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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
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.
  • 989
  • 01 Aug 2023
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.
  • 989
  • 21 Jan 2021
Topic Review
Myzus persicae Sulzer
The green peach aphid (Myzus persicae Sulzer), a major and harmful chili aphid usually managed using chemical pesticides, is responsible for massive annual agricultural losses. The efficacy of two protein elicitors, PeaT1 and PeBC1, to stimulate a defensive response against M. persicae in chili was studied in this study.
  • 988
  • 11 Nov 2021
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.
  • 988
  • 21 Jan 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. 
  • 988
  • 05 May 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.
  • 988
  • 18 Jul 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.
  • 987
  • 27 May 2021
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
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.
  • 987
  • 29 Feb 2024
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).
  • 987
  • 29 Mar 2022
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. 
  • 986
  • 03 Dec 2021
Topic Review
ClpB's Function in Bacterial Virulence
The molecular chaperone ClpB belongs to the Hsp100/Clp subfamily of the AAA+ ATPases. It has been established that ClpB disaggregates and reactivates aggregated cellular proteins. It has been postulated that ClpB’s protein disaggregation activity supports the survival of pathogenic bacteria under host-induced stresses (e.g., high temperature and oxidative stress), which allows them to rapidly adapt to the human host and establish infection. Interestingly, ClpB may also perform other functions in pathogenic bacteria, which are required for their virulence. Since ClpB is not found in human cells, this chaperone emerges as an attractive target for novel antimicrobial therapies in combating bacterial infections. 
  • 985
  • 11 Jun 2021
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. 
  • 985
  • 23 Jun 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.
  • 985
  • 03 Nov 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.
  • 984
  • 02 Jan 2024
Topic Review
Membrane Disruption Properties of EOs
Essential oils (EOs) is new possible weapons to fight antimicrobial resistance due to their inherent antimicrobial properties. However, the potential pharmaceutical use of EOs is confronted by several limitations, including being non-specific in terms of drug targeting, possessing a high cytotoxicity as well as posing a high risk for causing skin irritation.
  • 983
  • 22 Apr 2021
Topic Review
Yeast as a Model for VPS13-Dependent Neurodegenerative Diseases
Mutations in human VPS13A-D genes result in rare neurological diseases, including chorea-acanthocytosis (ChAc). The pathogenesis of these diseases is poorly understood, and no effective treatment is available. As VPS13 genes are evolutionarily conserved, the effects of the pathogenic mutations could be studied in model organisms, including yeast, where one VPS13 gene is present. Here, the researchers summarize advancements obtained using yeast. In recent studies, vps13Δ and vps13-I2749 yeast mutants, which are models of chorea-acanthocytosis, were used to screen for multicopy and chemical suppressors. Two of the suppressors, a fragment of the MYO3 and RCN2 genes, act by downregulating calcineurin activity. In addition, vps13Δ suppression was achieved by using calcineurin inhibitors. The other group of multicopy suppressors were genes: FET4, encoding iron transporter, and CTR1, CTR3 and CCC2, encoding copper transporters. Mechanisms of their suppression rely on causing an increase in the intracellular iron content. Moreover, among the identified chemical suppressors were copper ionophores, which require a functional iron uptake system for activity, and flavonoids, which bind iron. These findings point at areas for further investigation in a higher eukaryotic model of VPS13-related diseases and to new therapeutic targets: calcium signalling and copper and iron homeostasis. Furthermore, the identified drugs are interesting candidates for drug repurposing for these diseases.
  • 982
  • 18 May 2022
Topic Review
Targeting of Signaling Pathways by Thymoquinone in Cancer
Thymoquinone is isolated from Nigella sativa with a molecular weight of 164.2 g/mol. A series of cutting-edge research works have demonstrated the health-promoting and disease-ameliorating roles of thymoquinone.
  • 982
  • 13 Jun 2022
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