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Topic Review
Cell Cycle Checkpoints
Studies have shown that during early embryogenesis, preimplantation embryos exhibit higher levels of chromosomal abnormalities in the initial stages of cleavage compared to the late morula stage or blastocysts. Thus, preimplantation embryos can acquire an aneuploidy phenotype already in early developmental stages, which points to the fact that these first mitotic cycles are more susceptible to chromosomal aberrations. The monitoring of chromatin damage, the so-called cell cycle checkpoint, is therefore an essential aspect of the cell cycle.
  • 776
  • 12 May 2023
Topic Review
Approaches to Microsample Collections
Although the application of microsamples in metabolic phenotyping exists, it is still in its infancy, with whole blood being overwhelmingly the primary biofluid collected through the collection method of dried blood spots. 
  • 775
  • 19 Jul 2022
Topic Review
Hydrodynamically Closed Capillary Electrophoresis
Several research disciplines require fast, reliable and highly automated determination of pharmaceutically active compounds and their enantiomers in complex biological matrices. To address some of the challenges of Capillary Electrophoresis (CE), such as low concentration sensitivity and performance degradation linked to the adsorption and interference of matrix components, CE in a hydrodynamically closed system was evaluated using the model compounds Pindolol and Propranolol. Some established validation parameters such as repeatability of injection, efficiency, resolution and sensitivity were used to assess its performance, and it was found to be broadly identical to that of hydrodynamically opened systems. While some reduction in separation efficiency was observed, this was mainly due to dispersion caused by injection and it had no impact on the ability to resolve enantiomers of model compounds even when spiked into complex biological matrix such as blood serum. An approximately 18- to 23-fold increase in concentration sensitivity due to the employment of wide bore capillaries was observed. This brings the sensitivity of CE to a level similar to that of liquid chromatography techniques. In addition to this benefit and unlike in hydrodynamically opened systems, suppression of electroosmotic flow, which is essential for hydrodynamically closed systems practically eliminates the matrix effects that are linked to protein adsorption.
  • 774
  • 29 Sep 2020
Topic Review
Gliotoxins
Gliotoxin is a kind of epipolythiodioxopiperazine derived from different fungi that is characterized by a disulfide bridge. Gliotoxins can be biosynthesized by a gli gene cluster and regulated by a positive GliZ regulator. Gliotoxins show cytotoxic effects via the suppression the function of macrophage immune function, inflammation, antiangiogenesis, DNA damage by ROS production, peroxide damage by the inhibition of various enzymes, and apoptosis through different signal pathways. In the other hand, gliotoxins can also be beneficial with different doses. Low doses of gliotoxin can be used as an antioxidant, in the diagnosis and treatment of HIV, and as an anti-tumor agent in the future. Gliotoxins have also been used in the control of plant pathogens, including Pythium ultimum and Sclerotinia sclerotiorum.
  • 774
  • 23 Dec 2021
Topic Review
E3s That Target Wild-Type p53
p53 plays a role in different biological processes such as proliferation, invasion, pluripotency, metabolism, cell cycle control, ROS (reactive oxygen species) production, apoptosis, inflammation and autophagy. In the nucleus, p53 functions as a bona-fide transcription factor which activates and represses transcription of a number of target genes. In the cytoplasm, p53 can interact with proteins of the apoptotic machinery and by this also induces cell death. Despite being so important for the fate of the cell, expression levels of p53 are kept low in unstressed cells and the protein is largely inactive. 
  • 773
  • 27 Feb 2023
Topic Review
The Fibroblast Growth Factor Receptors
Breast cancer (BC) is the most frequent form of malignancy and second only to lung cancer as cause of deaths in women. Notwithstanding many progresses made in the field, metastatic BC has a very poor prognosis. As therapies are becoming more personalized to meet the needs of patients, a better knowledge of the molecular biology leading to the disease unfolds the possibility to project more precise compounds or antibodies targeting definite alteration at the molecular level and functioning on such cancer-causing molecules expressed in cancer cells of patients, or present as antigens on the surface of cancer cell membranes. Fibroblast growth factor receptor (FGFR) is one of such druggable targets, activated by its own ligands -namely the Fibroblast Growth Factors (FGFs). This pathway provides a vast range of interesting molecular targets pursued at different levels of clinical investigation.
  • 772
  • 01 Nov 2020
Topic Review
Microvesicles
Extracellular vesicles (EV) are secreted by all cell types in a tumor and its microenvironment (TME) and play an essential role in intercellular communication and the establishment of a TME favorable for tumor invasion and metastasis. They encompass a variety of vesicle populations, among them the well-known endosomal-derived small exosomes (Exo), but also larger vesicles (diameter >100 nm) that are shed directly from the plasma membrane, the so-called microvesicles (MV). Increasing evidence suggests that MV, although biologically different, share the tumor-promoting features of Exo in the TME. Due to their larger size, they can be readily harvested from patients’ blood and characterized by routine methods such as conventional flow cytometry exploiting the plethora of molecules expressed on their surface. In this review we summarize the current knowledge about the biology and the composition of MV as well as their role within the TME. We highlight not only the challenges and potential of MV as novel biomarkers for cancer, but also discuss their possible use for therapeutic intervention.
  • 772
  • 05 Nov 2020
Topic Review
Signal Peptide Interactions during ER Translocation
Cleavable endoplasmic reticulum (ER) signal peptides (SPs) and other non-cleavable signal sequences target roughly a quarter of the human proteome to the ER. These short peptides, mostly located at the N-termini of proteins, are highly diverse. For most proteins targeted to the ER, it is the interactions between the signal sequences and the various ER targeting and translocation machineries such as the signal recognition particle (SRP), the protein-conducting channel Sec61, and the signal peptidase complex (SPC) that determine the proteins’ target location and provide translocation fidelity. 
  • 771
  • 16 Dec 2021
Topic Review
Primary Cilia in Acquired Heart Disease
Primary cilia are non-motile plasma membrane extrusions that display a variety of receptors and mechanosensors. Loss of function results in ciliopathies, which have been strongly linked with congenital heart disease, as well as abnormal development and function of most organ systems. 
  • 771
  • 24 Mar 2022
Topic Review
The Dbf4-Dependent Kinase
The Dbf4-dependent kinase (DDK) is formed by the association of the kinase subunit, cell division cycle 7 (Cdc7), with its activating partner, dumb-bell factor 4 (Dbf4). By analogy with the cyclin-dependent kinases (CDK), Cdc7:Dbf4 is now most often referred to as ‘Dbf4-dependent kinase’ or DDK.
  • 771
  • 27 Jun 2022
Topic Review
C-type Lectin CD209L/L-SIGN and CD209/DC-SIGN
COVID-19 pandemic continues to pose a serious threat to global public health with overwhelming worldwide socio-economic disruption. SARS-CoV-2, the viral agent of COVID-19, uses its surface glycoprotein Spike (S) for host cell attachment and entry. The emerging picture of pathogenesis of SARS-CoV-2 demonstrates that S protein, in addition, to ACE2, interacts with the carbohydrate recognition domain (CRD) of C-type lectin receptors, CD209L and CD209. Recognition of CD209L and CD209 which are widely expressed in SARS-CoV-2 target organs can facilitate entry and transmission leading to dysregulation of the host immune response and other major organs including, cardiovascular system. Establishing a comprehensive map of the SARS-CoV-2 interaction with CD209 family proteins, and their roles in transmission and pathogenesis can provide new insights into host-pathogen interaction with implications in therapies and vaccine development. 
  • 769
  • 13 Jan 2021
Topic Review
Photodynamic Therapy (PDT)
Photodynamic therapy (PDT) using oxygen, light, and photosensitizers, which has potential for making up for the weakness of the existing therapies such as surgery, radiation therapy, and chemotherapy. It has been mainly used to treat cancer, and clinical tests for second-generation photosensitizers with improved physicochemical properties, pharmacokinetic profiles, or singlet oxygen quantum yield have been conducted.
  • 769
  • 13 Apr 2021
Topic Review
Prion Organotypic Slice Culture
The prion organotypic slice culture assay (POSCA) is a cerebellar slice culture that was originally developed to take advantage of the transmissible nature of prions, propagating prion infection ex vivo. Because much of the cytoarchitexture is preserved, this system allows the study of pathogenesis in an open system and is amenable to manipulation of cell types and testing of therapeutics. The culture has been adapted to other brain areas, different prion strains, and has also been applied to other neurodegenerative diseases that are prion-like in their transmissible propagation of protein misfolding, including Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease, amyotrophic lateral sclerosis and Huntington’s disease. This entry provides a review of POSCA as used in the prion field. For a review of its application to other neurodegenerative diseases, please see the associated review article in Biomolecules.
  • 768
  • 11 Aug 2020
Topic Review
ADAM9 in Cancers
ADAM9 plays an important role in tumor biology. It is overexpressed in several cancer types and is correlated with tumor aggressiveness and poor prognosis. Through either proteolytic or non-proteolytic pathways, ADAM9 promotes tumor progression, therapeutic resistance, and metastasis of cancers. Therefore, comprehensively understanding the mechanism of ADAM9 is crucial for the development of therapeutic anti-cancer strategies.
  • 768
  • 13 Jan 2021
Topic Review
RNA Interference in Fungi
RNA interference (RNAi) was discovered at the end of last millennium, changing the way scientists understood regulation of gene expression. Within the following two decades, a variety of different RNAi mechanisms were found in eukaryotes, reflecting the evolutive diversity that RNAi entails. The essential silencing mechanism consists of an RNase III enzyme called Dicer that cleaves double-stranded RNA (dsRNA) generating small interfering RNAs (siRNAs), a hallmark of RNAi. These siRNAs are loaded into the RNA-induced silencing complex (RISC) triggering the cleavage of complementary messenger RNAs by the Argonaute protein, the main component of the complex. Consequently, the expression of target genes is silenced. This mechanism has been thoroughly studied in fungi due to their proximity to the animal phylum and the conservation of the RNAi mechanism from lower to higher eukaryotes. However, the role and even the presence of RNAi differ across the fungal kingdom, as it has evolved adapting to the particularities and needs of each species. Fungi have exploited RNAi to regulate a variety of cell activities as different as defense against exogenous and potentially harmful DNA, genome integrity, development, drug tolerance, or virulence. This pathway has offered versatility to fungi through evolution, favoring the enormous diversity this kingdom comprises. 
  • 768
  • 11 Oct 2021
Topic Review
Electrospinning Proteins for Wound Healing
In recent years, there has been a growing interest for electrospun polymeric wound dressings with fiber diameters in the nano- and micrometer range. Such wound dressings display a number of properties, which support and accelerate wound healing. For instance, they provide physical and mechanical protection, exhibit a high surface area, allow gas exchange, are cytocompatible and biodegradable, resemble the structure of the native extracellular matrix, and deliver antibacterial agents locally into the wound.
  • 768
  • 22 Feb 2021
Topic Review
GSK-3
The serine/threonine kinase, GSK-3, is a promising drug discovery target for treating multiple pathological disorders. Most GSK-3 inhibitors that were developed function as ATP competitive inhibitors, with typical limitations in specificity, safety and drug-induced resistance. In contrast, substrate competitive inhibitors (SCIs), are considered highly selective, and more suitable for clinical practice. The development of SCIs has been largely neglected in the past because the ambiguous, undefined nature of the substrate-binding site makes them difficult to design. In this study, we used our previously described structural models of GSK-3 bound to SCI peptides, to design a pharmacophore model and to virtually screen the “drug-like” Zinc database (~6.3 million compounds). We identified leading hits that interact with critical binding elements in the GSK-3 substrate binding site and are chemically distinct from known GSK-3 inhibitors. Accordingly, novel GSK-3 SCI compounds were designed and synthesized with IC50 values of~1–4 μM. Biological activity of the SCI compound was confirmed in cells and in primary neurons that showed increased β-catenin levels and reduced tau phosphorylation in response to compound treatment. We have generated a new type of small molecule GSK-3 inhibitors and propose to use this strategy to further develop SCIs for other protein kinases.
  • 768
  • 11 Mar 2021
Topic Review
Defining Blood Plasma and Serum Metabolome by GC-MS
Metabolomics uses advanced analytical chemistry methods to analyze metabolites in biological samples. The most intensively studied samples are blood and its liquid components: plasma and serum. Armed with advanced equipment and progressive software solutions, the scientific community has shown that small molecules’ roles in living systems are not limited to traditional “building blocks” or “just fuel” for cellular energy. 
  • 768
  • 06 Jan 2022
Topic Review
Preventing and Treating Cancer by Green Tea Catechins
Green tea’s (Camellia sinensis) anticancer and anti-inflammatory effects are well-known. Catechins are the most effective antioxidants among the physiologically active compounds found in Camellia sinesis. Catechins have the ability to effectively neutralize reactive oxygen species. The catechin derivatives of green tea include epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG). EGCG has the greatest anti-inflammatory and anticancer potential. Notably, catechins in green tea have been explored for their ability to prevent a variety of cancers.
  • 768
  • 21 Sep 2022
Topic Review
BTK Targeting in Multiple Myeloma
Multiple myeloma (MM), a clonal plasma cell disorder, disrupts the bones’ hematopoiesis and microenvironment homeostasis and ability to mediate an immune response against malignant clones. Despite prominent survival improvement with newer treatment modalities since the 2000s, MM is still considered a non-curable disease. Patients experience disease recurrence episodes with clonal evolution, and with each relapse disease comes back with a more aggressive phenotype. Bruton’s Tyrosine Kinase (BTK) has been a major target for B cell clonal disorders and its role in clonal plasma cell disorders is under active investigation. BTK is a cytosolic kinase which plays a major role in the immune system and its related malignancies. The BTK pathway has been shown to provide survival for malignant clone and multiple myeloma stem cells (MMSCs). BTK also regulates the malignant clones’ interaction with the bone marrow microenvironment. Hence, BTK inhibition is a promising therapeutic strategy for MM patients
  • 766
  • 08 Jun 2021
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