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Topic Review
m6A Modification and Glucose Metabolism
The highly conserved and dynamically reversible N6-methyladenine (m6A) modification has emerged as a critical gene expression regulator by affecting RNA splicing, translation efficiency, and stability at the post-transcriptional level, which has been established to be involved in various physiological and pathological processes, including glycolipid metabolism and the development of glycolipid metabolic disease (GLMD). Hence, accumulating studies have focused on the effects and regulatory mechanisms of m6A modification on glucose metabolism, lipid metabolism, and GLMD. Glucose metabolism involves a very complex regulatory network, including anaerobic glycolysis, aerobic oxidation, pentose phosphate pathway, glycogen synthesis, and gluconeogenesis. An increasing number of studies have reported that m6A modification is an important regulatory mechanism of glucose homeostasis and downstream effects.
  • 807
  • 14 Feb 2023
Topic Review
Antimicrobial Compounds from Endolichenic Fungi
A lichen is a symbiotic relationship between a fungus and a photosynthetic organism, which is algae or cyanobacteria. Endolichenic fungi are a group of microfungi that resides asymptomatically within the thalli of lichens. Endolichenic fungi can be recognized as luxuriant metabolic artists that produce propitious bioactive secondary metabolites. 
  • 806
  • 06 Jul 2021
Topic Review
Estrogen-Related Receptor α
Bone homeostasis is maintained with the balance between bone formation and bone resorption, which is involved in the functional performance of osteoblast and osteoclast. Disruption of this equilibrium usually causes bone disorders including osteoporosis, osteoarthritis, and osteosclerosis. In addition, aberrant activity of bone also contributes to the bone metastasis that frequently occurs in the late stage of aggressive cancers. Orphan nuclear receptor estrogen-related receptor (ERRα) has been demonstrated to control the bone cell fate and the progression of tumor cells in bone through crosstalk with various molecules and signaling pathways. 
  • 806
  • 11 Jul 2022
Topic Review
Non-Coding RNAs in Renal Fibrosis
Fibrosis, or tissue scarring, is defined as the excessive, persistent and destructive accumulation of extracellular matrix components in response to chronic tissue injury. Renal fibrosis represents the final stage of most chronic kidney diseases and contributes to the progressive and irreversible decline in kidney function. The role of non-coding RNAs, and in particular microRNAs (miRNAs), has been described in kidney fibrosis. 
  • 806
  • 18 Oct 2022
Topic Review
Lactoferrin and Human Metabolism
Many pathological conditions, including obesity, diabetes, hypertension, heart disease, and cancer, are associated with abnormal metabolic states. The progressive loss of metabolic control is commonly characterized by insulin resistance, atherogenic dyslipidemia, inflammation, central obesity, and hypertension, a cluster of metabolic dysregulations usually referred to as the “metabolic syndrome”. Nutraceuticals have gained attention for the generalized perception that natural substances may be synonymous with health and balance, thus becoming favorable candidates for the adjuvant treatment of metabolic dysregulations. Among nutraceutical proteins, lactoferrin (Lf), an iron-binding glycoprotein of the innate immune system, has been widely recognized for its multifaceted activities and high tolerance. 
  • 806
  • 14 Nov 2023
Topic Review
TNFα
About 60 years ago, it was reported that bacterial endotoxin administration to mice resulted in the release of a serological protein with necrotic anti-tumor activity at high concentrations. Due to the latter characteristic, this protein was termed tumor necrosis factor (TNF)  and considered a breakthrough for cancer therapy. Today, the TNF superfamily consists of 19 members and 29 TNF receptors .Within this family, functional TNFα is represented by a trimer of 17.35 kDa monomers, folded into a rigid bell-shaped “jelly roll” composed of antiparallel filaments. It exists in two forms: a transmembrane form (tmTNFα) next to a soluble (sTNFα) form. The latter one is cleaved from tmTNFα by the metalloproteinase TNF-alpha-converting enzyme (TACE).
  • 805
  • 18 Aug 2021
Topic Review
Transmembrane Chloride Intracellular Channel 1
Identification of potential pathological biomarkers has proved to be essential for understanding complex and fatal diseases, such as cancer and neurodegenerative diseases. Ion channels are involved in the maintenance of cellular homeostasis. Moreover, loss of function and aberrant expression of ion channels and transporters have been linked to various cancers, and to neurodegeneration. The Chloride Intracellular Channel 1 (CLIC1), CLIC1 is a metamorphic protein belonging to a partially unexplored protein superfamily, the CLICs. In homeostatic conditions, CLIC1 protein is expressed in cells as a cytosolic monomer. In pathological states, CLIC1 is specifically expressed as transmembrane chloride channel. In the following review, we trace the involvement of CLIC1 protein functions in physiological and in pathological conditions and assess its functionally active isoform as a potential target for future therapeutic strategies.
  • 804
  • 11 Oct 2021
Topic Review
PIWI-Interacting RNAs (piRNAs) and Cancers
The P-Element-induced wimpy testis (PIWI)-interacting RNAs(piRNAs) were first described in 2001 in experiments usingDrosophilamodels evidencing their role in fertility. Then, piRNAs were involved in the function of mammalian germ cells. During the last two decades, researchers have described piRNAs as small RNA molecules able to bind PIWI proteins to form piRNA/PIWI complexes, which act as mediators in several processes including transposon silencing, spermiogenesis, genome rearrangement, epigenetic regulation, protein regulation, and germ stem-cell maintenance in both normal and abnormal cells.
  • 804
  • 20 Jan 2022
Topic Review
Protein Ser/Thr Phosphatase Folding
Post-translational modification (PTM) is a key mechanism providing the functional diversity of proteins in cellular signaling and physiology and changing the functions or stability of proteins. 
  • 804
  • 25 Jul 2023
Topic Review
Carbonic Anhydrase Sensitivity to Pesticides
Carbonic anhydrase (CA) is a widespread metalloenzyme playing a pivotal role in several physiological processes. Many studies have demonstrated the in vitro and in vivo sensitivity of CA to several classes of pesticides in both humans and wildlife. The review is aimed to discuss the literature to date available in this field, providing a comprehensive view useful to foresee perspectives for the development of novel CA-based pesticide biomarkers. The analysis of the available data highlighted the ability of several pesticide molecules to interact directly with the enzyme in humans and wildlife and to inhibit CA activity in vitro and in vivo. The analysis disclosed key areas of further research and at the same time identified some perspectives for the development of novel CA-based sensitive biomarkers to pesticide exposure, suitable to be used in several fields from human biomonitoring in occupational and environmental medicine to environmental biomonitoring on non-target species.
  • 803
  • 28 Oct 2020
Topic Review
Chronic Muscle Disuse
Periods of muscle disuse promote diminished muscle quality along with muscle atrophy that is characterized by reductions in muscle fiber cross-sectional area (CSA). Skeletal muscle disuse may be brought about by chronic sedentarism, periods of immobilization due to injury, bed rest as result of illness, or even exposure to microgravity. Such inactivity elicits functional and metabolic derangements in the affected tissue including marked mitochondrial alterations that contribute to the impaired metabolic health and degree of atrophy in the muscle. These impairments within the tissue prompt a net increase in catabolic processes in conjunction with reductions in skeletal muscle protein synthesis. Skeletal muscle mitochondrial decline and atrophy are underlying features of many diseases and they exacerbate disease progression and reduced mobility with aging. Thus, understanding the molecular underpinnings of muscle mitochondrial deficits with prolonged inactivity is of considerable interest.
  • 803
  • 21 May 2021
Topic Review
Extracellular Vesicles and Viruses
Multicellular organisms rely on intercellular communication to regulate many aspects of their physiology. It defines environmental niches that regulate cell growth and behavior, and it is essential for collective defense against host pathogens. The majority of intercellular communication is mediated via the transportation of bioactive molecules, such as proteins, nucleic acids, metabolites and lipids between cells. Passage of these molecules can occur by passive diffusion or by transport via carrier molecules such as extracellular vesicles (EVs). EVs are cell-secreted membrane vesicles of various sizes, compositions and origins that induce physiological changes in recipient cells through the delivery of bioactive molecules. The biomolecules contained within EVs vary depending on the tissue of origin, immune set-point and cellular context and web-based compendiums such as ExoCarta, Vesiclepedia and EVpedia are now used to document the vast array of biological molecules identified in EVs of different classes.
  • 803
  • 03 Feb 2023
Topic Review
Lysosomal Storage Disorders Linked to Impaired Autophagy
Lysosomes are the main organelles responsible for the degradation of macromolecules in eukaryotic cells. Beyond their fundamental role in degradation, lysosomes are involved in different physiological processes such as autophagy, nutrient sensing, and intracellular signaling. In some circumstances, lysosomal abnormalities underlie several human pathologies with different etiologies known as Lysosomal Storage Disorders (LSDs). These disorders can result from deficiencies in primary lysosomal enzymes, dysfunction of lysosomal enzyme activators, alterations in modifiers that impact lysosomal function, or changes in membrane-associated proteins, among other factors. 
  • 803
  • 10 Jan 2024
Topic Review
PGRP-LB: Mechanism of Amidase Reaction
Peptidoglycan recognition proteins (PGRPs) are ubiquitous among animals and play pivotal functions in insect immunity. Non-catalytic PGRPs are involved in the activation of immune pathways by binding to the peptidoglycan (PGN), whereas amidase PGRPs are capable of cleaving the PGN into non-immunogenic compounds. Drosophila PGRP-LB belongs to the amidase PGRPs and downregulates the immune deficiency (IMD) pathway by cleaving meso-2,6-diaminopimelic (meso-DAP or DAP)-type PGN. While the recognition process is well analyzed for the non-catalytic PGRPs, little is known about the enzymatic mechanism for the amidase PGRPs, despite their essential function in immune homeostasis. Here, we analyzed the specific activity of different isoforms of Drosophila PGRP-LB towards various PGN substrates to understand their specificity and role in Drosophila immunity. 
  • 802
  • 11 Jun 2021
Topic Review
Thrombin Cleavage of Osteopontin
Osteopontin (OPN) is a multi-functional protein that is involved in various cellular processes such as cell adhesion, migration, and signaling. There is a single conserved thrombin cleavage site in OPN that, when cleaved, yields two fragments with different properties from full-length OPN. In cancer, OPN has tumor-promoting activity and plays a role in tumor growth and metastasis. High levels of OPN expression in cancer cells and tumor tissue are found in various types of cancer, including breast, lung, prostate, ovarian, colorectal, and pancreatic cancer, and are associated with poor prognosis and decreased survival rates. OPN promotes tumor progression and invasion by stimulating cell proliferation and angiogenesis and also facilitates the metastasis of cancer cells to other parts of the body by promoting cell adhesion and migration. Furthermore, OPN contributes to immune evasion by inhibiting the activity of immune cells. 
  • 801
  • 12 Sep 2023
Topic Review
ALK+ lung cancer: targeted inhibitors and resistance mechanisms
EML4-ALK is an oncogenic fusion protein that accounts for approximately 5% of non-small cell lung cancer cases. Targeted inhibitors of ALK are now the standard of care treatment often leading to an excellent initial response and increased overall survival. A variety of resistance mechanisms have been identified that eventually lead to relapse highlighting the need for additional treatment options for these patients.
  • 800
  • 01 Aug 2022
Topic Review
REST/NRSF in Health and Disease
Chromatin modifications play a crucial role in the regulation of gene expression. The repressor element-1 (RE1) silencing transcription factor (REST), also known as neuron-restrictive silencer factor (NRSF) and X2 box repressor (XBR), was found to regulate gene transcription by binding to chromatin and recruiting chromatin-modifying enzymes. Earlier studies revealed that REST plays an important role in the development and disease of the nervous system, mainly by repressing the transcription of neuron-specific genes. Subsequently, REST was found to be critical in other tissues, such as the heart, pancreas, skin, eye, and vascular. Dysregulation of REST was also found in nervous and non-nervous system cancers. In parallel, multiple strategies to target REST have been developed. 
  • 800
  • 13 Nov 2023
Topic Review
Glutathionyl Hemoglobin
Hemoglobin is one of the proteins that are more susceptible to S-glutathionylation and the levels of its modified form, glutathionyl hemoglobin (HbSSG), increase in several human pathological conditions.
  • 800
  • 23 Jan 2024
Topic Review
Diamond Electrodes for Neurochemical Sensing
Carbon-based electrodes combined with fast-scan cyclic voltammetry (FSCV) enable neurochemical sensing with high spatiotemporal resolution and sensitivity. While their attractive electrochemical and conductive properties have established a long history of use in the detection of neurotransmitters both in vitro and in vivo, carbon fiber microelectrodes (CFMEs) also have limitations in their fabrication, flexibility, and chronic stability. Diamond is a form of carbon with a more rigid bonding structure (sp3-hybridized) which can become conductive when boron-doped. Boron-doped diamond (BDD) is characterized by an extremely wide potential window, low background current, and good biocompatibility. Additionally, methods for processing and patterning diamond allow for high-throughput batch fabrication and customization of electrode arrays with unique architectures.
  • 799
  • 20 Feb 2021
Topic Review
Synthetic mRNAs
The structure of synthetic mRNAs as used in vaccination against cancer and infectious diseases contain specifically designed caps followed by sequences of the 5′ untranslated repeats of β-globin gene. The strategy for successful design of synthetic mRNAs by chemically modifying their caps aims to increase resistance to the enzymatic deccapping complex, offer a higher affinity for binding to the eukaryotic translation initiation factor 4E (elF4E) protein and enforce increased translation of their encoded proteins. However, the cellular homeostasis is finely balanced and obeys to specific laws of thermodynamics conferring balance between complexity and growth rate in evolution. An overwhelming and forced translation even under alarming conditions of the cell during a concurrent viral infection, or when molecular pathways are trying to circumvent precursor events that lead to autoimmunity and cancer, may cause the recipient cells to ignore their differential sensitivities which are essential for keeping normal conditions. The elF4E which is a powerful RNA regulon and a potent oncogene governing cell cycle progression and proliferation at a post-transcriptional level, may then be a great contributor to disease development. This Fact Sheet underscores the basic elements from within the official text of publication to highlight the hallmarks of disease progression due to synthetic mRNAs stability structures (analogue caps, 5’ untranlslated repeats of β-globin gene and poly A tails) fundamentally used in design of all synthetic mRNAs to promote the efficiency of translation of their encoded sequences by the human cell and therefore the organism. Specific bullet points in bold mean for urgency of further toxicity evaluation studies that need to be overtaken in order to ensure for safety of mRNAs in vaccines at current stages of development.
  • 799
  • 01 Sep 2021
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