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International Journal of Molecular... Jun 2024β C-S lyases (β-CSLs; EC 4.4.1.8) are enzymes catalyzing the dissociation of β carbon-sulfur bonds of cysteine S-conjugates to produce odorant metabolites with a free... (Review)
Review
β C-S lyases (β-CSLs; EC 4.4.1.8) are enzymes catalyzing the dissociation of β carbon-sulfur bonds of cysteine S-conjugates to produce odorant metabolites with a free thiol group. These enzymes are increasingly studied for their role in flavor generation in a variety of food products, whether these processes occur directly in plants, by microbial β-CSLs during fermentation, or in the mouth under the action of the oral microbiota. Microbial β-CSLs react with sulfur aroma precursors present in beverages, vegetables, fruits, or aromatic herbs like hop but also potentially with some precursors formed through Maillard reactions in cooked foods such as meat or coffee. β-CSLs from microorganisms like yeasts and lactic acid bacteria have been studied for their role in the release of polyfunctional thiols in wine and beer during fermentation. In addition, β-CSLs from microorganisms of the human oral cavity were shown to metabolize similar precursors and to produce aroma in the mouth with an impact on retro-olfaction. This review summarizes the current knowledge on β-CSLs involved in flavor generation with a focus on enzymes from microbial species present either in the fermentative processes or in the oral cavity. This paper highlights the importance of this enzyme family in the food continuum, from production to consumption, and offers new perspectives concerning the utilization of β-CSLs as a flavor enhancer.
Topics: Humans; Flavoring Agents; Fermentation; Carbon-Sulfur Lyases; Bacteria; Taste
PubMed: 38928118
DOI: 10.3390/ijms25126412 -
International Journal of Molecular... Jun 2024Neural precursor cells (NPCs) that persist in the postnatal/adult subventricular zone (SVZ) express connexins that form hemichannels and gap junctions. Gap junctional...
Neural precursor cells (NPCs) that persist in the postnatal/adult subventricular zone (SVZ) express connexins that form hemichannels and gap junctions. Gap junctional communication plays a role in NPC proliferation and differentiation during development, but its relevance on postnatal age remains to be elucidated. In this work we aimed to evaluate the effect of the blockade of gap junctional communication on proliferation and cell fate of NPCs obtained from the SVZ of postnatal rats. NPCs were isolated and expanded in culture as neurospheres. Electron microscopy revealed the existence of gap junctions among neurosphere cells. Treatment of cultures with octanol, a broad-spectrum gap junction blocker, or with Gap27, a specific blocker for gap junctions formed by connexin43, produced a significant decrease in bromodeoxyuridine incorporation. Octanol treatment also exerted a dose-dependent antiproliferative effect on glioblastoma cells. To analyze possible actions on NPC fate, cells were seeded in the absence of mitogens. Treatment with octanol led to an increase in the percentage of astrocytes and oligodendrocyte precursors, whereas the percentage of neurons remained unchanged. Gap27 treatment, in contrast, did not modify the differentiation pattern of SVZ NPCs. Our results indicate that general blockade of gap junctions with octanol induces significant effects on the behavior of postnatal SVZ NPCs, by reducing proliferation and promoting glial differentiation.
Topics: Animals; Gap Junctions; Neural Stem Cells; Cell Proliferation; Cell Differentiation; Rats; Octanols; Neuroglia; Cells, Cultured; Lateral Ventricles; Connexin 43; Rats, Wistar; Astrocytes; Animals, Newborn; Humans
PubMed: 38927995
DOI: 10.3390/ijms25126288 -
Cancers Jun 2024Exposure to ionizing radiation is associated with an increased risk of hematologic malignancies in myeloid and lymphoid lineages in humans and experimental mice. Given... (Review)
Review
Exposure to ionizing radiation is associated with an increased risk of hematologic malignancies in myeloid and lymphoid lineages in humans and experimental mice. Given that substantial evidence links radiation exposure with the risk of hematologic malignancies, it is imperative to deeply understand the mechanisms underlying cellular and molecular changes during the latency period between radiation exposure and the emergence of fully transformed malignant cells. One experimental model widely used in the field of radiation and cancer biology to study hematologic malignancies induced by radiation exposure is mouse models of radiation-induced thymic lymphoma. Murine radiation-induced thymic lymphoma is primarily driven by aberrant activation of Notch signaling, which occurs frequently in human precursor T-cell lymphoblastic lymphoma (T-LBL) and T-cell lymphoblastic leukemia (T-ALL). Here, we summarize the literature elucidating cell-autonomous and non-cell-autonomous mechanisms underlying cancer initiation, progression, and malignant transformation in the thymus following total-body irradiation (TBI) in mice.
PubMed: 38927929
DOI: 10.3390/cancers16122224 -
Bioengineering (Basel, Switzerland) May 2024Esophageal carcinoma is the sixth-leading cause of cancer death worldwide. A precursor to esophageal adenocarcinoma (EAC) is Barrett's Esophagus (BE). Early-stage...
Design and Evaluation of ScanCap: A Low-Cost, Reusable Tethered Capsule Endoscope with Blue-Green Illumination Imaging for Unsedated Screening and Early Detection of Barrett's Esophagus.
Esophageal carcinoma is the sixth-leading cause of cancer death worldwide. A precursor to esophageal adenocarcinoma (EAC) is Barrett's Esophagus (BE). Early-stage diagnosis and treatment of esophageal neoplasia (Barrett's with high-grade dysplasia/intramucosal cancer) increase the five-year survival rate from 10% to 98%. BE is a global challenge; however, current endoscopes for early BE detection are costly and require extensive infrastructure for patient examination and sedation. We describe the design and evaluation of the first prototype of ScanCap, a high-resolution optical endoscopy system with a reusable, low-cost tethered capsule, designed to provide high-definition, blue-green illumination imaging for the early detection of BE in unsedated patients. The tethered capsule (12.8 mm diameter, 35.5 mm length) contains a color camera and rotating mirror and is designed to be swallowed; images are collected as the capsule is retracted manually via the tether. The tether provides electrical power and illumination at wavelengths of 415 nm and 565 nm and transmits data from the camera to a tablet. The ScanCap prototype capsule was used to image the oral mucosa in normal volunteers and ex vivo esophageal resections; images were compared to those obtained using an Olympus CV-180 endoscope. Images of superficial capillaries in intact oral mucosa were clearly visible in ScanCap images. Diagnostically relevant features of BE, including irregular Z-lines, distorted mucosa, and dilated vasculature, were clearly visible in ScanCap images of ex vivo esophageal specimens.
PubMed: 38927792
DOI: 10.3390/bioengineering11060557 -
Genes Jun 2024Brain lipid homeostasis is an absolute requirement for proper functionality of nerve cells and neurological performance. Current evidence demonstrates that lipid...
Multifactor Analyses of Frontal Cortex Lipids in the APP/PS1 Model of Familial Alzheimer's Disease Reveal Anomalies in Responses to Dietary n-3 PUFA and Estrogenic Treatments.
Brain lipid homeostasis is an absolute requirement for proper functionality of nerve cells and neurological performance. Current evidence demonstrates that lipid alterations are linked to neurodegenerative diseases, especially Alzheimer's disease (AD). The complexity of the brain lipidome and its metabolic regulation has hampered the identification of critical processes associated with the onset and progression of AD. While most experimental studies have focused on the effects of known factors on the development of pathological hallmarks in AD, e.g., amyloid deposition, tau protein and neurofibrillary tangles, neuroinflammation, etc., studies addressing the causative effects of lipid alterations remain largely unexplored. In the present study, we have used a multifactor approach combining diets containing different amounts of polyunsaturated fatty acids (PUFAs), estrogen availabilities, and genetic backgrounds, i.e., wild type (WT) and APP/PS1 (FAD), to analyze the lipid phenotype of the frontal cortex in middle-aged female mice. First, we observed that severe n-3 PUFA deficiency impacts the brain n-3 long-chain PUFA (LCPUFA) composition, yet it was notably mitigated by hepatic de novo synthesis. n-6 LCPUFAs, ether-linked fatty acids, and saturates were also changed by the dietary condition, but the extent of changes was dependent on the genetic background and hormonal condition. Likewise, brain cortex phospholipids were mostly modified by the genotype (FAD>WT) with nuanced effects from dietary treatment. Cholesterol (but not sterol esters) was modified by the genotype (WT>FAD) and dietary condition (higher in DHA-free conditions, especially in WT mice). However, the effects of estrogen treatment were mostly observed in relation to phospholipid remodeling in a genotype-dependent manner. Analyses of lipid-derived variables indicate that nerve cell membrane biophysics were significantly affected by the three factors, with lower membrane microviscosity (higher fluidity) values obtained for FAD animals. In conclusion, our multifactor analyses revealed that the genotype, diet, and estrogen status modulate the lipid phenotype of the frontal cortex, both as independent factors and through their interactions. Altogether, the outcomes point to potential strategies based on dietary and hormonal interventions aimed at stabilizing the brain cortex lipid composition in Alzheimer's disease neuropathology.
Topics: Alzheimer Disease; Animals; Fatty Acids, Omega-3; Mice; Frontal Lobe; Female; Disease Models, Animal; Amyloid beta-Protein Precursor; Estrogens; Mice, Transgenic; Presenilin-1; Lipid Metabolism; Humans
PubMed: 38927745
DOI: 10.3390/genes15060810 -
Genes Jun 2024Previous studies have demonstrated the essential role of the Kisspeptin/Neurokinin B/Dynorphin A (KNDy) pathway in female reproductive biology by regulating the activity...
Previous studies have demonstrated the essential role of the Kisspeptin/Neurokinin B/Dynorphin A (KNDy) pathway in female reproductive biology by regulating the activity of the hypothalamic-pituitary-gonadal axis. Identified loss-of-function mutations in these genes are linked to various reproductive disorders. This study investigated genetic disorders linked to mutations in the genes related to premature ovarian insufficiency (POI). A cohort of 14 Mexican POI patients underwent genetic screening using PCR-SSCP and Sanger sequencing, assessing the genetic variations' impact on protein function thereafter using multiple in silico tools. The PCR excluded extensive deletions, insertions, and duplications, while SSCP detected five genetic variants. Variations occurred in the (c.58G>A and c.242C>G), (c.1091A>T), (c.600C>T), and (c.36G>T) genes, whereas no genetic anomalies were found in genes. Each single-nucleotide variant underwent genotyping using PCR-SSCP in 100 POI-free subjects. Their allelic frequencies paralleled the patient group. These observations indicate that allelic variations in the genes may not contribute to POI etiology. Hence, screening for mutations in genes should not be a part of the diagnostic protocol for POI.
Topics: Humans; Female; Primary Ovarian Insufficiency; Mexico; Adult; Neurokinin B; Kisspeptins; Cohort Studies; Polymorphism, Single Nucleotide; Receptors, Kisspeptin-1; Enkephalins; Protein Precursors
PubMed: 38927724
DOI: 10.3390/genes15060788 -
Genes Jun 2024Climate change has resulted in an increased demand for Japanese bunching onions L., genomes FF) with drought resistance. A complete set of alien monosomic addition...
Climate change has resulted in an increased demand for Japanese bunching onions L., genomes FF) with drought resistance. A complete set of alien monosomic addition lines of with extra chromosomes from shallot ( L. Aggregatum group, AA), represented as FF + 1A-FF + 8A, displays a variety of phenotypes that significantly differ from those of the recipient species. In this study, we investigated the impact of drought stress on abscisic acid (ABA) and its precursor, β-carotene, utilizing this complete set. In addition, we analyzed the expression levels of genes related to ABA biosynthesis, catabolism, and drought stress signal transduction in FF + 1A and FF + 6A, which show characteristic variations in ABA accumulation. A number of unigenes related to ABA were selected through a database using TDB. Under drought conditions, FF + 1A exhibited significantly higher ABA and β-carotene content compared with FF. Additionally, the expression levels of all ABA-related genes in FF + 1A were higher than those in FF. These results indicate that the addition of chromosome 1A from shallot caused the high expression of ABA biosynthesis genes, leading to increased levels of ABA accumulation. Therefore, it is expected that the introduction of alien genes from the shallot will upwardly modify ABA content, which is directly related to stomatal closure, leading to drought stress tolerance in FF.
Topics: Abscisic Acid; Droughts; Gene Expression Regulation, Plant; Stress, Physiological; Onions; Monosomy; beta Carotene; Allium
PubMed: 38927690
DOI: 10.3390/genes15060754 -
Genes May 2024LONP1 is the principal AAA+ unfoldase and bulk protease in the mitochondrial matrix, so its deletion causes embryonic lethality. The AAA+ unfoldase CLPX and the... (Review)
Review
Knockout Mouse Studies Show That Mitochondrial CLPP Peptidase and CLPX Unfoldase Act in Matrix Condensates near IMM, as Fast Stress Response in Protein Assemblies for Transcript Processing, Translation, and Heme Production.
LONP1 is the principal AAA+ unfoldase and bulk protease in the mitochondrial matrix, so its deletion causes embryonic lethality. The AAA+ unfoldase CLPX and the peptidase CLPP also act in the matrix, especially during stress periods, but their substrates are poorly defined. Mammalian CLPP deletion triggers infertility, deafness, growth retardation, and cGAS-STING-activated cytosolic innate immunity. CLPX mutations impair heme biosynthesis and heavy metal homeostasis. CLPP and CLPX are conserved from bacteria to humans, despite their secondary role in proteolysis. Based on recent proteomic-metabolomic evidence from knockout mice and patient cells, we propose that CLPP acts on phase-separated ribonucleoprotein granules and CLPX on multi-enzyme condensates as first-aid systems near the inner mitochondrial membrane. Trimming within assemblies, CLPP rescues stalled processes in mitoribosomes, mitochondrial RNA granules and nucleoids, and the D-foci-mediated degradation of toxic double-stranded mtRNA/mtDNA. Unfolding multi-enzyme condensates, CLPX maximizes PLP-dependent delta-transamination and rescues malformed nascent peptides. Overall, their actions occur in granules with multivalent or hydrophobic interactions, separated from the aqueous phase. Thus, the role of CLPXP in the matrix is compartment-selective, as other mitochondrial peptidases: MPPs at precursor import pores, m-AAA and i-AAA at either IMM face, PARL within the IMM, and OMA1/HTRA2 in the intermembrane space.
Topics: Endopeptidase Clp; Animals; Mice; Mitochondria; Mitochondrial Proteins; Mice, Knockout; Heme; Protein Biosynthesis; Humans; Mitochondrial Membranes; Stress, Physiological
PubMed: 38927630
DOI: 10.3390/genes15060694 -
Biomedicines May 2024Endometriosis is a benign condition affecting women of reproductive age. A potential association with ovarian cancer has been documented. Atypical endometriosis (AE) is... (Review)
Review
Endometriosis is a benign condition affecting women of reproductive age. A potential association with ovarian cancer has been documented. Atypical endometriosis (AE) is characterized by deviations from the typical microscopic appearance of endometriosis, including cytologic and architectural atypia. AE has been recognized as a potential precursor to endometriosis-associated ovarian cancers (EAOC), particularly endometrioid and clear cell subtypes. AE presents challenges in diagnosis due to its diverse clinical and pathological features, often requiring careful histological evaluation for accurate identification. Architectural AE, defined by localized proliferation of crowded glands with atypical epithelium resembling endometrial neoplasia, and cytologic AE, characterized by nuclear atypia within the epithelial lining of endometriotic cysts, are key subtypes. Immunohistochemical and molecular studies have revealed aberrant expression of markers such as Ki67, COX-2, BAF250a, p53, estrogen receptor, progesterone receptor, and IMP-3. Long-term follow-up studies suggest relatively low recurrence and malignant transformation rates among patients with AE, but uncertainties persist regarding its exact malignancy potential and optimal management strategies. Integration of artificial intelligence and shared molecular aberrations between AE and EAOC may enhance diagnostic accuracy. Continuous interdisciplinary collaboration and ongoing research efforts are crucial for a deeper understanding of the relationship between endometriosis and carcinogenesis, ultimately improving patient care and surveillance.
PubMed: 38927416
DOI: 10.3390/biomedicines12061209 -
Biomedicines May 2024Alzheimer's disease (AD), the most common cause of dementia, is characterized by disruptions in memory, cognition, and personality, significantly impacting morbidity and...
Alzheimer's disease (AD), the most common cause of dementia, is characterized by disruptions in memory, cognition, and personality, significantly impacting morbidity and mortality rates among older adults. However, the exact pathophysiological mechanism of AD remains unknown, and effective treatment options for AD are still lacking. Human induced pluripotent stem cells (iPSC) are emerging as promising platforms for disease research, offering the ability to model the genetic mutations associated with various conditions. Patient-derived iPSCs are useful for modeling neurodegenerative and neurodevelopmental disorders. In this study, we generated AD iPSCs from peripheral blood mononuclear cells obtained from a 65-year-old patient with AD carrying the E682K mutation in the gene encoding the amyloid precursor protein. Cerebral organoids derived from AD iPSCs recapitulated the AD phenotype, exhibiting significantly increased levels of tau protein. Our analysis revealed that an iPSC disease model of AD is a valuable assessment tool for pathophysiological research and drug screening.
PubMed: 38927400
DOI: 10.3390/biomedicines12061193