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Topic Review
Relationships between N-Glycosylation and Disulfide Bonds
N-Glycosylation (NG) and disulfide bonds (DBs) are two prevalent co/post-translational modifications (PTMs) that are often conserved and coexist in membrane and secreted proteins involved in a large number of diseases. Both in the past and in recent times, the enzymes and chaperones regulating these PTMs have been constantly discovered to directly interact with each other or colocalize in the ER. However, beyond a few model proteins, how such cooperation affects N-glycan modification and disulfide bonding at selective sites in individual proteins is largely unknown. More investigations should be encouraged to unveil the hidden relationships of NG and DBs in the majority of membranes and secreted proteins for pathophysiological understanding and biotherapeutic development. 
  • 1.0K
  • 08 Apr 2022
Topic Review
Autophagy in Cancer Cells
The role of autophagy is to degrade damaged or unnecessary cellular structures. Both in vivo and in vitro studies suggest a dual role of autophagy in cancer—it may promote the development of neoplasms, but it may also play a tumor protective function. The mechanism of autophagy depends on the genetic context, tumor stage and type, tumor microenvironment, or clinical therapy used. Autophagy also plays an important role in cell death as well as in the induction of chemoresistance of cancer cells. The following review describes the extensive autophagic cell death in relation to dietary polyphenols and cancer disease. Polyphenols are organic chemicals that exhibit antioxidant, anti-inflammatory, anti-angiogenic, and immunomodulating properties, and can also initiate the process of apoptosis. In addition, polyphenols reduce oxidative stress and protect against reactive oxygen species. This review presents in vitro and in vivo studies in animal models with the use of polyphenolic compounds such as epigallocatechin-3-gallate (EGCG), oleuropein, punicalgin, apigenin, resveratrol, pterostilbene, or curcumin and their importance in the modulation of autophagy-induced death of cancer cells.
  • 1.0K
  • 22 Jan 2021
Topic Review
Carbonic Anhydrases Inhibitors
Carbon dioxide (CO2), a vital molecule of the carbon cycle, is a critical component in living organisms’ metabolism, performing functions that lead to the building of compounds fundamental for the life cycle. In all living organisms, the CO2/bicarbonate (HCO3−) balancing is governed by a superfamily of enzymes, known as carbonic anhydrases (CAs, EC 4.2.1.1). CAs catalyze the pivotal physiological reaction, consisting of the reversible hydration of the CO2 to HCO3− and protons.
  • 1.0K
  • 08 May 2021
Topic Review
Controlling Gene Expression in Hypoxia
Hypoxia—reduction in oxygen availability—plays key roles in both physiological and pathological processes. Given the importance of oxygen for cell and organism viability, mechanisms to sense and respond to hypoxia are in place. A variety of enzymes utilise molecular oxygen, but of particular importance to oxygen sensing are the 2-oxoglutarate (2-OG) dependent dioxygenases (2-OGDs). Of these, Prolyl-hydroxylases have long been recognised to control the levels and function of Hypoxia Inducible Factor (HIF), a master transcriptional regulator in hypoxia, via their hydroxylase activity. However, recent studies are revealing that dioxygenases are involved in almost all aspects of gene regulation, including chromatin organisation, transcription and translation. We highlight the relevance of HIF and 2-OGDs in the control of gene expression in response to hypoxia and their relevance to human biology and health. 
  • 1.0K
  • 05 Mar 2021
Topic Review
GSK-3 in Neurodegeneration
Glycogen synthase kinase-3 (GSK-3) is a central player in regulating mood behavior, cognitive functions, and neuron viability. Indeed, many targets controlled by GSK-3 are critically involved in progressing neuron deterioration and disease pathogenesis. 
  • 1.0K
  • 06 Mar 2021
Topic Review
HIF Activity
The Hypoxia Inducible Factor (HIF) family of heterodimeric transcription factors that consists of 3 HIFα members (namely HIF-1α, HIF-2α, and HIF-3α) and one HIFβ member (HIF-1β, best known as ARNT) is responsible for the transcriptional response of cells to oxygen deprivation.
  • 1.0K
  • 17 Mar 2021
Topic Review
Entrectinib—An Inhibitor of SARS-CoV-2 Cell Entry
This entry describes entrectinib as an antiviral drug.
  • 1.0K
  • 20 Jan 2022
Topic Review
Extracellular Vesicles in Tumour Microenvironment
The tumour microenvironment (TME) contains cells of different origin, including cancer, immune, endothelial, and stromal cells. In the last decades extracellular vesicles (EV) released by these cells have gained attention as drivers of the TME diversity and tumour behaviour. In the TME, EV can switch tumour growth, immune-escape and metastatic spread or exert anti-tumour activity depending on their cell of origin and cargo. Moreover, since potentially detectable in different biological fluids, EV have been proposed as diagnostic and therapeutic, or “theragnostic” tools. Specifically, EV cargo has been considered a tumour “fingerprint”, and differentially expressed proteins and genetic materials proposed as potential targets for anti-cancer based therapies. Approaches using engineered EV or EV as naturally delivery system for “therapeutics” have been explored in preclinical models and their effectiveness, in targeting the TME, proven in primary and metastatic tumours. More recently, CAR-T cells and CAR EV combo platform have been proposed to improve the CAR-based anti-cancer approach. Likewise, their potential application for immune cell targeting has provide significant insights to move towards anti-cancer immunotherapeutic approaches. On these bases, a number of clinical trials aimed to deeply explore EV clinical application as anti-tumour based approach or “theragnostics” are on-going. Should validated as diagnostic/prognostic/anti-cancer tools the still open questions would be hopefully addressed and their clinical application would become the on-coming challenge against cancer. However, to move towards EV clinical application several hurdles including potency tests, scalability and full characterization in agreement with the regulatory agency should be solved.
  • 1.0K
  • 09 Nov 2020
Topic Review
Human Mitochondrial Pyruvate Carrier
Human mitochondrial pyruvate carriers (hMPCs), which are required for the uptake of pyruvate into mitochondria, are associated with several metabolic diseases, including type 2 diabetes and various cancers. Yeast MPC was recently demonstrated to form a functional unit of heterodimers. However, human MPC-1 (hMPC-1) and MPC-2 (hMPC-2) have not yet been individually isolated for their detailed characterization, in particular in terms of their structural and functional properties, namely, whether they exist as homo- or heterodimers. In this study, hMPC-1 and hMPC-2 were successfully isolated in micelles and they formed stable homodimers. However, the heterodimer state was found to be dominant when both hMPC-1 and hMPC-2 were present. In addition, as heterodimers, the molecules exhibited a higher binding capacity to both substrates and inhibitors, together with a larger structural stability than when they existed as homodimers. Taken together, our results demonstrated that the hetero-dimerization of hMPCs is the main functional unit of the pyruvate metabolism, providing a structural insight into the transport mechanisms of hMPCs.
  • 1.0K
  • 24 Mar 2021
Topic Review
LEAFY COTYLEDON 2: A Regulatory Factor in Plant
Transcription factors are key molecules in the regulation of gene expression in all organisms. The transcription factor LEAFY COTYLEDON 2 (LEC2), which belongs to the DNA-binding protein family, contains a B3 domain. The transcription factor is involved in the regulation of important plant biological processes such as embryogenesis, somatic embryo formation, seed storage protein synthesis, fatty acid metabolism, and other important biological processes.
  • 1.0K
  • 13 Dec 2021
Topic Review
hIAPP Amyloidosis in Type 2 Diabetes Mellitus
Cases of Type 2 Diabetes Mellitus (T2DM) are increasing at an alarming rate due to the rise in obesity, sedentary lifestyles, glucose-rich diets and other factors. Numerous studies have increasingly illustrated the pivotal role that human islet amyloid polypeptide (hIAPP) plays in the pathology of T2DM through damage and subsequent loss of pancreatic β-cell mass. Here researchers provide an up-to-date summary of recent progress in the field, highlighting factors that contribute to hIAPP misfolding and aggregation which have been linked to β-cell cytotoxicity. Understanding the structure of hIAPP and how these factors affect amyloid formation will help better understand how hIAPP misfolds and aggregates and, importantly, help identify potential therapeutic targets for inhibiting amyloidosis so alternate and more effective treatments for T2DM can be developed.
  • 1.0K
  • 29 Apr 2022
Topic Review
Circulating Tumor DNA in Precision Oncology
Circulating tumor DNA (ctDNA) is a component of cell-free DNA (cfDNA) that is shed by malignant tumors into the bloodstream and other bodily fluids. ctDNA can comprise up to 10% of a patient’s cfDNA depending on their tumor type and burden.
  • 1.0K
  • 09 May 2022
Topic Review
Histone Deacetylases and Their Inhibitors in Ischemic Stroke
Cerebral ischemia is the second leading cause of death in the world and multimodal stroke therapy is needed. The ischemic stroke generally reduces the gene expression due to suppression of acetylation of histones H3 and H4. Histone deacetylases inhibitors have been shown to be effective in protecting the brain from ischemic damage. Histone deacetylases inhibitors induce neurogenesis and angiogenesis in damaged brain areas promoting functional recovery after cerebral ischemia.
  • 999
  • 29 Oct 2021
Topic Review
Whole Blood Polyamine Levels in Age-Related Diseases
The relationship between polyamines and healthy longevity has received much attention. The most fundamental consideration in conducting polyamine studies is that bovine serum used for cell culture contains bovine serum amine oxidase. Bovine serum amine oxidase, which is not inactivated by heat treatment, breaks down spermine and spermidine to produce the highly toxic aldehyde acrolein, which causes cell damage and activates autophagy. Polyamine catabolism does not produce toxic aldehydes under normal conditions, but inflammation and some pathogens provoke an inducible enzyme, spermine oxidase, which only breaks down spermine to produce acrolein, resulting in cytotoxicity and the activation of autophagy. Therefore, spermine oxidase activation reduces spermine concentration and the ratio of spermine to spermidine, a feature reported in patients with age-related diseases. Spermine, which is increased by a long-term, continuous high polyamine diet, suppresses aberrant gene methylation and the pro-inflammatory status that progress with age and are strongly associated with the development of several age-related diseases and senescence. Changes in spermine concentration and the spermine/spermidine ratio should be considered as indicators of human health status.
  • 997
  • 26 Oct 2023
Topic Review
Cannabinoids
Cannabinoids can be classified as (1) endocannabinoids (AEA, 2-AG), (2) phytocannabinoids (THC, CBD), and (3) synthetic analogs (AJA)—. Phytocannabinoids constitute more than 110 chemical compounds, while synthetic analogs are even more numerous.
  • 996
  • 05 Aug 2021
Topic Review
DSResSol
Protein solubility is an important thermodynamic parameter that is critical for the characterization of a protein’s function, and a key determinant for the production yield of a protein in both the research setting and within industrial (e.g., pharmaceutical) applications. Experimental approaches to predict protein solubility are costly, time-consuming, and frequently offer only low success rates. To reduce cost and expedite the development of therapeutic and industrially relevant proteins, a highly accurate computational tool for predicting protein solubility from protein sequence is sought. While a number of in silico prediction tools exist, they suffer from relatively low prediction accuracy, bias toward the soluble proteins, and limited applicability for various classes of proteins. In this study, researchers developed a novel deep learning sequence-based solubility predictor, DSResSol, that takes advantage of the integration of squeeze excitation residual networks with dilated convolutional neural networks and outperforms all existing protein solubility prediction models. This model captures the frequently occurring amino acid k-mers and their local and global interactions and highlights the importance of identifying long-range interaction information between amino acid k-mers to achieve improved accuracy, using only protein sequence as input. DSResSol outperforms all available sequence-based solubility predictors by at least 5% in terms of accuracy when evaluated by two different independent test sets. Compared to existing predictors, DSResSol not only reduces prediction bias for insoluble proteins but also predicts soluble proteins within the test sets with an accuracy that is at least 13% higher than existing models. Researchers derive the key amino acids, dipeptides, and tripeptides contributing to protein solubility, identifying glutamic acid and serine as critical amino acids for protein solubility prediction. Overall, DSResSol can be used for the fast, reliable, and inexpensive prediction of a protein’s solubility to guide experimental design.
  • 996
  • 14 Jan 2022
Topic Review
Natural Resistance of Plants
The over-reliance on herbicides to reduce weed infestation in crops has led to the rapid evolution of herbicide-resistant (HR) weeds. Weed resistance to herbicides should be minimized, as this can lead to serious limitations in the food security for people around the world. Landing page resistance can occur as a result of changes in the biochemical sites of the action of one herbicide. Inappropriate resistance occurs through mechanisms that reduce the number of herbicide molecules and reach their target site. In major field crops, synthetic herbicides are used to control weeds worldwide. Cross-resistance can occur with herbicides from the same or different herbicide families, and with the same or different sites of action. Multiple resistance refers to the evolved mechanisms of resistance to more than one herbicide (e.g., resistance to inhibitors (ALS) and (ACC), and this resistance has resulted from separate selection processes). Currently, weed re-sistance has been transferred to 161 different herbicides, covering twenty-three of the twenty-six known herbicide sites. We can protect crops that are associated with herbicide tolerant weeds through biochemical, genetic and crop control strategies. The “European Green Deal” forces producers to change their approaches to plant protection. The emphasizes the importance and advantages of enhancing the natural resistance of plants to pests, with particular emphasis on the importance of oxylipins in plant protection. The summarize the latest research on the reaction of plants to pesticides, including herbicides, in order to assess the possibility of using jasmonates and brassinosteroids to stimulate the natural, induced systemic immunity of plants, as well as investigate the possibility of the interaction of oxylipins with ethylene, salicylates and other compounds.
  • 996
  • 16 Nov 2022
Topic Review
Antibodies induced by Glycosphingolipids
Glycosphingolipids containing very-long-chain fatty acids (VLCFAs) regulate several immune responses, such as cytokine production, immune signaling, and antibody induction. Here, we report that immunization with glycosphingolipids containing-VLCFAs can efficiently induce the production of anti-glycan antibodies by B cells.
  • 995
  • 30 Oct 2020
Topic Review
Ankyrin Repeat-Containing Proteins
Ankyrin repeat (AR) domains are considered the most abundant repeat motif found in eukaryotic proteins. AR domains are predominantly known to mediate specific protein–protein interactions (PPIs) without necessarily recognizing specific primary sequences, nor requiring strict conformity within its own primary sequence.
  • 995
  • 27 Jan 2021
Topic Review
Animal Model Systems of Parkinson’s Disease
Parkinson's disease is an advancing condition characterized by different types of physical and mental impairments. The characteristic features of Parkinson's disease include the buildup of improperly folded protein known as α-synuclein as Lewy bodies, as well as the deterioration of dopamine-producing neurons in the substantia nigra pars compacta (SNc) region, which impacts the patient's motor functions. Significant studies have been conducted to investigate the use of animal models for Parkinson's disease.
  • 995
  • 05 Jun 2023
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