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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
DNA Damage Response (DDR)
DNA damage could occur in cells either endogenously, through normal cellular replication and metabolism, or exogenously through ultraviolet (UV), ionizing radiation (IR) or various genotoxic compounds] that could induce DNA damage. Different stressors will cause different types of DNA damage. Normal DNA replication could induce mismatch of the nucleotide and cause mutations. Stressors such as oxidative stress will produce reactive oxygen species (ROS) from normal cellular metabolism or from external genotoxic compound, which will cause DNA breaks, either single-stranded or double-stranded. Unrepaired DNA damage could cause severe mutations and chromosomal instability, which would have detrimental effects on the cells and lead to cell death, while DNA breaks that are repaired through non-homologous end joining (NHEJ) might cause mutations during the process.The DDR is the response mechanism which will detect any DNA damage that occurs throughout the chromosome and will activate a repair cascade to the damage site. This will help the cells either to proliferate normally if the repair was successful or to activate the cellular programmed cell death if the damage was too extensive and was unable to be repaired. The known DNA damage repair mechanisms include mismatch repair (MMR), base excision repair (BER), nucleotide excision repair (NER), homologous recombination (HR) and non-homologous end joining (NHEJ). Specific types of DNA damage could be fixed by a specific repair factor, such as the ATM kinase, which is the main factor in double-strand break repair through NHEJ. Figure 1 shows the causes and types of DNA damage as well as the response cascade involved in repairing the damages.
  • 1.2K
  • 08 Oct 2021
Topic Review
Aerobic Glycolysis in Cancer Cells
Aerobic glycolysis in cancer cells, which involves the production of lactate as the end product of glucose breakdown even in the presence of adequate oxygen, is the foundation for the current interest in the cancer-cell-specific reprograming of metabolic pathways. The renewed interest in cancer cell metabolism has now gone well beyond the original Warburg effect related to glycolysis to other metabolic pathways that include amino acid metabolism, one-carbon metabolism, the pentose phosphate pathway, nucleotide synthesis, antioxidant machinery, etc. Since glucose and amino acids constitute the primary nutrients that fuel the altered metabolic pathways in cancer cells, the transporters that mediate the transfer of these nutrients and their metabolites not only across the plasma membrane but also across the mitochondrial and lysosomal membranes have become an integral component of the expansion of the Warburg effect.
  • 1.2K
  • 31 Jan 2024
Topic Review
Molecular concepts in vascular disorders
In physiology and pathophysiology the molecules involved in blood cell–blood cell and blood cell–endothelium interactions have been identified. Platelet aggregation and adhesion to the walls belonging to vessels involve glycoproteins (GP), GP llb and GP llla and the GP Ib–IX–V complex. Red blood cells (RBCs) in normal situations have little interaction with the endothelium. Abnormal adhesion of RBCs was first observed in sickle cell anemia involving vascular cell adhesion molecule (VCAM)-1, α4β1, Lu/BCAM, and intercellular adhesion molecule (ICAM)-4. More recently RBC adhesion was found to be increased in retinal-vein occlusion (RVO) and in polycythemia vera (PV). The molecules which participate in this process are phosphatidylserine and annexin V in RVO, and phosphorylated Lu/BCAM and α5 laminin chain in PV. The additional adhesion in diabetes mellitus occurs due to the glycated RBC band 3 and the advanced glycation end-product receptors. The multiligand receptor binds advanced glycation end products (AGEs) or S100 calgranulins, or β-amyloid peptide. This receptor for advanced glycation end products is known as RAGE. The binding to RAGE-activated endothelial cells leads to an inflammatory reaction and a prothrombotic state via NADPH activation and altered gene expression. RAGE blockade is a potential target for drugs preventing the deleterious consequences of RAGE activation.
  • 1.2K
  • 28 Sep 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
Molecular Diagnosis of COVID-19
COVID-19 is no longer a global pandemic due to development and integration of different technologies for the diagnosis and treatment of the disease, technological advancement in the field of molecular biology, electronics, computer science, artificial intelligence, Internet of Things, nanotechnology, etc. has led to the development of molecular approaches and computer aided diagnosis for the detection of COVID-19. 
  • 1.2K
  • 11 Jan 2023
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
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
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
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
Sources of Reactive Oxygen Species
Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the cellular anti-oxidant defense mechanisms, plays a critical role in the pathogenesis of various human diseases. ROS are either produced through cellular processes or environmental factors. Of note, oxidative stress has been described as a secondary effect within the pathology of several rare monogenic diseases and sometimes been called a common denominator. 
  • 1.2K
  • 26 Feb 2024
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
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
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
Naringenin
Naringenin, a natural flavanone, was first identified from extracts of the dormant peach (Prunus persica) flower buds, with the chemical name of 5,7,4′-trihydroxyflavanone.
  • 1.2K
  • 25 Dec 2020
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
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
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
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 Video
Plant-Derived Extracellular Vesicles for Next-Generation Drug Delivery
Plant cells release tiny membranous vesicles called extracellular vesicles (EVs), which are rich in lipids, proteins, nucleic acids, and pharmacologically active compounds. These plant-derived EVs (PDEVs) are safe and easily extractable and have been shown to have therapeutic effects against inflammation, cancer, bacteria, and aging. They have shown promise in preventing or treating colitis, cancer, alcoholic liver disease, and even COVID-19. PDEVs can also be used as natural carriers for small-molecule drugs and nucleic acids through various administration routes such as oral, transdermal, or injection. The unique advantages of PDEVs make them highly competitive in clinical applications and preventive healthcare products in the future.
  • 1.2K
  • 31 May 2023
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