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Topic Review
Recombinant Anticancer Peptides
Cationic peptides have high aptitudes to interact with cancer cells, especially multidrug resistance (MDR) cells. This interaction occurs due to the more negative charge of the membrane of cancer cells compared to normal cells. Recent studies have shown the application of cationic peptides in cancer therapy minimized the side effects of chemotherapy on normal cells. The main limitation of developing the cationic peptides for practical applications is the high cost of automated chemical production. For that reason, it is important to develop a cost-effective method for the production of mass quantities of biologically active peptides.
  • 1.2K
  • 29 Oct 2020
Topic Review
Genome Editing Technologies
Genome editing is the technique of precise genome modifications that facilitate the targeted modifications within the genome through the deletions, insertions, or substitution of single base or specific sequences.
  • 1.2K
  • 08 Mar 2022
Topic Review
Antibiofilm Therapeutics Strategies to Overcome Antimicrobial Drug Resistance
Biofilms embrace the capability to resist and survive harsh environmental conditions and defeat the host immune system, so there is a desire for exploring new antibiofilm agents. Antibiofilm agents that can abet the process of dismantling the biofilm has provided research strategies for designing new biofilm dispersal inducers.
  • 1.2K
  • 10 Mar 2022
Topic Review
Ceramide Transport Protein CERT and Its Inhibitors
Lipid transfer proteins (LTPs) are recognized as key players in the inter-organelle trafficking of lipids and are rapidly gaining attention as a novel molecular target for medicinal products. In mammalian cells, ceramide is newly synthesized in the endoplasmic reticulum (ER) and converted to sphingomyelin in the trans-Golgi regions. The ceramide transport protein CERT, a typical LTP, mediates the ER-to-Golgi transport of ceramide at an ER-distal Golgi membrane contact zone. A potent inhibitor of CERT, named (1R,3S)-HPA-12, was found by coincidence among ceramide analogs. Since then, various ceramide-resembling compounds have been found to act as CERT inhibitors. Nevertheless, the inevitable issue remains that natural ligand-mimetic compounds might directly bind both to the desired target and to various undesired targets that share the same natural ligand. To resolve this issue, a ceramide-unrelated compound named E16A, or (1S,2R)-HPCB-5, that potently inhibits the function of CERT has been developed, employing a series of in silico docking simulations, efficient chemical synthesis, quantitative affinity analysis, protein–ligand co-crystallography, and various in vivo assays. (1R,3S)-HPA-12 and E16A together provide a robust tool to discriminate on-target effects on CERT from off-target effects. 
  • 1.2K
  • 14 Mar 2022
Topic Review
Impact of TRAP1 on Cancer Metabolism
The Hsp90 chaperone TNF-receptor-associated protein-1 (TRAP1) is primarily localized to the mitochondria and controls both cellular metabolic reprogramming and mitochondrial apoptosis. TRAP1 upregulation facilitates the growth and progression of many cancers by promoting glycolytic metabolism and antagonizing the mitochondrial permeability transition that precedes multiple cell death pathways. TRAP1 attenuation induces apoptosis in cellular models of cancer, identifying TRAP1 as a potential therapeutic target in cancer. Similar to cytosolic Hsp90 proteins, TRAP1 is also subject to post-translational modifications (PTM) that regulate its function and mediate its impact on downstream effectors, or ‘clients’.
  • 1.2K
  • 08 Jun 2022
Topic Review
Infrared and Resonance Raman Spectroscopies
Vibrational spectroscopy and in particular, resonance Raman (RR) spectroscopy can provide molecular details on metalloproteins, including those containing multiple cofactors, which are often challenging for other spectroscopies. Due to distinct spectroscopic fingerprints, RR spectroscopy has a unique capacity to monitor simultaneously and independently different metal cofactors that can have particular roles in metalloproteins. These include e.g., (i) different types of hemes, as well as their spin and redox states, (ii) different types of Fe-S clusters, and (iii) bi-metallic center and electron transfer (ET) Fe-S cluster in hydrogenases. IR spectroscopy can provide un-matched molecular details on specific enzymes like hydrogenases that possess catalytic centers coordinated by CO and CN- ligands, which exhibit spectrally well separated IR bands.
  • 1.2K
  • 12 Oct 2021
Topic Review
RNA Modifications and RNA Metabolism in Neurological Disease
The intrinsic cellular heterogeneity and molecular complexity of the mammalian nervous system relies substantially on the dynamic nature and spatiotemporal patterning of gene expression. These features of gene expression are achieved in part through mechanisms involving various epigenetic processes such as DNA methylation, post-translational histone modifications, and non-coding RNA activity, amongst others. In concert, another regulatory layer by which RNA bases and sugar residues are chemically modified enhances neuronal transcriptome complexity. Similar RNA modifications in other systems collectively constitute the cellular epitranscriptome that integrates and impacts various physiological processes. The epitranscriptome is dynamic and is reshaped constantly to regulate vital processes such as development, differentiation and stress responses. Perturbations of the epitranscriptome can lead to various pathogenic conditions, including cancer, cardiovascular abnormalities and neurological diseases. These RNA modifications modulate the stability, transport and, most importantly, translation of RNA.
  • 1.2K
  • 22 Nov 2021
Topic Review
Targeting Tryptophan Metabolism to Treat Cancers
Major hallmarks of cancers are connected to dysfunctions in many metabolic pathways aiming at providing the energetic needs and the raw material for cellular growth and the signaling molecules needed for oncogenesis. Tryptophan (TRP) catabolism through the kynurenine (KYN) pathway was reported to play immunosuppressive actions across many types of cancer. However, results from clinical trials assessing the benefit of inhibiting key limiting enzymes of this pathway such as indoleamine 2,3-dioxygenase (IDO1) or tryptophan 2,3-dioxygenase (TDO2) failed to meet the expectations. Bearing in mind the complexity of the tumoral terrain and the existence of different cancers with IDO1/TDO2 expressing and non-expressing tumoral cells, here we present a comprehensive analysis of the TRP global metabolic hub and the approach of inhibiting these pathways as a potential therapeutic option to treat cancers such as liver cancers. 
  • 1.2K
  • 29 Mar 2022
Topic Review
Tricyclodecan-9-yl-Xanthogenate (D609)
Tricyclodecan-9-yl xanthogenate (D609) is a synthetic tricyclic compound possessing a xanthate group. This xanthogenate compound is known for its diverse pharmacological properties. Over the last three decades, many studies have reported the biological activities of D609, including antioxidant, antiapoptotic, anticholinergic, anti-tumor, anti-inflammatory, anti-viral, anti-proliferative, and neuroprotective activities.
  • 1.2K
  • 06 Apr 2022
Topic Review
G Protein Coupled Receptor 158
G-protein-coupled receptors (GPCRs) remain one of the most successful targets for therapeutic drugs approved by the US Food and Drug Administration (FDA). Many novel orphan GPCRs have been identified by human genome sequencing and considered as putative targets for refractory diseases. Of note, a series of studies have been carried out involving GPCR 158 (or GPR158) since its identification in 2005, predominantly focusing on the characterization of its roles in the progression of cancer and mental illness. However, advances towards an in-depth understanding of the biological mechanism(s) involved for clinical application of GPR158 are lacking.
  • 1.2K
  • 28 Apr 2022
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
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
Potential of microRNAs to Attenuate Diabetic Kidney Disease
Diabetic Kidney Disease (DKD) is a significant complication of diabetes and primary cause of end-stage renal disease globally. The exact mechanisms underlying DKD remain poorly understood, but multiple factors, including the renin–angiotensin–aldosterone system (RAAS), play a key role in its progression. Aldosterone, a mineralocorticoid steroid hormone, is one of the key components of RAAS and a potential mediator of renal damage and inflammation in DKD. miRNAs, small noncoding RNA molecules, have attracted interest due to their regulatory roles in numerous biological processes. These processes include aldosterone signaling and mineralocorticoid receptor (MR) expression. Numerous miRNAs have been recognized as crucial regulators of aldosterone signaling and MR expression. These miRNAs affect different aspects of the RAAS pathway and subsequent molecular processes, which impact sodium balance, ion transport, and fibrosis regulation.
  • 1.2K
  • 17 Jan 2024
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.
  • 1.2K
  • 13 Jan 2021
Topic Review
Natural Products against DDP-Induced Apoptosis
Cisplatin (cis-diamminedichloroplatinum (II), DDP) is an antineoplastic agent widely used in the treatment of solid tumors because of its extensive cytotoxic activity. However, the main limiting side effect of DDP use is nephrotoxicity, a rapid deterioration in kidney function due to toxic chemicals. Noncoding RNAs (ncRNAs), a class of epigenetic processes, are molecules that regulate gene expression under physiological and pathological conditions. MicroRNAs (miRNAs) are the most characterized class of ncRNAs and are engaged in many cellular processes. DDP-induced nephrotoxicity can present in a several ways, but the most common and serious presentation is acute kidney injury (AKI), which occurs in 20–30% of patients.
  • 1.2K
  • 25 Nov 2022
Topic Review
Lipids in Atherosclerosis
The role of lipids is essential in any phase of the atherosclerotic process, which is considered a chronic lipid-related and inflammatory condition. The traditional lipid profile (including the evaluation of total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein) is a well-established tool to assess the risk of atherosclerosis and as such has been widely used as a pillar of cardiovascular disease prevention and as a target of pharmacological treatments in clinical practice over the last decades.
  • 1.2K
  • 30 Dec 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
RAB11-Mediated Trafficking and Human Cancers
RAB11 isoforms function as membrane organizers connecting the transport of cargoes towards the plasma membrane with the assembly of autophagic precursors and the generation of cellular protrusions. These processes dramatically impact normal cell physiology and their alteration significantly affects the survival, progression and metastatization as well as the accumulation of toxic materials of cancer cells. 
  • 1.2K
  • 28 Jan 2021
Topic Review
Dystroglycanopathy
Dystroglycanopathy is a collective term referring to muscular dystrophies with abnormal glycosylation of dystroglycan. At least 18 causative genes of dystroglycanopathy have been identified, and its clinical symptoms are diverse, ranging from severe congenital to adult-onset limb-girdle types. 
  • 1.2K
  • 12 Jan 2022
Topic Review
Role of Hexokinases in Metabolic Reprogramming
The role of hexokinases in metabolic reprogramming in cancer is multifaceted and pivotal for the altered metabolic phenotype observed in cancer cells. Hexokinases, a group of enzymes responsible for catalyzing the first step of glycolysis, play a critical role in regulating glucose metabolism in cancer cells. In cancer, hexokinases are upregulated and exhibit distinct isoform preferences. Hexokinases facilitate the Warburg effect, a hallmark metabolic alteration in cancer cells characterized by increased glycolysis and decreased oxidative phosphorylation by promoting high glucose consumption and ATP production. Furthermore, hexokinases also participate in other metabolic pathways, such as the pentose phosphate pathway and mitochondrial metabolism, contributing to the rewiring of cancer cell metabolism. The overexpression of hexokinases in cancer cells supports the high bioenergetic and biosynthetic demands of rapidly proliferating cells and confers survival advantages by modulating cellular redox status and apoptosis. The dysregulation of hexokinases in cancer cells presents a promising target for cancer therapy. Understanding their role in metabolic reprogramming provides crucial insights into cancer metabolism and potential therapeutic strategies.
  • 1.2K
  • 14 Apr 2023
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