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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. 
  • 1.2K
  • 09 Jan 2022
Topic Review
YAP/TAZ May Bridge Microgravity and Liver Dysfunction
Microgravity exposure during spaceflight causes the disordered regulation of liver function, presenting a specialized mechano-biological coupling process. While YAP/TAZ serves as a typical mechanosensitive pathway involved in hepatocyte metabolism, it remains unclear whether and how it is correlated with microgravity-induced liver dysfunction. Whether or not the data in liver functions are derived from infight or ground-based studies, or what types of observations are presented at the organism or cellular level, it is still critical to map out the potential gravity-sensitive signaling pathways from the above functional or phenotypic cues. 
  • 1.2K
  • 10 May 2023
Topic Review
Inflammatory Markers in Cancer Immunotherapy
Chronic inflammation is considered a major risk factor for cancer formation. Inflammation within the tumor environment plays a role in its response to therapy, growth, and prognosis. Cancer associated inflammation is known to occur in the tumor microenvironment and in the systemic circulation, and is correlated with disease progression and prognosis in many cancers. Blood cells such as neutrophils, lymphocytes, platelets, and circulating proteins such as C-reactive protein, and interleukins, such as IL-6, have been associated with inflammatory responses, which contribute to tumorigenesis. Cancer has found ways to evade the immune response; a pathway that can attenuate the innate immune response is via blocking immune checkpoints. Development of monoclonal antibodies against inhibitory immune checkpoints such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) have given rise to immunotherapy, which has shown remarkable responses in anti-tumor activity resulting in several U.S. Federal and Drug Administration (FDA)-approved checkpoint inhibitors. 
  • 1.2K
  • 27 Apr 2021
Topic Review
Neutrophils during Arboviral Infections
Arboviruses are known to cause large-scale epidemics in many parts of the world. These arthropod-borne viruses are a large group consisting of viruses from a wide range of families. The ability of their vector to enhance viral pathogenesis and transmission makes the development of treatments against these viruses challenging. Neutrophils are generally the first leukocytes to be recruited to a site of infection, playing a major role in regulating inflammation and, as a result, viral replication and dissemination. However, the underlying mechanisms through which neutrophils control the progression of inflammation and disease remain to be fully understood. In this review, we highlight the major findings from recent years regarding the role of neutrophils during arboviral infections. We discuss the complex nature of neutrophils in mediating not only protection, but also augmenting disease pathology. Better understanding of neutrophil pathways involved in effective protection against arboviral infections can help identify potential targets for therapeutics. 
  • 1.2K
  • 05 Jul 2021
Topic Review
Neuromuscular Junction as an Entity of Nerve-Muscle Communication
One of the crucial systems severely affected in several neuromuscular diseases is the loss of effective connection between muscle and nerve, leading to a pathological non-communication between the two tissues. The neuromuscular junction (NMJ) represents the critical region at the level of which muscle and nerve communicate. Defects in signal transmission between terminal nerve endings and muscle membrane is a common feature of several physio-pathologic conditions including aging and Amyotrophic Lateral Sclerosis (ALS). Nevertheless, controversy exists on whether pathological events beginning at the NMJ precede or follow loss of motor units.
  • 1.2K
  • 31 Mar 2022
Topic Review
Phosphatidylinositol Binding Clathrin-Assembly Protein and Alzheimer’s Disease
Genome-wide association studies (GWAS) have identified the PICALM (Phosphatidylinositol binding clathrin-assembly protein) gene as the most significant genetic susceptibility locus after APOE and BIN1. PICALM is a clathrin-adaptor protein that plays a critical role in clathrin-mediated endocytosis and autophagy.
  • 1.2K
  • 22 Dec 2022
Topic Review
Monoubiquitin Signaling in Genetic Diseases
Ubiquitination is a reversible post-translational modification that controls protein function and stability. Different types of ubiquitination were described including polyubiquitination, the attachment of multiple ubiquitin residues, or monoubiquitination, the attachment of a single ubiquitin molecule. While most of the studies have described the role of polyubiquitination, recent evidences show that monoubiquitination is a key regulator of different cellular processes, including vesicular trafficking and protein complex formation and degradation. Enzymes regulating monoubiquitination such as E2 conjugating enzymes, E3 ligases or ubiquitin hydrolases, are found altered in several genetic diseases, including Parkinson's disease or Noonan syndrome.
  • 1.2K
  • 29 Oct 2020
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. 
  • 1.2K
  • 26 Oct 2021
Topic Review
Autoimmune Diseases in Epidermolysis Bullosa
Gene therapy serves as a promising therapy in the pipeline for treatment of epidermolysis bullosa (EB). However, with great promise, the risk of autoimmunity must be considered. While EB is a group of inherited blistering disorders caused by mutations in various skin proteins, autoimmune blistering diseases (AIBD) have a similar clinical phenotype and are caused by autoantibodies targeting skin antigens. Often, AIBD and EB have the same protein targeted through antibody or mutation, respectively. Moreover, EB patients are also reported to carry anti-skin antibodies of questionable pathogenicity. It has been speculated that activation of autoimmunity is both a consequence and cause of further skin deterioration in EB due to a state of chronic inflammation.
  • 1.2K
  • 11 Oct 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. 
  • 1.2K
  • 26 Jan 2021
Topic Review
Iron and Anti-Cancer Immune Response
New insights into the field of iron metabolism within the tumor microenvironment have been uncovered in recent years. Iron promotes the production of reactive oxygen species, which may either trigger ferroptosis cell death or contribute to malignant transformation. Once transformed, cancer cells divert tumor-infiltrating immune cells to satisfy their iron demand, thus affecting the tumor immunosurveillance. In this review, we highlight how the bioavailability of this metal shapes complex metabolic pathways within the tumor microenvironment and how this affects both tumor-associated macrophages and tumor-infiltrating lymphocytes functions. Furthermore, we discuss the potentials as well as the current clinical controversies surrounding the use of iron metabolism as a target for new anticancer treatments in two opposed conditions: (i) the “hot” tumors, which are usually enriched in immune cells infiltration and are extremely rich in iron availability within the microenvironment, and (ii) the “cold” tumors, which are often very poor in immune cells, mainly due to immune exclusion.
  • 1.2K
  • 06 Apr 2021
Topic Review
Osteoporosis Treatments
A healthy and active lifestyle is vital for the proper maintenance of all body tissues, including bone. Several studies have highlighted the importance of physical exercise to improve the quality of life of patients with osteoporosis. Diet also plays a fundamental role in bone health. Calcium supplementation is able to decrease the rate of bone mineral density loss in women, presenting even better results in combination with vitamin D. Lately, isoflavones has gain interest as a treatment in osteoporosis but their effectiveness still remains unclear. Therefore, pharmacological therapies have been developed to counteract bone fragility based on molecular targets. Therapies for osteoporosis are focus on restoring the normal balance between bone resorption and bone formation. Bone anti-resorptive therapies focus on the inhibition or reduction of bone resorption process, these are; estrogens, selective estrogen receptor modulators (SERMs), bisphosphonates and monoclonal antibodies. On the other hand, bone formation agents target anabolic pathways to stimulate the osteoblastic activity. This include Teriparatide, a recombinant human parathyroid hormone (PTH), and Romosozumab; an anti-sclerostin monoclonal antibody with dual effect.  It increases bone formation and, to a lesser extent, it reduces bone resorption (or bone loss) which translates into a decrease in the risk of fracture. In summary, currently used osteoporosis therapies are not fully effective in all patients and present considerable side effects that seriously compromise their long-term use. Thus, the development of new therapeutic strategies for osteoporosis is necessary in an increasingly aging world population. In this context, cell-based therapeutic strategies based on mesenchymal stem cells are positioning as encouraging possibilities to address osteoporosis.
  • 1.2K
  • 27 Oct 2020
Topic Review
Mitochondrial Homeostasis
Mitochondria are essential organelles and crucial for cellular survival. Mitochondrial biogenesis and mitophagy are dynamic features that are essential for both maintaining the health of the mitochondrial network and cellular demands. The accumulation of damaged mitochondria has been shown to be related to a wide range of pathologies ranging from neurological to musculoskeletal.
  • 1.2K
  • 18 Oct 2022
Topic Review
Cell Wall Associated Kinase
Cell wall associated kinases (WAKs) are receptor-like protein kinases, found in plant cell walls, that have the capability to transmit signals directly by their cytoplasmic kinase domains. They usually link the plasma membrane to the protein and carbohydrate that composed the cell wall. The receptor-like proteins contain a cytoplasmic serine threonine kinase and a less conserved region; bound to the cell wall and contains a series of epidermal growth factor repeats. WAKs are found in various plants and crops like rice, and maize. In plants genome like Arabidopsis, WAKs, are encoded by five highly similar genes clustered in a 30-kb locus, among them WAK1 & WAK2 are highly distributed. They are primarily involved in regulating plant cell wall functions including cell expansion, bind as well as response to pectins, pathogen response and also protects plants from detrimental effects.
  • 1.2K
  • 03 Nov 2022
Topic Review
CRISPR-Cas and Its Wide-Ranging Applications
The CRISPR-Cas system is a powerful tool for in vivo editing the genome of most organisms, including man.
  • 1.2K
  • 24 May 2021
Topic Review
Targeting Ferroptosis against Ischemia/Reperfusion Cardiac Injury
Ischemic heart disease is a leading cause of death worldwide. Primarily, ischemia causes decreased oxygen supply, resulting in damage of the cardiac tissue. Naturally, reoxygenation has been recognized as the treatment of choice to recover blood flow through primary percutaneous coronary intervention. This treatment is the gold standard therapy to restore blood flow, but paradoxically it can also induce tissue injury. A number of different studies in animal models of acute myocardial infarction (AMI) suggest that ischemia-reperfusion injury (IRI) accounts for up to 50% of the final myocardial infarct size. Oxidative stress plays a critical role in the pathological process. Iron is an essential mineral required for a variety of vital biological functions but also has potentially toxic effects. A detrimental process induced by free iron is ferroptosis, a non-apoptotic type of programmed cell death. Accordingly, efforts to prevent ferroptosis in pathological settings have focused on the use of radical trapping antioxidants (RTAs), such as liproxstatin-1 (Lip-1). Hence, it is necessary to develop novel strategies to prevent cardiac IRI, thus improving the clinical outcome in patients with ischemic heart disease. 
  • 1.2K
  • 05 May 2022
Topic Review
Vascular Smooth Muscle Cells Biomechanics
Cardiovascular diseases are one of the leading causes of global death in developing countries. More than 80% of cardiovascular disease-associated mortality is attributable to atherosclerosis, a chronic inflammatory disease of the vessel wall. During the development of atherosclerosis and other cardiovascular diseases, vascular smooth muscle cells (SMCs) continuously shift from a contractile state towards other phenotypes that differ substantially from differentiated SMCs.
  • 1.2K
  • 22 Sep 2021
Topic Review
Three-Dimensional Culture Systems
It is getting more and more clear that cancer cell culture models are switching from two-dimension to three-dimensional, in order to better reflect in vivo situations where tumor cells have to cope with a highly interactive three-dimensional microenvironment. Several such culture models have been reported, predominantly multicellular tumor spheroids (MCTS) and patient-derived tumor organoids (PDTO). These are used both to investigate fundamental aspects of cancer development and as test systems for innovative therapies against gastric cancer, the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. The authors review the actual state of research in this field to provide an overview of the contribution of MCTS and PDTO, especially in the areas of molecular profiling, drug discovery, pathogen infection, and personalized medicine.
  • 1.2K
  • 18 Feb 2021
Topic Review
Enteric Glial Cells
 At first, enteric glial cells were considered to be just a structural support for neurons, but recent findings emphasized more on their functions, and they turned out to be equally as important as neural cells, due to their involvement in all aspects of neural functions for both the central and peripheral nervous system, including the ENS.They have been mostly underestimated, particularly regarding the modulation of their functions by nutraceuticals.
  • 1.2K
  • 09 Nov 2021
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.
  • 1.2K
  • 31 Mar 2022
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