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Topic Review
Arterial Hypertension and Tension-Type Headache
Arterial hypertension (AH) is a prevalent condition worldwide and is the key risk factor for non-fatal and fatal cardiovascular complications. Tension-type headache (TTH) is the most common type of primary headache and is considered a common everyday headache.
  • 796
  • 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.
  • 795
  • 26 Oct 2020
Topic Review
Hedgehog Signaling for Basal Cell Carcinoma
Basal Cell Carcinoma (BCC) is the most commonly diagnosed cancer worldwide. While the survivability of BCC is high, many patients are excluded from clinically available treatments due to health risks or personal choice. Further, patients with advanced or metastatic disease have severely limited treatment options. The dysregulation of the Hedgehog (Hh) signaling cascade drives onset and progression of BCC. As such, the modulation of this pathway has driven advancements in BCC research.
  • 795
  • 23 Nov 2022
Topic Review
Chelating Ability of Plant Polyphenols
Many studies have widely examined the effects of dietary polyphenols on human health. Polyphenols are well known for their antioxidant properties and for their chelating abilities, by which they can be potentially employed in cases of pathological conditions, such as iron overload. The iron-binding abilities of dietary polyphenols can be important in inflammatory/immunomodulatory responses, especially involving macrophages and dendritic cells, and they also might contribute to reshape the gut microbiota into a healthy profile. As the axes “polyphenol–iron metabolism–inflammatory responses” and “polyphenol–iron availability–gut microbiota” have not been very well explored so far, there is the need for further investigation to exploit such a potential to prevent or counteract pathological conditions.
  • 795
  • 16 Mar 2023
Topic Review
Irisin and Autophagy: First Update
Aging and sedentary life style are considered independent risk factors for many disorders. Under these conditions, accumulation of dysfunctional and damaged cellular proteins and organelles occurs, resulting in a cellular degeneration and cell death. Autophagy is a conserved recycling pathway responsible for the degradation, then turnover of cellular proteins and organelles. This process is a part of the molecular underpinnings by which exercise promotes healthy aging and mitigate age-related pathologies. Irisin is a myokine released during physical activity and acts as a link between muscles and other tissues and organs. Its main beneficial function is the change of subcutaneous and visceral adipose tissue into brown adipose tissue, with a consequential increase in thermogenesis. Irisin modulates metabolic processes, acting on glucose homeostasis, reduces systemic inflammation, maintains the balance between resorption and bone formation, and regulates the functioning of the nervous system. Recently, some of its pleiotropic and favorable properties have been attributed to autophagy induction, posing irisin as an important regulator of autophagy by exercise.
  • 794
  • 29 Oct 2020
Topic Review
Cancer Chemoprevention
Carcinogenesis is a multistep process characterized by a progression of molecular changes that ultimately transform a cell to undergo uncontrolled proliferation.
  • 794
  • 02 Apr 2021
Topic Review
Desmin Intermediate Filaments
Desmin intermediate filaments (IFs) is one of cytoskeleton components of muscle cells and play an important role in maintaining their structural and functional integrity .Disturbance of their network due to desmin mutations or deficiency leads to an infringement of myofibril organization and to a deterioration of mitochondrial distribution, morphology, and functions. The nature of the interaction of desmin IFs with mitochondria is not clear. To elucidate the possibility that desmin can directly bind to mitochondria, we have undertaken the study of their interaction in vitro. Using desmin mutant Des(Y122L) that forms unit-length filaments (ULFs) but is incapable of forming long filaments and, therefore, could be effectively separated from mitochondria by centrifugation through sucrose gradient, we probed the interaction of recombinant human desmin with mitochondria isolated from rat liver. Our data show that desmin can directly bind to mitochondria, and this binding depends on its N-terminal domain. We have found that mitochondrial cysteine protease can disrupt this interaction by cleavage of desmin at its N-terminus.
  • 793
  • 04 Nov 2020
Topic Review
Resveratrol in Human Male Fertility
Resveratrol (RSV) (3,4′,5 trihydroxystilbene) is a natural, non-flavonoid polyphenol widely present in the Mediterranean diet and, particularly, in grapes, peanuts, berries, and red wine.
  • 793
  • 13 May 2021
Topic Review
Glyphosate Pollution Treatment
Glyphosate (N-Phosphonomethyl-glycine) is a broad-spectrum herbicide extensively used worldwide to eliminate weeds in agricultural areas, control vegetation in urban areas, and accelerate the harvest of several crops. Recently was classified as a potentially carcinogenic compound, due to this several countries banned or are in the process of banning its use.
  • 793
  • 24 Nov 2021
Topic Review
Targeting CDK4/6 for Anticancer Therapy
Cyclin-dependent kinase 4/6 (CDK4/6) are key regulators of the cell cycle and are deemed as critical therapeutic targets of multiple cancers. Various approaches have been applied to silence CDK4/6 at different levels, i.e., CRISPR to knock out at the DNA level, siRNA to inhibit translation, and drugs that target the protein of interest. Here we summarize the current status in this field, highlighting the mechanisms of small molecular inhibitors treatment and drug resistance.
  • 793
  • 12 Apr 2022
Topic Review
Relationship between D-Amino Acids and Schizophrenia
D-amino acids may play key roles for specific physiological functions in different organs including the brain. Importantly, D-amino acids have been detected in several neurological disorders such as schizophrenia, amyotrophic lateral sclerosis, and age-related disorders, reflecting the disease conditions. Relationships between D-amino acids and neurophysiology may involve the significant contribution of D-Serine or D-Aspartate to the synaptic function, including neurotransmission and synaptic plasticity. Gut-microbiota could play important roles in the brain-function, since bacteria in the gut provide a significant contribution to the host pool of D-amino acids. In addition, the alteration of the composition of the gut microbiota might lead to schizophrenia. Furthermore, D-amino acids are known as a physiologically active substance, constituting useful biomarkers of several brain disorders including schizophrenia.
  • 793
  • 17 May 2022
Topic Review
Deubiquitinases in Breast Cancer
Deubiquitinase (DUB) is an essential component in the ubiquitin-proteasome system (UPS) by removing ubiquitin chains from substrates, thus modulating the expression, activity, and localization of many proteins that contribute to tumor development and progression. DUBs have emerged as promising prognostic indicators and drug targets. DUBs have shown significant roles in regulating breast cancer growth, metastasis, resistance to current therapies, and several canonical oncogenic signaling pathways. In addition, specific DUB inhibitors have been identified and are expected to benefit breast cancer patients in the future. 
  • 793
  • 09 Nov 2021
Topic Review
Extracellular Vesicles Cargo and Roles
Extracellular vesicles (EVs) are membranous structures produced in the endosomal system or generated by plasma membrane shedding, which have been identified as an important hallmark for intercellular communication. Among them, a particular category of EVs are the exosomes, which are nanovesicles of approximately 30-150 nm, produced in the endosomal pathway. 
  • 793
  • 27 Nov 2020
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. 
  • 792
  • 30 Oct 2020
Topic Review
Structure of the MRN Complex
The MRE11, RAD50, and NBN genes encode for the nuclear MRN protein complex, which senses the DNA double strand breaks and initiates the DNA repair. The MRN complex also participates in the activation of ATM kinase, which coordinates DNA repair with the p53-dependent cell cycle checkpoint arrest. Carriers of homozygous germline pathogenic variants in the MRN complex genes or compound heterozygotes develop phenotypically distinct rare autosomal recessive syndromes characterized by chromosomal instability and neurological symptoms. 
  • 792
  • 06 Apr 2023
Topic Review
Coenzyme Q10 Analogues
Coenzyme Q10 (CoQ10 or ubiquinone) is a mobile proton and electron carrier of the mitochondrial respiratory chain with antioxidant properties widely used as an antiaging health supplement and to relieve the symptoms of many pathological conditions associated with mitochondrial dysfunction. Even though the hegemony of CoQ10 in the context of antioxidant-based treatments is undeniable, the future primacy of this quinone is hindered by the promising features of its numerous analogues. Despite the unimpeachable performance of CoQ10 therapies, problems associated with their administration and intraorganismal delivery has led clinicians and scientists to search for alternative derivative molecules. Over the past few years, a wide variety of CoQ10 analogues with improved properties have been developed. These analogues conserve the antioxidant features of CoQ10 but present upgraded characteristics such as water solubility or enhanced mitochondrial accumulation.
  • 792
  • 16 Apr 2021
Topic Review
The Bile Salt Export Pump
The bile salt export pump (BSEP/ABCB11) is responsible for the transport of bile salts from hepatocytes into bile canaliculi. Malfunction of this transporter results in progressive familial intrahepatic cholestasis type 2 (PFIC2), benign recurrent intrahepatic cholestasis type 2 (BRIC2) and intrahepatic cholestasis of pregnancy (ICP). 
  • 791
  • 10 Feb 2021
Topic Review
Cell-Penetrating Peptides
Cell-penetrating peptides (CPPs) comprise a class of short polypeptides that possess the ability to selectively interact with the cytoplasmic membrane of certain cell types, translocate across plasma membranes and accumulate in the cell cytoplasm, organelles (e.g., the nucleus and mitochondria), and other subcellular compartments. CPPs are either of natural origin or de novo designed and synthesized from segments and patches of larger proteins or designed by algorithms. With such intrinsic characteristics, along with membrane permeation, translocation, and cellular uptake properties, CPPs can intracellularly convey diverse substances and nanomaterials, such as hydrophilic organic compounds and drugs, macromolecules (nucleic acids and proteins), nanoparticles (nanocrystals and polyplexes), metals and radionuclides, which can be covalently attached via CPP N- and C-terminals or through the preparation of CPP complexes. A cumulative number of studies on animal toxins, primarily isolated from the venom of arthropods and snakes, have revealed the cell-penetrating activities of venom peptides and toxins, which can be harnessed for application in biomedicine and pharmaceutical biotechnology.
  • 791
  • 12 Mar 2021
Topic Review
TRPM2
The transient receptor potential (TRP) melastatin-like subfamily member 2 (TRPM2) is a non-selective calcium-permeable cation channel. It is expressed by many mammalian tissues, including bone marrow, spleen, lungs, heart, liver, neutrophils, and endothelial cells. The best-known mechanism of TRPM2 activation is related to the binding of ADP-ribose to the nudix-box sequence motif (NUDT9-H) in the C-terminal domain of the channel.
  • 791
  • 01 Sep 2021
Topic Review
Polyphenols (PCs)
Polyphenols, a diverse group of naturally occurring molecules commonly found in higher plants, have been heavily investigated over the last two decades due to their potent biological activities—among which the most important are their antioxidant, antimicrobial, anticancer, anti-inflammatory and neuroprotective activities.
  • 791
  • 27 Jan 2022
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