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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
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
The Structure and Function of ABCA1
The adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) was identified by Luciani et al. over 36 years ago by PCR cloning and found to be located on chromosome 9q22-31. ABCA1 belongs to what was then a growing family of transmembrane proteins sharing many structural and functional similarities. ABCA1 was initially thought to be involved in the phagocytosis of apoptotic cells and to play a role in the regulation of the inflammatory response. Recent studies of structure-function relationships have shown that ABCA1 transports cholesterol and phospholipids across the plasma membrane to generate high-density lipoproteins (HDLs).
  • 1.1K
  • 28 Feb 2023
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
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
Pyoverdine Biosynthesis
Pyoverdines (PVDs) are a class of siderophores produced mostly by members of the genus Pseudomonas. Their primary function is to accumulate, mobilize, and transport iron necessary for cell metabolism. Moreover, PVDs also play a crucial role in microbes’ survival by mediating biofilm formation and virulence. 
  • 1.1K
  • 25 Nov 2022
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
Regulation of Cell Proliferation by Calcineurin
Calcineurin, a calcium-dependent serine/threonine phosphatase, integrates the alterations in intracellular calcium levels into downstream signaling pathways by regulating the phosphorylation states of several targets. Intracellular Ca2+ is essential for normal cellular physiology and cell cycle progression at certain critical stages of the cell cycle. Recently, it was reported that calcineurin is activated in a variety of cancers. Given that abnormalities in calcineurin signaling can lead to malignant growth and cancer, the calcineurin signaling pathway could be a potential target for cancer treatment. For example, NFAT, a typical substrate of calcineurin, activates the genes that promote cell proliferation. Furthermore, cyclin D1 and estrogen receptors are dephosphorylated and stabilized by calcineurin, leading to cell proliferation. 
  • 1.1K
  • 08 Feb 2022
Topic Review
Evaluation of Biological Activity of Natural Compounds
Natural compounds have diverse structures and are present in different forms of life. Metabolites such as tannins, anthocyanins, and alkaloids, among others, serve as a defense mechanism in live organisms and are undoubtedly compounds of interest for the food, cosmetic, and pharmaceutical industries.
  • 1.1K
  • 01 Aug 2022
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
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
The Xeroderma Pigmentosum Group A Protein
Nucleotide excision repair (NER) is a central DNA repair pathway responsible for removing a wide variety of DNA-distorting lesions from the genome. The highly choreographed cascade of core NER reactions requires more than 30 polypeptides. The xeroderma pigmentosum group A (XPA) protein plays an essential role in the NER process. XPA interacts with almost all NER participants and organizes the correct NER repair complex. In the absence of XPA’s scaffolding function, no repair process occurs. Researchers briefly summarize the knowledge about the XPA protein structure and analyze the formation of contact with its protein partners during NER complex assembling.
  • 1.1K
  • 30 Dec 2022
Topic Review
Pancreatic Stellate Cells
Pancreatic ductal adenocarcinoma (PDAC), is characterized by an overall poor prognosis and a five-year survival that is less than 10% due to late diagnosis, aggressive disease progression, and resistance to conventional chemotherapy. A large proportion of a pancreatic tumor is made up of stromal fibroblasts, the pancreatic stellate cells (PSCs, also known as cancer-associated fibroblasts – CAFs). Increasing evidence indicates that PSCs contribute to the overall tumor progression, drug resistance, and metabolic rewiring in PDAC.
  • 1.1K
  • 20 Feb 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
Biography
Gjumrakch Aliev
Professor Aliev had many projects underway that he looked forward to completing to better serve the world and all of its people. The scientific community has lost a bright, multidisciplinary scientist who could connect people with similar research interests across borders and continents. Gjumrakch (Figure 1) was the internationally recognized founder of Gally International Research Institute (h
  • 1.1K
  • 08 Oct 2022
Topic Review
Omega-3 PUFA in Pediatric Cancer
Epidemiological literature suggests a protective effect of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) against cancer. They are attributed to have significant anti-inflammatory properties, and are reported to directly inhibit carcinogenesis and tumor expansion, whilst also reducing the risk for secondary complications, thus representing a promising approach for adjunctive chemotherapy treatment. At the same time, the incidence of malnutrition amongst children with cancer is high and both under- and overnutrition are associated with detrimental consequences, including increased risks for morbidity and mortality, early relapse rates, and a higher prevalence of secondary complications during treatment. Taken together with the benefits of n-3 PUFA supplementation, an enhancement of the nutritional status is a potentially modifiable prognostic factor in pediatric oncology.
  • 1.1K
  • 08 Jun 2021
Topic Review
Ceramide Metabolism Enzymes
Sphingolipids are both structural molecules that are essential for cell architecture and second messengers that are involved in numerous cell functions. Ceramide is the central hub of sphingolipid metabolism. In addition to being the precursor of complex sphingolipids, ceramides induce cell cycle arrest and promote cell death and inflammation. At least some of the enzymes involved in the regulation of sphingolipid metabolism are altered in carcinogenesis, and some are targets for anticancer drugs.
  • 1.1K
  • 22 Sep 2021
Topic Review
DNA Methyltransferases
DNA methylation is an epigenetic mark that living beings have used in different environments. The MTases family catalyzes DNA methylation. This process is conserved from archaea to eukaryotes, from fertilization to every stage of development, and from the early stages of cancer to metastasis. The family of DNMTs has been classified into DNMT1, DNMT2, and DNMT3. Each DNMT has been duplicated or deleted, having consequences on DNMT structure and cellular function, resulting in a conserved evolutionary reaction of DNA methylation. DNMTs are conserved in the five kingdoms of life: bacteria, protists, fungi, plants, and animals. 
  • 1.1K
  • 30 Aug 2022
Topic Review
Forms of Parkinson Disease Epigenetic Aspects
Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting approximately 1% of the population over the age of 50. PD is the second most common neurodegenerative disorder, and the estimated prevalence is 94 cases per 100,000 people, or approximately 0.3 percent in the general population 40 years of age and older. The yearly incidence of new cases ranges from 8 to 18.6 per 100,000 person-years. PD is clinically characterized by uncontrollable tremors at rest, rigidity, slowness of movement and postural impairment. In addition to violations of motor function, PD is accompanied by gastrointestinal, olfactory, sleep, and cognitive pathologies and other disorders. PD is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). These neurons release dopamine (DA) from nerve endings in the striatum and control muscle tone and multiple brain functions including a broad array of behavioral processes such as mood, reward, addiction, and stress. Morphologically PD is characterized by the presence of intracellular inclusions called Lewy bodies (LB) consisting mainly of aggregated α-synuclein (αSyn) inside nerve cells including SNpc. The onset of PD is dependent on both genetic and environmental factors. The latter can alter gene expression by causing epigenetic changes, such as DNA methylation, and the post-translational modification of histones and non-coding RNAs (ncRNAs, the most studied of which are microRNAs or miRNAs). The regulation of genes responsible for monogenic forms of PD may also be involved in sporadic PD.
  • 1.1K
  • 12 Sep 2023
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