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Topic Review
Starvation-Induced Autophagy in Saccharomyces cerevisiae in Metabolomics Perspectives
The application of metabolomics has extended the scope of autophagy and provided newer intervention targets against cancer as well as neurodegenerative diseases in which autophagy is implicated. 
  • 1.1K
  • 02 Dec 2021
Topic Review
Tetrazoles as Antidiabetic Agents
Tetrazole heterocycle is a promising scaffold in drug design, and it is incorporated into active pharmaceutical ingredients of medications of various actions: hypotensives, diuretics, antihistamines, antibiotics, analgesics, and others. This heterocyclic system is metabolically stable and easily participates in various intermolecular interactions with different biological targets through hydrogen bonding, conjugation, or van der Waals forces.
  • 1.1K
  • 20 Dec 2023
Topic Review
Programmed DNA-Damage and Physiological DSBs
DNA double-strand breaks (DSBs) are well known for their deleterious effects. Improper repair of these breaks can result in mutations, translocations and even loss of genetic material, which can later lead to tumor formation and cancer progression. There are many exogenous agents that can cause DSBs. DSBs can also emerge due to replication stress activated by inhibition of DNA synthesis and/or activation of oncogenes. This review aims to summarize what is known about DNA damage in its physiological context. In addition, we will examine the advancements of the past several years, which have made an impact on the study of genome landscape and its organization. 
  • 1.1K
  • 30 Oct 2020
Topic Review
MSC-Derived Secretome in Parkinson’s Disease
       Mesenchymal stem cell (MSC)-derived secretome demonstrated therapeutic effects like those reported after MSCs transplantation. MSC-derived secretome may avoid various side effects of MSC-based therapy, comprising undesirable differentiation of engrafted MSCs and potential activation of the allogeneic immune response. MSC-derived secretome comprises soluble factors and encapsulated extravesicles (EVs). MSC-derived EVs comprise microvesicles, apoptotic bodies, and exosomes. In this review, we focus on the recent insights into the effects of MSC-derived secretome in Parkinson’s disease (PD). In particular, MSC-derived secretome and exosomal components counteracted neuroinflammation and enhanced antioxidant capacity and neurotrophic factors expression. In light of the insights reported in this review, MSC-derived secretome or their released exosomes may be used as a potential therapeutic approach or as adjuvant therapy to counteract the disease progression and improve PD symptoms. Also, MSC-derived secretome may be used as a vehicle in cell transplantation approaches to enhance the viability and survival of engrafted cells. Furthermore, since exosomes can cross the blood–brain barrier, they may be used as biomarkers of neural dysfunction. Further studies are necessary to fully characterize the bioactive molecules present in the secretome and to create a new, effective, cell-free therapeutic approach towards a robust clinical outcome for PD patients.
  • 1.1K
  • 28 Sep 2020
Topic Review
Methylglyoxal-derived AGEs-Induced mitochondrial dysfunction/ER stress
Advanced glycation end products (AGEs) are formed via nonenzymatic reactions between reducing sugars and proteins. Recent studies have shown that methylglyoxal, a potent precursor for AGEs, causes a variety of biological dysfunctions, including diabetes, inflammation, renal failure, and cancer. However, little is known about the function of methylglyoxal-derived AGEs (AGE4) in kidney cells. Therefore, we verified the expression of endoplasmic reticulum (ER) stress-related genes and apoptosis markers to determine the effects of AGE4 on human proximal epithelial cells (HK-2). Moreover, our results showed that AGE4 induced the expression of apoptosis markers, such as Bax, p53, and kidney injury molecule-1, but downregulated Bcl-2 and cyclin D1 levels. AGE4 also promoted the expression of NF-κB, serving as a transcription factor, and the phosphorylation of c-Jun NH2-terminal kinase (JNK), which induced cell apoptosis and ER stress mediated by the JNK inhibitor. Furthermore, AGE4 induced mitochondrial dysfunction by inducing the permeabilization of the mitochondrial membrane and ATP synthesis. 
  • 1.1K
  • 11 Oct 2021
Topic Review
Thirteen Potential TMPRSS2 Inhibitors
We identified a set of 13 approved or clinically investigational drugs with positively charged guanidinobenzoyl and/or aminidinobenzoyl groups, including the experimentally verified TMPRSS2 inhibitors Camostat and Nafamostat. Molecular docking suggested that the guanidinobenzoyl or aminidinobenzoyl group in all the drugs could form putative salt bridge interactions with the side-chain carboxyl group of Asp435 located in the S1 pocket of TMPRSS2. Molecular dynamics simulations further revealed the high stability of the putative salt bridge interactions over long-time simulations. These results suggest that the proposed compounds, in addition to Camostat and Nafamostat, could be effective TMPRSS2 inhibitors for COVID-19 treatment by occupying the S1 pocket with the hallmark positively charged groups.
  • 1.1K
  • 12 Jul 2021
Topic Review
Ursolic Acid in Cancer and Diabetic Neuropathy Diseases
Ursolic acid (UA) is a promising triterpenoid compound present in several plants’ leaves, flowers, and fruits. It shows a broad range of pharmaceutical properties and therapeutic effects. UA has been utilized as a herbal medicine with excellent pharmacological activities.
  • 1.1K
  • 19 Nov 2021
Topic Review
Oxidative Stress in Cancer Cells
Undue elevation of ROS levels commonly occurs during cancer evolution as a result of various antitumor therapeutics and/or endogenous immune response. Overwhelming ROS levels induced cancer cell death through the dysregulation of ROS-sensitive glycolytic enzymes, leading to the catastrophic depression of glycolysis and oxidative phosphorylation (OXPHOS), which are critical for cancer survival and progression. 
  • 1.1K
  • 25 Jul 2022
Topic Review
Farnesoid X Receptor
Farnesoid X receptor (FXR) has a central role in Bile Acids (BA) homeostasis and recent publications revealed that changes in autophagy due to BA-induced reactive oxygen species and increased anti-oxidant response via nuclear factor E2-related factor 2 (NRF2), result in dysregulation of FXR signaling. Several mechanistic studies have identified new dysfunctions of the cholestatic liver at cellular and molecular level, opening new venues for developing more performant therapies.
  • 1.1K
  • 12 Oct 2021
Topic Review
Aloperine
Aloperine is an alkaloid found in the seeds and leaves of the medicinal plant Sophora alopecuroides L. It has been used as herbal medicine in China for centuries due to its potent anti-inflammatory, antioxidant, antibacterial, and antiviral properties. Recently, aloperine has been widely investigated for its therapeutic activities. Aloperine is proven to be an effective therapeutic agent against many human pathological conditions, including cancer, viral diseases, and cardiovascular and inflammatory disorders. Aloperine is reported to exert therapeutic effects through triggering various biological processes, including cell cycle arrest, apoptosis, autophagy, suppressing cell migration, and invasion. It has also been found to be associated with the modulation of various signaling pathways in different diseases.
  • 1.1K
  • 05 May 2022
Topic Review
Peroxisome Proliferator-activated Receptors (PPARs)
Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-activated receptors/transcriptional factors composed by three distinct isoforms called PPARα (nuclear receptor subfamily 1 group C, NR1C1), PPARβ/δ (NR1C2), and PPARγ (NR1C3), each of which is encoded by independent genes in rodents and humans.
  • 1.1K
  • 29 Mar 2021
Topic Review
RIF1 Links Replication Timing
Replication timing (RT) is a cellular program to coordinate initiation of DNA replication in all origins within the genome. RIF1 (replication timing regulatory factor 1) is a master regulator of RT in human cells. This role of RIF1 is associated with binding G4-quadruplexes and changes in 3D chromatin that may suppress origin activation over a long distance. 
  • 1.1K
  • 01 Nov 2021
Topic Review
Gap-Juntions in the Oocyte
Connexins are proteins that form membrane channels and gap-junctions, and more precisely, these proteins enable the exchange of some ions and molecules, and therefore they do play a fundamental role in the communication between the oocyte and accompanying cells.
  • 1.1K
  • 11 Jun 2021
Topic Review
Targeting Immunosuppressive Pathways as Cancer Therapies
Immune response has been shown to play an important role in defining patient prognosis and response to cancer treatment. Tumor-induced immunosuppression encouraged the recent development of new chemotherapeutic agents that assists in the augmentation of immune responses. Molecular mechanisms that tumors use to evade immunosurveillance are attributed to their ability to alter antigen processing/presentation pathways and the tumor microenvironment. Cancer cells take advantage of normal molecular and immunoregulatory machinery to survive and thrive. Cancer cells constantly adjust their genetic makeup using several mechanisms such as nucleotide excision repair as well as microsatellite and chromosomal instability, thus giving rise to new variants with reduced immunogenicity and the ability to continue to grow without restrictions. 
  • 1.1K
  • 15 Nov 2022
Topic Review
Richter Syndrome
Richter syndrome (RS) represents the occurrence of an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), in patients with chronic lymphocytic leukemia (CLL).
  • 1.1K
  • 03 Feb 2023
Topic Review
Remote Ischemic Preconditioning
Autophagy is a cellular process by which mammalian cells degrade and assist in recycling damaged organelles and proteins. This study aimed to ascertain the role of autophagy in RIPC-induced cardioprotection. Sprague Dawley rats were subjected to RIPC at the hindlimb followed by 30 min transient blockade of the left coronary artery to simulate I/R injury. Hindlimb muscle and the heart were excised 24 h post reperfusion. RIPC prior to I/R upregulated autophagy in the rat heart at 24 h post reperfusion. In vitro, autophagy inhibition or stimulation prior to RIPC respectively, either ameliorated or stimulated the cardioprotective effect, measured as improved cell viability to mimic the preconditioning effect. Recombinant IL-6 treatment prior to I/R increased in vitro autophagy in a dose dependent manner activating the JAK-STAT pathway without affecting the other kinase pathways such as p38 MAPK, and GSK-3β pathways. Prior to I/R, in vitro inhibition of the JAK-STAT pathway reduced autophagy upregulation despite recombinant IL-6 pre-treatment. Autophagy is an essential component of RIPC-induced cardioprotection that may upregulate autophagy through an IL-6/JAK-STAT dependent mechanism, thus identifying a potentially new therapeutic option for the treatment of ischemic heart disease.
  • 1.1K
  • 29 Oct 2020
Topic Review
Plasmalogen Replacement Therapy
Plasmalogens, a subclass of glycerophospholipids containing a vinyl-ether bond, are one of the major components of biological membranes. Changes in plasmalogen content and molecular species have been reported in a variety of pathological conditions ranging from inherited to metabolic and degenerative diseases. Most of these diseases have no treatment, and attempts to develop a therapy have been focusing primarily on protein/nucleic acid molecular targets. However, recent studies have shifted attention to lipids as the basis of a therapeutic strategy. In these pathological conditions, the use of plasmalogen replacement therapy (PRT) has been shown to be a successful way to restore plasmalogen levels as well as to ameliorate the disease phenotype in different clinical settings.
  • 1.1K
  • 16 Nov 2021
Topic Review
Treat COVID-19 through Mass Spectrometry and Next-Generation Sequencing
COVID-19 is caused by a coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The difficulty in containing SARS-CoV-2 has underscored the need for techniques such as mass spectrometry in the diagnosis and treatment of COVID-19. Mass spectrometry-based methods have been employed in several studies to detect changes in interactions among host proteins, and between host and viral proteins in COVID-19 patients. The methods have also been used to characterize host and viral proteins, and analyze lipid metabolism in COVID-19 patients. Information obtained using the above methods are complemented by high-throughput analysis of transcriptomic and epigenomic changes associated with COVID-19, coupled with next-generation sequencing.
  • 1.1K
  • 22 Nov 2021
Topic Review
Glyoxalase 2
Glyoxalase 2 is a mitochondrial and cytoplasmic protein belonging to the metallo-β-lactamase family encoded by the hydroxyacylglutathione hydrolase (HAGH) gene. This enzyme is the second enzyme of the glyoxalase system that is responsible for detoxification of the α-ketothaldehyde methylglyoxal in cells. The two enzymes glyoxalase 1 (Glo1) and glyoxalase 2 (Glo2) form the complete glyoxalase pathway, which utilizes glutathione as cofactor in eukaryotic cells.
  • 1.1K
  • 14 Nov 2022
Topic Review
The Biological Radicals
Past and present knowledge on the most important biological radicals, the superoxide radical anion and the nitrogen monoxide radical, are briefly compiled. The contribution covers the history of their detection, their enzymology, their physiological role and their detrimental effects, if they are produced in an unbalanced way. An in-depth understanding of their formation and metabolic fate is considered to improve our understanding of important biomedical problems such as host defense, blood circulation, inflammation and oxidative tissue damage.
  • 1.1K
  • 26 Jan 2021
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