-
FASEB Journal : Official Publication of... Aug 2023Excessive lipid accumulation is a critical characteristic in the development of nonalcoholic steatohepatitis (NASH). The underlying molecular mechanism, however, is...
Excessive lipid accumulation is a critical characteristic in the development of nonalcoholic steatohepatitis (NASH). The underlying molecular mechanism, however, is unclear. In this study, we explored whether and how Krüppel-like factor 14 (KLF14) affects hepatic lipid metabolism in NASH. KLF14 expression was detected in NASH patients and mice fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Adeno-associated viruses and adenoviruses were used to alter hepatic KLF14 expression in vivo or in vitro to investigate how KLF14 functions in lipid regulation. The molecular mechanisms were explored using RNA-seq, luciferase reporter, and ChIP assays. The fatty liver phenotype was analyzed histopathologically, and serum and hepatocyte biochemical parameters were measured. The NASH mouse model developed quickly in C57BL/6J mice fed a CDAHFD for 8 weeks. We found that KLF14 expression was decreased in NASH patients and CDAHFD mice. Oleic acid and palmitic acid treatment also reduced KLF14 levels in hepatocytes. KLF14 knockdown downregulated the genes involved in fatty acid oxidation, promoting the progression of hepatic steatosis. In contrast, hepatic KLF14 overexpression alleviated lipid accumulation and oxidative stress in CDAHFD mice. These effects resulted from direct activation of the PPARα signaling pathway. PPARα inhibition diminished the KLF14 overexpression-reduced protective effects against steatosis in OA&PA-treated MPHs and AAV-KLF14-infected CDAHFD mice. These data reveal that hepatic KLF14 regulates lipid accumulation and oxidative stress through the KLF14-PPARα pathway as NASH progresses. KLF14 may be a novel therapeutic target for hepatic steatosis.
Topics: Animals; Mice; Kruppel-Like Transcription Factors; Lipid Metabolism; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Oleic Acid; PPAR alpha
PubMed: 37389939
DOI: 10.1096/fj.202300448R -
Military Medicine May 2024Acute respiratory distress syndrome (ARDS) is a widespread and often fatal clinical syndrome marked by the acute onset of pulmonary edema and inflammatory-mediated...
INTRODUCTION
Acute respiratory distress syndrome (ARDS) is a widespread and often fatal clinical syndrome marked by the acute onset of pulmonary edema and inflammatory-mediated disruptions in alveolar-capillary permeability resulting in impaired gas exchange and tissue oxygenation with subsequent acute respiratory failure that accounts for 10.4% of all intensive care unit admissions worldwide and boasts a mortality rate of 38.5%. The current treatment for ARDS remains largely supportive. This is largely because of the many challenges of achieving a stable and sustainable animal model that recreates the pathophysiology of ARDS experimentally in a controlled setting to allow research to elucidate potential treatments of ARDS moving forward.
MATERIALS AND METHODS
The bronchoalveolar lavage and oleic acid models are currently the 2 most frequently used experimental models in inducing ARDS in animal models. This study demonstrated that combining them into a "two-hit model" can produce sustained ARDS in swine models per the Horowitz index (PaO2/FiO2 ratio of ≤300 mmHg). Additionally, expected changes in pH, pCO2, lung compliance, cytokines, and tissue histopathology were observed and add to our confidence and reliability that the "two-hit model" produces symptomatic ARDS in a manner very similar to that observed in humans.
RESULTS AND CONCLUSIONS
In conclusion, we demonstrated a viable animal model of human ARDS that is maintained for a prolonged period, suitable for continuous monitoring of the progression, and evaluation of potential future treatments and procedures to reduce patient morbidity and mortality. To carry out this two-hit model, lung injury was induced through a combination of bronchoalveolar lavage and oleic acid administration and the disease process of ARDS is subsequently tracked through clinically relevant parameters such as respiratory mechanics, cytokine response, aretrial blood gas (ABG) changes, and observation of postmortem histopathologic changes. This promising new model has the capacity to successfully replicate human ARDS which is a well-known and notoriously multifactorial pathogenic process to reproduce experimentally for an extended period of time. The "two-hit model" is a viable and appropriate model for the research of novel treatments for ARDS.
PubMed: 38771004
DOI: 10.1093/milmed/usae191 -
Journal of Cosmetic Dermatology Aug 2023Redness of the facial skin is an important cosmetic concern. Although qualitative and quantitative modifications of sebum on the skin surface are major pathogenic...
BACKGROUND
Redness of the facial skin is an important cosmetic concern. Although qualitative and quantitative modifications of sebum on the skin surface are major pathogenic factors of chronic inflammatory skin conditions, the relationship between skin redness, sebum, and mild inflammation on the cheeks of healthy subjects remains elusive.
AIMS
We aimed to explore the correlation between cheek redness and sebum and inflammatory cytokines in the stratum corneum (SC) of healthy subjects. We also examined the effects of representative sebum lipids on the gene expression of inflammatory cytokines in cultured keratinocytes.
PATIENTS/METHODS
This study included 198 healthy participants. Skin sebum was analyzed using flow injection analysis, and skin redness was assessed using a spectrophotometer. Inflammatory cytokines in tape-stripped SC were measured using enzyme-linked immunosorbent assay.
RESULTS
Cheek redness parameters positively correlated with the amount of skin sebum and the proportion of monounsaturated free fatty acids (C16:1 and C18:1) in the sebum. They also positively correlated with the interleukin (IL)-36γ/IL-37 ratio in the SC. Among the representative sebum lipids examined, oleic acid (C18:1, cis-9) dose- and time-dependently regulated the mRNA expression of IL-36γ and IL-37 in cultured keratinocytes, and this effect was attenuated by the N-methyl-D-aspartate (NMDA)-type glutamate receptor antagonist, MK801.
CONCLUSIONS
Skin surface sebum may be related to cheek redness in healthy subjects, and oleic acid-induced IL-36γ through NMDA-type glutamate receptors may be a link between them. Our study provides a possible skincare strategy for mitigating unfavorable increase in skin redness by targeting the facial skin sebum, particularly oleic acid.
Topics: Humans; Cytokines; Erythema; Interleukins; N-Methylaspartate; Oleic Acid; Sebum; Skin
PubMed: 36891608
DOI: 10.1111/jocd.15697 -
ACS Omega Oct 2023This study aimed to use oleic acid-based ultrasonic-assisted extraction (UAE) to recover carotenoids from carrot pomace and emulsify the enriched-carotenoid oleic acid...
This study aimed to use oleic acid-based ultrasonic-assisted extraction (UAE) to recover carotenoids from carrot pomace and emulsify the enriched-carotenoid oleic acid using spontaneous and ultrasonic-assisted emulsification. The extraction performance of oleic acid was compared with traditional organic solvents, including hexane, acetone, and ethyl acetate. The one-factor experiments were employed to examine the impact of UAE conditions, including liquid-to-solid ratios, temperature, ultrasonic power, and time, on the extraction yield of carotenoids and to find the conditional ranges for the optimization process. The response surface methodology was employed to optimize the UAE process. The second-order extraction kinetic model was used to find the mechanism of oleic acid-based UAE. After that, the enriched-carotenoid oleic acid obtained at the optimal conditions of UAE was used to fabricate nanoemulsions using spontaneous emulsification (SE), ultrasonic-assisted emulsification (UE), and SE-UE. The effect of SE and UE conditions on the turbidity of nanoemulsion was determined. Then, the physiochemical attributes of the nanoemulsion from SE, UE, and spontaneous ultrasonic-assisted emulsification (SE-UE) were determined using the dynamic light scattering method. The extraction yield of carotenoids from carrot pomace by using sonication was the highest. The adjusted optimal conditions were 39 mL/g of LSR, 50 °C, 12.5 min, and 350 W of ultrasonic power. Under optimal conditions, the carotenoid content attained was approximately 163.43 ± 1.83 μg/g, with the anticipated value (166 μg/g). The particle sizes of nanoemulsion fabricated at the proper conditions of SE, UE, and SE-UE were 31.2 ± 0.83, 33.8 ± 0.52, and 109.7 ± 8.24 nm, respectively. The results showed that SE and UE are suitable methods for fabricating nanoemulsions. The research provided a green approach for extracting and emulsifying carotenoids from carrot pomace.
PubMed: 37901568
DOI: 10.1021/acsomega.3c05301 -
Experimental Cell Research Aug 2023Lipotoxicity caused by excess free fatty acids, particularly saturated fatty acids (SFAs) such as palmitic acid (PA), is one of the most important pathogenesis of...
Lipotoxicity caused by excess free fatty acids, particularly saturated fatty acids (SFAs) such as palmitic acid (PA), is one of the most important pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, unsaturated fatty acids (UFAs), such as oleic acid (OA), are nontoxic and can combat SFA-induced toxicity through alleviation of cell apoptosis, endoplasmic reticulum stress (ER stress) and lipids metabolism disorder. However, whether OA is able to regulate autophagy is largely unknown. So, this study aims to investigate the mechanism underlying OA mediated modulation of autophagy in hepatocytes and mice with NAFLD. In vitro, human hepatoma cell line HepG2 cells, human normal liver cells L-02 and mouse normal liver cells AML12 were treated with palmitic acid (PA)/tunicamycin (TM) or/and OA for 48 h. In vivo, C57/BL6 mice were fed with high fat diet (HFD) to induce NAFLD. And the HFD was partial replaced by olive oil to observe the protective effects of olive oil. We demonstrated that PA/TM impaired cell viability and induced cellular apoptosis in HepG2 cells and L-02 cells. Moreover, PA/TM induced autophagy impairment by reducing the nuclear translocation of transcription factor EB (TFEB) and inhibiting the activity of CTSB. However, OA substantially alleviated PA/TM induced cellular apoptosis and autophagy dysfunction in hepatocytes. Additionally, restoring autophagy function is able to reduce ER stress. Similarly, HFD for 20 weeks successfully established NAFLD model in C57/BL6 mice, and significant autophagy impairment were observed in liver tissues. Noteworthily, 30% replacement of HFD with olive oil had profoundly reversed NAFLD. It significantly impoved steatosis, and reduced autophagy dysfunction, ER stress and apoptosis in liver tissue. Conclusively, these data demonstrated that OA is able to effectively impove autophagy dysfunction under the context of both PA and ER stress inducer induced lipotoxicity, and OA mediated regulation of lysosome dysfunction through TFEB plays an important role, suggesting that the regulation of ER stress-autophagy axis is a critical mechanism in OA driven protection in NAFLD.
Topics: Mice; Humans; Animals; Non-alcoholic Fatty Liver Disease; Oleic Acid; Olive Oil; Liver; Hepatocytes; Palmitic Acid; Autophagy; Endoplasmic Reticulum Stress; Diet, High-Fat
PubMed: 37253404
DOI: 10.1016/j.yexcr.2023.113655 -
Current Molecular Medicine Jun 2024Pregabalin and diclofenac diethylamine are anti-inflammatory molecules that are effective in relieving inflammation and pain associated with musculoskeletal disorders,...
Pregabalin and diclofenac diethylamine are anti-inflammatory molecules that are effective in relieving inflammation and pain associated with musculoskeletal disorders, arthritis, and post-traumatic pain, among others. Intravenous and oral delivery of these two molecules has their limitations. However, the transdermal route is believed to be an alternate viable option for the delivery of therapeutic molecules with desired physicochemical properties. To this end, it is vital to understand the physicochemical properties of these drugs, dosage, and strategies to enhance permeation, thereby surmounting the associated constraints and concurrently attaining a sustained release of these therapeutic molecules when administered in combination. The present work hypothesizes the enhanced permeation and sustained release of Pregabalin and diclofenac diethylamine across the skin, entrapped in the adhesive nano-organogel formulation, including permeation enhancers. The solubility studies of Pregabalin and diclofenac diethylamine in combination were performed in different permeation enhancers. Oleic acid was optimized as the best permeation enhancer based on in vitro studies. Pluronic organogel containing Pregabalin and diclofenac diethylamine with oleic acid was fabricated. Duro-Tak® (87-2196) was added to the organogel formulation as a pressure-sensitive adhesive to sustain the release profile of these two therapeutic molecules. The adhesive organogel was characterized for particle size, scanning electron microscopy, and contact angle measurement. The HPLC method developed for the quantification of the dual drug showed a retention time of 3.84 minutes and 9.69 minutes for pregabalin and diclofenac, respectively. The fabricated nanogel adhesive formulation showed the desired results with particle size and contact angle of 282 ± 57 nm and ≥120⁰, respectively. In vitro studies showed the percentage cumulative release of 24.90 ± 4.65% and 33.29 ± 4.81% for pregabalin and diclofenac, respectively. In order to accomplish transdermal permeation, the suggested hypothesis of fabricating PG and DEE nano-organogel in combination with permeation enhancers will be a viable drug delivery method. In comparison to a traditional gel formulation, oleic acid as a permeation enhancer increased the penetration of both PG and DEE from the organogel formulation. Notably, the studies showed that the use of pressure-sensitive adhesives enabled the sustained release of both PG and DEE.Therefore, the results anticipated the hypothesis that the transdermal delivery of adhesive PG and DEE-based nanogel across the human skin can be achieved to inhibit inflammation and pain.
PubMed: 38847251
DOI: 10.2174/0115665240291343240306054318 -
Cryo Letters 2023When sperm are cryopreserved, reactive oxygen species (ROS) are formed that are detrimental to the sperm.
BACKGROUND
When sperm are cryopreserved, reactive oxygen species (ROS) are formed that are detrimental to the sperm.
OBJECTIVE
To evaluate the effects of oleic acid and trehalose added to ram semen extender on sperm parameters, lipid peroxidation (MDA), and superoxide dismutase (SOD) enzyme levels of spermatozoa following the freeze/thawing processes.
MATERIALS AND METHODS
Ejaculates were collected from four rams and pooled at 35 degree C. Pooled ejaculates were diluted with oleic acid at 0 mM and trehalose at 0 mM (O0 T0) as the control. The Tris-based extender was supplemented with either 0.5 (O0.5) or 1 (O1) mM of oleic acid or 25 (T25) or 50 (T50) mM of trehalose alone, and in combination [0.5 mM oleic acid + 25 mM trehalose (O0.5 T25), 0.5 mM oleic acid + 50 mM trehalose (O0.5 T50), 1 mM oleic acid + 25 mM trehalose (O1 T25) and 1 mM oleic acid + 50 mM trehalose (O1 T50)]. The semen was frozen by the traditional liquid nitrogen vapour method and stored at -196C in the liquid nitrogen tank.
RESULTS
Semen extender containing O1T25 significantly improved the total motility, when compared with other treatment groups (P<0.05), except for O1 T50. O1 T50 had a higher viability rate than any other treatment. The addition of O1 T25 and O1 T50 increased DNA and membrane integrity of spermatozoa post-thawing compared to other treatments (P<0.05). The level of MDA was significantly (P<0.05) lower in extenders supplemented with O1, O0.5 T25, O0.5 T50, O1 T25 and O1T50 compared to the other treatment groups. In addition, SOD levels were higher in groups treated with O1 T25 and O1 T50 than the other treatment groups (P<0.05).
CONCLUSION
The addition of a combination of oleic acid and trehalose concentrations to Tris-based extender improved the quality of ram semen post-thawing. Doi.org/10.54680/fr23610110712.
Topics: Male; Sheep; Animals; Semen; Oleic Acid; Trehalose; Cryopreservation; Cryoprotective Agents; Sperm Motility; Spermatozoa; Semen Analysis; Superoxide Dismutase; Nitrogen; Semen Preservation
PubMed: 38311928
DOI: No ID Found -
Materials (Basel, Switzerland) May 2024One of the most effective strategies for modifying the surface properties of nano-fillers and enhancing their composite characteristics is through polymer grafting. In...
Epoxidized Soybean Oleic Acid/Oligomeric Poly(lactic acid)-Grafted Nano-Hydroxyapatite and Its Role as a Filler in Poly(L-lactide) for Potential Bone Fixation Application.
One of the most effective strategies for modifying the surface properties of nano-fillers and enhancing their composite characteristics is through polymer grafting. In this study, a coprecipitation method was employed to modify hydroxyapatite (HAP) with epoxidized soybean oleic acid (ESOA), resulting in ESOA-HAP. Subsequently, oligomeric poly(lactic acid) (OPLA) was grafted onto the surface of ESOA-HAP, yielding OPLA-ESOA-HAP. HAP, ESOA-HAP, and OPLA-ESOA-HAP were comprehensively characterized. The results demonstrate the progressive grafting of ESOA and OPLA onto the surface of HAP, resulting in enhanced hydrophobicity and improved dispersity in organic solvent for OPLA-ESOA-HAP compared to HAP. The vitality and adhesion of Wistar rat mesenchymal stem cells (MSCs) were assessed using HAP and modified HAP materials. Following culture with MSCs for 72 h, the OPLA-ESOA-HAP showed an inhibition rate lower than 23.0% at a relatively high concentration (1.0 mg/mL), which is three times lower compared to HAP under similar condition. The cell number for OPLA-ESOA-HAP was 4.5 times higher compared to HAP, indicating its superior biocompatibility. Furthermore, the mechanical properties of the OPLA-ESOA-HAP/PLLA composite almost remained unaltered ever after undergoing two stages of thermal processing involving melt extrusion and inject molding. The increase in the biocompatibility and relatively high mechanical properties render OPLA-ESOA-HAP/PLLA a potential material for the biodegradable fixation system.
PubMed: 38893884
DOI: 10.3390/ma17112620 -
BMC Psychiatry Nov 2023As the most abundant fatty acid in plasma, oleic acid has been found to be associated with multiple neurological diseases; however, results from studies of the...
BACKGROUND
As the most abundant fatty acid in plasma, oleic acid has been found to be associated with multiple neurological diseases; however, results from studies of the relationship between oleic acid and depression are inconsistent.
METHODS
This cross-sectional study analyzed 4,459 adults from the National Health and Nutrition Examination Survey 2011-2014. The following covariates were adjusted in multivariable logistic regression models: age, sex, race/ethnicity, education level, marital status, body mass index, physical activity, smoking status, alcohol status, metabolic syndrome, omega-3 polyunsaturated fatty acids, and total cholesterol.
RESULTS
Serum oleic acid levels were positively associated with depression. After adjusting for all covariates, for every 1 mmol/L increase in oleic acid levels, the prevalence of depression increased by 40% (unadjusted OR: 1.35, 95%CI: 1.16-1.57; adjusted OR: 1.40, 95% CI: 1.03-1.90).
CONCLUSIONS
Our study suggests that oleic acid may play a role in depression. Further research is needed to investigate the potential benefits of changing oleic acid levels for the treatment and prevention of depression.
Topics: Adult; Humans; United States; Depression; Oleic Acid; Cross-Sectional Studies; Nutrition Surveys; Fatty Acids, Omega-3
PubMed: 37974120
DOI: 10.1186/s12888-023-05271-0 -
Animals : An Open Access Journal From... Nov 2023Skeletal muscle satellite cells have the ability to differentiate into various cells under different conditions. This study aimed to investigate the effects of different...
Skeletal muscle satellite cells have the ability to differentiate into various cells under different conditions. This study aimed to investigate the effects of different concentrations of oleic acid (50, 100, and 200 µmol/L) on the process of lipogenic transdifferentiation in Yanbian bovine satellite cells, as well as its molecular regulatory mechanism. After inducing differentiation with oleic acid for 96 h, it was observed that the addition of oleic acid resulted in the formation of lipid droplets in the bovine satellite cells, and the triglyceride content showed a dose-dependent relationship with the concentration of OA. qPCR results demonstrated a significant downregulation of myogenesis-related factors ( and ) and upregulation of lipogenesis-related factors ( and ) ( < 0.05). Fatty acid metabolism-related factors, SCD and PLIN2, were also significantly upregulated ( < 0.05). These finding were consistent with the results obtained from Western blotting. Transcriptome sequencing analysis identified 278 differentially expressed genes between the control group and the groups treated with OA. KEGG enrichment analysis showed that differentially expressed genes were mainly concentrated in the adenosine monophosphate-activated protein kinase signaling pathway and fatty acid metabolic pathway. Our study presents that the OA induction of Yanbian bovine skeletal muscle satellite cells can promote cellular lipid transdifferentiation and reveals the potential genes and pathways related to OA induction of these satellite cells.
PubMed: 38066969
DOI: 10.3390/ani13233618