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Topic Review
Energy-Saving Mechanism in Skeletal Muscle
Exercise produces oxidants from a variety of intracellular sources, including NADPH oxidases (NOX) and mitochondria. Exercise-derived reactive oxygen species (ROS) are beneficial, and the amount and location of these ROS is important to avoid muscle damage associated with oxidative stress.
  • 873
  • 22 Aug 2023
Topic Review
Synaptotagmin-13 Is a Neuroendocrine Marker
Synaptotagmin-13 (Syt13) is an atypical member of the vesicle trafficking synaptotagmin protein family. The expression pattern and the biological function of this Ca2+-independent protein are not well resolved. Here, we have generated a novel Syt13-Venus fusion (Syt13-VF) fluorescence reporter allele to track and isolate tissues and cells expressing Syt13 protein. The reporter allele is regulated by endogenous cis-regulatory elements of Syt13 and the fusion protein follows an identical expression pattern of the endogenous Syt13 protein. The homozygous reporter mice are viable and fertile.
  • 872
  • 01 Dec 2021
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). 
  • 872
  • 10 Oct 2023
Topic Review
Exosomes to Head and Neck Cancer
Head and neck squamous cell carcinoma (HNSCC) represents an aggressive and heterogenous group of cancers whose pathologies remain largely unresolved. Exosomes are a subtype of extracellular vesicles secreted by a variety of cells that have begun to spark significant interest in their roles in cancer. As membranous vesicles, spanning from 30–150 nm in diameter, exosomes mediate the transport of various molecules, such as proteins, nucleic acids, and lipids, intercellularly throughout the body. In doing so, exosomes not only act to deliver materials to cancer cells but also as signals that can confer their progression. Accumulating evidence shows the direct correlation between exosomes and the aggressiveness of HNSCC. 
  • 871
  • 24 Nov 2021
Topic Review
Cytokines in Schizophrenia
Schizophrenia is a chronic mental disorder with a complex etiopathogenesis, which involves both congenital and environmental factors. It leads to neurodegenerative changes in the central nervous system (CNS) and a significant impairment of social functioning. Its lifetime incidence has been estimated at 7.1 per 1000 people, and the male to female risk ratio is 1.4:1.
  • 870
  • 07 Dec 2021
Topic Review
Targeting Akt in Treating Head and Neck Cancer
When Akt, a signalling protein, is activated by different growth factors such as epidermal growth factor, transforming growth factor α/β, vascular endothelial growth factor and nerve growth factor, head and neck cancer cell spreading is stimulated. Tumour microenvironment plays an important role in cancer spreading by synthesising and secreting growth factors and suggests that targeting growth-factor-activated Akt in combination therapy could be a valuable therapeutic approach in treating head and neck cancer patients. 
  • 869
  • 31 May 2022
Topic Review
RAD52 in Genome Maintenance
The maintenance of genome integrity is critical for cell survival. Homologous recombination (HR) is considered the major error-free repair pathway in combatting endogenously generated double-stranded lesions in DNA. Nevertheless, a number of alternative repair pathways have been described as protectors of genome stability, especially in HR-deficient cells. One of the factors that appears to have a role in many of these pathways is human RAD52, a DNA repair protein that was previously considered to be dispensable due to a lack of an observable phenotype in knock-out mice. In later studies, RAD52 deficiency has been shown to be synthetically lethal with defects in BRCA genes, making RAD52 an attractive therapeutic target, particularly in the context of BRCA-deficient tumors.
  • 866
  • 14 Sep 2021
Topic Review
Neutrophil Interactions with Lymphatic System
The lymphatic system is a complex network of lymphatic vessels and lymph nodes designed to balance fluid homeostasis and facilitate host immune defence. Neutrophils are rapidly recruited to sites of inflammation to provide the first line of protection against microbial infections. The traditional view of neutrophils as short-lived cells, whose role is restricted to providing sterilizing immunity at sites of infection, is rapidly evolving to include additional functions at the interface between the innate and adaptive immune systems. Neutrophils travel via the lymphatics from the site of inflammation to transport antigens to lymph nodes. They can also enter lymph nodes from the blood by crossing high endothelial venules. Neutrophil functions in draining lymph nodes include pathogen control and modulation of adaptive immunity. Another facet of neutrophil interactions with the lymphatic system is their ability to promote lymphangiogenesis in draining lymph nodes and inflamed tissues.
  • 866
  • 19 Jan 2022
Topic Review
Role of lncRNA in Cancer
Here, we summarize several studies of lncRNAs SNPs relevant to chemotherapy responses to further clarify the potential of lncRNAs as potential biomarkers of cancer risk and predictors of drug resistance as well as toxicity.
  • 865
  • 15 Jun 2021
Topic Review
Nanoparticles to Treat Macrophages
Nanoparticles are nanomaterials with three external nanoscale dimensions and an average size ranging from 1 to 1000 nm. Nanoparticles have gained notoriety in technological advances due to their tunable physical, chemical, and biological characteristics. However, the administration of functionalized nanoparticles to living beings is still challenging due to the rapid detection and blood and tissue clearance by the mononuclear phagocytic system. The major exponent of this system is the macrophage. Regardless the nanomaterial composition, macrophages can detect and incorporate foreign bodies by phagocytosis. Therefore, the simplest explanation is that any injected nanoparticle will be probably taken up by macrophages. This explains, in part, the natural accumulation of most nanoparticles in the spleen, lymph nodes, and liver (the main organs of the mononuclear phagocytic system). For this reason, recent investigations are devoted to design nanoparticles for specific macrophage targeting in diseased tissues. The aim of this review is to describe current strategies for the design of nanoparticles to target macrophages and to modulate their immunological function involved in different diseases with special emphasis on chronic inflammation, tissue regeneration, and cancer. 
  • 865
  • 02 Sep 2021
Topic Review
CD137+ T-Cells
The CD137 receptor is expressed by activated antigen-specific T-cells. CD137+ T-cells were identified inside TILs and PBMCs of different tumor types and have proven to be the naturally occurring antitumor effector cells, capable of expressing a wide variability in terms of TCR specificity against both shared and neoantigenic tumor-derived peptides. The aim of this review is thus summarizing and highlighting their role as drivers of patients’ immune responses in anticancer therapies as well as their potential role in future and current strategies of immunotherapy.
  • 864
  • 08 Mar 2021
Topic Review
Nurse-Like Cells and CLL-B Cells
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries and is an example of hematological disease where cooperation between genetic defects and tumor microenvironmental interaction is involved in pathogenesis. CLL is a disease that is considered as “addicted to the host”; indeed, the crosstalk between leukemic cells and the tumor microenvironment is essential for leukemic clone maintenance supporting CLL cells’ survival, proliferation, and protection from drug-induced apoptosis. CLL cells are not innocent bystanders but actively model and manipulate the surrounding microenvironment to their own advantage. Besides the different players involved in this crosstalk, nurse-like cells (NLC) resemble features related to leukemia-associated macrophages with an important function in preserving CLL cell survival and supporting an immunosuppressive microenvironment.
  • 864
  • 14 May 2021
Topic Review
Myelin Basic Protein Interaction Landscape
Intrinsically disordered myelin basic protein (MBP) is one of the key autoantigens in autoimmune neurodegeneration and multiple sclerosis particularly. MBP is highly positively charged and lacks a distinct structure in solution, and therefore its intracellular partners are still mostly enigmatic. Here authors used combination of formaldehyde-induced cross-linking followed by immunoprecipitation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to elucidate the interaction network of MBP in mammalian cells and provide the list of potential MBP interacting proteins.
  • 863
  • 15 Nov 2021
Topic Review
Spatiotemporal Distribution of VPS13A in the Mouse Brain
Loss-of-function mutations in the human vacuolar protein sorting 13 homolog A (VPS13A) gene cause Chorea-acanthocytosis (ChAc). As very little is known about the VPS13A expression in the brain, The main objective of this work was to assess for the first time the spatiotemporal distribution of VPS13A in the mouse brain. Understanding the distinct expression pattern of VPS13A provides relevant information to unravel pathophysiological hallmarks of ChAc.
  • 863
  • 14 Jan 2022
Topic Review
Thymic Aging Associated with COVID-19
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the global pandemic of coronavirus disease 2019 (COVID-19) and particularly exhibits severe symptoms and mortality in elderly individuals. Mounting evidence shows that the characteristics of the age-related clinical severity of COVID-19 are attributed to insufficient antiviral immune function and excessive self-damaging immune reaction, involving T cell immunity and associated with pre-existing basal inflammation in the elderly. Age-related changes to T cell immunosenescence is characterized by not only restricted T cell receptor (TCR) repertoire diversity, accumulation of exhausted and/or senescent memory T cells, but also by increased self-reactive T cell- and innate immune cell-induced chronic inflammation, and accumulated and functionally enhanced polyclonal regulatory T (Treg) cells. Many of these changes can be traced back to age-related thymic involution/degeneration. How these changes contribute to differences in COVID-19 disease severity between young and aged patients is an urgent area of investigation.
  • 862
  • 28 Apr 2021
Topic Review
Stress Accelerates Tumor Progression via Sympathetic Nervous System
The sympathetic nervous system (SNS) originates in the ventral brainstem, where sympathetic premotor neurons are found. They are found predominantly in the rostral ventrolateral medulla (RVLM) and in the rostral ventromedial medulla (RVMM). These neurons project to the intermediolateral nucleus (IML, also known as the sympathetic preganglionic nucleus), which then projects to the dorsal root ganglia (DRG) for terminal output to peripheral organs which control heart rate, blood pressure, respiration, glycemia, vigilance and other physiological responses. When negative emotions are induced under chronic stress, the sympathetic nervous system is continuously activated and increases the release of catecholamines (such as epinephrine and norepinephrine). In a spontaneous colon tumor model, ablation of sympathetic premotor neurons in APCmin/+ mice reduces the number of polyps in the mouse intestine. Sympathetic denervation also leads to decreased tumorigenesis in a spontaneous prostate tumor mouse model. These results suggest that loss of SNS function may slow tumorigenesis.
  • 862
  • 01 Nov 2022
Topic Review
CCCTC-Binding Factor for Chromatin Regulation
Chromatin, a macromolecular complex of DNA, RNA, and proteins, provides a framework for the packaging of genetic material within the cell nucleus. Its organization plays a crucial role in gene expression and is regulated by a diverse array of protein complexes in response to a dynamic code of histone posttranslational modifications and DNA modifications. Architectural proteins are essential epigenetic regulators that play a critical role in organizing chromatin and controlling gene expression. CTCF (CCCTC-binding factor) is a key architectural protein responsible for maintaining the intricate 3D structure of chromatin. Because of its multivalent properties and plasticity to bind various sequences, CTCF is similar to a Swiss knife for genome organization.
  • 862
  • 25 May 2023
Topic Review
Cytokine Production in Human Pathology
Cytokines can perform a dual role, being growth promotors or inhibitors and having pro- and anti-inflammatory properties. The complex interactions between cytokines, vascular cells and immune cells are responsible for dramatic conditions and lead to the concept of cytokine storm observed during sepsis, multi-organ failure and in some cases of COVID-19 infection. Cytokines such as interferon and hematopoietic growth factor have been used as therapy. Alternatively, the inhibition of cytokine functions has been largely developed using anti-interleukin or anti-TNF monoclonal antibodies in the treatment of sepsis or chronic inflammation.
  • 862
  • 19 Jun 2023
Topic Review
Cerebral Cavernous Malformations (CCM)
Cerebral cavernous malformations (CCMs): an overall view from genes to endothelial cells.
  • 861
  • 21 Apr 2021
Topic Review
The Endocannabinoid System and Kidney Disease
The endocannabinoid system (ECS) is an important signaling pathway that involves the binding of lipid ligands, known as cannabinoids, to cannabinoid receptors, and it encompasses, as well, the metabolic enzymes of endocannabinoids. Endocannabinoid signaling plays crucial roles in human physiology in the function of multiple systems. The two cannabinoid receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), are cell membrane proteins that interact with both exogenous and endogenous bioactive lipid ligands, or endocannabinoids. The evidence has established that endocannabinoid signaling operates within the human kidney, as well as suggests the important role it plays in multiple renal pathologies. 
  • 860
  • 23 May 2023
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