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Antioxidants (Basel, Switzerland) Jun 2024Oxidative stress plays a central role in most chronic liver diseases and, in particular, in metabolic dysfunction-associated fatty liver disease (MAFLD), the new... (Review)
Review
Oxidative stress plays a central role in most chronic liver diseases and, in particular, in metabolic dysfunction-associated fatty liver disease (MAFLD), the new definition of an old condition known as non-alcoholic fatty liver disease (NAFLD). The mechanisms leading to hepatocellular fat accumulation in genetically predisposed individuals who adopt a sedentary lifestyle and consume an obesogenic diet progress through mitochondrial and endoplasmic reticulum dysfunction, which amplifies reactive oxygen species (ROS) production, lipid peroxidation, malondialdehyde (MDA) formation, and influence the release of chronic inflammation and liver damage biomarkers, such as pro-inflammatory cytokines. This close pathogenetic link has been a key stimulus in the search for therapeutic approaches targeting oxidative stress to treat steatosis, and a number of clinical trials have been conducted to date on subjects with NAFLD using drugs as well as supplements or nutraceutical products. Vitamin E, Vitamin D, and Silybin are the most studied substances, but several non-pharmacological approaches have also been explored, especially lifestyle and diet modifications. Among the dietary approaches, the Mediterranean Diet (MD) seems to be the most reliable for affecting liver steatosis, probably with the added value of the presence of extra virgin olive oil (EVOO), a healthy food with a high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations of phenols (oleocanthal) and phenolic alcohols, such as hydroxytyrosol (HT) and tyrosol (Tyr). In this review, we focus on non-pharmacological interventions in MAFLD treatment that target oxidative stress and, in particular, on the role of EVOO as one of the main antioxidant components of the MD.
PubMed: 38929170
DOI: 10.3390/antiox13060731 -
Foods (Basel, Switzerland) Jun 2024This study aims to improve press equipment for safflower oil production by using a mechanism that optimizes pressure distribution within screw turns. A detailed analysis...
This study aims to improve press equipment for safflower oil production by using a mechanism that optimizes pressure distribution within screw turns. A detailed analysis of the main components of the produced safflower oil was performed, encompassing both quantitative and qualitative assessments. Through the exploration of dependencies governing the safflower oil pressing process on the screw press, the optimal parameters were determined. As a result of the research, the optimal diaphragm gap between the gape cylinder and the pressing screw was determined, with the optimal oil yield percentage achieved at ω = 6.2 rad/s and δ = 5 mm. The study also compared the performance of the existing Dream Modern ODM-01 screw press and its upgraded version by analyzing the extracted oil. The results reveal changes in the quantitative and qualitative composition of the main oil components following the operation of the existing and the modernized screw presses. For instance, the amount of unsaturated fatty acids, such as oleic acid (7.7 ± 0.566%), linoleic acid (85.3 ± 1.185%), and linolenic acid (1.2 ± 0.223%), increased. There was an increase in the presence of inorganic substances in safflower oil: iron (0.023 ± 0.031 mg/kg), phosphorus (0.086 ± 0.059 mg/kg), silicium (0.136 ± 0.075 mg/kg), and others. The findings of this study hold significant commercial value and offer promising prospects for global market implementation.
PubMed: 38928850
DOI: 10.3390/foods13121909 -
Biomolecules May 2024Nuclear hormone receptors exist in dynamic equilibrium between transcriptionally active and inactive complexes dependent on interactions with ligands, proteins, and...
Nuclear hormone receptors exist in dynamic equilibrium between transcriptionally active and inactive complexes dependent on interactions with ligands, proteins, and chromatin. The present studies examined the hypothesis that endogenous ligands activate peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in keratinocytes. The phorbol ester treatment or HRAS infection of primary keratinocytes increased fatty acids that were associated with enhanced PPARβ/δ activity. Fatty acids caused PPARβ/δ-dependent increases in chromatin occupancy and the expression of angiopoietin-like protein 4 () mRNA. Analyses demonstrated that stearoyl Co-A desaturase 1 () mediates an increase in intracellular monounsaturated fatty acids in keratinocytes that act as PPARβ/δ ligands. The activation of PPARβ/δ with palmitoleic or oleic acid causes arrest at the G2/M phase of the cell cycle of HRAS-expressing keratinocytes that is not found in similarly treated HRAS-expressing -null keratinocytes. HRAS-expressing -null mouse keratinocytes exhibit enhanced cell proliferation, an effect that is mitigated by treatment with palmitoleic or oleic acid. Consistent with these findings, the ligand activation of PPARβ/δ with GW0742 or oleic acid prevented UVB-induced non-melanoma skin carcinogenesis, an effect that required PPARβ/δ. The results from these studies demonstrate that PPARβ/δ has endogenous roles in keratinocytes and can be activated by lipids found in diet and cellular components.
Topics: Keratinocytes; PPAR-beta; Animals; Mice; Stearoyl-CoA Desaturase; PPAR delta; Fatty Acids; Angiopoietin-Like Protein 4; Humans; Oleic Acid; Proto-Oncogene Proteins p21(ras); Fatty Acids, Monounsaturated; Skin Neoplasms
PubMed: 38927010
DOI: 10.3390/biom14060606 -
MSphere Jun 2024Basic leucine zipper domain transcription factors (TFs), of which yeast activator protein (Yap) is a significant class, are crucial for the development of sclerotia, the...
The basic leucine zipper domain (bZIP) transcription factor promotes evasion of host humoral immunity and regulates lipid homeostasis contributing to fungal virulence in .
UNLABELLED
Basic leucine zipper domain transcription factors (TFs), of which yeast activator protein (Yap) is a significant class, are crucial for the development of sclerotia, the stress response, vegetative growth, and spore adhesion. Nevertheless, nothing is known about how Yap TFs contribute to the pathogenicity of entomopathogenic fungus. In this work, was used to identify and knock out the yeast gene , which is similar to Yap. The gene deletion has an impact on lipid homeostasis of ; oleic acid, for example, dropped by 95.69%. The mutant exhibited much less virulence and vegetative development in comparison to the wild strain, while demonstrating a greater sensitivity to chemical stress. It is noteworthy that the physiological abnormalities brought on by deletion were largely repaired by the addition of exogenous oleic acid, as seen by the notable increase in insect survival in the blood cavity injection group. Following infection with the mutant, the host exhibits a considerable down-regulation of the expression of β-1,3-glucan recognition protein, gallerimycin, gloverin, and moricin-like protein genes. Likewise, the introduction of exogenous oleic acid markedly increased the host's expression of the aforementioned genes. In summary, regulates cellular enzyme lipid homeostasis and fungal virulence by eluding host humoral defense, which contributes to fungal chemical stress and vegetative development.
IMPORTANCE
Entomopathogenic fungi (EPF) offer an effective and eco-friendly alternative to curb insect populations in biocontrol strategy. When EPF enter the hemolymph of their host, they encounter a variety of stress reactions, such as immunological and oxidative stress. Basic leucine zipper domain transcription factors, of which yeast activator protein (Yap) is a significant class, have diverse biological functions related to metabolism, development, reproduction, conidiation, stress responses, and pathogenicity. This study demonstrates that of regulates cellular enzyme lipid homeostasis and fungal virulence by eluding host humoral defense, which contributes to fungal chemical stress and vegetative development. These findings offer fresh perspectives for comprehending molecular roles of YAP in EPF.
PubMed: 38926907
DOI: 10.1128/msphere.00351-24 -
Gels (Basel, Switzerland) May 2024Mesoporous silica nanoparticles (MSNs) are inorganic nanocarriers presenting versatile properties and the possibility to deliver drug molecules via different routes of...
Mesoporous silica nanoparticles (MSNs) are inorganic nanocarriers presenting versatile properties and the possibility to deliver drug molecules via different routes of application. Their modification with lipids could diminish the burst release profile for water-soluble molecules. In the case of oleic acid (OA) as a lipid component, an improvement in skin penetration can be expected. Therefore, in the present study, aminopropyl-functionalized MSNs were modified with oleic acid through carbodiimide chemistry and were subsequently incorporated into a semisolid hydrogel for dermal delivery. Doxorubicin served as a model drug. The FT-IR and XRD analysis as well as the ninhydrin reaction showed the successful preparation of the proposed nanocarrier with a uniform particle size (352-449 nm) and negative zeta potential. Transmission electron microscopy was applied to evaluate any possible changes in morphology. High encapsulation efficiency (97.6 ± 1.8%) was achieved together with a sustained release profile over 48 h. The composite hydrogels containing the OA-modified nanoparticles were characterized by excellent physiochemical properties (pH of 6.9; occlusion factor of 53.9; spreadability of factor 2.87 and viscosity of 1486 Pa·s) for dermal application. The in vitro permeation study showed 2.35 fold improvement compared with the hydrogel containing free drug. In vitro cell studies showed that loading in OA-modified nanoparticles significantly improved doxorubicin's cytotoxic effects toward epidermoid carcinoma cells (A431). All of the results suggest that the prepared composite hydrogel has potential for dermal delivery of doxorubicin in the treatment of skin cancer.
PubMed: 38920903
DOI: 10.3390/gels10060356 -
The EMBO Journal Jun 2024Phosphatidylserine (PS) is an important anionic phospholipid that is synthesized within the endoplasmic reticulum (ER). While PS shows the highest enrichment and serves...
Phosphatidylserine (PS) is an important anionic phospholipid that is synthesized within the endoplasmic reticulum (ER). While PS shows the highest enrichment and serves important functional roles in the plasma membrane (PM) but its role in the nucleus is poorly explored. Using three orthogonal approaches, we found that PS is also uniquely enriched in the inner nuclear membrane (INM) and the nuclear reticulum (NR). Nuclear PS is critical for supporting the translocation of CCTα and Lipin1α, two key enzymes important for phosphatidylcholine (PC) biosynthesis, from the nuclear matrix to the INM and NR in response to oleic acid treatment. We identified the PS-interacting regions within the M-domain of CCTα and M-Lip domain of Lipin1α, and show that lipid droplet formation is altered by manipulations of nuclear PS availability. Our studies reveal an unrecognized regulatory role of nuclear PS levels in the regulation of key PC synthesizing enzymes within the nucleus.
PubMed: 38918635
DOI: 10.1038/s44318-024-00151-z -
BioRxiv : the Preprint Server For... Jun 2024Lipid nanoparticles (LNPs) have transformed genetic medicine, recently shown by their use in COVID-19 mRNA vaccines. While loading LNPs with mRNA has many uses, loading...
Lipid nanoparticles (LNPs) have transformed genetic medicine, recently shown by their use in COVID-19 mRNA vaccines. While loading LNPs with mRNA has many uses, loading DNA would provide additional advantages such as long-term expression and availability of promoter sequences. However, here we show that plasmid DNA (pDNA) delivery via LNPs (pDNA-LNPs) induces acute inflammation in naïve mice which we find is primarily driven by the cGAS-STING pathway. Inspired by DNA viruses that inhibit this pathway for replication, we co-loaded endogenous lipids that inhibit STING into pDNA-LNPs. Specifically, loading nitro-oleic acid (NOA) into pDNA-LNPs (NOA-pDNA-LNPs) ameliorates serious inflammatory responses enabling prolonged transgene expression (at least 1 month). Additionally, we demonstrate the ability to iteratively optimize NOA-pDNA-LNPs' expression by performing a small LNP formulation screen, driving up expression 50-fold . Thus, NOA-pDNA-LNPs, and pDNA-LNPs co-loaded with other bioactive molecules, will provide a major new tool in the genetic medicine toolbox, leveraging the power of DNA's long-term and promoter-controlled expression.
PubMed: 38915627
DOI: 10.1101/2024.06.11.598533 -
Biotechnology For Biofuels and... Jun 2024Soybean (Glycine max) is a vital oil-producing crop. Augmenting oleic acid (OA) levels in soybean oil enhances its oxidative stability and health benefits, representing...
BACKGROUND
Soybean (Glycine max) is a vital oil-producing crop. Augmenting oleic acid (OA) levels in soybean oil enhances its oxidative stability and health benefits, representing a key objective in soybean breeding. Pongamia (Pongamia pinnata), known for its abundant oil, OA, and flavonoid in the seeds, holds promise as a biofuel and medicinal plant. A comparative analysis of the lipid and flavonoid biosynthesis pathways in Pongamia and soybean seeds would facilitate the assessment of the potential value of Pongamia seeds and advance the genetic improvements of seed traits in both species.
RESULTS
The study employed multi-omics analysis to systematically compare differences in metabolite accumulation and associated biosynthetic genes between Pongamia seeds and soybean seeds at the transcriptional, metabolic, and genomic levels. The results revealed that OA is the predominant free fatty acid in Pongamia seeds, being 8.3 times more abundant than in soybean seeds. Lipidomics unveiled a notably higher accumulation of triacylglycerols (TAGs) in Pongamia seeds compared to soybean seeds, with 23 TAG species containing OA. Subsequently, we identified orthologous groups (OGs) involved in lipid biosynthesis across 25 gene families in the genomes of Pongamia and soybean, and compared the expression levels of these OGs in the seeds of the two species. Among the OGs with expression levels in Pongamia seeds more than twice as high as in soybean seeds, we identified one fatty acyl-ACP thioesterase A (FATA) and two stearoyl-ACP desaturases (SADs), responsible for OA biosynthesis, along with two phospholipid:diacylglycerol acyltransferases (PDATs) and three acyl-CoA:diacylglycerol acyltransferases (DGATs), responsible for TAG biosynthesis. Furthermore, we observed a significantly higher content of the flavonoid formononetin in Pongamia seeds compared to soybean seeds, by over 2000-fold. This difference may be attributed to the tandem duplication expansions of 2,7,4'-trihydroxyisoflavanone 4'-O-methyltransferases (HI4'OMTs) in the Pongamia genome, which are responsible for the final step of formononetin biosynthesis, combined with their high expression levels in Pongamia seeds.
CONCLUSIONS
This study extends beyond observations made in single-species research by offering novel insights into the molecular basis of differences in lipid and flavonoid biosynthetic pathways between Pongamia and soybean, from a cross-species comparative perspective.
PubMed: 38915078
DOI: 10.1186/s13068-024-02538-w -
PLoS Genetics Jun 2024The outer membrane of gram-negative bacteria is a barrier to chemical and physical stress. Phospholipid transport between the inner and outer membranes has been an area...
The outer membrane of gram-negative bacteria is a barrier to chemical and physical stress. Phospholipid transport between the inner and outer membranes has been an area of intense investigation and, in E. coli K-12, it has recently been shown to be mediated by YhdP, TamB, and YdbH, which are suggested to provide hydrophobic channels for phospholipid diffusion, with YhdP and TamB playing the major roles. However, YhdP and TamB have different phenotypes suggesting distinct functions. It remains unclear whether these functions are related to phospholipid metabolism. We investigated a synthetic cold sensitivity caused by deletion of fadR, a transcriptional regulator controlling fatty acid degradation and unsaturated fatty acid production, and yhdP, but not by ΔtamB ΔfadR or ΔydbH ΔfadR. Deletion of tamB recuses the ΔyhdP ΔfadR cold sensitivity further demonstrating the phenotype is related to functional diversification between these genes. The ΔyhdP ΔfadR strain shows a greater increase in cardiolipin upon transfer to the non-permissive temperature and genetically lowering cardiolipin levels can suppress cold sensitivity. These data also reveal a qualitative difference between cardiolipin synthases in E. coli, as deletion of clsA and clsC suppresses cold sensitivity but deletion of clsB does not. Moreover, increased fatty acid saturation is necessary for cold sensitivity and lowering this level genetically or through supplementation of oleic acid suppresses the cold sensitivity of the ΔyhdP ΔfadR strain. Together, our data clearly demonstrate that the diversification of function between YhdP and TamB is related to phospholipid metabolism. Although indirect regulatory effects are possible, we favor the parsimonious hypothesis that YhdP and TamB have differential phospholipid-substrate transport preferences. Thus, our data provide a potential mechanism for independent control of the phospholipid composition of the inner and outer membranes in response to changing conditions based on regulation of abundance or activity of YhdP and TamB.
PubMed: 38913742
DOI: 10.1371/journal.pgen.1011335 -
Nature Communications Jun 2024Adenosine-5'-triphosphate (ATP), the primary energy currency in cellular processes, drives metabolic activities and biosynthesis. Despite its importance, understanding...
Adenosine-5'-triphosphate (ATP), the primary energy currency in cellular processes, drives metabolic activities and biosynthesis. Despite its importance, understanding intracellular ATP dynamics' impact on bioproduction and exploiting it for enhanced bioproduction remains largely unexplored. Here, we harness an ATP biosensor to dissect ATP dynamics across different growth phases and carbon sources in multiple microbial strains. We find transient ATP accumulations during the transition from exponential to stationary growth phases in various conditions, coinciding with fatty acid (FA) and polyhydroxyalkanoate (PHA) production in Escherichia coli and Pseudomonas putida, respectively. We identify carbon sources (acetate for E. coli, oleate for P. putida) that elevate steady-state ATP levels and boost FA and PHA production. Moreover, we employ ATP dynamics as a diagnostic tool to assess metabolic burden, revealing bottlenecks that limit limonene bioproduction. Our results not only elucidate the relationship between ATP dynamics and bioproduction but also showcase its value in enhancing bioproduction in various microbial species.
Topics: Adenosine Triphosphate; Biosensing Techniques; Escherichia coli; Pseudomonas putida; Fatty Acids; Polyhydroxyalkanoates; Energy Metabolism; Carbon; Oleic Acid
PubMed: 38906854
DOI: 10.1038/s41467-024-49579-1