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ACS Nano Feb 2023Treatment of cardiac arrest/cardiopulmonary resuscitation (CA/CPR)-induced brain injury remains a challenging issue without viable therapeutic options. Octanoic acid...
A Nanotherapy of Octanoic Acid Ameliorates Cardiac Arrest/Cardiopulmonary Resuscitation-Induced Brain Injury RVG29- and Neutrophil Membrane-Mediated Injury Relay Targeting.
Treatment of cardiac arrest/cardiopulmonary resuscitation (CA/CPR)-induced brain injury remains a challenging issue without viable therapeutic options. Octanoic acid (OA), a lipid oil that is mainly metabolized in the astrocytes of the brain, is a promising treatment for this type of injury owing to its potential functions against oxidative stress, apoptosis, inflammation, and ability to stabilize mitochondria. However, the application of OA is strictly limited by its short half-life and low available concentration in the target organ. Herein, based on our previous research, an OA-based nanotherapy coated with a neutrophil membrane highly expressing RVG29, RVG29-H-NP, was successfully constructed by computer simulation-guided supramolecular assembly of polyethylenimine and OA. The and experiments showed that RVG29-H-NP could target and be distributed in the injured brain focus the relay-targeted delivery mediated by RVG29-induced blood-brain barrier (BBB) penetration and neutrophil membrane protein-induced BBB binding and injury targeting. This results in enhancements of the antioxidant, antiapoptotic, mitochondrial stability-promoting and anti-inflammatory effects of OA and exhibited systematic alleviation of astrocyte injury, neuronal damage, and inflammatory response in the brain. Due to their systematic intervention in multiple pathological processes, RVG29-H-NP significantly increased the 24 h survival rate of CA/CPR model rats from 40% to 100% and significantly improved their neurological functions. Thus, RVG29-H-NP are expected to be a promising therapeutic for the treatment of CA/CPR-induced brain injury.
Topics: Rats; Animals; Computer Simulation; Neutrophils; Heart Arrest; Brain; Cardiopulmonary Resuscitation; Brain Injuries; Disease Models, Animal
PubMed: 36758159
DOI: 10.1021/acsnano.2c09931 -
ACS Synthetic Biology May 2021Octanoic acid is an industrially relevant compound with applications in antimicrobials or as a precursor for biofuels. Microbial biosynthesis through yeast is a...
Octanoic acid is an industrially relevant compound with applications in antimicrobials or as a precursor for biofuels. Microbial biosynthesis through yeast is a promising alternative to current unsustainable production methods. To increase octanoic acid titers in , we use a previously developed biosensor that is based on the octanoic acid responsive promotor coupled to GFP. We establish a biosensor strain amenable for high-throughput screening of an octanoic acid producer strain library. Through development, optimization, and execution of a high-throughput screening approach, we were able to detect two new genetic targets, and , which increased octanoic acid titers through combined overexpression by about 55% compared to the parental strain. Neither target has yet been reported to be involved in fatty acid biosynthesis. The presented methodology can be employed to screen any genetic library and thereby more genes involved in improving octanoic acid production can be detected in the future.
Topics: Biosensing Techniques; Caprylates; Fatty Acids; Flow Cytometry; Gene Expression; Gene Library; Green Fluorescent Proteins; High-Throughput Screening Assays; Metabolic Engineering; Microorganisms, Genetically-Modified; Phosphotransferases (Phosphate Group Acceptor); Promoter Regions, Genetic; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Serine Proteases
PubMed: 33979526
DOI: 10.1021/acssynbio.0c00600 -
Lipids in Health and Disease Jun 2024The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to...
BACKGROUND
The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to enhance its efficacy. As an eight-carbon medium-chain fatty acid, octanoic acid (OCA) shows promise for improving health, yet its impact on spermatogenesis remains inadequately researched.
METHODS
Mass spectrometry was performed to determine the fatty acid content and screen for a pivotal lipid component in the serum of patients with severe spermatogenesis disorders. The sperm quality was examined, and histopathological analysis and biotin tracer tests were performed to assess spermatogenesis function and the integrity of the blood-testis barrier (BTB) in vivo. Cell-based in vitro experiments were carried out to investigate the effects of OCA administration on Sertoli cell dysfunction. This research aimed to elucidate the mechanism by which OCA may influence the function of Sertoli cells.
RESULTS
A pronounced reduction in OCA content was observed in the serum of patients with severe spermatogenesis disorders, indicating that OCA deficiency is related to spermatogenic disorders. The protective effect of OCA on reproduction was tested in a mouse model of spermatogenic disorder induced by busulfan at a dose 30 mg/kg body weight (BW). The mice in the study were separated into distinct groups and administered varying amounts of OCA, specifically at doses of 32, 64, 128, and 256 mg/kg BW. After evaluating sperm parameters, the most effective dose was determined to be 32 mg/kg BW. In vivo experiments showed that treatment with OCA significantly improved sperm quality, testicular histopathology and BTB integrity, which were damaged by busulfan. Moreover, OCA intervention reduced busulfan-induced oxidative stress and autophagy in mouse testes. In vitro, OCA pretreatment (100 µM) significantly ameliorated Sertoli cell dysfunction by alleviating busulfan (800 µM)-induced oxidative stress and autophagy. Moreover, rapamycin (5 µM)-induced autophagy led to Sertoli cell barrier dysfunction, while OCA administration exerted a protective effect by alleviating autophagy.
CONCLUSIONS
This study demonstrated that OCA administration suppressed oxidative stress and autophagy to alleviate busulfan-induced BTB damage. These findings provide a deeper understanding of the toxicology of busulfan and a promising avenue for the development of novel OCA-based therapies for male infertility.
Topics: Male; Animals; Blood-Testis Barrier; Busulfan; Caprylates; Oxidative Stress; Mice; Sertoli Cells; Humans; Spermatogenesis; Autophagy; Infertility, Male; Testis; Spermatozoa; Adult
PubMed: 38862993
DOI: 10.1186/s12944-024-02157-2 -
Synergistic antimicrobial effect of nisin-octanoic acid nanoemulsions against E. coli and S. aureus.Archives of Microbiology Apr 2023Food safety is a major public health concern all over the world. Therefore, the prevention of food contamination is becoming extremely crucial. In this study, an...
Food safety is a major public health concern all over the world. Therefore, the prevention of food contamination is becoming extremely crucial. In this study, an antimicrobial nanoemulsion composed of water-soluble nisin and fat-soluble octanoic acid was successfully prepared. The results showed that the average particle size and the polymer dispersity index of the nisin-octanoic acid (NOA) nanoemulsion were around 52.21 nm and 0.253, respectively. The NOA nanoemulsion required less amounts of nisin and octanoic acid to achieve the effective antimicrobial effect against Escherichia coli and Staphylococcus aureus. In addition, the growth curves of E. coli and S. aureus were determined. The OD of NOA nanoemulsion was significantly lower than free nisin after being incubated for 24 h (p < 0.001), indicating that the antimicrobial effect of NOA nanoemulsion was outstanding. Meanwhile, the synergistic antimicrobial property of NOA nanoemulsion against E. coli and S. aureus was significantly better than free nisin under nonacid conditions (p < 0.05). Overall, the results of this study may provide guidance for the further application of nisin in more forms.
Topics: Nisin; Anti-Bacterial Agents; Staphylococcus aureus; Escherichia coli; Methicillin-Resistant Staphylococcus aureus; Anti-Infective Agents; Microbial Sensitivity Tests
PubMed: 37086306
DOI: 10.1007/s00203-023-03545-5 -
Pesticide Biochemistry and Physiology Jun 2023Root knot nematodes are the most devastating root pathogens, causing severe damage and serious economic losses to agriculture worldwide. Octanoic acid has been reported...
Root knot nematodes are the most devastating root pathogens, causing severe damage and serious economic losses to agriculture worldwide. Octanoic acid has been reported as one of the nematicides, and its mode of action is not fully understood. The main objective of this study was to elucidate the effect of octanoic acid on Meloidogyne incognita by transcriptomic analysis combined with physiological and biochemical assays. In the toxicity assays with octanoic acid, the threshold concentration with nematicidal activity and the maximum concentration to which nematodes could respond were 0.03 μL/mL and 0.08 μL/mL respectively. Microscopic observation combined with protein and carbohydrates assays confirmed that the structure of the second-stage juveniles (J2s) was severely disrupted after 72 h of immersion in octanoic acid. Transcriptome analysis has shown that octanoic acid can interfere with the nematode energy metabolism, lifespan and signaling. Although the effects are multifaceted, the findings strongly point to the cuticle, lysosomes, and extracellular regions and spaces as the primary targets for octanoic acid. In addition, nematodes can withstand the negative effects of low concentration of octanoic acid to some extent by up-regulating the defense enzyme system and heterologous metabolic pathways. These findings will help us to explore the nematicidal mechanism of octanoic acid and provide important target genes for the development of new nematicides in the future.
Topics: Animals; Tylenchoidea; Transcriptome; Antinematodal Agents; Gene Expression Profiling
PubMed: 37247998
DOI: 10.1016/j.pestbp.2023.105432 -
The Journal of Endocrinology May 2020Circulating growth hormone (GH) concentrations increase during pregnancy in mice and remain pituitary-derived. Whether abundance or activation of the GH secretagogue...
Circulating growth hormone (GH) concentrations increase during pregnancy in mice and remain pituitary-derived. Whether abundance or activation of the GH secretagogue ghrelin increase during pregnancy, or in response to dietary octanoic acid supplementation, is unclear. We therefore measured circulating GH profiles in late pregnant C57BL/6J mice and in aged-matched non-pregnant females fed with standard laboratory chow supplemented with 5% octanoic or palmitic (control) acid (n = 4-13/group). Serum total and acyl-ghrelin concentrations, stomach and placenta ghrelin mRNA and protein expression, Pcsk1 (encoding prohormone convertase 1/3) and Mboat4 (membrane bound O-acyl transferase 4) mRNA were determined at zeitgeber (ZT) 13 and ZT23. Total and basal GH secretion were higher in late pregnant than non-pregnant mice (P < 0.001), regardless of diet. At ZT13, serum concentrations of total ghrelin (P = 0.004), but not acyl-ghrelin, and the density of ghrelin-positive cells in the gastric antrum (P = 0.019) were higher, and gastric Mboat4 and Pcsk1 mRNA expression were lower in pregnant than non-pregnant mice at ZT23. In the placenta, ghrelin protein was localised mostly to labyrinthine trophoblast cells. Serum acyl-, but not total, ghrelin was lower at mid-pregnancy than in non-pregnant mice, but not different at early or late pregnancy. In conclusion, dietary supplementation with 5% octanoic acid did not increase activation of ghrelin in female mice. Our results further suggest that increases in maternal GH secretion throughout murine pregnancy are not due to circulating acyl-ghrelin acting at the pituitary. Nevertheless, time-dependent increased circulating total ghrelin could potentially increase ghrelin action in tissues that express the acylating enzyme and receptor.
Topics: Acylation; Animals; Caprylates; Dietary Supplements; Female; Gastric Mucosa; Ghrelin; Growth Hormone; Mice; Mice, Inbred C57BL; Placenta; Pregnancy; RNA, Messenger
PubMed: 32176867
DOI: 10.1530/JOE-20-0072 -
Islets 2019A potentiating effect of medium-chain triglycerides on glucose-stimulated insulin secretion (GSIS) has been observed since the 1960s. Subsequent observations identified...
A potentiating effect of medium-chain triglycerides on glucose-stimulated insulin secretion (GSIS) has been observed since the 1960s. Subsequent observations identified octanoic acid (OA), the main component of medium-chain triglyceride, as the potentiator of GSIS, but the mechanism was unclear. We used wild-type (WT), short-chain 3-hydroxyacyl-CoA dehydrogenase knockout (), and sulfonylurea receptor 1 knockout () mouse islets to define the mechanism of OA potentiation of insulin secretion. Application of OA alone induced a 2- to 3- fold increase of insulin secretion with an apparent threshold of 3 mM in WT mouse islets, suggesting that OA itself is a weak insulin secretagogue. However, OA at 1 mM strongly potentiated fuel-stimulated insulin secretion, especially GSIS. The potentiating effect on fuel-stimulated insulin secretion by OA did not require fatty acid β-oxidation because OA also potentiated amino acid-stimulated insulin secretion in islets isolated from mice, which cannot fully oxidize OA. Measurements using islets indicated that the potentiating effect of OA on fuel-stimulated insulin secretion is Ca dependent and is often accompanied by β-cell membrane potential depolarization, and may also involve the Ca/calmodulin complex. Experiments using DCPIB, an ethacrynic acid derivative, to inhibit volume-sensitive anion channels (VSACs) in islets demonstrated that the potentiation effects of OA on insulin secretion are in part medicated by activation of VSAC. In addition, inhibition of IP3 receptor also abolishes the OA-induced intracellular Ca increase in islets.
Topics: Animals; Caprylates; Cells, Cultured; Drug Synergism; Glucose; Insulin; Insulin Secretion; Insulin-Secreting Cells; Islets of Langerhans; Male; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Signal Transduction
PubMed: 30849280
DOI: 10.1080/19382014.2019.1566683 -
Neurotherapeutics : the Journal of the... Jul 2012Recent work exploring the use of high-molecular weight alcohols to treat essential tremor (ET) has identified octanoic acid as a potential novel tremor-suppressing...
Recent work exploring the use of high-molecular weight alcohols to treat essential tremor (ET) has identified octanoic acid as a potential novel tremor-suppressing agent. We used an established harmaline-based mouse model of ET to compare tremor suppression by 1-octanol and octanoic acid. The dose-related effect on digitized motion power within the tremor bandwidth as a fraction of overall motion power was analyzed. Both 1-octanol and octanoic acid provided significant reductions in harmaline tremor. An 8-carbon alkyl alcohol and carboxylic acid each suppress tremor in a pre-clinical mouse model of ET. Further studies are warranted to determine the safety and efficacy of such agents in humans with ET.
Topics: Animals; Caprylates; Central Nervous System Stimulants; Disease Models, Animal; Dose-Response Relationship, Drug; Essential Tremor; Harmaline; Male; Mice; Mice, Inbred ICR
PubMed: 22454323
DOI: 10.1007/s13311-012-0121-1 -
The Laryngoscope Aug 2019The purpose of this study was to determine the effects of octanoic acid on acoustic, perceptual, and functional aspects of essential voice tremor (EVT). (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES/HYPOTHESIS
The purpose of this study was to determine the effects of octanoic acid on acoustic, perceptual, and functional aspects of essential voice tremor (EVT).
STUDY DESIGN
Prospective, double-blind, placebo-controlled, crossover study.
METHODS
Sixteen participants with a diagnosis of EVT were randomized to a 3-week dosing condition of octanoic acid or placebo, followed by a 2-week washout period and crossover to the other condition for an additional 3 weeks. Baseline and post-testing sessions were completed before and at the completion of each condition. Primary outcome measures were the magnitude of amplitude and frequency tremor, measured from the acoustic signal. Secondary outcomes were auditory-perceptual ratings of tremor severity and self-ratings of voice handicap.
RESULTS
Magnitude of amplitude and frequency tremor were significantly lower after 3 weeks of octanoic acid dosing as compared to the placebo condition. Auditory-perceptual ratings of tremor severity did not show significant differences between conditions. A trend toward better voice was seen for the sustained vowel ratings, but not the sentence-level ratings. No significant differences between conditions were seen on self-reported voice disability as assessed on the Voice Handicap Index-10.
CONCLUSIONS
The results of this controlled investigation support the potential utility of octanoic acid for reducing the magnitude of tremor in people with EVT. Further research is needed to determine whether different dosing or treatment combinations can improve functional communication in EVT.
LEVEL OF EVIDENCE
1 Laryngoscope, 129:1882-1890, 2019.
Topics: Aged; Caprylates; Cross-Over Studies; Double-Blind Method; Essential Tremor; Female; Humans; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Treatment Outcome; Voice; Voice Disorders
PubMed: 30585335
DOI: 10.1002/lary.27695 -
Biotechnology and Bioengineering Aug 2021The eight-carbon fatty acid octanoic acid (OA) is an important platform chemical and precursor of many industrially relevant products. Its microbial biosynthesis is...
The eight-carbon fatty acid octanoic acid (OA) is an important platform chemical and precursor of many industrially relevant products. Its microbial biosynthesis is regarded as a promising alternative to current unsustainable production methods. In Saccharomyces cerevisiae, the production of OA had been previously achieved by rational engineering of the fatty acid synthase. For the supply of the precursor molecule acetyl-CoA and of the redox cofactor NADPH, the native pyruvate dehydrogenase bypass had been harnessed, or the cells had been additionally provided with a pathway involving a heterologous ATP-citrate lyase. Here, we redirected the flux of glucose towards the oxidative branch of the pentose phosphate pathway and overexpressed a heterologous phosphoketolase/phosphotransacetylase shunt to improve the supply of NADPH and acetyl-CoA in a strain background with abolished OA degradation. We show that these modifications lead to an increased yield of OA during the consumption of glucose by more than 60% compared to the parental strain. Furthermore, we investigated different genetic engineering targets to identify potential factors that limit the OA production in yeast. Toxicity assays performed with the engineered strains suggest that the inhibitory effects of OA on cell growth likely impose an upper limit to attainable OA yields.
Topics: Caprylates; Metabolic Engineering; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 34003487
DOI: 10.1002/bit.27814