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Topic Review
Oxidative Stress in Pulmonary Hypertension
Pulmonary hypertension (PH) is a progressive disease characterized by elevated artery pressures and pulmonary vascular resistance. Underlying mechanisms comprise endothelial dysfunction, pulmonary artery remodeling and vasoconstriction. Several studies have shown evidence of the critical role of oxidative stress in PH pathophysiology. Alteration of redox homeostasis produces excessive generation of reactive oxygen species, inducing oxidative stress and the subsequent alteration of biological molecules. Exacerbations in oxidative stress production can lead to alterations in nitric oxide signaling pathways, contributing to the proliferation of pulmonary arterial endothelial cells and smooth muscle cells, inducing PH development. 
  • 1.1K
  • 12 May 2023
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
Posttranscriptional Defects of Selenoenzymes
Methylmercury (MeHg) is a well-known neurotoxicant that causes severe intoxication in humans. Research progress has pointed out the importance of oxidative stress in the pathogenesis of MeHg toxicity. MeHg-induced intracellular relative selenium deficiency due to the greater affinity of MeHg for selenohydryl groups and selenides leads to failure in the recoding of a UGA codon for selenocysteine and results in the degradation of antioxidant selenoenzyme mRNA by nonsense-mediated mRNA decay. The defect of antioxidant selenoenzyme replenishment exacerbates MeHg-mediated oxidative stress. 
  • 1.1K
  • 09 Nov 2020
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.
  • 1.1K
  • 14 Jan 2021
Topic Review
Intersection of AhR and Wnt Signaling
This entry is focused on recent studies about the mutual interactions of key mediators of AhR and Wnt/β-catenin signaling pathways and on the assessment of the complexity of the crosstalk between the AhR signaling cascade and the canonical Wnt pathway. AhR performs many endogenous functions by integrating its signaling pathway into organ homeostasis and into the maintenance of crucial cellular functions and biological processes. The Wnt signaling pathway regulates cell proliferation, differentiation, and many other phenomena, and this regulation is important for embryonic development and the dynamic balance of adult tissues. AhR and Wnt are the main signaling pathways participating in the control of cell fate and function and occupy a central position in a variety of processes linked with development and various pathological conditions. 
  • 1.1K
  • 22 May 2023
Topic Review
Chemical Changes in Atherosclerosis
Fiberoptic Raman spectroscopy and Raman microscopy were used to investigate alterations in the aorta wall and the surrounding perivascular adipose tissue (PVAT) in the murine model of atherosclerosis (Apoe-/-/Ldlr-/- mice). Both abdominal and thoracic parts of the aorta were studied to account for the heterogenic chemical composition of aorta and its localization-dependent response in progression of atherosclerosis. The average Raman spectra obtained for both parts of aorta cross sections revealed that the chemical composition of intima-media layers along aorta remains relatively homogeneous while the lipid content in the adventitia layer markedly increases with decreasing distance to PVAT. Moreover, our results demonstrate that the increase of the lipid to protein ratio in the aorta wall correlates directly with the increased unsaturation level of lipids in PVAT and these changes occur only in the abdominal, but not in thoracic, aorta. In summary, distinct pathophysiological response in the aortic vascular wall could be uncovered by fiber optic Raman spectroscopy based on simple parameters detecting chemical contents of lipids in PVAT.
  • 1.1K
  • 21 Jul 2020
Topic Review
HMGB1 in Chemotherapy-Induced Peripheral Neuropathy
Chemotherapy-induced peripheral neuropathy (CIPN), one of major dose-limiting side effects of first-line chemotherapeutic agents such as paclitaxel, oxaliplatin, vincristine, and bortezomib is resistant to most of existing medicines.
  • 1.1K
  • 15 Apr 2021
Topic Review
Transcriptomic Harmonization
Emergence of methods interrogating gene expression at high throughput gave birth to quantitative transcriptomics, but also posed a question of inter-comparison of expression profiles obtained using different equipment and protocols and/or in different series of experiments. Addressing this issue is challenging, because all of the above variables can dramatically influence gene expression signals and, therefore, cause a plethora of peculiar features in the transcriptomic profiles. Millions of transcriptomic profiles were obtained and deposited in public databases of which the usefulness is however strongly limited due to the inter-comparison issues. Platform/protocol/batch bias can be efficiently reduced not only for the comparisons of limited transcriptomic datasets. Instead, instruments were proposed for transforming gene expression profiles into the universal, uniformly shaped format that can support multiple inter-comparisons for reasonable calculation costs. This forms a basement for universal indexing of all or most of all types of RNA sequencing and microarray hybridization profiles.
  • 1.1K
  • 02 Dec 2022
Topic Review
Active Transport and Solute Transporters
A phospholipid membrane covers all living cells, forming an impenetrable barrier circumvented by solute transporters in the cell membrane. These proteins comprise energy-requiring systems, called active transporters, and those not requiring energy, called passive transporters. The major facilitator superfamily harbors thousands of transport proteins found in all living organisms, from bacteria to humans. Alignments of multiple amino acid sequences uncovered highly conserved sequence motifs are known to play important functional roles. One of these conserved sequences, the antiporter sequence motif or motif C, participates in the molecular mechanism of antimicrobial efflux in cancer cells and bacterial pathogens.
  • 1.1K
  • 03 Nov 2023
Topic Review
Bone Healing
Main methods of biophysical enhancement in treating bone nonunions.
  • 1.1K
  • 23 Feb 2021
Topic Review
Archaeal DNA Repair
DNA repair is essential across all organisms to maintain levels genomic stability suitable for life. Archaea often thrive in environmental extremes, enduring levels of heat, pressure, salinity, pH, and radiation that prove intolerable to most life. Many environmental extremes raise the propensity for DNA damaging events and thus, impact DNA stability, placing greater reliance on molecular mechanisms that recognize DNA damage and initiate accurate repair. Archaea can presumably prosper in harsh and DNA-damaging environments in part due to robust DNA repair pathways but surprisingly, no DNA repair pathways unique to Archaea have been described.
  • 1.1K
  • 16 Nov 2020
Topic Review
Oxidative Stress in Sepsis
Sepsis is the leading cause of acute kidney injury (AKI) and leads to increased morbidity and mortality in intensive care units. Current treatments for septic AKI are largely supportive and are not targeted towards its pathophysiology. Sepsis is commonly characterized by systemic inflammation and increased production of reactive oxygen species (ROS), particularly superoxide. Concomitantly released nitric oxide (NO) then reacts with superoxide, leading to the formation of reactive nitrogen species (RNS), predominantly peroxynitrite. Sepsis-induced ROS and RNS can reduce the bioavailability of NO, mediating renal microcirculatory abnormalities, localized tissue hypoxia and mitochondrial dysfunction, thereby initiating a propagating cycle of cellular injury culminating in AKI. 
  • 1.1K
  • 11 Oct 2021
Topic Review
Dnmt3a2/Dnmt3L
This study investigates how DNA methylation regulates motor behavior in single neuron type resolution. This topic is important for understanding that the behaviors like hyperactivity in relevant diseases are also regulated by epigenetic factors. Although accumulative researches have demonstrated that epigenetic factor is a potential regulator for brain function, the specific role of these factors in certain type of neurons is still unclear, especially in motor neurons, has not been studied. We aim to examine if the DNA methylation level of neurons are regulated by DNA methyltransferase and how is the consequence in locomotion. The study generated a transgenic mouse model with overexpression of Dnmt3a2 and Dnmt3L, the DNA methyltransferase and its partner, in dopaminergic neurons which controls locomotor function. We found that the DNA methylation level was up-regulated in neurons with overexpression, and the spontaneous activity and exercise performance of the mice were increased significantly. Furthermore, the higher fire frequency and excitability of dopaminergic neuron were detected without dopaminergic biosynthesis change.
  • 1.1K
  • 26 Oct 2020
Topic Review
Ion Channels Involved in Oxidative Stress-Related Gastrointestinal Diseases
Ion channels (ICs) are integral membrane proteins that play a crucial role in regulating the ions’ flow across cell membranes. They are essential for maintaining cellular homeostasis and are involved in various physiological processes. The pathogenesis of various gastrointestinal (GI) disorders, including gastritis, ulcers, inflammatory bowel disease (IBD) and cancer, can be linked to oxidative stress. It is known that reactive species carry out a crucial role in the genesis and progression of these pathologies; however, the contribution of ionic channels in their development is still under discussion. The function of ion channels in the gastrointestinal tract influences a variety of cellular processes.
  • 1.1K
  • 31 Aug 2023
Topic Review
Protein Lipoxidation
Protein lipoxidation is a non-enzymatic post-translational modification that consists of the covalent addition of reactive lipid species to proteins. This occurs under basal conditions but increases in situations associated with oxidative stress. Protein targets for lipoxidation include metabolic and signalling enzymes, cytoskeletal proteins, and transcription factors, among others. There is strong evidence for the involvement of protein lipoxidation in disease, including atherosclerosis, neurodegeneration, and cancer. Nevertheless, the involvement of lipoxidation in cellular regulatory mechanisms is less understood. Moreover, given the great structural variety of electrophilic lipid species, protein lipoxidation can contribute to the generation of multiple structurally and functionally diverse protein species. Finally, the nature of the lipoxidised proteins and residues provides a frameshift for a complex interplay with other post-translational modifications, including redox and redox-regulated modifications, such as oxidative modifications and phosphorylation.
  • 1.1K
  • 08 Apr 2021
Topic Review
NGF Peptides Bind Copper(II)
Nerve growth factor (NGF) is a protein essential to neurons survival, which interacts with its receptor as a non-covalent dimer. Copper affects biological activity of NGF and conversely NGF may regulates copper trafficking in synaptic cleft.
  • 1.1K
  • 10 Jun 2021
Topic Review
Voltage-Dependent Anion Selective Channel
VDAC (voltage-dependent anion selective channel) proteins, also known as mitochondrial porins, are the most abundant proteins of the outer mitochondrial membrane (OMM) where they play a vital role in various cellular processes, in the regulation of metabolism, and in survival pathways.
  • 1.1K
  • 19 Apr 2022
Topic Review
MicroRNA Modulation
The prevalence of obesity has dramatically increased over the last decades. Weight loss obtained through diet and exercise leads to a  significant decrease in morbidity and mortality. Recently, there has been growing interest in the possible beneficial effects of dietary supplements (DSs), including polyphenols, fatty acids, and other plant-derived substances, as adjuvants in the management of obesity and metabolic diseases. Specifically, polyphenols, widely spread in vegetables and fruits, significantly modulate adipose tissue activities,  contrasting inflammation and improving insulin sensitivity in preclinical and clinical studies. Remarkably, polyphenols are involved in complex microRNA networks, which play crucial roles in metabolic processes. The administration of different polyphenols and other plant-derived compounds led to significant changes in the microRNA expression profile in peripheral tissues in a growing number of preclinical studies. In particular, these compounds were able to revert obesity-induced microRNA dysregulation, leading to the inhibition of adipogenesis and the induction of weight loss. Furthermore, through microRNA modulation, they attenuated key metabolic alterations, including insulin resistance and lipid anomalies, in animal models of obesity. Some of them were also able to reduce proinflammatory cytokines in adipose tissue. The aim of this review is to summarize current evidence about the effect of plant-derived DSs on microRNA expression in obesity.
  • 1.1K
  • 29 Jan 2021
Topic Review
Chloride Channels and Transporters in Cancers
The canonical roles of chloride channels and chloride-associated transporters have been physiologically determined; these roles include the maintenance of membrane potential, pH balance, and volume regulation and subsequent cellular functions such as autophagy and cellular proliferative processes. Although complicated ion movements, crosstalk among channels/transporters through homeostatic electric regulation, difficulties with experimental implementation such as activity measurement of intracellular location were disturbed to verify the precise modulation of channels/transporters, recently defined cancerous function and communication with tumor microenvironment of chloride channels/transporters should be highlighted beyond classical homeostatic ion balance.
  • 1.1K
  • 21 Feb 2022
Topic Review
Lysophosphatidic Acid and Cancer
Lysophosphatidic acid (LPA) is a bioactive lipid mediator primarily derived from membrane phospholipids. LPA initiates cellular effects upon binding to a family of G protein-coupled receptors, termed LPA receptors (LPAR1 to LPAR6). LPA signaling drives cell migration and proliferation, cytokine production, thrombosis, fibrosis, angiogenesis, and lymphangiogenesis.
  • 1.1K
  • 14 Jul 2021
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