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Topic Review
Leptin in Inflammation
Leptin is an important regulator of basal metabolism and food intake, with a pivotal role in obesity. Leptin exerts many different actions on various tissues and systems, including cancer, and is considered as a linkage between metabolism and the immune system. 
  • 839
  • 05 Jul 2021
Topic Review
S100P-Induced Cell Migration and Metastasis
The presence of S100P protein in cancer cells is strongly associated with reduced survival times of patients suffering from a number of cancers. It has been shown previously that S100P is a potent inducer of metastasis in a model system and it is likely that this metastasis-inducing ability underlies its association with reduced patient survival. However, the molecular mechanisms involved in S100P-driven metastasis are only now beginning to be elucidated and the evidence points to S100P enhancing cell migration and cell invasion.  It is now shown that in the same cell system S100P enhances cell migration by two separate mechanisms. One pathway being intracellular, involves changes in the numbers of focal adhesions.  The second pathway occurs at the cell membrane and does not involve changes in the number of focal adhesions, but involves extracellular/membrane bound S100P and is inhibited by specific inhibitors of plasmin. Importantly, mutation of the C-terminal amino acid of S100P, not only abolishes both pathways, but also markedly reduces the metastasis-inducing ability of S100P, thus identifying a possible target for the reduction of S100P-induced metastasis.
  • 839
  • 27 Oct 2021
Topic Review
Cancer-Associated Fibroblasts in Cholangiocarcinoma
Cholangiocarcinoma (CCA) is an aggressive neoplasia with an increasing incidence and mortality. It is characterized by a strong desmoplastic stroma surrounding cancer cells. Cancer-associated fibroblasts (CAFs) are the main cell type of CCA stroma and they have an important role in modulating cancer microenvironments. CAFs originate from multiple lines of cells and mainly consist of fibroblasts and alpha-smooth muscle actin (α-SMA) positive myofibroblast-like cells. The continuous cross-talking between CCA cells and desmoplastic stroma is permitted by CAF biochemical signals, which modulate a number of pathways. Stromal cell-derived factor-1 expression increases CAF recruitment to the tumor reactive stroma and influences apoptotic pathways. The Bcl-2 family protein enhances susceptibility to CAF apoptosis and PDGFRβ induces fibroblast migration and stimulates tumor lymphangiogenesis. Many factors related to CAFs may influence CCA prognosis.
  • 839
  • 10 Nov 2022
Topic Review
Ovarian Aging
Ovarian aging has a genetic basis that conditions the ovarian activity via a plethora of cell-signaling pathways that control the functions of different types of cells in the ovary. There are various factors that can influence these pathways so as to reduce their efficiency. Oxidative stress, often related to mitochondrial dysfunction, leading to the apoptosis of ovarian cells, can be at the origin of vicious circles in which the primary cause feeds back other abnormalities, resulting in an overall decline in the ovarian activity and in the quantity and quality of oocytes.
  • 838
  • 27 Feb 2021
Topic Review
Salivary Volatile Metabolites in Oral Diseases
Oral diseases (ODs) are highly prevalent affecting over 3.5 billion people, particularly in low- and middle-income countries (LMICs). Saliva is often described as the "mirror of the body" and so different omics approaches such us proteomics, metabolomics and more recently, volatomics are being employed to explore the potential of this biofluid towards the non-invasive diagnosis of ODs.
  • 838
  • 30 Nov 2021
Topic Review
Modification of Glyceraldehyde-3-Phosphate Dehydrogenase with Nitric Oxide
One of the main targets of NO in cells is glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is due to the presence of a highly reactive cysteine residue in the active center of this protein, as well as to the high content of this protein in all cells. The main products of GAPDH modification with nitric oxide are S-nitrosylated GAPDH and S-sulfenated GAPDH (GAPDH-SNO and GAPDH-SOH, respectively). Modification of GAPDH with nitric oxide is of particular interest due to the fact that it causes the accumulation of GAPDH in the nucleus and induction of apoptosis. According to the most popular hypothesis, a wide range of apoptotic stimuli augment NO production in the cells, GAPDH is nitrosylated by NO, which leads to inactivation of the protein and to conformational changes in its molecule. These alterations facilitate the binding of GAPDH with the E3-ubiquitin-ligase Siah1. Siah1, which possesses a nuclear localization signal (NLS), translocates GAPDH to the nucleus and stimulates a cascade of apoptotic reactions. However, the molecular mechanisms of this signaling pathway have not yet been studied in detail. There are no direct data on the selective interaction of the S-nitrosylated GAPDH with Siah1. It cannot be excluded that any modifications of the catalytic cysteine residue, which are accompanied by a weakening of interactions between the enzyme and NAD+, lead to a change in the conformation of GAPDH, and stimulate its binding to some partner proteins—in particular, Siah1.
  • 837
  • 03 Dec 2021
Topic Review
NADPH Oxidase and Cellular Metabolism
Reactive oxygen species (ROS) represent a group of high reactive molecules with dualistic natures since they can induce cytotoxicity or regulate cellular physiology. The NADPH oxidase (NOX) family represents the main source of controlled ROS formation and includes seven isoforms with a broad tissue distribution and activation mechanism. Their subcellular distribution varies in the different cell types, ranging from plasma membrane to intracellular compartments and nuclear membrane. The NOX family includes NOX1, NOX2, NOX3, NOX4, NOX5, and the dual oxidase Duox1 and Duox2.
  • 837
  • 08 Feb 2023
Topic Review
Protein Phosphatases and Their Role in Spermatozoa Function
Male fertility relies on the ability of spermatozoa to fertilize the egg in the female reproductive tract (FRT). Spermatozoa acquire activated motility during epididymal maturation; however, to be capable of fertilization, they must achieve hyperactivated motility in the FRT. Extensive research found that three protein phosphatases (PPs) are crucial to sperm motility regulation, the sperm-specific protein phosphatase type 1 (PP1) isoform gamma 2 (PP1γ2), protein phosphatase type 2A (PP2A) and protein phosphatase type 2B (PP2B). 
  • 836
  • 09 Jan 2023
Topic Review
Bacterial-Artificial-Chromosome-Based Genome Editing in Herpesvirus
Herpesviruses are major pathogens that infect humans and animals. Manipulating the large genome is critical for exploring the function of specific genes and studying the pathogenesis of herpesviruses and developing novel anti-viral vaccines and therapeutics. Bacterial artificial chromosome (BAC) technology significantly advanced the capacity of herpesviruses researchers to manipulate the virus genomes.
  • 836
  • 20 Apr 2023
Topic Review
Anticancer Potentials of the Lignan Magnolin
Magnolin is a compound found in many different plants. It has been demonstrated to have anticancer activity in numerous experimental models by inhibiting the cell cycle (G1 and G2/M phase); inducing apoptosis; and causing antiinvasion, antimetastasis, and antiproliferative effects via the modulation of several pathways.
  • 836
  • 26 Apr 2023
Topic Review
LncRNAs in the Regulation of Translation
Long non-coding RNAs (lncRNAs), a group of non-protein coding RNAs with lengths of more than 200 nucleotides, exert their effects by binding to DNA, mRNA, microRNA, and proteins and regulate gene expression at the transcriptional, post-transcriptional, translational, and post-translational levels. 
  • 836
  • 16 Jun 2023
Topic Review
Ultrastructural Features of the Blood-Brain Barrier
The blood-brain barrier (BBB) is a dynamic barrier separating neurocytes and brain tissues from blood that is extremely sealed and strictly regulated by transporters such as aquaporin-4 (AQP-4), glucose transporter (GLUT), and specialized tight junctional complexes (TJCs) including tight junctions (TJs), adherens junctions (AJs), and Zonulae occludens (ZOs). With specifically selective transcellular and paracellular permeability, the BBB maintains a homeostatic microenvironment to protect the central nervous system (CNS).
  • 836
  • 27 Jul 2023
Topic Review
Small Heat Shock Proteins Cancers
Small heat shock proteins (sHSPs) are ubiquitous ATP-independent chaperones that play essential roles in response to cellular stresses and protein homeostasis. Investigations of sHSPs reveal that sHSPs are ubiquitously expressed in numerous types of tumors, and their expression is closely associated with cancer progression. sHSPs have been suggested to control a diverse range of cancer functions, including tumorigenesis, cell growth, apoptosis, metastasis, and chemoresistance, as well as regulation of cancer stem cell properties. Recent advances in the field indicate that some sHSPs have been validated as a powerful target in cancer therapy. In this entry, we present and highlight current understanding, recent progress, and future challenges of sHSPs in cancer development and therapy.
  • 835
  • 27 Sep 2020
Topic Review
Iron-Binding Catecholato Chelators
Siderophores are iron-complexing compounds synthesized by bacteria and fungi. They are low molecular weight compounds (500-1500 Daltons) possessing high affinity for iron(III). This entry reports an integrated computational/synthetic approach towards a rational development of peptide-based siderophores.
  • 834
  • 16 Oct 2020
Topic Review
Diseases Associated with Fli1 Deficiency
Being initially described as a factor of virally induced leukemias, Fli1 (Friend leukemia integration 1) lately has attracted considerable interest due to its role in both healthy physiology and a variety of pathological conditions. Over the past years Fli1 was found to be one of the crucial regulators of normal hematopoiesis, vasculogenesis and immune responses. However, abnormal expression of Fli1 due to genetic predisposition, epigenetic reprogramming (modifications) or environmental factors is associated with a few diseases of different etiology. Fli1 hyperexpression leads to malignant transformation of cells and progression of cancers such as Ewing’s sarcoma. The deficiency of Fli1 implicates in development of systemic sclerosis and hypertensive disorders, which are often accompanied by pronounced fibrosis in different organs. 
  • 834
  • 02 Feb 2023
Topic Review
Mitochondrial Complex I
In mammals during aging, reactive oxygen species (ROS), produced by the mitochondrial respiratory chain, cause oxidative damage of macromolecules leading to respiratory chain dysfunction, which in turn increases ROS mitochondrial production. Many efforts have been made to understand the role of oxidative stress in aging and age-related diseases. The complex I of the mitochondrial respiratory chain is the major source of ROS production and its dysfunctions have been associated with several forms of neurodegeneration, other common human diseases and aging. Complex I-ROS production and complex I content have been proposed as one of the major determinants for longevity. The cAMP signal has a role in the regulation of complex I activity and the decrease of ROS production. 
  • 834
  • 10 Feb 2023
Topic Review
Hydrogen Sulfide in Mammalian Cells
Hydrogen sulfide (H2S) was recognized as a gaseous signaling molecule, similar to nitric oxide (-NO) and carbon monoxide (CO). It's important to provide an overview of the formation of hydrogen sulfide (H2S) in the human body. H2S is synthesized by enzymatic processes involving cysteine and several enzymes, including cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), cysteine aminotransferase (CAT), 3-mercaptopyruvate sulfurtransferase (3MST) and D-amino acid oxidase (DAO). The physiological and pathological effects of hydrogen sulfide (H2S) on various systems in the human body have led to extensive research efforts to develop appropriate methods to deliver H2S under conditions that mimic physiological settings and respond to various stimuli. These functions span a wide spectrum, ranging from effects on the endocrine system and cellular lifespan to protection of liver and kidney function. The exact physiological and hazardous thresholds of hydrogen sulfide (H2S) in the human body are currently not well understood and need to be researched in depth. 
  • 832
  • 18 Dec 2023
Topic Review
Ablative Radiotherapy in Prostate Cancer
Prostate cancer (PCa) is the most common noncutaneous solid organ malignancy among men worldwide. Radiation therapy is a standard of care treatment option that has historically been delivered in the form of small daily doses of radiation over the span of multiple weeks. PCa appears to have a unique sensitivity to higher doses of radiation per fraction, rendering it susceptible to abbreviated forms of treatment. Stereotactic body radiation therapy (SBRT) and high-dose-rate brachytherapy (HDRBT) are both modern radiation modalities that allow the precise delivery of ablative doses of radiation to the prostate while maximally sparing sensitive surrounding normal structures. In this review, we highlight the evidence regarding the radiobiology, oncological outcomes, toxicity and dose/fractionation schemes of SBRT and HDRBT monotherapy in men with low-and intermediate-risk PCa.
  • 831
  • 18 Dec 2020
Topic Review
Inflammasome in Neurodegenerative Diseases
Neurodegenerative diseases are chronic, progressive disorders that occur in the central nervous system (CNS). They are characterized by the loss of neuronal structure and function and are associated with inflammation. Inflammation of the CNS is called neuroinflammation, which has been implicated in most neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Much evidence indicates that these different conditions share a common inflammatory mechanism: the activation of the inflammasome complex in peripheral monocytes and in microglia, with the consequent production of high quantities of the pro-inflammatory cytokines IL-1β and IL-18. Inflammasomes are a group of multimeric signaling complexes that include a sensor Nod-like receptor (NLR) molecule, the adaptor protein ASC, and caspase-1. The NLRP3 inflammasome is currently the best-characterized inflammasome. Multiple signals, which are potentially provided in combination and include endogenous danger signals and pathogens, trigger the formation of an active inflammasome, which, in turn, will stimulate the cleavage and the release of bioactive cytokines including IL-1β and IL-18.
  • 831
  • 03 Mar 2021
Topic Review
Targeting Nrf2 and NF-κB Signaling Pathways in Cancer
Plant secondary metabolites, known as phytochemicals, have gained much attention in light of the “circular economy”, to reutilize waste products deriving from agriculture and food industry. Phytochemicals are known for their onco-preventive and chemoprotective effects, among several other beneficial properties. Apple phytochemicals have been extensively studied for their effectiveness in a wide range of diseases, cancer included.
  • 831
  • 15 Feb 2023
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