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Topic Review
MS-Based Proteomics for Bipolar Disorder Potential Biomarkers Assessment
Bipolar disorder (BD) is a clinically heterogeneous condition, presenting a complex underlying etiopathogenesis that is not sufficiently characterized. Without molecular biomarkers being used in the clinical environment, several large screen proteomics studies have been conducted to provide valuable molecular information. Mass spectrometry (MS)-based techniques can be a powerful tool for the identification of disease biomarkers, improving prediction and diagnosis ability.
  • 668
  • 27 May 2022
Topic Review
Nucleosome Structures Built from Highly Divergent Histones
In eukaryotes, genomic DNA is bound with histone proteins and packaged into chromatin. The nucleosome, a fundamental unit of chromatin, regulates the accessibility of DNA to enzymes involved in gene regulation. Structural analyses of chromatin architectures have been limited to evolutionarily related organisms. The amino acid sequences of histone proteins are highly conserved from humans to yeasts, but are divergent in the deeply branching protozoan groups, including human parasites that are directly related to human health. Certain large DNA viruses, as well as archaeal organisms, contain distant homologs of eukaryotic histone proteins. The divergent sequences give rise to unique and distinct nucleosome architectures, although the fundamental principles of histone folding and DNA contact are highly conserved. 
  • 668
  • 27 Sep 2022
Topic Review
δ-Cells
Somatostatin-secreting δ-cells have aroused great attention due to their powerful roles in coordination of islet insulin and glucagon secretion and maintenance of glucose homeostasis. δ-cells exhibit neuron-like morphology with projections which enable pan-islet somatostatin paracrine regulation despite their scarcity in the islets. 
  • 667
  • 06 Apr 2021
Topic Review
Human Lectins
Lectins are a class of proteins responsible for several biological roles such as cell-cell interactions, signaling pathways, and several innate immune responses against pathogens.
  • 666
  • 16 Feb 2021
Topic Review
Regenerative Medicine
The use of biological templates for the suitable growth of adipose-derived mesenchymal stem cells (AD-MSC) and “neo-tissue” construction has exponentially increased over the last years. The bioengineered scaffolds still have a prominent and biocompatible framework playing a role in tissue regeneration. In order to supply AD-MSCs, biomaterials, as the stem cell niche, are more often supplemented by or stimulate molecular signals that allow differentiation events into several strains, besides their secretion of cytokines and effects of immunomodulation. This systematic review aims to highlight the details of the integration of several types of biomaterials used in association with AD-MSCs, collecting notorious and basic data of in vitro and in vivo assays, taking into account the relevance of the interference of the cell lineage origin and handling cell line protocols for both the replacement and repairing of damaged tissues or organs in clinical application. Our group analyzed the quality and results of the 98 articles selected from PubMed, Scopus and Web of Science. A total of 97% of the articles retrieved demonstrated the potential in clinical applications. The synthetic polymers were the most used biomaterials associated with AD-MSCs and almost half of the selected articles were applied on bone regeneration.
  • 666
  • 22 Sep 2021
Topic Review
Post-Translational Control of Protein Expression
Proteins are fundamental biomolecules of living cells, and their expression levels depend on the balance between the synthesis and degradation. The genetic manipulation of the target protein using CRISPR/Cas9, Cre/loxP, tetracyclin system, and RNA interference, are widely used for the regulation of proteins at the DNA, transcriptional, or mRNA level. Recently, researchers have developed various types of molecular tools for the regulation of protein expression at the post-translational level, which rely on harnessing cellular proteolytic machinery including ubiquitin–proteasome pathway, autophagy-lysosome pathway, and endocytosis. The post-translational control of protein expression using small molecules, antibodies, and light can offer significant advantages regarding speed, tunability, and reversibility. These technologies are expected to be applied to pharmacotherapy and cell therapy, as well as research tools for fundamental biological studies.
  • 666
  • 23 Sep 2021
Topic Review
Curved Lipid Membranes
Eukaryotic cells contain membranes with various curvatures, from the near-plane plasma membrane to the highly curved membranes of organelles, vesicles, and membrane protrusions. These curvatures are generated and sustained by curvature-inducing proteins, peptides, and lipids, and describing these mechanisms is an important scientific challenge. In addition to that, some molecules can sense membrane curvature and thereby be trafficked to specific locations. 
  • 666
  • 08 Aug 2022
Topic Review
Phytochemicals in Redox Homeostasis
Redox homeostasis, a dynamic process ensuring a balance between cellular oxidizing and reducing reactions, is crucial for maintaining healthy cellular physiology and regulating many biological processes, requiring continuous monitoring and fine-tuning. Reactive species play a critical role in intra/intercellular signaling, and each cell has a specific system guarding cellular redox homeostasis. Reactive oxygen species (ROS) signaling and oxidative stress are involved in cancer initiation and progression.
  • 666
  • 24 Apr 2023
Topic Review
HVCN1 Channels Related Sperm Motility
In mammals, sperm capacitation is characterized by a set of physiological changes preparing the male gamete for fertilization, being the intracellular alkalinization a key event. Changes in intracellular pH (pHi) during capacitation are induced by different channels, including HCO3- membrane transporters, Na+-H+ exchangers (NHEs), monocarboxylate transporters (MCTs) and voltage-gated proton channels (HVCN1). HVCN1 channels belong to the superfamily of voltage-gated cation channels; they drive protons more quickly and efficiently than transporters or exchangers do and lead them unidirectionally to the extracellular medium. HVCN1 channels have been identified in human, bull and boar sperm, forming dimers of a molecular weight of 70-73 kDa; however, their action and regulation mechanisms are poorly understood.A recent study has focused on the physiological role of HVCN1 channels during in vitro capacitation using the pig sperm as a model. This functional approach was carried out pharmacologically through using 2-guanidino benzimidazole (2-GBI), a specific blocker of HVCN1 channels. Sperm samples were incubated in in vitro capacitating medium for 300 min; after 240 min of incubation, progesterone was added to induce sperm hyperactivation and acrosomal exocytosis. To address the physiological role of HVCN1 channels during in vitro capacitation of pig sperm, some samples were incubated in the presence of 2-GBI blocker added at time 0 (Experiment 1). Moreover, and in order to understand the functional relationship between progesterone and HVCN1 channels, 2-GBI blocker was added together with progesterone at 240 min of incubation, in a second group of samples (Experiment 2). Sperm viability, sperm motility and kinematics, acrosomal exocytosis, membrane lipid disorder, intracellular calcium levels of the sperm head and tail, and mitochondrial membrane potential were evaluated after 0, 60, 120, 180, 240, 250, 270 and 300 min of incubation.The results obtained showed that HVCN1 channels are essential for the maintenance of viability, motility and kinematics of pig sperm during in vitro capacitation and progesterone-induced acrosomal exocytosis. While a close relationship between HVCN1 activation and mitochondrial membrane potential was observed, HVCN1 channels were not found to be involved in the regulation of Ca2+ influx to the sperm tail. Despite further research being necessary, HVCN1 activation could also modulate Ca2+ entrance to the sperm head and prevent premature acrosomal exocytosis during in vitro capacitation of pig sperm.
  • 665
  • 30 Oct 2020
Topic Review
Curcumin as an Antimycobacterial Agent
Curcumin is the principal curcuminoid obtained from the plant Curcuma longa and has been extensively studied for its biological and chemical properties. Curcumin displays a vast range of pharmacological properties, including antimicrobial, anti-inflammatory, antioxidant, and antitumor activity. Specifically, curcumin has been linked to the improvement of the outcome of tuberculosis. There are many reviews on the pharmacological effects of curcumin; however, reviews of the antitubercular activity are comparatively scarcer. 
  • 664
  • 10 Sep 2021
Topic Review
Gap Junctions in Atrial Fibrillation
Atrial fibrillation (AF) represents the most common type of clinical cardiac arrhythmia worldwide and contributes to substantial morbidity, mortality and socioeconomic burden. Aggregating evidence highlights the strong genetic basis of AF. In addition to chromosomal abnormalities, pathogenic mutations in over 50 genes have been causally linked to AF, of which the majority encode ion channels, cardiac structural proteins, transcription factors and gap junction channels. In the heart, gap junctions comprised of connexins (Cxs) form intercellular pathways responsible for electrical coupling and rapid coordinated action potential propagation between adjacent cardiomyocytes. Among the 21 isoforms of connexins already identified in the mammal genomes, 5 isoforms (Cx37, Cx40, Cx43, Cx45 and Cx46) are expressed in human heart. Abnormal electrical coupling between cardiomyocytes caused by structural remodeling of gap junction channels (alterations in connexin distribution and protein levels) has been associated with enhanced susceptibility to AF and recent studies have revealed multiple causative mutations or polymorphisms in 4 isoforms of connexins predisposing to AF.
  • 664
  • 11 Apr 2022
Topic Review
Gap junctions (GJ)
Gap junctions (GJ) are specialized cell-cell contacts formed by connexins (Cx), which provide direct communication between adjacent cells, allowing for the passage of small molecules and ions. GJ intercellular communication can be modulated through gating of the channel pore and also through mechanisms that regulate the amount of connexin-containing channels at the plasma membrane
  • 663
  • 30 Oct 2020
Topic Review
LRRFIP1 is a DAPK1 Interactor
Death-associated protein kinase 1 (DAPK1) is a pleiotropic hub of a number of networked distributed intracellular processes. Among them, DAPK1 is known to interact with the excitotoxicity driver NMDA receptor (NMDAR), and in sudden pathophysiological conditions of the brain, e.g., stroke, several lines of evidence link DAPK1 with the transduction of glutamate-induced events that determine neuronal fate. In turn, DAPK1 expression and activity are known to be affected by the redox status of the cell. To delineate specific and differential neuronal DAPK1 interactors in stroke-like conditions in vitro, we exposed primary cultures of rat cortical neurons to oxygen/glucose deprivation (OGD), a condition that increases reactive oxygen species (ROS) and lipid peroxides. OGD or control samples were co-immunoprecipitated separately, trypsin-digested, and proteins in the interactome identified by high-resolution LC-MS/MS. Data were processed and curated using bioinformatics tools. OGD increased total DAPK1 protein levels, cleavage into shorter isoforms, and dephosphorylation to render the active DAPK1 form. The DAPK1 interactome comprises some 600 proteins, mostly involving binding, catalytic and structural molecular functions. OGD up-regulated 190 and down-regulated 192 candidate DAPK1-interacting proteins. Some differentially up-regulated interactors related to NMDAR and specially the interaction of DAPK1 with the protein leucine-rich repeat of flightless interacting protein 1 (LRRFIP1), that we observed upregulated during OGD and ferroptosis , were validated by WB.
  • 663
  • 04 Dec 2020
Topic Review
Taxol®
Taxol®, which is also known as paclitaxel, is a chemotherapeutic agent widely used to treat different cancers. Since the discovery of its antitumoral activity, Taxol® has been used to treat over one million patients, making it one of the most widely employed antitumoral drugs.
  • 663
  • 13 Jan 2021
Topic Review
JAK/STAT in Bone Development
The Janus kinase (JAK) signal transducer and activator of transcription (STAT) signaling pathway serves as an important downstream mediator for a variety of cytokines, hormones, and growth factors. Based on the knowledge gained from JAK and STAT knockout animals, the JAK/STAT signaling pathway was identified as important for bone development and homeostasis, recognizing that JAKs and STATs are not equally important for the biology of osteoblasts and osteoclasts. Moreover, their overall role in the musculoskeletal system is still not fully understood. Understanding the underlying mechanisms of how bone remodeling is regulated, how metabolic processes take place, and how bone responds to mechanical stimulation is central to maintaining the integrity of the skeletal system.
  • 663
  • 14 Jan 2021
Topic Review
NADPH Oxidase in Glaucoma
Glaucoma is a heterogeneous group of disorders unified by loss of retinal ganglion cells (RGCs) and their axons, resulting in a characteristic phenotype consisting of an excavated optic nerve head with corresponding visual field defects. The pathogenesis of glaucoma is incompletely understood with multiple pathophysiological factors and pathways postulated to be causative, such as mechanical, vascular, and immunological factors, leading to the final result of apoptotic death of RGCs. Increasingly it is becoming apparent that these factors do not contribute to glaucoma independently, but rather they can be viewed as a continuum in which each factor contributes to the damage of retinal ganglion cell axons.
  • 663
  • 22 Sep 2021
Topic Review
Vimentin-Binding Aptamer Motifs for Ovarian Cancer
The application of aptamers in biomedicine is emerging as an essential technology in the field of cancer research. As small single-stranded DNA or RNA ligands with high specificity and low immunogenicity for their targets, aptamers provide many advantages in cancer therapeutics over protein-based molecules, such as antibodies. Vimentin is an intermediate filament protein that is overexpressed in endothelial cells of cancerous tissue. High expression levels of vimentin have been associated with increased capacity for migration and invasion of the tumor cells. We have selected and identified thioated aptamers with high specificity for vimentin using human ovarian cancer tissues. Tentative binding motifs were chosen for two vimentin aptamers based on predicted secondary structures. Each of these shorter, tentative binding motifs was synthesized, purified, and characterized via cell binding assays. Two vimentin binding motifs with high fidelity binding were selected and further characterized via cell and tissue binding assays, as well as flow cytometric analysis. The equilibrium binding constants of these small thioated aptamer constructs were also determined. Future applications for the vimentin binding aptamer motifs include conjugation of the aptamers to synthetic dyes for use in targeted imaging and therapy, and ultimately more detailed and precise monitoring of treatment response and tumor progression in ovarian pathology. 
  • 663
  • 11 Nov 2021
Topic Review
Links between Epigenetics, COVID-19 Infection, and Vitamin D
The highly transmittable and infectious COVID-19 remains a major threat worldwide, with the elderly and comorbid individuals being the most vulnerable. While vaccines are currently available, therapeutic drugs will help ease the viral outbreak and prevent serious health outcomes. Epigenetic modifications regulate gene expression through changes in chromatin structure and have been linked to viral pathophysiology. Since epigenetic modifications contribute to the life cycle of the virus and host immune responses to infection, epigenetic drugs are promising treatment targets to ameliorate COVID-19. Deficiency of the multifunctional secosteroid hormone vitamin D is a global health threat. Vitamin D and its receptor function to regulate genes involved in immunity, apoptosis, proliferation, differentiation, and inflammation. Amassed evidence also indicates the biological relations of vitamin D with reduced disease risk, while its receptor can be modulated by epigenetic mechanisms. The immunomodulatory effects of vitamin D suggest a role for vitamin D as a COVID-19 therapeutic agent.
  • 663
  • 23 Nov 2022
Topic Review
Extracellular Vesicles Based Drug Delivery
Extracellular vesicles (EVs) play major roles in intracellular communication and participate in several biological functions in both normal and pathological conditions. Surface modification of EVs via various ligands, such as proteins, peptides, or aptamers, offers great potential as a means to achieve targeted delivery of therapeutic cargo, i.e., in drug delivery systems (DDS). This study summarizes recent studies pertaining to the development of EV-based DDS and its advantages compared to conventional nano drug delivery systems (NDDS). 
  • 663
  • 30 Mar 2021
Topic Review
Nuclear P38
One of the hallmarks of MAPK signaling is the nuclear translocation of some of its components upon stimulation. This is important for the regulation of transcription, activation of enzymes and stabilisation of proteins that lead to the induced  processes involved in the response to the particular stimulation or pathologies. Here we describe the nuclear function regulation and mechanism of translocation of two central MAPKs, namely P38α/β that are involved in the regulation of a variety of processes including mainly stress response. 
  • 662
  • 26 Oct 2020
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