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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
JNKs in Development of Disease
c-Jun N-terminal kinases (JNKs) have emerged as suitable therapeutic strategies. In fact, it has been demonstrated that some unspecific JNK inhibitors exert antidiabetic and neuroprotective effects, albeit they usually show high toxicity or lack therapeutic value. In this sense, natural specific JNK inhibitors, such as Licochalcone A, are promising candidates. Nonetheless, research on the understanding of the role of each of the JNKs remains mandatory in order to progress on the identification of new selective JNK isoform inhibitors. In the present review, a summary on the current gathered data on the role of JNKs in pathology is presented, as well as a discussion on their potential role in pathologies like epilepsy and metabolic-cognitive injury. Moreover, data on the effects of synthetic small molecule inhibitors that modulate JNK-dependent pathways in the brain and peripheral tissues is reviewed.
  • 1.5K
  • 23 Oct 2020
Topic Review
KRAS
The RAS family consists of membrane-associated small GTPases which play essential roles in cell survival, proliferation, and differentiation. There are four RAS protein isoforms in humans: HRAS, NRAS, and two splice variants, KRAS4A and KRAS4B. 
  • 1.5K
  • 12 Oct 2021
Topic Review
Antioxidants and Human Oocyte Mitochondrial
Mitochondria produce adenosine triphosphate (ATP) while also generating high amounts of reactive oxygen species (ROS) derived from oxygen metabolism. ROS are small but highly reactive molecules that can be detrimental if unregulated. While normally functioning mitochondria produce molecules that counteract ROS production, an imbalance between the amount of ROS produced in the mitochondria and the capacity of the cell to counteract them leads to oxidative stress and ultimately to mitochondrial dysfunction. This dysfunction impairs cellular functions through reduced ATP output and/or increased oxidative stress. Mitochondrial dysfunction may also lead to poor oocyte quality and embryo development, ultimately affecting pregnancy outcomes. Improving mitochondrial function through antioxidant supplementation may enhance reproductive performance. Recent studies suggest that antioxidants may treat infertility by restoring mitochondrial function and promoting mitochondrial biogenesis. Antioxidant properties of coenzyme-Q10, resveratrol, melatonin and several vitamins have been evaluated in the human oocyte, although their direct action on mitochondrial function has yet to be elucidated.
  • 1.5K
  • 10 Jan 2021
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
Therapeutic Potential of Intrabodies for Cancer Immunotherapy
Tumor cells are characterized by overexpressed tumor-associated antigens or mutated neoantigens, which are expressed on the cell surface or intracellularly. One strategy of cancer immunotherapy is to target cell-surface-expressed tumor-associated antigens (TAAs) with therapeutic antibodies. Intrabodies are suitable to knockdown TAAs and neoantigens without off-target effects. Intrabodies can now be selected against virtually any protein inside the cell. RNA sequencing and proteome analysis of single tumor cells combined with computational methods is bringing forward the identification of new neoantigens for the selection of anti-cancer intrabodies, which can be easily performed using phage display antibody repertoires. Anti-cancer intrabodies demonstrated tumor growth inhibition in appropriate xenograft tumor mouse models. At the moment, the biggest challenge in translating TAA/neoantigen-directed intrabodies into the clinic is the specific targeting of the intrabodies to the tumor cells. The promising development of tumor-specific lipid nanoparticles which could be embedded with an mRNA transgene or new capsid-modified and tumor-specific recombinant AAVs should enable tumor-cell-specific intrabody transfection/transduction in cancer patients and may finally bring intrabodies into the clinic.
  • 1.5K
  • 02 Sep 2022
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
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
Insulin Growth-Factor-Binding Protein 2
Evidence from observational and in vitro studies suggests that insulin growth-factor-binding pro-tein type 2 (IGFBP2) is a promising protein in non-communicable diseases, such as obesity, insulin resistance, metabolic syndrome, or type 2 diabetes. Accordingly, great efforts have been carried out to explore the role of IGFBP2 in obesity state and insulin-related diseases, which it is typically found decreased.
  • 1.5K
  • 28 Jan 2021
Topic Review
CYP3A in Health and Disease
CYP3A is an enzyme subfamily in the cytochrome P450 (CYP) superfamily and includes isoforms CYP3A4, CYP3A5, CYP3A7, and CYP3A43. CYP3A enzymes are indiscriminate toward substrates and are unique in that these enzymes metabolize both endogenous compounds and diverse xenobiotics. Constitutive regulation of CYP3A4 transcription, both positive and negative, is mediated by hepatocyte nuclear factor 4α (HNF4α) and other hepatic transcription factors. CYP3A4 expression is modulated by various mechanisms involving nuclear receptors, hormones, xenobiotics, and signaling molecules. CYP3A4 is regulated by a large number of xenobiotics, including many drugs, endogenous compounds, and many hormones, such as triiodothyronine, dexamethasone, and growth hormone. Xenobiotic- and endobiotic-mediated CYP3A4 induction is indirect and entails activation of such ligand-dependent nuclear receptors as PXR, CAR, VDR, glucocorticoid receptor (GR) α, estrogen receptor (ER) α, bile acid receptor (farnesoid X receptor; FXR), oxysterol receptor (liver X receptor; LXR), and peroxisome proliferator-activated receptor alpha (PPARα) as well as by binding to the three major cis-acting modules: CLEM4, distal XREM, and prPXRE.
  • 1.5K
  • 14 Nov 2022
Topic Review
The IGF1 Signaling Pathway
Insulin-like growth factor 1 (IGF1) is a peptide growth factor with important functions in multiple aspects of growth, development and metabolism. The biological actions of IGF1 are mediated by the IGF1 receptor (IGF1R), a cell-surface protein that is evolutionarily related to the insulin receptor (InsR).
  • 1.5K
  • 12 Oct 2023
Topic Review
Amperometric Biosensors and Biofuel Cells
Amperometric biosensors and biofuel cells are mostly based on immobilized enzymes or living cells. Among the many oxidoreductases, glucose oxidase (GOx) is used mostly in biosensor design. The same GOx can be well applied for the development of biofuel cells and self-charging capacitors based on the operation of biofuel cells. 
  • 1.5K
  • 24 Aug 2021
Topic Review
Mitochondrial Calcium
Mitochondria calcium is a double-edged sword. The low levels of calcium are essential to maintain optimal rates of ATP production, extreme levels of calcium overcoming the mitochondrial calcium retention capacity leads to loss of mitochondrial function. In moderate amounts, ATP synthesis rates are inhibited in a calcium-titratable manner.
  • 1.5K
  • 31 Jan 2023
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 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
Bone Resorption
Bone resorption, the process by which bone is broken down to liberate products needed by the body’s metabolism, most prominently, but not exclusively, calcium, is incompletely understood.
  • 1.5K
  • 29 Jan 2022
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
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
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
Two phytochrome A Types in Plants
The phytochrome (phy) system of plants with the main phyA and phyB controls their development beginning from seed germination to fruiting and senescence. The regulation reactions are categorized into three modes—the very low and low fluence responses (VLFR and LFR) and the high irradiance responses (HIR). The phyA is unique among the other phytochromes; it is major in etiolated seedlings and light-labile, and mediates all the three photoresponse modes. The phyB is light-stable, dominates in deetiolated plants, and performs the LFR. The phyA is itself heterogeneous which may explain its functional complexity. It comprises two native types, phyA′ and phyA″, the products of post-translational modification of the molecule at the N-terminus, possibly, via serine phosphorylation. This alters chromophore-apoprotein interactions resulting in the different photochemical, phenomenological, and functional properties of the two phyA pools. The phyA′ is major, water-soluble, and light-labile; the phyA″ is minor, amphiphilic, and relatively light-stable. The phyA′ mediates the VLFR whereas the water-soluble fraction of phyA″ is responsible for the HIR and LFR, the processes taking place in the nucleus. The membrane- (protein-) associated fraction of phyA” is likely to participate in the cytoplasmic photoregulation processes. The phyA pools' functions—their mode, intensity and sign—depend on plant's species, genotype and organ/tissue. The evidence of the existence of the two distinct phyA types in a plant, and their physicochemical properties and their role in the phyA functioning are discussed.
  • 1.5K
  • 17 May 2023
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