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Topic Review
Rab Proteins in Mitophagy
Mitochondrial dysfunction and vesicular trafficking alterations have been implicated in the pathogenesis of several neurodegenerative diseases. It has become clear that pathogenetic pathways leading to neurodegeneration are often interconnected. Indeed, growing evidence suggests a concerted contribution of impaired mitophagy and vesicles formation in the dysregulation of neuronal homeostasis, contributing to neuronal cell death. Among the molecular factors involved in the trafficking of vesicles, Ras analog in brain (Rab) proteins seem to play a central role in mitochondrial quality checking and disposal through both canonical PINK1/Parkin-mediated mitophagy and novel alternative pathways. In turn, the lack of proper elimination of dysfunctional mitochondria has emerged as a possible causative/early event in some neurodegenerative diseases.
  • 1.2K
  • 14 Apr 2023
Topic Review
Molecular Microbial Community Analysis
The microbial diversity in anaerobic digestion (AD) is important because it affects process robustness. High-throughput sequencing offers high-resolution data regarding the microbial diversity and robustness of biological systems including AD; however, to understand the dynamics of microbial processes, knowing the microbial diversity is not adequate alone. Advanced meta-omic techniques have been established to determine the activity and interactions among organisms in biological processes like AD. Results of these methods can be used to identify biomarkers for AD states. This can aid a better understanding of system dynamics and be applied to producing comprehensive models for AD. 
  • 1.2K
  • 08 Jun 2021
Topic Review
Neurofibromin Functions
Neurofibromin is a large and multifunctional protein encoded by the tumor suppressor gene NF1, mutations of which cause the tumor predisposition syndrome neurofibromatosis type 1 (NF1). Neurofibromatosis type 1 is an autosomal dominant disorder caused by inherited or de novo germline mutations in the NF1 tumor suppressor gene. It is the most common tumor-predisposing disease in humans. It affects approximately one in 3000 live births and patients present widely heterogeneous clinical manifestations, even within the same family.
  • 1.2K
  • 28 Oct 2022
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.
  • 1.2K
  • 11 Mar 2021
Topic Review
Intrapancreatic Parenchymal Cell Transplantation
In vivo inoculation of cells such as cancer cells and induced pluripotent stem (iPS)/embryonic stem (ES) cells into immunocompromised mice, such as nude mice, has been considered a powerful technique for evaluating these cells' potential to form solid tumors made of proliferating cells or teratomas made of various types of differentiated cells originating from three germ cell layers. Two major approaches, i.e., subcutaneous grafting and grafting under the kidney capsule, have been widely utilized for this purpose. Unfortunately, large numbers of tumor cells are required for successful inoculation, and often, failure of tumorigenesis is encountered. This is attributable to dispersion/escaping of grafted cells from the inoculation site. To avoid such cell dispersion/escaping, choosing an appropriate inoculation site from where grafted cells cannot easily disperse is important. Intrapancreatic parenchymal injection of tumorigenic cells is apparently very effective for this purpose; the grafted cells seldom escape from the injection site and are found to form solid tumors even from small numbers (~15 × 103 cells) of cells. The procedure is very simple—it requires only surgical exposure of the pancreas over the dorsal skin under anesthesia and subsequent injection of cells toward the pancreatic parenchyma under dissecting microscope-based observation using a mouthpiece-controlled glass micropipette. The inoculated cells generally grow as solid tumors 1–1.5 months after surgery. This novel technique is known as “intrapancreatic parenchymal cell transplantation (IPPCT).” Apart from the abovementioned benefit, IPPCT may be useful for those wanting to obtain large amounts of tumorigenic cells for biochemical or molecular biological analyses or for those rescuing specific cells that are difficult to cultivate in vitro.
  • 1.2K
  • 30 Oct 2020
Topic Review
Causes and Mechanisms of PARP Inhibitor Resistance
Poly (ADP-ribose) polymerase (PARP) inhibitors are one of the most successful examples of clinical translation of targeted therapies in medical oncology, and this has been demonstrated by their effective management of BRCA1/BRCA2 mutant cancers, most notably in breast and ovarian cancers. PARP inhibitors target DNA repair pathways that BRCA1/2-mutant tumours are dependent upon. Inhibition of the key components of these pathways leads to DNA damage triggering subsequent critical levels of genomic instability, mitotic catastrophe and cell death. This ultimately results in a synthetic lethal relationship between BRCA1/2 and PARP, which underpins the effectiveness of PARP inhibitors.
  • 1.2K
  • 04 May 2023
Topic Review
Extended Myc Network
Among the first discovered and most prominent cellular oncogenes is MYC, which encodes a bHLH-ZIP transcription factor (Myc) that both activates and suppresses numerous genes involved in proliferation, energy production, metabolism and translation. Myc belongs to a small group of bHLH-ZIP transcriptional regulators (the Myc Network) that includes its obligate heterodimerization partner Max and six “Mxd proteins” (Mxd1–4, Mnt and Mga), each of which heterodimerizes with Max and largely opposes Myc’s functions.
  • 1.2K
  • 13 Apr 2022
Topic Review
Caseinolytic Protease Protease Families
Bacterial proteases participate in the proteolytic elimination of misfolded or aggregated proteins, carried out by members of the AAA+ protein superfamily such as Hsp100/Clp (heat shock protein-100/caseinolytic protease), Lon, and FtsH. It is estimated that the Clp and Lon families perform around 80% of cellular proteolysis in bacteria. The HSP100/Clp family of ATPases plays crucial roles in the folding, assembly, and degradation of proteins during normal growth and, mainly, under stress-inducing conditions. This family is formed by several ATPase chaperones and the peptidase ClpP (caseinolytic protease proteolytic subunit).
  • 1.2K
  • 18 Jan 2023
Topic Review
Heteroelement Analogues of Benzoxaborole
Heteroelement analogues of benzoxaboroles constitute an interesting class of boracyclic compounds and may offer the opportunity for various applications while retaining high stability arising from the presence of a strong B-O bond in the ring structure. The replacement of a carbon atom in the boracycle or an adjacent benzene ring with a heteroatom may result in a significant change of structural behaviour. Moreover,  physicochemical properties, including solubility, lipophilicity, hydrolytic stability, boron Lewis acidity, and others, can be modified. The aim of this review is to highlight several emerging groups of boracyclic systems which comprise various heteroelement atoms such as another boron, silicon, tin, nitrogen, phosphorus, and iodine. The information on synthesis and properties of such systems is complemented by presentation of their practical potential encompassing especially organic synthesis and catalysis as as medicinal chemistry. 
  • 1.2K
  • 22 Sep 2021
Topic Review
The Neuroprotective Effect of Hydrogen Sulfide
Hydrogen sulfide (H2S) is a gaseous signaling molecule that performs various cellular functions in normal and pathological conditions. H2S has great neuroprotective potential. H2S reduces oxidative stress, lipid peroxidation, and neuroinflammation; inhibits processes associated with apoptosis, autophagy, ferroptosis and pyroptosis; prevents the destruction of the blood-brain barrier; increases the expression of neurotrophic factors; and models the activity of Ca2+ channels in neurotrauma. In addition, H2S activates neuroprotective signaling pathways in psychiatric and neurodegenerative diseases. However, high levels of H2S can cause cytotoxic effects. Thus, the development of H2S-associated neuroprotectors seems to be especially relevant.
  • 1.2K
  • 14 Jul 2023
Topic Review
Effect of G-Quadruplexes on DNA Mismatch Repair Pathway
DNA G-quadruplexes (G4s) are known to be an integral part of the complex regulatory systems in both normal and pathological cells. Here we studied the effect of G4s on the DNA mismatch repair pathway. To assess the role of the distance between G4 and DNA mismatch on the functioning of the key mismatch repair protein, MutS, from E. coli on G4-containing substrates, a set of DNA duplexes with an embedded intramolecular parallel G4 structure and a monomethylated recognition site for the MutH endonuclease was prepared; the distance between the mismatched G/T pair and the G4 structure varied from 18 to 3 bp. It has been shown that this non-B form structure is not perceived by the E. coli system as damage that needs to be repaired; at the same time, it does not prevent activation of DNA mismatch repair, even when the G4 structure and G/T pair are at the distance of 3 bp. Thus, the preferential binding of MutS to G4 does not correlate with DNA mismatch repair activity, suggesting an unexpected role of these DNA-protein interactions in genome maintenance.
  • 1.2K
  • 09 Oct 2021
Topic Review
Effect of Anesthetics on Cancer Treatment
Propofol, fentanyl, rocuronium, sugammadex, and dexamethasone are commonly used to induce anesthesia and prevent pain during surgery. The mechanisms of these drugs to induce the state of anesthesia are not yet fully understood, despite their use being considered safe. An association between anesthetic agents and cancer progression has been determined; therefore, it is essential to recognize the effects of all agents during cancer treatment and to evaluate whether the treatment provided to the patients could be more precise. 
  • 1.2K
  • 11 Nov 2022
Topic Review
Small Peptides of Marine Origin
Cancer is one of the leading causes of death in the world, and antineoplastic drug research continues to be a major field in medicine development. The marine milieu has thousands of biological species that are a valuable source of novel functional proteins and peptides, which have been used in the treatment of many diseases, including cancer. In contrast with proteins and polypeptides, small peptides (with a molecular weight of less than 1000 Da) have overwhelming advantages, such as preferential and fast absorption, which can decrease the burden on human gastrointestinal function. Besides, these peptides are only connected by a few peptide bonds, and their small molecular weight makes it easy to modify and synthesize them. Specifically, small peptides can deliver nutrients and drugs to cells and tissues in the body. These characteristics make them stand out in relation to targeted drug therapy. Nowadays, the anticancer mechanisms of the small marine peptides are still largely not well understood; however, several marine peptides have been applied in preclinical treatment. 
  • 1.2K
  • 10 Mar 2021
Topic Review
Tyrosine Hydroxylase Phosphorylation
Tyrosine hydroxylase (TH) is the rate-limiting enzyme of dopamine biosynthesis. The phosphorylation of TH is strictly regulated.
  • 1.2K
  • 06 Nov 2020
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.
  • 1.2K
  • 22 Feb 2021
Topic Review
Liquid Biopsies on Breast Cancer
Breast cancer is the most common cancer among women worldwide. In the clinic today, imaging techniques like mammography and tissue biopsies are used to diagnose breast cancer. Even though these methods are important in primary diagnosis, they have limitations when it comes to longitudinal monitoring of residual disease after treatment, disease progression, therapy responses, and disease recurrence. Circulating cancer-derived material, including circulating cancer cells (CTCs), circulating DNA (ctDNA), and biomolecules encapsulated in extracellular vesicles,  acquired through liquid biopsies are currently focus of research as diagnostic, prognostic, and predictive biomarkers in breast cancer.
  • 1.2K
  • 08 Jan 2021
Topic Review
Applications of Two-Photon Microscopy
Fluorescence microscopy has represented a crucial technique to explore the cellular and molecular mechanisms in the field of biomedicine. However, the conventional one-photon microscopy exhibits many limitations when living samples are imaged. The new technologies, including two-photon microscopy (2PM), have considerably improved the in vivo study of pathophysiological processes, allowing the investigators to overcome the limits displayed by previous techniques. 2PM enables the real-time intravital imaging of the biological functions in different organs at cellular and subcellular resolution thanks to its improved laser penetration and less phototoxicity. The development of more sensitive detectors and long-wavelength fluorescent dyes as well as the implementation of semi-automatic software for data analysis allowed to gain insights in essential physiological functions, expanding the frontiers of cellular and molecular imaging. The future applications of 2PM are promising to push the intravital microscopy beyond the existing limits. 
  • 1.2K
  • 17 May 2022
Topic Review
Quality Control of the 26S Proteasome
The ubiquitin-26S proteasome system and autophagy are two major protein degradation machineries encoded in all eukaryotic organisms. While the ubiquitin-26S proteasome system (UPS) is responsible for the turnover of short-lived and/or soluble misfolded proteins under normal growth conditions, the autophagy-lysosomal/vacuolar protein degradation machinery is activated under stress conditions to remove long-lived proteins in the forms of aggregates, either soluble or insoluble, in the cytoplasm and damaged organelles. 
  • 1.2K
  • 31 Jan 2023
Topic Review
PVT1: novel colorectal cancer biomarker
Colorectal cancer is a very deadly disease with a current lack of a reliable biomarker for early detection, non-invasive diagnosis, treatment, prognostication, and monitoring of treatment. This entry provides information that indicates that PVT1 is a novel biomarker in colorectal cancer. Further research is required to establish how this knowledge can be used for clinical applications.
  • 1.2K
  • 04 Aug 2020
Topic Review
Biosynthetic Strategies for Macrocyclic Peptides
Macrocyclic peptides are predominantly peptide structures bearing one or more rings and spanning multiple amino acid residues. Macrocyclization has become a common approach for improving the pharmacological properties and bioactivity of peptides. A variety of ribosomal-derived and non-ribosomal synthesized cyclization approaches have been established.
  • 1.2K
  • 16 Jul 2021
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