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Topic Review
Effects of Berberine against Pancreatic Cancer
The pancreas is a glandular organ with endocrine and exocrine functions necessary for the maintenance of blood glucose homeostasis and secretion of digestive enzymes. Pancreatitis is characterized by inflammation of the pancreas leading to temporary or permanent pancreatic dysfunction. Inflammation and fibrosis caused by chronic pancreatitis exacerbate malignant transformation and significantly increase the risk of developing pancreatic cancer, the world’s most aggressive cancer with a 5-year survival rate less than 10%. Berberine (BBR) is a naturally occurring plant-derived polyphenol present in a variety of herbal remedies used in traditional medicine to treat ulcers, infections, jaundice, and inflammation.
  • 1.4K
  • 20 Dec 2022
Topic Review
Kinesin-1
The most of the transportations in cells are realized through a kind of proteins, the molecular motor. Molecular motor can be classed into three families, myosin, kinesin and dynein. Kinesin-1 (also called conventional kinesin) is the founding member of the kinesin family and mainly exists in the nerve axons to transport membranous organelles along the microtubule lattice. By using the energy stored in the ATP molecule, kinesin-1 can “walk” along the microtubule lattice in a hand-over-hand manner. In the walking process of the kinesin-1, the conformational changes of the compact motor domain transmit and amplify the small changes of the nucleotide-binding site to the force-generation element to produce the processive movement. The chemical cycle and mechanical cycle of kinesin-1 are highly coupled to ensure the processivity of the kinesin-1 and to avoid the futile ATP hydrolysis.
  • 1.4K
  • 27 Oct 2020
Topic Review
Sphingosine Kinase 1
Sphingosine kinase (SPHK) catalyses the ATP-dependent phosphorylation of sphingosine to form sphingosine 1-phosphate (S1P), which acts as an intracellular second messenger and extracellular ligand for specific receptors. S1P can be released through specific transporters to act as a ligand for the family of G protein-coupled S1P receptors 1 to 5 (S1P1 to S1P5) and regulates a wide range of biological effects including transformation and cancer cell survival. S1P levels are tightly regulated by the balance between synthesis by SPHK, reversible conversion to sphingosine by specific S1P phosphatases (SPP1 and SPP2), and degradation by S1P lyase. 
  • 1.4K
  • 27 Oct 2020
Topic Review
Advanced Glycation End Products and Cardiovascular Disease
Epidemiological studies demonstrate the role of early and intensive glycemic control in the prevention of micro and macrovascular disease in both type 1 and type 2 diabetes mellitus (DM). Hyperglycemia elicits several pathways related to the etiopathogenesis of cardiovascular disease (CVD), including the generation of advanced glycation end products (AGEs). 
  • 1.4K
  • 11 Mar 2022
Topic Review
WASF3
WASF3 (WAVE3), a Wiskott–Aldrich syndrome protein family member, appears to play a major role not only in the regulation of actin cytoskeleton dynamics but also in cancer cell invasion/metastasis. Blocking the WASF3-dependent metastatic signaling network remains an attractive and promising therapeutic option for the treatment of advanced tumors. 
  • 1.4K
  • 02 Feb 2021
Topic Review
Sirtuins
The sirtuin system consists of seven highly conserved regulatory enzymes responsible for metabolism, antioxidant protection, and cell cycle regulation. The great interest in sirtuins is associated with the potential impact on life extension. 
  • 1.4K
  • 05 Jan 2023
Topic Review
The Autophagic Pathway
Autophagy is a catabolic pathway that accounts for degradation and recycling of cellular components to extend cell survival under stress conditions. In addition to this prominent role, recent evidence indicates that autophagy is crucially involved in the regulation of the inflammatory response, a tightly controlled process aimed at clearing the inflammatory stimulus and restoring tissue homeostasis. To be efficient and beneficial to the host, inflammation should be controlled by a resolution program, since uncontrolled inflammation is the underlying cause of many pathologies. Resolution of inflammation is an active process mediated by a variety of mediators, including the so-called specialized pro-resolving lipid mediators (SPMs), a family of endogenous lipid autacoids known to regulate leukocyte infiltration and activities, and counterbalance cytokine production. Recently, regulation of autophagic mechanisms by these mediators has emerged, uncovering unappreciated connections between inflammation resolution and autophagy. Here, we summarize mechanisms of autophagy and resolution, focusing on the contribution of autophagy in sustaining paradigmatic examples of chronic inflammatory disorders. Then, we discuss the evidence that SPMs can restore dysregulated autophagy, hypothesizing that resolution of inflammation could represent an innovative approach to modulate autophagy and its impact on the inflammatory response.
  • 1.4K
  • 09 Nov 2020
Topic Review
Extreme Microorganisms in the Context of Biogeochemical Nitrogen Cycle
Extreme microorganisms (extremophile) are organisms that inhabit environments characterized by inhospitable parameters for most live beings (extreme temperatures and pH values, high or low ionic strength, pressure, or scarcity of nutrients). To grow optimally under these conditions, extremophiles have evolved molecular adaptations affecting their physiology, metabolism, cell signaling, etc. Due to their peculiarities in terms of physiology and metabolism, they have become good models for (i) understanding the limits of life on Earth, (ii) exploring the possible existence of extraterrestrial life (Astrobiology), or (iii) to look for potential applications in biotechnology. Recent research has revealed that extremophilic microbes play key roles in all biogeochemical cycles on Earth. Nitrogen cycle (N-cycle) is one of the most important biogeochemical cycles in nature; thanks to it, nitrogen is converted into multiple chemical forms, which circulate among atmospheric, terrestrial and aquatic ecosystems. This review summarizes recent knowledge on the role of extreme microorganisms in the N-cycle in extremophilic ecosystems, with special emphasis on members of the Archaea domain. Potential implications of these microbes in global warming and nitrogen balance, as well as their biotechnological applications are also discussed.
  • 1.4K
  • 17 Jun 2020
Topic Review
Quadruplex Structures: Cancer Therapeutic Targets
Non-canonical, four-stranded nucleic acids secondary structures are present within regulatory regions in the human genome and transcriptome. To date, these quadruplex structures include both DNA and RNA G-quadruplexes, formed in guanine-rich sequences, and i-Motifs, found in cytosine-rich sequences, as their counterparts. Quadruplexes have been extensively associated with cancer, playing an important role in telomere maintenance and control of genetic expression of several oncogenes and tumor suppressors. Therefore, quadruplex structures are considered attractive molecular targets for cancer therapeutics with novel mechanisms of action.
  • 1.4K
  • 11 Dec 2020
Topic Review
FGCaMP7 Genetically Encoded Calcium Indicator
Genetically encoded calcium indicators (GECIs) have become a widespread tool for the visualization of neuronal activity. As compared to popular GCaMP GECIs, the FGCaMP indicator benefits from calmodulin from the Aspergillus niger fungus, which prevent its interaction with the intracellular environment. However, FGCaMP exhibits a two-phase fluorescence behavior with the variation of calcium ion concentration, has moderate sensitivity in neurons (as compared to the GCaMP6s indicator), and has not been fully characterized in vitro and in vivo. To address these limitations, we developed an enhanced version of FGCaMP, called FGCaMP7. FGCaMP7 preserves the ratiometric phenotype of FGCaMP, with a 3.1-fold larger ratiometric dynamic range in vitro. FGCaMP7 demonstrates 2.7- and 8.7-fold greater photostability compared to mEGFP and mTagBFP2 fluorescent proteins in vitro, respectively. The ratiometric response of FGCaMP7 is 1.6- and 1.4-fold higher, compared to the intensiometric response of GCaMP6s, in non-stimulated and stimulated neuronal cultures, respectively. We reveal the inertness of FGCaMP7 to the intracellular environment of HeLa cells using its truncated version with a deleted M13-like peptide; in contrast to the similarly truncated variant of GCaMP6s. We characterize the crystal structure of the parental FGCaMP indicator. Finally, we test the in vivo performance of FGCaMP7 in mouse brain using a two-photon microscope and an NVista miniscope; and in zebrafish using two-color ratiometric confocal imaging.
  • 1.4K
  • 29 Oct 2020
Topic Review
Alignment-Free Approaches
Alignment-free (AF) methodologies have increased in popularity in the last decades as alternative tools to alignment-based (AB) algorithms for performing comparative sequence analyses. They have been especially useful to detect remote homologs within the twilight zone of highly diverse gene/protein families and superfamilies. The most popular alignment-free methodologies, as well as their applications to classification problems, have been described in previous reviews. Despite a new set of graph theory-derived sequence/structural descriptors that have been gaining relevance in the detection of remote homology, they have been omitted as AF predictors when the topic is addressed. Here, we first go over the most popular AF approaches used for detecting homology signals within the twilight zone and then bring out the state-of-the-art tools encoding graph theory-derived sequence/structure descriptors and their success for identifying remote homologs.
  • 1.4K
  • 29 Oct 2020
Topic Review
Cells Fusion
The biological phenomenon of cell fusion remains a mystery. Even though it is mandatory for several physiological and pathopyhsiological processes considerably less is still known how the merging of two (and more) cells is regulated. Cells are not fusogenic per se. They first have to be converted into a pro-fusogenic state and have to re-enter to a non-fusogenic state after hybridisation. Likewise, different cell fusion mechanisms have been developed during evolution depending on different proteins and different membrane merging strategies. This entry gives a brief overview about those molecules and conditions that direct cell fusion.
  • 1.4K
  • 27 Oct 2020
Topic Review
BMSC Osteogenic or Adipogenic Differentiation
Bone marrow stromal cells (BMSCs) are multipotent cells in the bone marrow which can differentiate into chondrocytes, osteoblasts, adipocytes (fat cells) and other cell types. Many factors have been identified to control the process of BMSC osteogenic or adipogenic differentiation in the bone.
  • 1.4K
  • 12 Aug 2021
Topic Review
Cell Lysis
Cell lysis is the first step of sample preparation for nucleic acid (NA) detection. Its purpose is to release NAs from the cells by disrupting the structure of cell membranes, which are also known as phospholipid bilayer membranes or plasmalemma. As NA detection typically relies on amplification using polymerase chain reaction (PCR) or isothermal alternatives, carry-over of inhibitory agents including the reagents used for lysis needs to be avoided or minimised. While washing steps are easily implemented in a laboratory setting, for Point of Need testing, the trend is towards substitution of strong inhibitory lytic reagents for more benign alternatives to minimise processing steps and reagent use. Additionally, sustainability of the reagents and their disposal are growing concerns. Here, an overview of lysis methods is provided from the perspective of their suitability for for point of need testing.
  • 1.4K
  • 16 Nov 2023
Topic Review
Homocysteine and Mitochondria
Elevated concentration of homocysteine (Hcy) in the blood plasma, hyperhomocysteinemia (HHcy), has been implicated in various disorders, including cardiovascular and neurodegenerative diseases. Accumulating evidence indicates that pathophysiology of these diseases is linked with mitochondrial dysfunction. Mitochondria are essential for maintaining cellular homeostasis and function. The interaction between Hcy and mitochondria is complex and reactive oxygen species (ROS) seem to be important mediators of Hcy effects. Although oxidative damage to mitochondria is frequently demonstrated under HHcy, Hcy may have also beneficial effects on mitochondrial function and cell viability.
  • 1.4K
  • 11 Nov 2020
Topic Review
The HD-Domain Metalloprotein Superfamily
The histidine–aspartate (HD)-domain protein superfamily contains metalloproteins that share common structural features but catalyze vastly different reactions ranging from oxygenation to hydrolysis. This chemical diversion is afforded by (i) their ability to coordinate most biologically relevant transition metals in mono-, di-, and trinuclear configurations, (ii) sequence insertions or the addition of supernumerary ligands to their active sites, (iii) auxiliary substrate specificity residues vicinal to the catalytic site, (iv) additional protein domains that allosterically regulate their activities or have catalytic and sensory roles, and (v) their ability to work with protein partners. More than 500 structures of HD-domain proteins are available to date that lay out unique structural features which may be indicative of function. In this respect, we describe the three known classes of HD-domain proteins (hydrolases, oxygenases, and lyases) and identify their apparent traits with the aim to portray differences in the molecular details responsible for their functional divergence and reconcile existing notions that will help assign functions to yet-to-be characterized proteins.
  • 1.4K
  • 29 Oct 2020
Topic Review
Pheomelanin
Pheomelanin is a natural yellow-reddish sulfur-containing pigment derived from tyrosinase-catalyzed oxidation of tyrosine in presence of cysteine. It is one of the existing forms of the natural pigment melanin, which is present in the skin in two forms: eumelanin and pheomelanin. Generally, the formation of melanin pigments is a protective response against the damaging effects of UV radiation in skin.
  • 1.4K
  • 20 Jan 2022
Topic Review
ADP-ribosylation
Adenosine diphosphate (ADP)-ribosylation is a nicotinamide adenine dinucleotide (NAD+)-dependent post-translational modification that is found on proteins as well as on nucleic acids. Promising technological advances have enabled the development of innovative tools to detect NAD+ and NAD+/NADH (H for hydrogen) ratios as well as ADP-ribosylation. These tools have significantly enhanced our current understanding of how intracellular NAD dynamics contribute to the regulation of ADP-ribosylation as well as to how mono-ADP-ribosylation integrates into various cellular processes.
  • 1.4K
  • 23 Jun 2021
Topic Review
Histone deacetylase (HDAC)
Histone deacetylase (HDAC) enzymes play crucial roles in epigenetic gene expression and are an attractive therapeutic target. Five HDAC inhibitors have been approved for cancer treatment to date, however clinical applications have been limited due to poor single agent drug efficacy and side effects associated with a lack of HDAC isoform or complex selectivity. An emerging strategy aiming to address these limitations is the development of bifunctional HDAC therapeutics – single molecules comprising a HDAC inhibitor conjugated to another specificity targeting moiety. There has been many recent advancements in novel types of dual-targeting HDAC modulators, including PROTACs, often achieving high HDAC isoform selectivity, as well as some dual inhibitor examples affording HDAC complex selectivity. Such bifunctional molecules have future potential in achieving enhanced drug efficacy and therapeutic benefits in treating disease.
  • 1.4K
  • 12 Oct 2020
Topic Review
Acetylation
Acetylation, also known as acetylation or acetylation, refers to the chemical reaction of adding an acetyl functional group to an organic compound. Conversely, the reaction in which the acetyl group is removed is called deacetylation or deacetylation. Acetylation of proteins is a post-translational modification.
  • 1.4K
  • 16 Nov 2022
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