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Topic Review
AKR1B10 in Physiology and Pathophysiology
AKR1B10 is a human nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase belonging to the aldo-keto reductase (AKR) 1B subfamily. It catalyzes the reduction of aldehydes, some ketones and quinones, and interacts with acetyl-CoA carboxylase and heat shock protein 90α. The enzyme is highly expressed in epithelial cells of the stomach and intestine, but down-regulated in gastrointestinal cancers and inflammatory bowel diseases. In contrast, AKR1B10 expression is low in other tissues, where the enzyme is upregulated in cancers, as well as in non-alcoholic fatty liver disease and several skin diseases. In addition, the enzyme’s expression is elevated in cancer cells resistant to clinical anti-cancer drugs. Thus, growing evidence supports AKR1B10 as a potential target for diagnosing and treating these diseases. Herein, we reviewed the literature on the roles of AKR1B10 in a healthy gastrointestinal tract, the development and progression of cancers and acquired chemoresistance, in addition to its gene regulation, functions, and inhibitors.
  • 875
  • 24 Jun 2021
Topic Review
Extracellular Vesicle-Mediated Mitochondrial Reprogramming in Cancer
Tumors are complex systems in constant communication with their microenvironment on which they rely for growth and survival. EVs, as intercellular communicators, are involved in several hallmarks of cancers, being active players in the remodeling of the TME and priming metastatic niches to support tumor survival, progression, and invasion. Although the importance of mitochondrial state and reprogramming in cancer progression has been established, the underlying mechanisms and metabolic phenotypes are incredibly varied, and knowledge is still lacking.
  • 875
  • 07 May 2022
Topic Review
Chemokine uptake in Endothelial Cells
The chemokines CCL5 and CXCL4 are deposited by platelets onto endothelial cells, inducing monocyte arrest. Here, the fate of CCL5 and CXCL4 after endothelial deposition was investigated. Human umbilical vein endothelial cells (HUVECs) and EA.hy926 cells were incubated with CCL5 or CXCL4 for up to 120 min, and chemokine uptake was analyzed by microscopy and by ELISA. Intracellular calcium signaling was visualized upon chemokine treatment, and monocyte arrest was evaluated under laminar flow. Whereas CXCL4 remained partly on the cell surface, all of the CCL5 was internalized into endothelial cells. Endocytosis of CCL5 and CXCL4 was shown as a rapid and active process that primarily depended on dynamin, clathrin, and G protein-coupled receptors (GPCRs), but not on surface proteoglycans. Intracellular calcium signals were increased after chemokine treatment. Confocal microscopy and ELISA measurements in cell organelle fractions indicated that both chemokines accumulated in the nucleus. Internalization did not affect leukocyte arrest, as pretreatment of chemokines and subsequent washing did not alter monocyte adhesion to endothelial cells. Endothelial cells rapidly and actively internalize CCL5 and CXCL4 by clathrin and dynamin-dependent endocytosis, where the chemokines appear to be directed to the nucleus. These findings expand our knowledge of how chemokines attract leukocytes to sites of inflammation.
  • 874
  • 22 Sep 2021
Topic Review
Pivotal Role of Inflammation in Celiac Disease
Celiac disease (CD) is an immune mediate disease characterised by gluten dependent T-cell mediated activation, autoimmunity and derangement of the intestinal mucosa in a specific genetic background. Although the activation of the T-cells has been studied in dept, the central question remains still unanswered, namely, why a pro-inflammatory T cell response to gluten is generated instead of a regulatory response, which normally promotes oral tolerance to dietary protein antigens. There is an inflamed environment in CD intestine, enriched in cytokines, such as IL-15, or type I interferons, in which T cells tend to acquire a pro- inflammatory phenotype. The factors that create a pro-inflammatory environment in the CD intestine, leading to an expansion of gliadin-specific T cells in genetically susceptible individuals and further shifting them towards a pro-inflammatory phenotype, remain to be identified. Gluten exacerbates these constitutive alterations, by increasing the same markers already altered before the gluten introduction, both in vitro and in vivo. All these new observations add this disease “tout court” to the big family of increasing chronic inflammatory diseases where nutrients can have pro-inflammatory or anti-inflammatory effects, directly or indirectly mediated by the intestinal microbiota, where the intestine functions as a cross road for the control of the inflammation both local and at distance.
  • 874
  • 20 Jul 2022
Topic Review
Epithelial Stem Cell Innovation
The field of epithelial stem cell development has been irrevocably shaped by the work of American scientist Howard Green, whose breakthroughs in stem cell culture methods translated to therapeutic practice.
  • 874
  • 20 Mar 2023
Topic Review
Cell Receptors for Collagen
Collagen, an extracellular protein, covers the entire human body and has several important biological functions in normal physiology. Collagen possibly binds with at least six different groups of receptors in biological cells. These are integrins, DDR, Glycoprotein VI, Osteoclast-associated receptor (OSCAR), LAIR-1, and uPARAP/Endo180.
  • 873
  • 10 Mar 2022
Topic Review
TRPC Channels in Cardiac Plasticity
The heart flexibly changes its structure in response to changing environments and oxygen/nutrition demands of the body. Increased and decreased mechanical loading induces hypertrophy and atrophy of cardiomyocytes, respectively. In physiological conditions, these structural changes of the heart are reversible. However, chronic stresses such as hypertension or cancer cachexia cause irreversible remodeling of the heart, leading to heart failure. Accumulating evidence indicates that calcium dyshomeostasis and aberrant reactive oxygen species production cause pathological heart remodeling. Canonical transient receptor potential (TRPC) is a nonselective cation channel subfamily whose multimodal activation or modulation of channel activity play important roles in a plethora of cellular physiology.
  • 872
  • 03 Jun 2021
Topic Review Video
Photodynamic Therapy for Prostate Cancer
Prostate cancer is a major health concern worldwide, and current treatments, such as surgery, radiation therapy, and chemotherapy, are associated with significant side effects and limitations. Photodynamic therapy (PDT) is a promising alternative that has the potential to provide a minimally invasive and highly targeted approach to treating prostate cancer. PDT involves the use of photosensitizers (PSs) that are activated by light to produce reactive oxygen species (ROS), which can induce tumor cell death. 
  • 871
  • 03 Sep 2023
Topic Review
Purinergic Signaling in Colorectal Cancer
Colorectal cancer is a leading cause of cancer-related death. Activated immune cells have the potential to eliminate tumor cells, but cancers gain the ability to suppress immune cell functions and escape immune attack. The researchers explored one mechanism that cancers use to evade immune cells in colorectal cancer. This mechanism alters levels of molecules known as purines. Purines are key players in cellular energetics and many cellular processes and can also lead to immune suppression in cancer.
  • 871
  • 21 Nov 2022
Topic Review
Pseudophosphatases in Disease
Pseudophosphatases are important regulators, and their proper regulation is important for maintaining homeostasis and preventing diseases.
  • 870
  • 14 Jul 2021
Topic Review
Microbial Consortia for Plant Protection against Diseases
Biological plant protection presents a promising and exciting alternative to chemical methods for safeguarding plants against the increasing threats posed by plant diseases. This approach revolves around the utilization of biological control agents (BCAs) to suppress the activity of significant plant pathogens. Microbial BCAs have the potential to effectively manage crop disease development by interacting with pathogens or plant hosts, thereby increasing their resistance.
  • 869
  • 28 Nov 2023
Topic Review
Extracellular Vesicles in Hepatocellular Carcinoma
Extracellular vesicles (EVs) are defined as lipid bilayer particles naturally released from cells into the extracellular space. EVs have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA).Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In the liver, EVs play a crucial role in regulating cell-cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo.
  • 868
  • 23 Jun 2021
Topic Review
EVs–PEG–cECMH Product
The combination of cardiosphere-derived extracellular vesciles (EVs), polyethylene glycol (PEG), and cardiac extracellular matrix hydrogel (cECMH), EVs–PEG–cECMH, is a potential multipronged product with improved gelation time and mechanical properties, increased on-site retention, and maintained bioactivity that, all together, may translate into boosted therapeutic efficacy.
  • 868
  • 14 Sep 2021
Topic Review
Efficient Mucosal Repair Limits Morbidity from Colic
Colic is a leading cause of death in horses, with the most fatal form being strangulating obstruction which directly damages the intestinal barrier. Following surgical intervention, it is imperative that the intestinal barrier rapidly repairs to prevent translocation of gut bacteria and their products and ensure survival of the patient. Age-related disparities in survival have been noted in many species, including horses, humans, and pigs, with younger patients suffering poorer clinical outcomes. Maintenance and repair of the intestinal barrier is regulated by a complex mucosal microenvironment, of which the ENS, and particularly a developing network of subepithelial enteric glial cells, may be of particular importance in neonates with colic. Postnatal development of an immature enteric glial cell network is thought to be driven by the microbial colonization of the gut and therefore modulated by diet-influenced changes in bacterial populations early in life.
  • 868
  • 13 Dec 2021
Topic Review
Golgi Proteostasis
The Golgi apparatus is a central hub for cellular protein trafficking and signaling. Golgi structure and function is tightly coupled and undergoes dynamic changes in health and disease. A crucial requirement for maintaining Golgi homeostasis is the ability of the Golgi to target aberrant, misfolded, or otherwise unwanted proteins to degradation. Recent studies have revealed that the Golgi apparatus may degrade such proteins through autophagy, retrograde trafficking to the ER for ER-associated degradation (ERAD), and locally, through Golgi apparatus-related degradation (GARD).
  • 868
  • 02 Mar 2022
Topic Review
Stem-Cell-Based Therapy in Alzheimer’s Disease
Stem cells are a versatile source for cell therapy. Their use is particularly significant for the treatment of neurological disorders for which no definitive conventional medical treatment is available. Neurological disorders are of diverse etiology and pathogenesis. Alzheimer’s disease (AD) is caused by abnormal protein deposits, leading to progressive dementia.
  • 867
  • 15 Nov 2022
Topic Review
Membrane Lipids in Light-Activation of Drosophila TRP Channels
Transient Receptor Potential (TRP) channels constitute a large superfamily of polymodal channel proteins with diverse roles in many physiological and sensory systems that function both as ionotropic and metabotropic receptors. From the early days of TRP channel discovery, membrane lipids were suggested to play a fundamental role in channel activation and regulation. A prominent example is the Drosophila TRP and TRP-like (TRPL) channels, which are predominantly expressed in the visual system of Drosophila. Light activation of the TRP and TRPL channels, the founding members of the TRP channel superfamily, requires activation of phospholipase Cβ (PLC), which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into Diacylglycerol (DAG) and Inositol 1, 4,5-trisphosphate (IP3).
  • 867
  • 19 Apr 2022
Topic Review
Unravelling Plant Cell Death in Host Plants
Pathogens within the oomycete genus Phytophthora are among some of the most destructive plant pathogens globally, causing disease and significant losses in important agricultural and forestry crops, damaging the environment, as well as impeding attempts to mitigate climate change. What is of increasing interest is the involvement of Phytophthora effectors in regulating programed cell death (PCD)—in particular, the hypersensitive response. 
  • 866
  • 14 Jul 2022
Topic Review
Therapeutic Strategies for Pantothenate Kinase
The term neurodegeneration with brain iron accumulation (NBIA) brings together a broad set of progressive and disabling neurological genetic disorders in which iron is deposited preferentially in certain areas of the brain. Among NBIA disorders, the most frequent subtype is pantothenate kinase-associated neurodegeneration (PKAN) caused by pathologic variants in the PANK2 gene codifying the enzyme pantothenate kinase 2 (PANK2). 
  • 866
  • 10 Oct 2023
Topic Review
Resveratrol against Cervical Cancer
Overall, the scientific data show that resveratrol has the ability to target/inhibit certain signaling molecules (EGFR, VEGFR, PKC, JNK, ERK, NF-kB, and STAT3) involved in cervical cancer cell proliferation and survival. Further in vivo experiments and clinical studies are required to better understand the potential of resveratrol against cervical cancer.
  • 865
  • 15 Dec 2022
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