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Biofilm Dec 2023Antibiotic therapy is the primary treatment for bovine mastitis, but the drawbacks of this strategy include poor cure rate and economic losses from the need to discard...
Antibiotic therapy is the primary treatment for bovine mastitis, but the drawbacks of this strategy include poor cure rate and economic losses from the need to discard milk with antibiotic residues. Unfortunately, few other treatment options are currently available for mastitis. Failure of antibiotic treatments is often attributed to formation of bacterial biofilms and abscesses in the mammary gland tissue, which lead to chronic infections that are difficult to eradicate and drive recurrent disease. A major mastitis-causing pathogen (MCP) associated with biofilms in bovine mastitis is . In this study, we demonstrate that octanoic acid has broad-spectrum microbicidal activity against MCPs and effectively inhibits biofilm formation in milk (>50% inhibition at 3.13 mM). Octanoic acid effectively clears biofilms (95% eradication at 1 minimum bactericidal concentration, MBC) and infrequently induces small colony variants (SCVs) that may cause recurrent mastitis. Additionally, octanoic acid rapidly kills persistent biofilm cells and cells with antibiotic tolerance (within 4 h). In contrast, antibiotics treated at >100 MBC cannot eradicate biofilms but do induce SCVs and antibiotic-tolerant cells. These effects may accelerate the transition from biofilm to chronic infection. Thus, octanoic acid exhibits bactericidal action against biofilms, and it is less likely than antibiotic therapy to induce persistent cells and pathogen tolerance. Moreover, octanoic acid acts additively with antibiotics against , and it attenuates tetracycline-induced virulence factor gene expression in cells. According to these data, octanoic acid may prevent the pathological progression of bovine mastitis and offer a new strategy for treating the condition.
PubMed: 37635811
DOI: 10.1016/j.bioflm.2023.100149 -
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 -
IUBMB Life Jun 2024Having evolved from a prokaryotic origin, mitochondria retain pathways required for the catabolism of energy-rich molecules and for the biosynthesis of molecules that... (Review)
Review
Having evolved from a prokaryotic origin, mitochondria retain pathways required for the catabolism of energy-rich molecules and for the biosynthesis of molecules that aid catabolism and/or participate in other cellular processes essential for life of the cell. Reviewed here are details of the mitochondrial fatty acid biosynthetic pathway (FAS II) and its role in building both the octanoic acid precursor for lipoic acid biosynthesis (LAS) and longer-chain fatty acids functioning in chaperoning the assembly of mitochondrial multisubunit complexes. Also covered are the details of mitochondrial lipoic acid biosynthesis, which is distinct from that of prokaryotes, and the attachment of lipoic acid to subunits of pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and glycine cleavage system complexes. Special emphasis has been placed on presenting what is currently known about the interconnected paths and loops linking the FAS II-LAS pathway and two other mitochondrial realms, the organellar translation machinery and Fe-S cluster biosynthesis and function.
Topics: Thioctic Acid; Mitochondria; Fatty Acids; Humans; Animals; Ketoglutarate Dehydrogenase Complex; Biosynthetic Pathways; Iron-Sulfur Proteins; Amino Acid Oxidoreductases; Multienzyme Complexes; Transferases
PubMed: 38088214
DOI: 10.1002/iub.2802 -
Neurogastroenterology and Motility Nov 2023Gastroparesis is defined by delayed gastric emptying (GE) without obstruction. Studies suggest targeting heme oxygenase-1 (HO1) may ameliorate diabetic gastroparesis....
BACKGROUND
Gastroparesis is defined by delayed gastric emptying (GE) without obstruction. Studies suggest targeting heme oxygenase-1 (HO1) may ameliorate diabetic gastroparesis. Upregulation of HO1 expression via interleukin-10 (IL-10) in the gastric muscularis propria is associated with reversal of delayed GE in diabetic NOD mice. IL-10 activates the M2 cytoprotective phenotype of macrophages and induces expression of HO1 protein. Here, we assess delivery of HO1 by recombinant adeno-associated viruses (AAVs) in diabetic mice with delayed GE.
METHODS
C57BL6 diabetic delayed GE mice were injected with 1 × 10 vg scAAV9-cre, scAAV9-GFP, or scAAV9-HO1 particles. Changes to GE were assessed weekly utilizing our [ C]-octanoic acid breath test. Stomach tissue was collected to assess the effect of scAAV9 treatment on Kit, NOS1, and HO1 expression.
KEY RESULTS
Delayed GE returned to normal within 2 weeks of treatment in 7/12 mice receiving scAAV9-cre and in 4/5 mice that received the scAAV9-GFP, whereas mice that received scAAV9-HO1 did not respond in the same manner and had GE that took significantly longer to return to normal (6/7 mice at 4-6 weeks). Kit, NOS1, and HO1 protein expression in scAAV9-GFP-treated mice with normal GE were not significantly different compared with diabetic mice with delayed GE.
CONCLUSIONS AND INFERENCES
Injection of scAAV9 into diabetic C57BL6 mice produced a biological response that resulted in acceleration of GE independently of the cargo delivered by the AAV9 vector. Further research is needed to determine whether use of AAV mediated gene transduction in the gastric muscularis propria is beneficial and warranted.
Topics: Mice; Animals; Gastroparesis; Dependovirus; Interleukin-10; Diabetes Mellitus, Experimental; Mice, Inbred NOD; Mice, Inbred C57BL
PubMed: 37702100
DOI: 10.1111/nmo.14669 -
Appetite Oct 2023Older adults are advised to increase their protein intake to maintain their muscle mass. However, protein is considered the most satiating macronutrient and this... (Randomized Controlled Trial)
Randomized Controlled Trial
Older adults are advised to increase their protein intake to maintain their muscle mass. However, protein is considered the most satiating macronutrient and this recommendation may cause a decrease in total energy intake. To date, satiety studies comparing all three macronutrients have been undertaken in young adults, and it is unclear if the same response is seen in older adults. The objective of this study was to compare the effect of preloads high in protein, fat, and carbohydrate but equal in energy (∼300 kcal) and volume (250 ml) on energy intake, perceived appetite, and gastric emptying in younger and older adults. Twenty older and 20 younger adults completed a single-blinded randomised crossover trial involving three study visits. Participants consumed a standard breakfast, followed by a preload milkshake high in either carbohydrate, fat, or protein. Three hours after the preload, participants were offered an ad libitum meal to assess food intake. Visual analogue scales were used to measure perceived appetite and gastric emptying was measured via the C-octanoic acid breath test. There was no significant effect of preload type or age on energy intake either at the ad libitum meal, self-recorded food intake for the rest of the test day or subjective appetite ratings. There was a significant effect of preload type on gastric emptying latency phase and ascension time, and an effect of age on gastric emptying latency and lag phase such that older adults had faster emptying. In conclusion, energy intake, and perceived appetite were not affected by macronutrient content of the preloads in both younger and older adults, but gastric emptying times differed.
Topics: Young Adult; Humans; Aged; Satiation; Appetite; Energy Intake; Nutrients; Eating; Carbohydrates; Cross-Over Studies
PubMed: 37507052
DOI: 10.1016/j.appet.2023.106982 -
Analytica Chimica Acta Oct 2023A novel pH switchable water stationary phase is presented for use in supercritical fluid chromatography (SFC). By adding NHOH to the water coating and system hydration,...
A novel pH switchable water stationary phase is presented for use in supercritical fluid chromatography (SFC). By adding NHOH to the water coating and system hydration, changes in CO pressure and temperature allow a wide range of stationary phase pH conditions (∼3-9) to be achieved, which impact analyte retention properties. For example, 100 atm and 50 °C produces an acidic water stationary phase (pH near 4.0) where octanoic acid readily elutes while the base caffeine does not. Conversely, at 80 atm and 120 °C a basic water stationary phase (pH near 8.0) is obtained and the opposite occurs. Further, under constant pressure and temperature conditions, simply adding or removing NHOH from the system is also found to readily allow switching between the basic and acidic water stationary phase modes and demonstrates control over ionizable analyte elution. For instance, hexanoic acid elution is near 40 times more delayed on a basic water stationary phase and, as such, it can be eluted at later points in time as desired by removing the NHOH and switching to an acidic stationary phase. Experiments indicate that stationary phase pH switching occurs uniformly across the 15 m column length within about 18 s and that analyte retention times are very reproducible upon performing a switch (1.4% RSD; n = 3). Results demonstrate the selectivity factor between acidic and neutral analytes can be reversed and increased about 35 times, while in other trials resolution also similarly increased near 40-fold. By rapidly switching the stationary phase pH back and forth between acidic and basic modes, the selectivity between ionizable analytes could also be increased as desired. Various applications with the system show that it can vastly increase the separation between target analytes and matrix components as required by the dynamics of a particular separation.
PubMed: 37709440
DOI: 10.1016/j.aca.2023.341686 -
Journal of Colloid and Interface Science Nov 2023Lipopeptides have become one of the most potent antibacterial agents, however, there is so far no consensus about the link between their physic-chemical properties and...
Lipopeptides have become one of the most potent antibacterial agents, however, there is so far no consensus about the link between their physic-chemical properties and biological activity, in particular their inherent aggregation propensity and antibacterial potency. To this end, we here de novo design a series of lipopeptides (CHO-(VVKK)V-NH), in which an alkyl chain is covalently attached onto the N-terminus of a short cationic peptide sequence with an alternating pattern of hydrophobic VV (Val) and positively charged KK (Lys) motifs. By varying the alkyl chain length (ortho-octanoic acid (C8), lauric acid (C12), and palmitic acid (C16)), the lipopeptides show distinct physicochemical properties and self-assembly behaviors, which have great effect on their antibacterial activities. CHO-(VVKK)V-NH, which contains the lowest hydrophobicity and surface activity has the lowest antibacterial activity. CHO-(VVKK)V-NH and CHO-(VVKK)V-NH both have high hydrophobicity and surface activity, and self-assembled into long nanofibers. However, the nanofibers formed by CHO-(VVKK)V-NH disassembled by dilution, resulting in its high antibacterial activity via bacterial membrane disruption. Comparatively, the nanofibers formed by CHO-(VVKK)V-NH were very stable, which can closely attach on bacterial surface but not permeate bacterial membrane, leading to its low antibacterial activity. Thus, the stability other than the morphologies of lipopeptides' nanostructures contribute to their antibacterial ability. Importantly, this study enhances our understanding of the antibacterial mechanisms of self-assembling lipopeptides that will be helpful in exploring their biomedical applications.
Topics: Lipopeptides; Anti-Bacterial Agents; Bacteria; Amino Acid Sequence; Microbial Sensitivity Tests
PubMed: 37356155
DOI: 10.1016/j.jcis.2023.05.168 -
Natural Product Research Dec 2023Dibromosterculic acid [8-(1,2-dibromo-2-octylcyclopropyl)-octanoic acid], a new synthetic derivative was prepared by bromination of sterculic acid. This synthetic...
Dibromosterculic acid [8-(1,2-dibromo-2-octylcyclopropyl)-octanoic acid], a new synthetic derivative was prepared by bromination of sterculic acid. This synthetic derivative showed strong fungicidal activity against two pathogenic fungal species namely and with minimum inhibitory concentration (MIC) value of 0.007 mg/ml and good bactericidal activity against and with MIC value of 0.015 mg/ml. Cytotoxic activity on both normal (MCF-10A) and cancerous (MDA-MB-468) cell lines revealed that the survivability percentage of normal cells was unaffected, whereas cancerous cells were decreased greatly by dibromosterculic acid with 50% survivability at 9 µg/ml concentration. Molecular-docking using AutoDock 4.2 with Bax exhibited strong pi-sigma interaction with PHE-93, pi-alkyl and alkyl interaction with TRP-139, ARG-89 and PHE-92 whereas MDM2 revealed strong hydrogen bond interaction with GLN-59 and pi-alkyl interaction with PHE-55. All experimental parameters suggested that this synthetic derivative would be valuable for target-specific drug development with nominal side effects.
PubMed: 38148119
DOI: 10.1080/14786419.2023.2294107 -
Frontiers in Endocrinology 2024Ghrelin is a peptide hormone with various important physiological functions. The unique feature of ghrelin is its serine 3 acyl-modification, which is essential for...
Ghrelin is a peptide hormone with various important physiological functions. The unique feature of ghrelin is its serine 3 acyl-modification, which is essential for ghrelin activity. The major form of ghrelin is modified with n-octanoic acid (C8:0) by ghrelin O-acyltransferase. Various acyl modifications have been reported in different species. However, the underlying mechanism by which ghrelin is modified with various fatty acids remains to be elucidated. Herein, we report the purification of bovine, porcine, and equine ghrelins. The major active form of bovine ghrelin was a 27-amino acid peptide with an n-octanoyl (C8:0) modification at Ser3. The major active form of porcine and equine ghrelin was a 28-amino acid peptide. However, porcine ghrelin was modified with n-octanol (C8:0), whereas equine ghrelin was modified with n-butanol (C4:0) at Ser3. This study indicates the existence of structural divergence in ghrelin and suggests that it is necessary to measure the minor and major forms of ghrelin to fully understand its physiology.
Topics: Animals; Ghrelin; Horses; Cattle; Swine; Amino Acid Sequence; Acylation; Caprylates
PubMed: 38828411
DOI: 10.3389/fendo.2024.1411483 -
The Journal of Physical Chemistry. C,... Feb 2024Perfluorooctanoic acid (PFOA) is an environmentally prevalent and persistent organic pollutant with toxic and bioaccumulative properties. Despite the known importance of...
Perfluorooctanoic acid (PFOA) is an environmentally prevalent and persistent organic pollutant with toxic and bioaccumulative properties. Despite the known importance of perfluorinated pollutants in the global environment, molecular-level details of the physicochemical behavior of PFOA on aqueous interfaces remain poorly understood. Here, we utilized two surface-specific techniques, vibrational sum frequency generation spectroscopy (SFG) and surface tensiometry, to investigate the pH-induced structural changes of PFOA and octanoic acid (OA) and determined the apparent p at the air-water surface. The SFG spectra and surface activity model were investigated over a wide range of pHs. With the surface tension measurements, the surface p values for OA and PFOA are determined to be 3.8 ± 0.1 and 2.2 ± 0.2, respectively. These results could provide insights into improved remediation of PFOAs and may impact climate modeling of perfluorinated alkyl chain molecules.
PubMed: 38352857
DOI: 10.1021/acs.jpcc.3c07235