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Topic Review
DNA Methylation in Low-Grade Gliomas
Gliomas, the most common type of malignant primary brain tumor, were conventionally classified through WHO Grades I–IV (now 1–4), with low-grade gliomas being entities belonging to Grades 1 or 2. While the focus of the WHO Classification for Central Nervous System (CNS) tumors had historically been on histopathological attributes, the recently released fifth edition of the classification (WHO CNS5) characterizes brain tumors, including gliomas, using an integration of histological and molecular features, including their epigenetic changes such as DNA methylation which are increasingly being used for the classification of low-grade gliomas. 
  • 911
  • 01 Mar 2023
Topic Review
P-21 Activated Kinases in Liver Disorders
The p21 Activated Kinases (PAKs) are serine threonine kinases and play important roles in many biological processes, including cell growth, survival, cytoskeletal organization, migration, and morphology. PAKs have emerged in the process of liver disorders, including liver cancer, hepatic ischemia-reperfusion injury, hepatitis, and liver fibrosis, owing to their effects in multiple signaling pathways in various cell types. Activation of PAKs promotes liver cancer growth and metastasis and contributes to the resistance of liver cancer to radiotherapy and chemotherapy, leading to poor survival of patients. PAKs also play important roles in the development and progression of hepatitis and other pathological processes of the liver such as fibrosis and ischemia-reperfusion injury.
  • 911
  • 10 Mar 2023
Topic Review
Sodium-Glucose Cotransporter-2 Inhibitors
Recent randomized controlled trials (RCTs) tested the efficacy of sodium-glucose cotransporter-2 (SGLT-2) inhibitors to specifically treat nonalcoholic fatty liver disease (NAFLD). We systematically searched three large electronic databases (up to 31 October 2020) for identifying placebo-controlled or active-controlled RCTs that used different SGLT-2 inhibitors (dapagliflozin, empagliflozin, ipragliflozin or canagliflozin) for treatment of NAFLD.
  • 910
  • 11 Jan 2021
Topic Review
Analyses of HCV Strains
Approximately 71 million people worldwide are infected with the hepatitis C virus (HCV). Injectable drug use represents the most common route of transmission in Europe and other developed countries. We studied the molecular characteristics of the HCV infection among mono-infected people who used drugs (PWUD) in Italy. Among 208 PWUD with anti-HCV antibodies, 101 (48.6%) were HCV RNA-positive, the majority (47%) were infected with the HCV genotype (Gt)1a, followed by Gt3a (34.9%), Gt4 (9.1%), Gt1b (4.5%), and Gt2 (4.5%). Bayesian phylogenetic analyses of clustered HCV NS5B sequences from 66 HCV-positive PWUDs with available plasma samples indicated age and neighborhood proximity as the most common characteristics between closely related HCV strains. Population dynamics, as measured by a coalescent Bayesian skyline analysis, revealed an increase in HCV Gt1a infections from the mid-1980s to mid-1990s. While HCV Gt3a infections were first detected in the 1980s, patient numbers with this genotype subtype remained relatively constant. For both Gt1a and Gt3a, Birth–Death Bayesian Skyline analyses produced higher reproduction numbers post 2014. For earlier time intervals, slow growths were observed for both Gt1a and Gt3a with reproduction numbers (Re) of approximately 1. The evolutionary rates for Gt1a and Gt3a were estimated as 2.23 × 10−4 and 3.85 × 10−4, respectively. 
  • 910
  • 05 Jul 2021
Topic Review
Microbiota-Derived Short-Chain Fatty Acids in Colorectal Cancer Therapy
Microbiota-derived short-chain fatty acids (SCFAs), namely acetate, butyrate, and propionate, have the ability to modulate the tumor microenvironment in distinct ways. SCFAs promote immune cell differentiation, downregulate the expression of pro-inflammatory mediators, and restrict the tumor-induced angiogenesis. SCFAs also sustain the integrity of basement membranes and modulate the intestinal pH. Colorectal cancer (CRC) patients have lower concentrations of SCFAs than healthy individuals. Increasing the production of SCFAs through the manipulation of the gut microbiota could constitute an important therapeutic strategy towards CRC due to their antitumorigenic effect and ability of modulating tumor microenvironment.
  • 910
  • 23 Apr 2023
Topic Review
Dlx Genes in Skeletal Development and Maintenance
Skeletal shape and mechanical properties define, to a large extent, vertebrate morphology and physical capacities. During development, skeletal morphogenesis results from dynamic communications between chondrocytes, osteoblasts, osteoclasts and other cellular components of the skeleton. Later in life, skeletal integrity depends from the regulatory cascades that assure the equilibrium between bone formation and resorption. Finally, during aging, skeletal catabolism prevails over anabolism resulting in progressive skeletal degradation. These cellular processes depend on the transcriptional cascades that control cell division and differentiation in each cell type. Most Distal-less (Dlx) homeobox transcription factors are directly involved in determining the proliferation and differentiation of chondrocytes and osteoblasts and, indirectly, of osteoclasts. The role of these genes in the maintenance of bone integrity has been only partially studied. Dlx genes appear to be involved in several bone pathologies including, for example, osteoporosis. Indeed, at least five large-scale GWAS studies aimed to detect loci associated to human bone mineral density (BMD) have identified a known DLX5/6 regulatory region within chromosome 7q21.3 in proximity of SEM1/FLJ42280/DSS1 coding sequences, suggesting that DLX5/6 expression is critical in determining healthy BMD. 
  • 909
  • 08 Nov 2022
Topic Review
Mechanisms of Myofibroblast Formation
At least three local events are needed to generate mature α-SMA-positive, fully differentiated myofibroblasts: (i) biologically active TGF-β1; (ii) extracellular stress, arising from the mechanical properties of the ECM (particularly collagen) and EDA–FN/integrin interactions; and (iii) the precursory production of phenotypic modulators (EDA–FN, HA) following activation. Increasing evidence strongly supports the role of inflammatory cell interactions in promoting myofibroblast development. Regardless of the origin, the resultant myofibroblast cells share the same properties and signalling cascade events that led to their formation.
  • 908
  • 11 Aug 2023
Topic Review
Ink4a/Arf Expression in Pancreatic Progenitor
The identification of the molecular mechanisms controlling early cell fate decisions in mammals is of paramount importance as the ability to determine specific lineage differentiation represents a significant opportunity for new therapies. Pancreatic Progenitor Cells (PPCs) constitute a regenerative reserve essential for the maintenance and regeneration of the pancreas. Besides, PPCs represent an excellent model for understanding pathological pancreatic cellular remodelling. Given the lack of valid markers of early endoderm, the identification of new ones is of fundamental importance. Both products of the Ink4a/Arf locus, in addition to being critical cell-cycle regulators, appear to be involved in several disease pathologies. Moreover, the locus’ expression is epigenetically regulated in ES reprogramming processes, thus constituting the ideal candidates to modulate PPCs homeostasis. 
  • 907
  • 22 Sep 2021
Topic Review
Mutations in TSC Genes and Synaptic Transmission
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease featuring localized uncontrolled growth of tissues, known as hamartomas, in many organs, including the central nervous system (CNS). A large proportion of the cases are sporadic mutations (ca. two thirds). The disease results from a loss-of-function mutation in either the TSC1 or TSC2 gene, which encode for hamartin and tuberin proteins, respectively; two proteins that together form the Tsc1–Tsc2 complex. This complex, which is the converging center of several signaling pathways, has GTPase activity and can inhibit the activity of Ras homolog enriched in the brain (Rheb). The complex itself is modulated by phosphorylation via, for example, Akt or AMPK (Figure 1).
  • 907
  • 09 Nov 2021
Topic Review
Major Components of Air Pollution Affecting Skin Appearance
The human skin is exposed daily to different environmental factors such as air pollutants and ultraviolet (UV) light. Air pollution is considered a harmful environmental risk to human skin and is known to promote aging and inflammation of this tissue, leading to the onset of skin disorders and to the appearance of wrinkles and pigmentation issues. Besides this, components of air pollution can interact synergistically with ultraviolet light and increase the impact of damage to the skin. 
  • 906
  • 19 Jul 2022
Topic Review
Ferroptosis Modulation as Therapeutic Target for Glioblastoma Treatment
Glioblastoma multiforme is a lethal disease and represents the most common and severe type of glioma. Drug resistance and the evasion of cell death are the main characteristics of its malignancy, leading to a high percentage of disease recurrence and the patients’ low survival rate. Exploiting the modulation of cell death mechanisms could be an important strategy to prevent tumor development and reverse the high mortality and morbidity rates in glioblastoma patients. Ferroptosis is a recently described type of cell death, which is characterized by iron accumulation, high levels of polyunsaturated fatty acid (PUFA)-containing phospholipids, and deficiency in lipid peroxidation repair. Several studies have demonstrated that ferroptosis has a potential role in cancer treatment and could be a promising approach for glioblastoma patients.
  • 906
  • 08 Jul 2022
Topic Review
Host Cell Signatures within Beta-Herpes Virions
Beta-herpesviruses infect a large proportion of the human population and are associated with a variety of pathophysiological conditions. They are DNA viruses with a large genome that encodes a relatively large number of gene products for the construction of new viral progeny and the establishment of a complex series of interactions with infected cells.
  • 905
  • 22 Sep 2022
Topic Review
Rho GTPase Regulators
The Rho family GTPases are small G proteins that act as molecular switches shuttling between active and inactive forms. Rho GTPases are regulated by two classes of regulatory proteins, guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Rho GTPases transduce the upstream signals to downstream effectors, thus regulating diverse cellular processes, such as growth, migration, adhesion, and differentiation. In particular, Rho GTPases play essential roles in regulating neuronal morphology and function. Recent evidence suggests that dysfunction of Rho GTPase signaling contributes substantially to the pathogenesis of autism spectrum disorder (ASD). It has been found that 20 genes encoding Rho GTPase regulators and effectors are listed as ASD risk genes by Simons foundation autism research initiative (SFARI).
  • 904
  • 02 Jun 2021
Topic Review
Tour of the Nuclear Pore Complex Architecture
Nuclear pore complexes (NPCs) are the only transport channels that cross the nuclear envelope. Constructed from ~500–1000 nucleoporin proteins each, they are among the largest macromolecular assemblies in eukaryotic cells. Thanks to advances in structural analysis approaches, the construction principles and architecture of the NPC have recently been revealed at submolecular resolution. Although the overall structure and inventory of nucleoporins are conserved, NPCs exhibit significant compositional and functional plasticity even within single cells and surprising variability in their assembly pathways. Once assembled, NPCs remain seemingly unexchangeable in post-mitotic cells. 
  • 904
  • 17 Jun 2022
Topic Review
Glycosaminoglycans in Metastatic Renal Cell Carcinoma
Renal cell carcinoma (RCC) makes up the majority of kidney cancers, with a poor prognosis for metastatic RCC (mRCC). Challenges faced in the management of mRCC, include a lack of reliable prognostic markers and biomarkers for precise monitoring of disease treatment, together with the potential risk of toxicity associated with more recent therapeutic options. Glycosaminoglycans (GAGs) are a class of carbohydrates that can be categorized into four main subclasses, viz., chondroitin sulfate, hyaluronic acid, heparan sulfate and keratan sulfate. GAGs are known to be closely associated with cancer progression and modulation of metastasis by modification of the tumor microenvironment. Alterations of expression, composition and spatiotemporal distribution of GAGs in the extracellular matrix (ECM), dysregulate ECM functions and drive cancer invasion.
  • 904
  • 17 Jan 2023
Topic Review
Non-Catalytic Tyrosine-Phosphorylated Receptors
Non-catalytic tyrosine-phosphorylated receptors (NTRs), also called immunoreceptors or Src-family kinase-dependent receptors, are a group of cell surface receptors expressed by leukocytes that are important for cell migration and the recognition of abnormal cells or structures and the initiation of an immune response. These transmembrane receptors are not grouped into the NTR family based on sequence homology, but because they share a conserved signalling pathway utilizing the same signalling motifs. A signaling cascade is initiated when the receptors bind their respective ligand resulting in cell activation. For that tyrosine residues in the cytoplasmic tail of the receptors have to be phosphorylated, hence the receptors are referred to as tyrosine-phosphorylated receptors. They are called non-catalytic receptors, as the receptors have no intrinsic tyrosine kinase activity and cannot phosphorylate their own tyrosine residues. Phosphorylation is mediated by additionally recruited kinases. A prominent member of this receptor family is the T-cell receptor.
  • 903
  • 28 Nov 2022
Topic Review
Crucial Roles of Ez-Metastasizing in Ezrin in Metastasis
Ezrin is the cytoskeletal organizer and functions in the modulation of membrane–cytoskeleton interaction, maintenance of cell shape and structure, and regulation of cell–cell adhesion and movement, as well as cell survival. Ezrin plays a critical role in regulating tumor metastasis through interaction with other binding proteins. Notably, Ezrin has been reported to interact with immune cells, allowing tumor cells to escape immune attack in metastasis. 
  • 903
  • 25 Jun 2023
Topic Review
Neuropeptide B
Neuropeptide B (NPB) is a peptide hormone that was initially described in 2002. In humans, the biological effects of NPB depend on the activation of two G protein-coupled receptors, NPBWR1 (GPR7) and NPBWR2 (GPR8), and, in rodents, NPBWR1. NPB and its receptors are expressed in the central nervous system (CNS) and in peripheral tissues. NPB is also present in the circulation. In the CNS, NPB modulates appetite, reproduction, pain, anxiety, and emotions. In the peripheral tissues, NPB controls secretion of adrenal hormones, pancreatic beta cells, and various functions of adipose tissue. Experimental downregulation of either NPB or NPBWR1 leads to adiposity. 
  • 902
  • 29 Jul 2021
Topic Review
The Role of Formins in Wound Repair
The restoration of an intact epidermal barrier after wound injury is the culmination of a highly complex and exquisitely regulated physiological process involving multiple cells and tissues, overlapping dynamic events and protein synthesis and regulation. Central to this process is the cytoskeleton, a system of intracellular proteins that are instrumental in regulating important processes involved in wound repair including chemotaxis, cytokinesis, proliferation, migration, and phagocytosis. One highly conserved family of cytoskeletal proteins that are emerging as major regulators of actin and microtubule nucleation, polymerization, and stabilization are the formins. The formin family includes 15 different proteins categorized into seven subfamilies based on three formin homology domains (FH1, FH2, and FH3). The formins themselves are regulated in different ways including autoinhibition, activation, and localization by a range of proteins, including Rho GTPases
  • 902
  • 04 Oct 2022
Topic Review
Drosophila Melanogaster Research
Parkinson’s disease (PD) is a complex neurodegenerative disorder that is currently incurable. As a consequence of an incomplete understanding of the etiology of the disease, therapeutic strategies mainly focus on symptomatic treatment. Even though the majority of PD cases remain idiopathic (~90%), several genes have been identified to be causative for PD, facilitating the generation of animal models that are a good alternative to study disease pathways and to increase our understanding of the underlying mechanisms of PD. Drosophila melanogaster has proven to be an excellent model in these studies.
  • 901
  • 23 Mar 2021
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