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Topic Review
C/EBPs
CCAAT-enhancer-binding proteins (C/EBPs) is a family of six structurally homologous transcription factors that promote the expression of genes involved in different cellular responses, such as proliferation, growth, and differentiation. These transcription factors control the differentiation of several cell types, and have key roles in regulating cellular proliferation, through interaction with cell cycle proteins. The molecular structure of C/EBPs and their ability to interact with a multitude of factors determine their complex functions in different cells. In fact, C/EBPs can be activated or inhibited by a variety of intracellular or extracellular signals. In addition, post-translational modifications and interaction with other proteins can regulate their expression and activity in a complex manner. C/EBPs can activate or repress several classes of genes implicated in cell differentiation, metabolism, inflammation, and immune response. Moreover, C/EBPs play an important role in cancer progression and metastasis, showing both pro-oncogenic and onco-suppressor functions. Interestingly, the same isotype of C/EBP can exhibit both of these opposite functions. This “Janus” role of C/EBPs in cancer could depend on their particular position at the crossroads between proliferation and differentiation. Specific conditions such as cell type, microenvironment, type of heterodimerization, or interaction with different regulatory proteins can tip the balance towards pro- or anti-oncogenic action.
  • 1.5K
  • 13 Sep 2021
Topic Review
The Physiological and Pathological Role of Acyl-CoA Oxidation
Fatty acid metabolism, including β-oxidation (βOX), plays an important role in human physiology and pathology. βOX is an essential process in the energy metabolism of most human cells. Moreover, βOX is also the source of acetyl-CoA, the substrate for (a) ketone bodies synthesis, (b) cholesterol synthesis, (c) phase II detoxication, (d) protein acetylation, and (d) the synthesis of many other compounds, including N-acetylglutamate—an important regulator of urea synthesis. 
  • 1.5K
  • 20 Oct 2023
Topic Review
Exposome
The “exposome” is the cumulative exposures (diet, exercise, environmental exposure, vaccination, genetics, etc.) an individual has experienced and provides a mechanism for the establishment of immune training or immunotolerance. It is becoming increasingly clear that trained immunity constitutes a delicate balance between the dose, duration, and order of exposures. Upon innate stimuli, trained immunity or tolerance is shaped by epigenetic and metabolic changes that alter hematopoietic stem cell lineage commitment and responses to infection. Due to the immunomodulatory role of the exposome, understanding innate immune training is critical for understanding why some individuals exhibit protective phenotypes while closely related individuals may experience immunotolerant effects (e.g., the order of exposure can result in completely divergent immune responses). Research on the exposome and trained immunity may be leveraged to identify key factors for improving vaccination development, altering inflammatory disease development, and introducing potential new prophylactic treatments, especially for diseases such as COVID-19, which is currently a major health issue for the world. Furthermore, continued exposome research may prevent many deleterious effects caused by immunotolerance that frequently result in host morbidity or mortality. 
  • 1.5K
  • 09 Dec 2020
Topic Review
Vascularization and Cancer Biology
Vascularization is another hallmark of cancer, whereby cancer cells promote the formation of blood vessels to deliver nutrients for fast-growing solid tumors. The most well-known process of vascularization is angiogenesis. In normal cells and tissues, the angiogenesis is a controlled process that is turned on or off depending on the needs of the cells; however, in cancerous cells and tumors, the angiogenesis process is continuous and there is a dysregulation of pro- and antiangiogenesis factors . This continuous activation of angiogenesis allows the cancer cells to form blood vessels to obtain sufficient nutrients for continuous growth and proliferation. There are other ways tumors can achieve vascularization, such as vascular co-option, intussusceptive microvascular growth and vasculogenic mimicry.
  • 1.5K
  • 22 Apr 2022
Topic Review
Congenital Lung Malformations
Congenital lung malformations arise during development and include numerous anatomical anomalies of the lung and respiratory tree. They are usually detected prenatally by ultrasonography and comprise congenital pulmonary airway malformation (CPAM), bronchopulmonary sequestration (BPS), bronchogenic cysts (BC), and more rarely bronchial atresia, congenital lobar emphysema (CLE), and congenital tracheal obstruction. This entry focuses on the molecular and genetic determinants of the most frequent anomalies: CPAM, BPS, and BC. Congenital diaphragmatic hernia (CDH) is not usually included in this group; however, since the lung is also highly affected in this condition, we have also incorporated evidence related to lung hypoplasia.
  • 1.5K
  • 30 Nov 2021
Topic Review
UFM1
Post-translational modification with Ubiquitin-like proteins represents a complex signaling language regulating virtually every cellular process. Among these post-translational modifiers is Ubiquitin-fold modifier (UFM1), which is covalently attached to its substrates through the orchestrated action of a dedicated enzymatic cascade. Originally identified to be involved embryonic development, its biological function remains enigmatic. Recent research reveals that UFM1 regulates a variety of cellular events ranging from DNA repair to autophagy and ER stress response implicating its involvement in a variety of diseases. Given the contribution of UFM1 to numerous pathologies, the enzymes of the UFM1 cascade represent attractive targets for pharmacological inhibition.
  • 1.5K
  • 26 Feb 2021
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.
  • 1.5K
  • 16 Apr 2021
Topic Review
Inhibitors of Cyclin-Dependent Kinases
Protein phosphorylation is a necessary mechanism to drive numerous cellular processes such as cell division, migration, differentiation and programmed cell death. This process is regulated by many enzymes, including cyclin-dependent kinases (CDKs) which phosphorylate proteins on their serine and threonine amino acid residues. The 20 members of CDK family known to this day regulate the cell cycle, transcription and splicing.
  • 1.5K
  • 28 Apr 2021
Topic Review
Dermatan Sulfate in Tissue Development
The crucial roles of dermatan sulfate (DS) have been demonstrated in tissue development of the cutis, blood vessels, and bone through construction of the extracellular matrix and cell signaling. DS classically exerts physiological functions via interaction with collagens, growth factors, and heparin cofactor-II.
  • 1.5K
  • 14 Jul 2022
Topic Review
Macrophage Polarization States
The M1/M2 macrophage paradigm plays a key role in tumor progression. M1 macrophages are historically regarded as anti-tumor, while M2-polarized macrophages, commonly deemed tumor-associated macrophages (TAMs), are contributors to many pro-tumorigenic outcomes in cancer through angiogenic and lymphangiogenic regulation, immune suppression, hypoxia induction, tumor cell proliferation, and metastasis.
  • 1.5K
  • 21 Jul 2021
Topic Review
FTO Intronic SNP
Browning of white adipose tissue shifts adipocytes from energy storage white to energy expenditure beige types. The balance between the two adipocyte populations in white adipose tissue is highly determined by noncoding variants of the Fat mass and obesity-associated (FTO) locus which has the strongest association with obesity. The rs1421085 FTO risk allele results in a loss of ARID5B repression of IRX3 and IRX5 which promotes excess white adipocyte formation. Recent studies have revealed the presence of brown adipose tissues at several anatomical sites in humans including the deep-neck (DN).  We found that the characteristic gene expression profile and associated pathways of DN brown adipocytes were determined by partially overlapping effects of tissue site specific commitments of the stem cells, PPARγ stimulation and the FTO status of donors. The presence of FTO rs1421085 risk alleles had a strong influence, manifested during differentiation, on browning resulting in compromised expression of metabolic and mitochondrial genes as well as pathways which are decisive in thermogenesis.
  • 1.5K
  • 30 Oct 2020
Topic Review
Chemical Chaperones
Chemical chaperones are well known as inhibitors of protein and peptide self-assembly, as well as structural stabilizers of misfolded enzymes. We discovered that chemical chaperones inhibit adenine self-assembly both in a yeast model and in vitro. According to our study, chemical chaperones might have a dual function as enhancers of enzyme stability and as inhibitors of toxic metabolite self-assembly. This novel approach could be implemented for the rational design of inhibitors that target metabolite self-assembly as therapeutics for inborn errors of metabolism.
  • 1.5K
  • 15 Sep 2021
Topic Review
Cardioprotective Role of Vascular Endothelial Growth Factor B
Coronary heart disease (CHD) is the leading cause of death around the world. Based on the roles of vascular endothelial growth factor (VEGF) family members to regulate blood and lymphatic vessels and metabolic functions, several therapeutic approaches have been attempted. However proangiogenic therapies based on classical VEGF-A have been disappointing. Therefore, it has become important to focus on other VEGFs, like VEGF-B, which is a novel member of the VEGF family. 
  • 1.5K
  • 03 Jan 2023
Topic Review
TRPM7
The transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a ubiquitously expressed membrane protein, which forms a cation channel linked to a cytosolic protein kinase.
  • 1.5K
  • 02 Nov 2020
Topic Review
Human Paraoxonase-2 (PON2)
PON1, PON2, and PON3 belong to a family of lactone hydrolyzing enzymes endowed with various substrate specificities. Among PONs, PON2 shows the highest hydrolytic activity toward many acyl-homoserine lactones (acyl-HL) involved in bacterial quorum-sensing signaling. Accordingly, defense against pathogens, such as Brevundimonas aeruginosa (B. aeruginosa), was postulated to be the principal function of PON2. Moreover, findings have highlighted the importance of PON2 in oxidative stress control, inhibition of apoptosis, and the progression of various types of malignancies.
  • 1.5K
  • 17 Jun 2022
Topic Review
The Identity of Thrombosis
Since “two-path unifying theory” of hemostasis was published, it has been confirmed that hemostasis is blood clotting mechanism forming “hemostatic plug” in bleeding from external and internal bodily injury, and is also thrombosis promoting mechanism in intravascular injury by producing “thrombus”.
  • 1.5K
  • 10 Nov 2022
Topic Review
Treatment of Galactosemia
Galactosemia is an inborn disorder of carbohydrate metabolism characterized by the inability to metabolize galactose, a sugar contained in milk (the main source of nourishment for infants), and convert it into glucose, the sugar used by the body as the primary source of energy. Galactosemia is an autosomal recessive genetic disease that can be diagnosed at birth, even in the absence of symptoms, with newborn screening by assessing the level of galactose and the GALT enzyme activity, as GALT defect constitutes the most frequent cause of galactosemia. Currently, galactosemia cannot be cured, but only treated by means of a diet with a reduced content of galactose and lactose. Although the diet is able to reverse the neonatal clinical picture, it does not prevent the development of long-term complications. 
  • 1.5K
  • 29 Jul 2022
Topic Review
The HMOX1 Pathway
Heme oxygenase (HMOX1) is a key enzyme that catalyzes the rate-limiting first step in the heme degradation process, generating carbon monoxide, ferrous, and biliverdin, and therefore HMOX1 has a cytoprotective role as excess free heme has been shown to induce apoptosis. HMOX1 is expressed at high levels in the lungs and has been shown to mediate the anti-inflammatory effect of interleukin-10 (IL-10) in mice. Given these functions of HMOX1, it has been implicated in a variety of pathological states, including myocardial infarction, diabetes, chronic obstructive pulmonary disease (COPD). The upregulation of HMOX1 has been shown to have a protective role against the oxidative stress produced upon HIV, DENV, HCV, and IAV infections.
  • 1.5K
  • 26 Oct 2020
Topic Review
The Effects of Diets on the “Gut–Brain” Pathways
With depression becoming increasingly prevalent, being closely associated with stress, and many patients exhibiting resistance to current treatments, depression pathophysiology requires further elucidation. Recent research has shown complex bidirectional links between the brain and the gut, and the gut microbiota and the influence of diet is beginning to provide new clues to the complex nature of this disorder. It is well known that diet is a key modulator of gut microbial composition. In humans, good quality plant-based diets such as the Mediterranean diet have been shown to reduce pathogenic bacteria in the gut, increase Bifidobacterium and Clostridium, as well as lower the risk of depression, while poorer quality diets such as the Western diet have been shown to reduce Lactobacillus in the gut, reduce overall gut microbial diversity and have been associated with increased depression risk. Evaluating the effects of diets on the brain-to-gut and gut-to-brain mechanisms in animal models of stress and depression may aid in the elucidation of the pathophysiology of depression and may provide novel therapeutic approaches. 
  • 1.5K
  • 21 Feb 2022
Topic Review
Mitochondrial Transporter Protein Families
Mitochondrial carriers facilitate the transfer of small molecules across the inner mitochondrial membrane (IMM) to support mitochondrial function and core cellular processes. In addition to the classical SLC25 (solute carrier family 25) mitochondrial carriers, the past decade has led to the discovery of additional protein families with numerous members that exhibit IMM localization and transporter-like properties. These include mitochondrial pyruvate carriers, sideroflexins, and mitochondrial cation/H+ exchangers. These transport proteins were linked to vital physiological functions and disease.
  • 1.5K
  • 20 Jan 2021
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