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Topic Review
Dietary Modulation of Bacteriophages
The role and function of bacteriophages (phages) has been underestimated so far. Natural compounds such as essential oils and tea have been used successfully in naturopathy and folk medicine for hundreds of years. Current research is unveiling the molecular role of their antibacterial, anti-inflammatory, and anticancer properties. The current interdisciplinary review summarizes current knowledge on dietary compounds as to their capacity to modulate the activity of phages, thus potentially contributing to (the modulation of) several gastrointestinal diseases, such as (chronic) inflammation, and even cancer.
  • 540
  • 27 Apr 2021
Topic Review
Different Types of Adipocytes
Adipose tissue resides in specific depots scattered in peripheral or deeper locations all over the body and it enwraps most of the organs. This tissue is always in a dynamic evolution as it must adapt to the metabolic demand and constraints. It exhibits also endocrine functions important to regulate energy homeostasis. This complex organ is composed of depots able to produce opposite functions to monitor energy: the so called white adipose tissue acts to store energy as triglycerides preventing ectopic fat deposition while the brown adipose depots dissipate it. It is composed of many cell types. Different types of adipocytes constitute the mature cells specialized to store or burn energy. Immature adipose progenitors (AP) presenting stem cells properties contribute not only to the maintenance but also to the expansion of this tissue as observed in overweight or obese individuals.
  • 3.3K
  • 28 Apr 2021
Topic Review
Diffuse Large B-Cell Lymphomas
Diffuse large B-cell lymphoma (DLBCL) is the commonest form of lymphoid malignancy, with a prevalence of about 40% worldwide. The term DLBCL reflects the growth pattern and size of the neoplastic cells, which tend to diffusely efface the normal structure of the involved organ (most frequently the lymph node) and are provided with a diameter at least twice that of normal lymphocytes. Although during the last few years several distinct clinical-pathological categories of DLBCL have been reported in the literature, which are nowadays listed in the Revised 4th Edition of the WHO Classification of the Tumours of Haematopoietic and Lymphoid Tissues, about 80% of DLBCLs do not enter into any of these categories and are therefore termed not otherwise specified (NOS). DLBCL-NOS displays a quite variable morphology and only rarely consists of only one cytotype (centroblastic, immunoblastic or anaplastic). Thus, microscopic examination fails to define the cell of origin, prognostic indicators and novel potential therapeutic targets. The standard of care  is the immuno-chemotherapy R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), which cures up to 65% of patients. The remaining individuals with DLBCL-NOS experience resistant or relapsing disease and eventually die of it. This situation has promoted a huge number of studies focusing on the pathobiology of the tumour and based on high-throughput techniques, including gene expression profiling and next generation sequencing. In addition, attention has been focused on the mcroenvironmental composition, which can influence the behaviour and response to therapy of the tumour in conjunction with the molecular characteristics of neoplastic cells. The aim of the present review is to discuss the most recent acquisitions in the field of DLBCL-NOS based on the extensive application of molecular techniques, which paves the way to a more rational classification of the tumour along with the identification of effective prognostic indicators and novel therapeutic targets for  ad hoc personalised approaches. 
  • 560
  • 23 Jun 2021
Topic Review
Direct and Indirect Myc Regulation by Mitotic Kinases
c-Myc and the other protein family members (i.e., N-Myc and L-Myc), collectively known as “Myc”, are ubiquitous basic helix–loop–helix–leucine zipper (bHLH-LZ) transcription factors that are critical for several cellular processes during cancer genesis and progression. The importance of kinases in Myc regulation goes beyond their ability to phosphorylate the protein. Some kinases can also indirectly affect Myc protein stability by inducing the degradation of the ubiquitin ligase (PLK1 and PKA). Additionally, some kinases physically interact with Myc, protecting it from proteasomal degradation, such as Aurora-A in neuroblastoma.
  • 248
  • 08 Mar 2023
Topic Review
Disabled-2 Structure and Function
Disabled-2 (DAB2), a key adaptor protein in clathrin mediated endocytosis, is implicated in the regulation of key signalling pathways involved in homeostasis, cell positioning and epithelial to mesenchymal transition (EMT).
  • 330
  • 12 Jan 2023
Topic Review
Disruption of Claudin-Made Tight Junction Barriers by CpE
Claudins are a family of integral membrane proteins that enable epithelial cell/cell interactions by localizing to and driving the formation of tight junctions. Via claudin self-assembly within the membranes of adjoining cells, their extracellular domains interact, forming barriers to the paracellular transport of small molecules and ions. The bacterium Clostridium perfringens causes prevalent gastrointestinal disorders in mammals by employing an enterotoxin (CpE) that targets claudins. CpE binds to claudins at or near tight junctions in the gut and disrupts their barrier function, potentially by disabling their assembly or via cell signaling means—the mechanism(s) remain unclear.
  • 467
  • 10 Mar 2022
Topic Review
Diverse Calpain Family in Trypanosomatidae
The Trypanosomatidae family, class Kinetoplastea, encompasses exclusively parasitic protozoa, some of which cause important human diseases. About 37 million people worldwide are infected either with Trypanosoma brucei, the etiological agent of African sleeping sickness; Trypanosoma cruzi, the causative agent of Chagas disease; or with different species of the genus Leishmania, responsible for different clinical manifestations known as leishmaniasis. The current therapy to treat these diseases is unsatisfying due to their low efficacy, high cost, toxicity, and tough administration routes, like parenteral. Therefore, the search for more effective drugs is still an urgent need, which can lead to alternative strategies, such as a repurposed approach with compounds already approved for human usage. In view of this scenario, calpains are an interesting target due to the intense efforts to develop means of identifying selective inhibitors in this group of calcium-dependent cysteine peptidases. Since these enzymes are involved in crucial physiological roles in mammals, their deregulated activity is implicated in several pathophysiological processes, especially in fibrotic diseases and neurological disorders. Moreover, trypanosomatids harbor a large and diverse family of calpain sequences in their genomes, comprising a wide range of associated domains, differential gene expression among life-cycle forms, and ubiquitous distribution in the parasite cell body. However, due to the difficulties in assaying calpain activity in these microorganisms, there is still an open question: are trypanosomatid calpains proteolytically active?
  • 352
  • 13 Apr 2021
Topic Review
DNA Damage and Repair Pathway
DNA injuries occur as a result of intrinsic or extrinsic agents and can include modifications to bases and sugars, single- and double-strand breaks (SSBs, DSBs), DNA-protein crosslinks, and base-free sites. While some specific DNA lesions can lead to mutations that cause cancer, the main consequence of DNA injuries is the threat they pose to DNA integrity and stability. To prevent accumulated DNA lesions from causing irreversible harm, cells initiate DDR, which senses the DNA damage, signals its presence, and mediates its repair.
  • 401
  • 06 Apr 2023
Topic Review
DNA Damage Response and Repair
DNA damage response and repair (DDR) genes are necessary to maintain the integrity of cell DNA. Alterations of these mechanisms have been found in many cancer types, and may influence treatment outcomes as well as the prognosis of cancer patients. Recently, several treatment strategies taking advance of the presence of DDR alterations are emerging in oncology.
  • 560
  • 10 Aug 2021
Topic Review
DNA Homeostasis and Senescence
As we age, our bodies accrue damage in the form of DNA mutations. These mutations lead to the generation of sub-optimal proteins, resulting in inadequate cellular homeostasis and senescence. The build-up of senescent cells negatively affects the local cellular micro-environment and drives ageing associated disease, including neurodegeneration. Therefore, limiting the accumulation of DNA damage is essential for healthy neuronal populations.  
  • 618
  • 17 Jun 2021
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