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Topic Review
Fluorescent Biosensors for Chemotherapy Development
Genetically-encoded fluorescent sensors have been actively developed over the last few decades and used in live imaging and drug screening. Real-time monitoring of drug action in a specific cellular compartment, organ, or tissue type; the ability to screen at the single-cell resolution; and the elimination of false-positive results caused by low drug bioavailability that is not detected by in vitro testing methods are a few of the obvious benefits of using genetically-encoded fluorescent sensors in drug screening. In combination with high-throughput screening (HTS), some genetically encoded fluorescent sensors may provide high reproducibility and robustness to assays. Here, we provide an overview of attempts at using genetically encoded fluorescent sensors in HTS of anticancer compounds.
  • 992
  • 21 Jan 2021
Topic Review
P43
P43 is a truncated form of thyroid hormone receptor α localized in mitochondria, which stimulates mitochondrial respiratory chain activity. Previously, we showed that deletion of p43 led to reduction of pancreatic islet density and a loss of glucose-stimulated insulin secretion in adult mice. The present study was designed to determine whether p43 was involved in the processes of β cell development and maturation. We used neonatal, juvenile, and adult p43-/- mice, and we analyzed the development of β cells in the pancreas. Here, we show that p43 deletion affected only slightly β cell proliferation during the postnatal period. However, we found a dramatic fall in p43-/- mice of MafA expression (V-Maf Avian Musculoaponeurotic Fibrosarcoma Oncogene Homolog A), a key transcription factor of beta-cell maturation. Analysis of the expression of antioxidant enzymes in pancreatic islet and 4-hydroxynonenal (4-HNE) (a specific marker of lipid peroxidation) staining revealed that oxidative stress occurred in mice lacking p43. Lastly, administration of antioxidants cocktail to p43-/- pregnant mice restored a normal islet density but failed to ensure an insulin secretion in response to glucose. Our findings demonstrated that p43 drives the maturation of β cells via its induction of transcription factor MafA during the critical postnatal window.
  • 992
  • 10 Mar 2021
Topic Review
Applications of the Comet Assay in Plant Studies
Contrarily to chronic stresses, acute (i.e., fast and dramatic) changes in environmental factors like temperature, radiation, concentration of toxic substances, or pathogen attack often lead to DNA damage. Some of the stress factors are genotoxic, i.e., they damage the DNA via physical interactions or via interference with DNA replication/repair machinery. However, cytotoxic factors, i.e., those that do not directly damage the DNA, can lead to secondary genotoxic effects either via the induction of the production of reactive oxygen, carbon, or nitrogen species, or via the activation of programmed cell death and related endonucleases. The extent of this damage, as well as the ability of the cell to repair it, represent a significant part of plant stress responses. Information about DNA damage is important for physiological studies as it helps to understand the complex adaptive responses of plants and even to predict the outcome of the plant’s exposure to acute stress. Single cell gel electrophoresis (Comet assay) provides a convenient and relatively inexpensive tool to evaluate DNA strand breaks in the different organs of higher plants, as well as in unicellular algae. Comet assays are widely used in ecotoxicology and biomonitoring applications.
  • 992
  • 29 Feb 2024
Topic Review
PTP1B Inhibitors
Protein-tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling pathways and plays an important role in type 2 diabetes mellitus (T2DM), as its overexpression may induce insulin resistance.
  • 991
  • 21 Jan 2022
Topic Review
Naturally Occurring Aristolochic Acid Analogues
Aristolochic acids are known for nephrotoxicity, and implicated in multiple cancer types such as hepatocellular carcinomas.
  • 991
  • 25 Feb 2022
Topic Review
DNA-Dependent Protein Kinase in Non-Homologous End Joining
DNA-dependent protein kinase (DNA-PK), which is composed of a DNA-PK catalytic subunit (DNA-PKcs) and Ku80-Ku70 heterodimer, acts as the molecular sensor for DSB and plays a pivotal role in DSB repair through non-homologous end joining (NHEJ). Cells deficient for DNA-PKcs show hypersensitivity to IR and several DNA-damaging agents. Cellular sensitivity to IR and DNA-damaging agents can be augmented by the inhibition of DNA-PK. A number of small molecules that inhibit DNA-PK have been developed. 
  • 991
  • 05 May 2022
Topic Review
RhoH in TCR Signalling
As an atypical member of the Rho family small GTPases, RhoH shares less than 50% sequence similarity with other members, and its expression is commonly observed in the haematopoietic lineage. To date, RhoH function was observed in regulating T cell receptor signalling, and less is known in other haematopoietic cells. Its activation may not rely on the standard GDP/GTP cycling of small G proteins and is thought to be constitutively active because critical amino acids involved in GTP hydrolysis are absent. Alternatively, its activation can be regulated by other types of regulation, including lysosomal degradation, somatic mutation and transcriptional repressor, which also results in an altered protein expression. Aberrant protein expression of RhoH has been implicated not only in B cell malignancies but also in immune-related diseases, such as primary immunodeficiencies, systemic lupus erythematosus and psoriasis, wherein its involvement may provide the link between immune-related diseases and cancer.
  • 990
  • 27 May 2021
Topic Review
Natural Polyphenols and Cervical Cancer
From all types of cancer, cervical cancer manages to be in top four most frequent types, with a 6.5% rate of occurrence. The infectious vector that induces the disease, the high-risk Human papillomavirus (HPV), which is a sexually transmitted virus, is capable of transforming the host cell by modulating some of the principal signaling pathways responsible for cell cycle arrest, proliferation, and survival. Fortunately, like other cancer types, cervical cancer can be treated by chirurgical interventions or chemoradiotherapy, but these methods are not exactly the lucky clover of modern medicine because of the adverse effects they have. That is the reason why in the last years the emphasis has been on alternative medicine, more specifically on phytochemicals, as a substantial number of studies showed that diet contributes to cancer prevention and treatment. All these studies are trying to find new chemopreventive agents with less toxicity but high effectiveness both in vitro and in vivo. Polyphenols have great potential in cervical cancer prevention, with strong effects on gene modulation.
  • 990
  • 23 Sep 2021
Topic Review
Posttranslational Modifications in PD-L1 Turnover and Function
Programmed death-ligand 1 (PD-L1) is one of the most classic immune checkpoint molecules. Cancer cells express PD-L1 to inhibit the activity of effector T cells’ cytotoxicity through programmed death 1 (PD-1) engagement in exposure to inflammatory cytokines. PD-L1 expression levels on cancer cells might affect the clinical response to anti-PD-1/PD-L1 therapies. Hence, understanding molecular mechanisms for regulating PD-L1 expression is essential for improving the clinical response rate and efficacy of PD-1/PD-L1 blockade. Posttranslational modifications (PTMs), including phosphorylation, glycosylation, ubiquitination, and acetylation, regulate PD-L1 stability, cellular translocation, and interaction with its receptor. A coordinated positive and negative regulation via PTMs is required to ensure the balance and function of the PD-L1 protein. 
  • 990
  • 03 Dec 2021
Topic Review
Pharmaceutical Drug and Metabolic Adaptions/Reprogramming in β-Cells
Islet inflammation in T1DM is characterized by leukocyte infiltrates, in particular macrophages and T-cells which damage β-cells by release of cytokines, ROS and NO and also activation of death-receptor-mediated death pathways and subsequent phagocytosis. Production of cytokines such as INF-γ, TNFα and IL-1β act in synergy to promote elevation in concentration and increase in activity of NADPH oxidase and iNOS consequently increasing the formation of products including ROS and NO, respectively. The mechanism of action of INF-γ, TNFα and IL-1β involves stimulation of transcription factors including NFκB (in mouse islet β-cells).
  • 990
  • 29 Mar 2022
Topic Review
Monomers and Oligomers of Arrestin Proteins
Three out of four subtypes of arrestin proteins expressed in mammals self-associate, each forming oligomers of a distinct kind. Monomers and oligomers have different subcellular localization and distinct biological functions. Visual arrestin (a.k.a. S-antigen, 48 kDa protein, and rod arrestin; systematic name arrestin-1) is expressed in rod and cone photoreceptor cells in the retina, whereas arrestin-4 is expressed exclusively in cones at a much lower level than arrestin-1.
  • 990
  • 18 Jul 2022
Topic Review
CMGC Kinases in Health and Cancer
CMGC kinases, encompassing cyclin-dependent kinases (CDKs), mitogen-activated protein kinases (MAPKs), glycogen synthase kinases (GSKs), and CDC-like kinases (CLKs), play pivotal roles in cellular signaling pathways, including cell cycle regulation, proliferation, differentiation, apoptosis, and gene expression regulation. The dysregulation and aberrant activation of these kinases have been implicated in cancer development and progression, making them attractive therapeutic targets. Kinase inhibitors targeting CMGC kinases, such as CDK4/6 inhibitors and BRAF/MEK inhibitors, have demonstrated clinical success in treating specific cancer types.
  • 990
  • 01 Aug 2023
Topic Review
Redox Homeostasis in Poultry
Redox biology is a very quickly developing area of modern biological sciences, and roles of redox homeostasis in health and disease have recently received tremendous attention. There are a range of redox pairs in the cells/tissues responsible for redox homeostasis maintenance/regulation. In general, all redox elements are interconnected and regulated by various means, including antioxidant and vitagene networks. The redox status is responsible for maintenance of cell signaling and cell stress adaptation. Physiological roles of redox homeostasis maintenance in avian species, including poultry, have received limited attention and are poorly characterized. However, for the last 5 years, this topic attracted much attention, and a range of publications covered some related aspects. In fact, transcription factor Nrf2 was shown to be a master regulator of antioxidant defenses via activation of various vitagenes and other protective molecules to maintain redox homeostasis in cells/tissues. It was shown that Nrf2 is closely related to another transcription factor, namely, NF-κB, responsible for control of inflammation; however, its roles in poultry have not yet been characterized. Therefore, the aim of this study is to describe a current view on NF-κB functioning in poultry with a specific emphasis to its nutritional modulation under various stress conditions.
  • 989
  • 02 Feb 2021
Topic Review
Bioactivity of Steroidal Arylidene Derivatives
Steroids constitute a unique class of chemical compounds, playing an important role in physiopathological processes, and have high pharmacological interest. Due to their straightforward preparation and intrinsic chemical reactivity, steroidal arylidene derivatives are important synthetic intermediates for the preparation of other compounds, particularly bearing heterocyclic systems, in addition to their relevant bioactivity with potential pharmacological interest. 
  • 989
  • 29 Apr 2021
Topic Review
Sirtuins in Breast and Prostate Cancer
In mammals, seven sirtuins (SIRT1–7) have been identified, which primarily function as NAD-dependent deacetylases (SIRT1–3 and SIRT5–7) and ADP-ribosyl transferases (SIRT4 and 6). Additionally, sirtuins have been reported to function as demyristoylases (SIRT1–3 and 6), lipoamidases (SIRT4), and desuccinylases/demalonylases/deglutarylases (SIRT5). The forcus herein is the information on the tumor promotion or suppression roles of SIRT1–7 in breast and prostate cancers. Precisely, it is highlighted that sirtuins regulate various proteins implicated in proliferation, apoptosis, autophagy, chemoresistance, invasion, migration, and metastasis of both breast and prostate cancer.
  • 988
  • 03 Nov 2022
Topic Review
Proteomics in CSF of AD
The fact that cerebrospinal fluid (CSF) deeply irrigates the brain together with the relative simplicity of sample extraction from patients make this biological fluid the best target for biomarker discovery in neurodegenerative diseases. Biomarker discovery has been especially fruitful for the identification new proteins that appear in the CSF of Alzheimer’s disease (AD) patients together with amyloid-β (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau). Thus, several proteins have been already stablished as important biomarkers, due to an increase (i.e., CHI3L1) or a decrease (i.e., VGF) in AD patients’ CSF. Notwithstanding this, only a deep analysis of a database generated with all the changes observed in CSF across multiple proteomic studies, and especially those using state-of-the-art methodologies, may expose those components or metabolic pathways disrupted at different levels in AD. Deep comparative analysis of all the up- and down-regulated proteins across these studies revealed that 66% of the most consistent protein changes in CSF correspond to intracellular proteins.
  • 987
  • 08 Oct 2021
Topic Review
Targeting Fatty Acid Metabolism in Gynaecological Cancers
Fatty acid (FA) metabolism plays a vital role in promoting the development and progression of gynaecological cancers. Therefore, enzymes involved in FA metabolism are attractive targets in treating these cancer types. Moreover, inhibiting these enzymes can synergistically augment the antitumour effects of chemotherapeutic agents targeting the oestradiol pathway (e.g., selective ER modulators (SERM) and aromatase inhibitors) or to overcome chemotherapeutic resistance against these agents in gynaecological cancers. In addition to the developing pharmacological inhibitors specifically targeting FA metabolism enzymes, interest is also growing in implementing diet-based intervention to supplement conventional chemotherapeutic regime.
  • 987
  • 12 May 2022
Topic Review
Plant Toxins: Recombinant Production as Components of Immunotoxins
Plant toxins that target eukaryotic 28S ribosomal RNA (Ribosome Inactivating Proteins, RIPs), such as the catalytic (A) chain of ricin (a dimeric A-B toxin from Ricinus communis) and saporin (a single chain A toxin from Saponaria officinalis), have found widespread use in the construction of immunotoxins. Both these toxins depurinate ribosomal 28S RNA at a specific site (GAGA loop) inhibiting the binding of elongation factor 2 and blocking protein synthesis. Their high toxicity towards eukaryotic cells has thus justified their use as components of chimeric toxins in cancer treatment. A brief description of recombinant RIPs production is given.
  • 987
  • 02 Jan 2024
Topic Review
Pathophysiology of Nitrergic Enteric Neurons
Nitrergic enteric neurons are key players of the descending inhibitory reflex of intestinal peristalsis, therefore loss or damage of these neurons can contribute to developing gastrointestinal motility disturbances suffered by patients worldwide. There is accumulating evidence that the vulnerability of nitrergic enteric neurons to neuropathy is strictly region-specific and that the two main enteric plexuses display different nitrergic neuronal damage. Alterations both in the proportion of the nitrergic subpopulation and in the total number of enteric neurons suggest that modification of the neurochemical character or neuronal death occurs in the investigated gut segments. 
  • 986
  • 23 Jun 2021
Topic Review
Oxidative Stress-Induced Cellular Senescence
Cellular senescence, a cell state characterized by a generally irreversible cell cycle arrest, is implicated in various physiological processes and a wide range of age-related pathologies. Oxidative stress, a condition caused by an imbalance between the production and the elimination of reactive oxygen species (ROS) in cells and tissues, is a common driver of cellular senescence. ROS encompass free radicals and other molecules formed as byproducts of oxygen metabolism, which exhibit varying chemical reactivity. 
  • 986
  • 28 Jun 2023
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