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Topic Review
Eukaryotic DNA Polymerases
DNA polymerases constitute a versatile group of enzymes that not only perform the essential task of genome duplication but also participate in various genome maintenance pathways, such as base and nucleotide excision repair, non-homologous end-joining, homologous recombination, and translesion synthesis. Polymerases catalyze DNA synthesis via the stepwise addition of deoxynucleoside monophosphates to the 3′ primer end in a partially double-stranded DNA.
  • 1.1K
  • 04 Jan 2024
Topic Review
Prophylaxis and Treatment Against Kp
Klebsiella pneumoniae (Kp) is an opportunistic pathogen and the leading cause of healthcare-associated infections, mostly affecting subjects with compromised immune systems or suffering from concurrent bacterial infections. However, the dramatic increase in hypervirulent strains and the emergence of new multidrug-resistant clones resulted in Kp occurrence among previously healthy people and in increased morbidity and mortality, including neonatal sepsis and death across low- and middle-income countries. As a consequence, carbapenem-resistant and extended spectrum β-lactamase-producing Kp have been prioritized as a critical anti-microbial resistance threat by the World Health Organization and this has renewed the interest of the scientific community in developing a vaccine as well as treatments alternative to the now ineffective antibiotics. Capsule polysaccharide is the most important virulence factor of Kp and plays major roles in the pathogenesis but its high variability (more than 100 different types have been reported) makes the identification of a universal treatment or prevention strategy very challenging. However, less variable virulence factors such as the O-Antigen, outer membrane proteins as fimbriae and siderophores might also be key players in the fight against Kp infections.
  • 1.1K
  • 10 May 2021
Topic Review
Endothelial Dysfunction
Any damage to the endothelial cells leads to the interruption of the barrier, an increased permeability, and an inflow of molecules that generate inflammatory response. Pulmonary endothelium is able to generate bioactive molecules and/or to use compounds present in the cell to reduce the effects of toxic stimuli and restore its conditions. If the damage is particularly extensive, the endothelium cannot tackle it and its permeability undergoes some alterations. The pulmonary endothelial barrier is completely destroyed in the case of chronic lung damages. A typical example of chronic inflammation of the alveolus-capillary unit is represented by virus infections.
  • 1.1K
  • 18 Jan 2022
Topic Review
Dendritic Cell-Based Approaches in Autoimmunity
Dendritic cells (DCs) dictate the outcomes of tissue-specific immune responses. DCs instruct T cells to respond to antigens (Ags), including self-Ags, leading to organ damage in the context of autoimmune diseases, or to becoming regulatory T cells (Tregs) promoting and perpetuating immune tolerance. DCs can acquire tolerogenic properties in vitro and in vivo in response to several stimuli, a feature that opens the possibility to generate or to target DCs to restore tolerance in autoimmune settings.
  • 1.1K
  • 09 Oct 2021
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
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
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
Sphingolipids in Central Nervous System
Bioactive lipids are a newly defined class of lipids that are actively involved in the regulation of a variety of cellular events. As the name indicates, these molecular factors are subjected to action at the arrival of a specific stimulus and undergo subsequent transitions to cope up with the insult. Among these bioactive lipids, sphingolipids have emerged as distinctive mediators of various cellular processes, ranging from cell growth and proliferation to cellular apoptosis, executing immune responses to regulating inflammation. Recent studies have made it clear that sphingolipids, their metabolic intermediates (ceramide, sphingosine-1-phosphate, and N-acetyl sphingosine), and enzyme systems (cyclooxygenases, sphingosine kinases, and sphingomyelinase) harbor diverse yet interconnected signaling pathways in the central nervous system (CNS), orchestrate CNS physiological processes, and participate in a plethora of neuroinflammatory and neurodegenerative disorders.
  • 1.1K
  • 05 Aug 2021
Topic Review
Oxi-Inflamm-Aging Related Cardiorenal Syndrome
Kidney failure is also a major cause of cardiovascular morbidity and mortality. Indeed, epidemiological studies have demonstrated that chronic kidney disease (CKD) is a significant risk for cardiovascular events independently of classical risk. 
  • 1.1K
  • 06 Jan 2022
Topic Review
Impact of the Renin-Angiotensin System on Neurodegenerative Diseases
The renin-angiotensin-aldosterone system (RAS) is an endocrine axis which has important peripheral physiological functions (blood pressure and cardiovascular homeostasis, water and sodium balance, and systemic vascular resistance). In addition to the systemic action of RAS, recent research highlights its paracrine and autocrine actions in many tissues, including the central nervous system. The complex is located intracellularly and is involved in various intracellular processes.
  • 1.1K
  • 04 Nov 2022
Topic Review
Natural Salicylates
Salicylic acid (SA) is a plant hormone which plays a crucial role in the plant defense against various pathogens and abiotic stresses.
  • 1.1K
  • 18 Mar 2021
Topic Review
Phytochemistry and Pharmacological Effect of Annona muricata
The Annonaceae family contains different types of bioactive chemical properties, such as alkaloids, acetogenins, flavonoids, terpenes, and essential oil, meaning the plants in this family are potential therapeutic agents. In vitro and in vivo studies have shown that A. muricata has the pharmacological effects of anti-cancer, anti-microbial, antioxidant, anti-ulcer, anti-diabetic, anti-hypertensive, and wound healing. 
  • 1.1K
  • 08 May 2023
Topic Review
Trans-Synaptic Neurexin–Neuroligin Interaction
Synapses serve as the interface for the transmission of information between neurons in the central nervous system. The structural and functional characteristics of synapses are highly dynamic, exhibiting extensive plasticity that is shaped by neural activity and regulated primarily by trans-synaptic cell-adhesion molecules (CAMs). Prototypical trans-synaptic CAMs, such as neurexins (Nrxs) and neuroligins (Nlgs), directly regulate the assembly of presynaptic and postsynaptic molecules, including synaptic vesicles, active zone proteins, and receptors. Therefore, the trans-synaptic adhesion mechanisms mediated by Nrx–Nlg interaction can contribute to a range of synaptopathies in the context of pathological pain and other neurological disorders.
  • 1.1K
  • 01 Jul 2022
Topic Review
Milk Exosomes as Drug Delivery Agents
Milk is a unique natural source of exosomes available in semi-preparative and preparative quantities. Milk exosomes are highly resistant to the harsh conditions of the gastrointestinal tract. In vitro studies have demonstrated that milk exosomes have an affinity to epithelial cells, are digested by cells by endocytosis mechanism, and can be used for oral delivery. With milk exosome membranes containing hydrophilic and hydrophobic components, exosomes can be loaded with hydrophilic and lipophilic drugs.
  • 1.1K
  • 21 Jun 2023
Topic Review
ORP5 and ORP8
Oxysterol binding related proteins 5 and 8 (ORP5 and ORP8) are two close homologs of the larger oxysterol binding protein (OSBP) family of sterol sensors and lipid transfer proteins (LTP). Early studies indicated these transmembrane proteins, anchored to the endoplasmic reticulum (ER), bound and sensed cholesterol and oxysterols. They were identified as important for diverse cellular functions including sterol homeostasis, vesicular trafficking, proliferation and migration. In addition, they were implicated in lipid-related diseases such as atherosclerosis and diabetes, but also cancer, although their mechanisms of action remained poorly understood. Then, alongside the increasing recognition that membrane contact sites (MCS) serve as hubs for non-vesicular lipid transfer, added to their structural similarity to other LTPs, came discoveries showing that ORP5 and 8 were in fact phospholipid transfer proteins that rather sense and exchange phosphatidylserine (PS) for phosphoinositides, including phosphatidylinositol-4-phosphate (PI(4)P) and potentially phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2). Evidence now points to their action at MCS between the ER and various organelles including the plasma membrane, lysosomes, mitochondria, and lipid droplets. Dissecting exactly how this unexpected phospholipid transfer function connects with sterol regulation in health or disease remains a challenge for future studies.
  • 1.1K
  • 15 Jul 2021
Topic Review
Land Use for Critical Cemeteries in Central Ecuador
Cemeteries are sites for the final disposal of human bodies that constitute a source of contamination of soil and water as a result of the cadaveric decomposition generated. In addition, land use conflicts were encountered in the cemetery grounds. It is concluded that the existing cemeteries should be subjected to more detailed environmental analysis and subsequently should be treated as security landfills in the closure and post-closure stage. Also, it has been concluded that the cemeteries should not be located in urban or peri-urban areas.
  • 1.1K
  • 11 Feb 2022
Topic Review
The Fibroblast Growth Factor Receptors
Breast cancer (BC) is the most frequent form of malignancy and second only to lung cancer as cause of deaths in women. Notwithstanding many progresses made in the field, metastatic BC has a very poor prognosis. As therapies are becoming more personalized to meet the needs of patients, a better knowledge of the molecular biology leading to the disease unfolds the possibility to project more precise compounds or antibodies targeting definite alteration at the molecular level and functioning on such cancer-causing molecules expressed in cancer cells of patients, or present as antigens on the surface of cancer cell membranes. Fibroblast growth factor receptor (FGFR) is one of such druggable targets, activated by its own ligands -namely the Fibroblast Growth Factors (FGFs). This pathway provides a vast range of interesting molecular targets pursued at different levels of clinical investigation.
  • 1.1K
  • 01 Nov 2020
Topic Review
Ischemic Stroke and Excitotoxicity
Stroke is a relevant cause of death, disability and dementia worldwide. In ischemic stroke, excitotoxicity is the main mechanism of neuronal death in the penumbra area, a potentially recoverable tissue surrounding the irreversibly damaged infarct core. In excitatory neurons, scaffold protein PSD-95 plays a central role in neuronal function but also survival/death choices. Thus, this protein is a promising target for development of neuroprotective strategies for stroke and other pathologies similarly associated to excitotoxicity.
  • 1.1K
  • 13 Dec 2021
Topic Review
γ-aminobutyric Acid and Barley Seedlings
It has been revealed that high NaCl stress (>60 mmol L−1) induced phenolics accumulation in barley seedlings, with γ-aminobutyric acid (GABA) playing a key role. Interestingly, low NaCl stimulus (20 mmol L−1) enhancing phenolics synthesis and growth of barley seedlings was also reported recently. Hence, exogenous GABA and its bio-synthesis inhibitor 3-mercaptopropionic acid (3-MP) were applied to reveal the mechanism of GABA regulating phenolics metabolism in barley seedlings treated with 20 mmol L−1 NaCl. The contents of total phenolics and flavonoids significantly increased by 11.64% and 14.52% under NaCl, respectively. The addition of GABA further increased phenolics and flavonoids contents, especially for gallic acid, protocatechuic acid, caffeic acid, and quercetin, compared with NaCl treatment. Simultaneously, GABA increased the activities and mRNA levels of phenylalanine ammonia lyase (PAL), cinnamic acid 4-hydroxylase (C4H), and 4-coumalyl CoA ligase (4CL). The addition of 3-MP suppressed the above effects, except for increasing the protein levels of PAL, C4H, and 4CL. Low concentration of NaCl not only promoted growth, but also stimulated endogenous GABA metabolism to affect key enzymes activities and mRNA levels for phenolics synthesis in barley seedlings.
  • 1.1K
  • 15 Oct 2021
Topic Review
SARS-CoV-2 Infection and Parkinson’s Disease Overlaps
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease after Alzheimer’s disease, globally. Dopaminergic neuron degeneration in substantia nigra pars compacta and aggregation of misfolded alpha-synuclein are the PD hallmarks, accompanied by motor and non-motor symptoms. Several viruses have been linked to the appearance of a post-infection parkinsonian phenotype. Coronavirus disease 2019 (COVID-19), caused by emerging severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, has evolved from a novel pneumonia to a multifaceted syndrome with multiple clinical manifestations, among which neurological sequalae appear insidious and potentially long-lasting.
  • 1.1K
  • 13 Sep 2022
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