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Topic Review
MTOR Signaling
The identification of mammalian TOR (mTOR; later renamed mechanistic target of rapamycin) soon followed, revealing that TOR/mTOR, a serine/threonine protein kinase, is a conserved protein kinase from yeast to man
  • 1.3K
  • 31 May 2021
Topic Review
Resveratrol
Resveratrol (3,4′,5-trihy- droxystilbene), a natural phytoalexin polyphenol, exhibits anti-oxidative, anti-inflammatory, and anti-carcinogenic properties. This phytoalexin is well-absorbed， rapidly and extensively metabolized in the body. 
  • 1.3K
  • 30 Sep 2021
Topic Review
Gluten Enteropathy
Gluten enteropathy, namely Celiac disease (CD), is a hereditary predisposed disease, accompanied by the atrophy of the small intestine mucosa, associated malabsorption syndrome, and the development of various deficiency conditions. Celiac disease is caused by food containing gluten—the proteins of cereals that are the diet of the majority of the world population. Some immunogenic peptides of gluten proteins formed during digestion, mainly gliadins from wheat, rye, and barley, are resistant to proteolysis by human digestive peptidases and cause CD in predisposed people.
  • 1.3K
  • 19 Oct 2021
Topic Review
Databases in Metabolomics
Metabolomics has advanced from innovation and functional genomics tools and is currently a basis in the big data-led precision medicine era. Metabolomics is promising in the pharmaceutical field and clinical research.
  • 1.3K
  • 27 Oct 2022
Topic Review
MiR-615
miR-615, a miRNA highly conserved across eutherian mammals. It is involved not only during embryogenesis in the regulation of growth and development, for instance during osteogenesis and angiogenesis, but also in the regulation of cell growth and the proliferation and migration of cells, acting as a tumor suppressor or tumor promoter. It, therefore, serves as a biomarker for several types of cancer and recently has also been found to be involved in reparative processes and neural repair.
  • 1.3K
  • 27 Oct 2020
Topic Review
Heparan Sulfate Proteoglycans in Tauopathy
Tauopathies are a class of neurodegenerative diseases, including Alzheimer’s disease, and are characterized by intraneuronal tau inclusion in the brain and the patient’s cognitive decline with obscure pathogenesis. Heparan sulfate proteoglycans, a major type of extracellular matrix, have been believed to involve in tauopathies. The heparan sulfate proteoglycans co-deposit with tau in Alzheimer’s patient brain, directly bind to tau and modulate tau secretion, internalization, and aggregation.
  • 1.3K
  • 09 Dec 2022
Topic Review
Lysine63Ubiquitination and Fibrosis in Diabetes
Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease. We previously showed that tubulo-interstitial accumulation of lysine 63 (K63)-ubiquitinated (Ub) proteins drives the progression of fibrosis in DN and that the extent of renal K63-Ub can be easily monitored through the assessment of urinary miR-27b-3p. In the present manuscript we explored the renoprotective effect of a specific K63-Ub inhibitor (NSC697923), alone and in combination with the ACE inhibitor molecule Ramipril. In vitro, in tubular epithelial cells, we found that NSC697923, aside from suppressing tubular accumulation of K63-Ub proteins was also capable to inhibit hyperglycemia-induced epithelial to mesenchymal transition (EMT); specifically, treatment with NSC697923 reduced the expression of EMT markers such as α-SMA, Collagen I, Vimentin, FSP-1 and Collagen III along with tubulointerstitial and glomerular fibrosis both in vitro and in vivo. Diabetic DBA/2J mice treated with NSC697923 also displayed recovery of urinary miR-27b-3p and restored expression of p16INK4A, indicating a protective effect of this compund on cellular senescence in tubular cells. Moreover, we found that the combination of NSC697923 and Ramipril was effective to reduce uACR in diabetic DBA/2J mice. In conclusion, we suggest that selective inhibition of K63-Ub, when combined with the conventional treatment with ACE inhibitors, might represent a novel treatment strategy to prevent the progression of fibrosis and proteinuria in DN. Finally we suggest the dosage of urinary miR-27b-3p levels to monitor treatment efficacy.
  • 1.3K
  • 23 Jun 2021
Topic Review
Oxidative Stress in Cancer Cell Metabolism
Reactive oxygen species (ROS) are important in regulating normal cellular processes whereas deregulated ROS leads to the development of a diseased state in humans including cancers. Several studies have been found to be marked with increased ROS production which activates pro-tumorigenic signaling, enhances cell survival and proliferation and drives DNA damage and genetic instability. However, higher ROS levels have been found to promote anti-tumorigenic signaling by initiating oxidative stress-induced tumor cell death. Tumor cells develop a mechanism where they adjust to the high ROS by expressing elevated levels of antioxidant proteins to detoxify them while maintaining pro-tumorigenic signaling and resistance to apoptosis. Therefore, ROS manipulation can be a potential target for cancer therapies as cancer cells present an altered redox balance in comparison to their normal counterparts.
  • 1.3K
  • 11 May 2022
Topic Review
Click Reaction in Chemical Proteomics
Proteomics is a kind of omics which studies the protein composition, distribution and changing rules in cells, tissues or organisms. Essentially, it refers to the macroscale study of protein characteristics, including protein expression level, post-translational modification, small molecule–protein interaction and so on. Research on the proteome cannot only provide the material foundation for the law of the activities of life, but also provides a theoretical foundation and solutions to elucidate and conquer numerous types of mechanisms of illness. Click chemistry was first put forward by K B Sharpless in 2001 which provides a quick and reliable synthesis method for different molecules to offer a range of reactivities, orthogonality and utility in various applications. Click chemistry is characterized by good chemical selectivity, favorable solvent compatibility, diverse modularization, minimum synthesis requirements and high yield, upon which it considerably reduces the effect of sensor incorporation on protein activity and reveals the structure and functionality of proteins.
  • 1.3K
  • 24 Sep 2021
Topic Review
Coenzyme Q
Coenzyme Q (CoQ), ubiquinone or 2,3-dimethoxy-5-methyl-6-polyprenyl-1,4-benzoquinone is a two-part molecule composed of a benzoquinone ring, which has redox active sites, and a long polyisoprenoid lipid chain that positions the molecule in the mid-plane of a membrane bilayer. It is an essential endogenously synthesized molecule that links different metabolic pathways to mitochondrial energy production thanks to its location in the mitochondrial inner membrane and its redox capacity, which also provide it with the capability to work as an antioxidant. 
  • 1.3K
  • 26 Aug 2021
Topic Review
CRISPR/Cas in Research of Telomeres
Telomeres are highly specialized nucleoprotein complexes that play a critical role in cell senescence and aging. Each chromosomal end must be “capped” with a critical amount of telomere repeats to prevent DNA repair pathways from being activated. As a result of the clustered regularly interspaced short palindromic repeats (CRISPR)-associated system’s (Cas) method, targeted genetic studies are now underway to change telomerase, the genes that govern it as well as telomeres.
  • 1.3K
  • 24 Mar 2022
Topic Review
Age-Related Lysosomal Dysfunctions
Aging is a process associated with the detriment of normal physiological functions, which leads to the manifestation of diverse diseases such as cardiovascular and neurodegenerative diseases, joint degenerative diseases, and metabolic diseases such as diabetes, among others. Lysosomes are heterogeneous organelles enclosed by a lipid bilayer and filled with hydrolytic enzymes. The lysosomes are traditionally described as the subcellular structures where the degradation of other organelles and macromolecules takes place, a fundamental process for maintaining cellular proteostasis. There are several degradation processes in which the lysosomes are involved. If the substrate reaching the lysosomes comes from the extracellular environment, the degradation process is called endocytosis. If the material to be digested comes from the cell itself, the process is classified as autophagy. The lysosomes are also involved in plasma membrane repair through a mechanism called lysosomal exocytosis.  During aging, damage in cellular organelles disbalances the cellular homeostatic processes. Lysosomal dysfunction is emerging as an important factor that could regulate the production of inflammatory molecules, metabolic cellular state, or mitochondrial function. Thus, lysosomal alkalinization, amino acid storage, iron disturbances and lipofuscin accummulation are characteristic features of the lysosome during aging. 
  • 1.3K
  • 30 Jul 2022
Topic Review
CRISPR-Cas9 Innovations in Saccharomyces cerevisiae
Saccharomyces cerevisiae has been for a long time a common model for fundamental biological studies and a popular biotechnological engineering platform to produce chemicals, fuels, and pharmaceuticals due to its peculiar characteristics. Both lines of research require an effective editing of the native genetic elements or the inclusion of heterologous pathways into the yeast genome. Although S. cerevisiae is a well-known host with several molecular biology tools available, a more precise tool is still needed. The clustered, regularly interspaced, short palindromic repeats–associated Cas9 (CRISPR-Cas9) system is a current, widespread genome editing tool. The implementation of a reprogrammable, precise, and specific method, such as CRISPR-Cas9, to edit the S. cerevisiae genome has revolutionized laboratory practices.
  • 1.3K
  • 17 Jan 2022
Topic Review
Aptamers as Theragnostic Tools in Prostate Cancer
Aptamers are DNA and RNA oligonucleotides that can adopt tridimensional structures that enable them to join specifically to any desired target. Aptamers are capable of binding to specific molecules including drugs, proteins, carbohydrates, cells, and viruses. Aptamers were first described in 1990, and since then several groups have used their binding properties to isolate a diversity of specific aptamers. Aptamers have been studied for treatment and detection of many diseases including cancer. In Prostate Cancer, numerous works have reported their use in the development of new approaches in diagnostics and treatment strategies. Aptamers have been joined with drugs or other specific molecules such as silencing RNAs (aptamer–siRNA chimeras) to specifically reduce the expression of oncogenes in prostate cancer (PCa) cells. These studies have shown good results in the early stages, more research is still needed to demonstrate the clinical value of aptamers in PCa. 
  • 1.3K
  • 19 Aug 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. 
  • 1.3K
  • 27 Sep 2022
Topic Review
Ubisol-Q10 for Neurodegenerative Disease Treatment
It is well established and accepted that excessive oxidative stress is a key contributor to neurodegenerative diseases, driving interest in the development and application of redox therapies including the use of coenzyme-Q10 (CoQ10). However, in several human clinical trials, CoQ10 has failed to show efficacy, possibly due to poor tissue penetration and inability to deliver it parenterally. Ubisol-Q10 is a nanomicellar, water-dispersible formulation of CoQ10 that was created by combining CoQ10 with an amphiphilic and self-emulsifying molecule of polyoxyethanyl α-tocopheryl sebacate (PTS). This stable formulation is suitable for parenteral delivery and when tested at micromolar concentrations (well within FDA guidelines), it showed unprecedented neuroprotection, both in cellular models and animal models of chronic progressive neurodegeneration of both Parkinson’s and Alzheimer’s type. Systemic application of Ubisol-Q10 in drinking water stopped further progression of ongoing neurodegeneration as long as Ubisol-Q10 was provided. Mechanistically, this treatment with Ubisol-Q10 mobilized astroglia response in the CNS, quenched reactive oxygen species, prevented cell senescence, activated autophagy, reduced inflammation, and stabilized mitochondria. Importantly, these biochemical outcomes are accompanied by a significant improvement in behavioral deficits typically observed in animals with Parkinson’s and Alzheimer’s disease. Thus, Ubisol-Q10 is a promising candidate for developing a disease-modifying therapeutic intervention for neurodegenerative diseases that can be easily administered as drinking tonic.
  • 1.3K
  • 20 May 2021
Topic Review Peer Reviewed
Ecdysteroids
Ecdysteroid: member of a class of polyhydroxylated steroids found in invertebrate animals (zooecdysteroids; moulting hormones), plants (phytoecdysteroids) and fungi (mycoecdysteroids). Over 500 structural analogues are currently known. Biosynthetically, they derive from C27-, C28- or C29-sterols. The most frequently encountered analogue (in arthropods and plants) is 20-hydroxyecdysone (2β,3β,14α,20R,22R,25-hexahydroxycholest-7-en-6-one). In arthropods, ecdysteroids occur universally and regulate development by inducing moulting and reproduction, where their action is mediated by high-affinity binding to an intracellular member of the class of nuclear receptor (NR) proteins (ecdysteroid receptor; EcR) dimerised with a second NR (USP/RxR). This receptor complex binds to specific DNA promoter sites and regulates gene expression. In plants, ecdysteroids are a class of secondary compounds, occurring in varying amounts in certain species, but not all in others. Phytoecdysteroids are believed to contribute to the reduction of invertebrate predation by acting as feeding deterrents or endocrine disruptors. Ecdysteroids also possess a wide range of positive pharmacological effects in mammals, where the mode of action involves moderate-affinity binding to plasma-membrane-bound receptors and not interaction with the classical NRs for vertebrate steroid hormones.
  • 1.3K
  • 13 Apr 2022
Topic Review
Mechanisms of α-Syn Aggregation In Vitro
The aggregation of proteins into amyloid fibers is linked to more than forty still incurable cellular and neurodegenerative diseases such as Parkinson’s disease (PD), multiple system atrophy, Alzheimer’s disease and type 2 diabetes, among others. The process of amyloid formation is a main feature of cell degeneration and disease pathogenesis. Despite being methodologically challenging, a complete understanding of the molecular mechanism of aggregation, especially in the early stages, is essential to find new biological targets for innovative therapies. Here, chemical and biophysical methodologies that provided insights on Alpha-synuclein aggregation that would help to investigate other less-known aggregation-prone peptides and proteins were presented.
  • 1.3K
  • 03 Jan 2023
Topic Review
Differential Inhibitors of Aldose Reductase
Aldose reductase, classified within the aldo-keto reductase family as AKR1B1, is an NADPH dependent enzyme that catalyzes the reduction of hydrophilic as well as hydrophobic aldehydes. AKR1B1 is the first enzyme of the so-called polyol pathway that allows the conversion of glucose into sorbitol, which in turn is oxidized to fructose by sorbitol dehydrogenase. The activation of the polyol pathway in hyperglycemic conditions is generally accepted as the event that is responsible for a series of long-term complications of diabetes such as retinopathy, cataract, nephropathy and neuropathy. The role of AKR1B1 in the onset of diabetic complications has made this enzyme the target for the development of molecules capable of inhibiting its activity.
  • 1.3K
  • 11 Apr 2022
Topic Review
Heterogeneous Nuclear Ribonucleoproteins
Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a superfamily of RNA-binding proteins consisting of more than 20 members. These proteins play a crucial role in various biological processes by regulating RNA splicing, transcription, and translation through their binding to RNA.
  • 1.3K
  • 09 Oct 2023
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