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Topic Review
ADAM Proteases
Limited proteolysis reactions by a disintegrin and metalloproteases (ADAMs) are key events in several paracrine signalling pathways. Therefore, ADAM proteases might also represent master-switches during hepatic fibrosis and other pathophysiologic events. Known and potential fibrosis-associated pathways regulated by ADAM proteases are discussed and the current knowledge on ADAM protease implication in several disease states is reviewed.
  • 1.1K
  • 13 Jul 2023
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
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
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
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
Bone Healing
Main methods of biophysical enhancement in treating bone nonunions.
  • 1.1K
  • 23 Feb 2021
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
Pharmacotherapeutic Approaches to Treatment of Muscular Dystrophies
Muscular dystrophies are a heterogeneous group of genetic muscle-wasting disorders that are subdivided based on the region of the body impacted by muscle weakness as well as the functional activity of the underlying genetic mutations. A common feature of the pathophysiology of muscular dystrophies is chronic inflammation associated with the replacement of muscle mass with fibrotic scarring. With the progression of these disorders, many patients suffer cardiomyopathies with fibrosis of the cardiac tissue. Anti-inflammatory glucocorticoids represent the standard of care for Duchenne muscular dystrophy, the most common muscular dystrophy worldwide; however, long-term exposure to glucocorticoids results in highly adverse side effects, limiting their use. Thus, it is important to develop new pharmacotherapeutic approaches to limit inflammation and fibrosis to reduce muscle damage and promote repair.
  • 1.1K
  • 18 Dec 2023
Topic Review
Role of TRPA1 and TRPV1
TRPA1 and TRPV1 are structurally related thermosensitive cation channels and are often co-expressed in sensory nerve endings. TRPA1 and TRPV1 can also indirectly influence some, but not all, primary taste qualities via the release of substance P and calcitonin gene-related peptide (CGRP) from trigeminal neurons and their subsequent effects on CGRP receptor expressed in Type III taste receptor cells. Here, we will review the effect of some chemesthetic agonists of TRPA1 and TRPV1 and their influence on bitter, sour, and salt taste qualities.
  • 1.1K
  • 13 Apr 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
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
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
Epigenetic Changes and Chromatin Reorganization in Brain Function
Healthy brain functioning in mammals requires a continuous fine-tuning of gene expression. Accumulating evidence over the past demonstrates that epigenetic mechanisms and dynamic changes in chromatin organization are critical components during the control of gene transcription in neural cells. Genome-wide analyses show that the regulation of brain genes requires the contribution of both promoter and long-distance enhancer elements, which must functionally interact to upregulate gene expression in response to physiological cues. Hence, a deep comprehension of the mechanisms mediating these enhancer–promoter interactions (EPIs) is critical if people are to understand the processes associated with learning, memory and recall. Moreover, the onset and progression of several neurodegenerative diseases and neurological alterations are found to be strongly associated with changes in the components that support and/or modulate the dynamics of these EPIs. 
  • 1.1K
  • 28 Oct 2022
Topic Review
Multienzymatic Processes Involving Baeyer–Villiger Monooxygenases
Baeyer–Villiger monooxygenases (BVMOs) are flavin-dependent oxidative enzymes capable of catalyzing the insertion of an oxygen atom between a carbonylic Csp2 and the Csp3 at the alpha position, therefore transforming linear and cyclic ketones into esters and lactones. These enzymes are dependent on nicotinamides (NAD(P)H) for the flavin reduction and subsequent reaction with molecular oxygen. BVMOs can be included in cascade reactions, coupled to other redox enzymes, such as alcohol dehydrogenases (ADHs) or ene-reductases (EREDs), so that the direct conversion of alcohols or α,β-unsaturated carbonylic compounds to the corresponding esters can be achieved. 
  • 1.1K
  • 11 May 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
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
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
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
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
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