downregulation signature equals and sometimes outperforms the Gleason and pathological scores in prostate cancer. TMEFF2 is downregulated in glioma and cotricotropinomas, and it impairs the production of adrenocorticotropic hormone in glioma cells. Through binding the amyloid β protein, its precursor and derivatives, TMEFF2 provides neuroprotection in Alzheimer’s disease. Primary literature regarding TMEFF2 is incoherent and offers conflicting information, in particular, the oncogenic vs. onco-suppressive role of TMEFF2 in prostate cancer. 
  • 1.3K
  • 26 Jan 2021
Topic Review
CREB Protein Family Members in Radioresistance Mechanisms
In the framework of space flight, the risk of radiation carcinogenesis is considered a “red” risk due to the high likelihood of occurrence as well as the high potential impact on the quality of life in terms of disease-free survival after space missions. The cyclic AMP response element-binding protein (CREB) is overexpressed both in haematological malignancies and solid tumours and its expression and function are modulated following irradiation. The CREB protein is a transcription factor and member of the CREB/activating transcription factor (ATF) family. As such, it has an essential role in a wide range of cell processes, including cell survival, proliferation, and differentiation. Among the CREB-related nuclear transcription factors, NF-κB and p53 have a relevant role in cell response to ionising radiation. Their expression and function can decide the fate of the cell by choosing between death or survival. 
  • 1.3K
  • 09 Jan 2022
Topic Review
Lysosomes in Maintaining Stem Cell Quiescence
Lysosomes are a critical component of the inner membrane system and are involved in various cellular biological processes, including macromolecular degradation, antigen presentation, intracellular pathogen destruction, plasma membrane repair, exosome release, cell adhesion/migration, and apoptosis. Lysosomes are a critical regulator of cellular metabolism, cancer, metastasis, and resistance to anticancer therapy. Additionally, lysosomal activities play a crucial role in acute myeloid leukemia (AML) development and progression, as well as maintaining the hematopoietic stem cells (HSCs) pool. It has been shown that AML cells undergo metabolic alterations due to chemotherapy or targeted treatment.
  • 1.3K
  • 31 Mar 2022
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