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Acta Pharmaceutica (Zagreb, Croatia) Jun 2024Remifentanil is an ultra-short-acting synthetic opioid-class analgesic which might be increasingly used "off-label" as pain management during labour. Side effects in...
Remifentanil is an ultra-short-acting synthetic opioid-class analgesic which might be increasingly used "off-label" as pain management during labour. Side effects in parturients during labour, and in the infant at birth are of particular concern, especially respiratory depression which is concentration-dependent, and can occur at levels as low as 3-5 ng mL. The safety of such use, particularly in newborns due to remifentanil placental transfer, has not been fully demonstrated yet, partly due to the lack of a suitable non-invasive analytical method. The aim of our work was to develop a sensitive method to monitor the levels of remifentanil in neonates by a non-invasive sampling of umbi lical cord blood to support efficacy and safety trials. The presented LC-MS method is sensitive enough to reliably quantify remifentanil in just 20 µL of blood at only 0.3 ng mL. The dried blood spot sample preparation included solvent extraction with subsequent solid-phase extraction. The method was validated in terms of accuracy, precision, recovery, matrix effect, and stability, and was successfully applied to a small pilot study. The estimated arterial blood concentrations at the time of delivery ranged from 0.2 to 0.3, and up to 0.9 ng mL in neonatal, and maternal samples, respectively.
Topics: Remifentanil; Humans; Tandem Mass Spectrometry; Infant, Newborn; Dried Blood Spot Testing; Analgesics, Opioid; Female; Fetal Blood; Chromatography, Liquid; Pregnancy; Piperidines; Pilot Projects; Reproducibility of Results; Solid Phase Extraction
PubMed: 38815198
DOI: 10.2478/acph-2024-0010 -
PloS One 2024The skin microbiome maintains healthy human skin, and disruption of the microbiome balance leads to inflammatory skin diseases such as folliculitis and atopic...
The skin microbiome maintains healthy human skin, and disruption of the microbiome balance leads to inflammatory skin diseases such as folliculitis and atopic dermatitis. Staphylococcus aureus and Cutibacterium acnes are pathogenic bacteria that simultaneously inhabit the skin and cause inflammatory diseases of the skin through the activation of innate immune responses. Silkworms are useful invertebrate animal models for evaluating innate immune responses. In silkworms, phenoloxidase generates melanin as an indicator of innate immune activation upon the recognition of bacterial or fungal components. We hypothesized that S. aureus and C. acnes interact to increase the innate immunity-activating properties of S. aureus. In the present study, we showed that acidification is involved in the activation of silkworm hemolymph melanization by S. aureus. Autoclaved-killed S. aureus (S. aureus [AC]) alone does not greatly activate silkworm hemolymph melanization. On the other hand, applying S. aureus [AC] treated with C. acnes culture supernatant increased the silkworm hemolymph melanization. Adding C. acnes culture supernatant to the medium decreased the pH. S. aureus [AC] treated with propionic acid, acetic acid, or lactic acid induced higher silkworm hemolymph melanization activity than untreated S. aureus [AC]. S. aureus [AC] treated with hydrochloric acid also induced silkworm hemolymph melanization. The silkworm hemolymph melanization activity of S. aureus [AC] treated with hydrochloric acid was inhibited by protease treatment of S. aureus [AC]. These results suggest that acid treatment of S. aureus induces innate immune activation in silkworms and that S. aureus proteins are involved in the induction of innate immunity in silkworms.
Topics: Animals; Hemolymph; Bombyx; Staphylococcus aureus; Melanins; Immunity, Innate; Hydrogen-Ion Concentration; Monophenol Monooxygenase
PubMed: 38814922
DOI: 10.1371/journal.pone.0298502 -
PloS One 2024This study aimed to evaluate the effectiveness of topical clascoterone (TC) compared to oral spironolactone for acne vulgaris treatment. (Meta-Analysis)
Meta-Analysis Comparative Study
OBJECTIVES
This study aimed to evaluate the effectiveness of topical clascoterone (TC) compared to oral spironolactone for acne vulgaris treatment.
METHODS
A computerized search through PubMed/MEDLINE, SCOPUS, and the Cochrane Library was conducted to find relevant papers. We used the "netmeta" and "meta" packages for network meta-analysis (NMA) in RStudio 1.2.5019 (2009-2019 RStudio, Inc.) to conduct all of our statistical tests.
RESULTS
Seven articles (n = 2,006 patients) were included. The fixed-effect size showed that TC 1% bis in die (BID) showed potential effectiveness in reducing the inflammatory and non-inflammatory lesion count compared to placebo (Standardized mean difference, SMD = -0.27, 95% CI: -0.36 to -0.17) and (SMD = -0.31, 95% CI: -0.41 to -0.22), respectively. The random-effect size showed that TC 1% BID was significantly associated with a 12-week treatment success compared to placebo (Odds ratio, OR = 2.44, 95% CI: 1.12 to 5.30). Spironolactone 200 mg was associated with a significant reduction in total lesion count (SMD = -4.46, 95% CI: -5.60 to -3.32).
CONCLUSION
TC appears to reduce both inflammatory and non-inflammatory lesion count and may lead to treatment success. Spironolactone at 200 mg showed potential effectiveness in terms of total lesion count reduction. These results suggest that both TC and Spironolactone could be beneficial in treating patients with acne vulgaris.
Topics: Acne Vulgaris; Humans; Spironolactone; Network Meta-Analysis; Treatment Outcome; Administration, Topical; Cortodoxone; Propionates
PubMed: 38814916
DOI: 10.1371/journal.pone.0298155 -
PloS One 2024Coronary microvascular dysfunction (CMD) is a critical pathogenesis of cardiovascular diseases. Lower endothelial nitric oxide synthase (eNOS) phosphorylation leads to...
Coronary microvascular dysfunction (CMD) is a critical pathogenesis of cardiovascular diseases. Lower endothelial nitric oxide synthase (eNOS) phosphorylation leads to reduced endothelium-derived relaxing factor nitric oxide (NO) generation, causing and accelerating CMD. Endoplasmic reticulum stress (ER stress) has been shown to reduce NO production in umbilical vein endothelial cells. Oxidized low-density lipoprotein (ox-LDL) damages endothelial cell function. However, the relationship between ox-LDL and coronary microcirculation has yet to be assessed. Short-chain fatty acid (SCFA), a fermentation product of the gut microbiome, could improve endothelial-dependent vasodilation in human adipose arterioles, but the effect of SCFA on coronary microcirculation is unclear. In this study, we found ox-LDL stimulated expression of ER chaperone GRP78. Further, we activated downstream PERK/eIF2a, IRE1/JNK, and ATF6 signaling pathways, decreasing eNOS phosphorylation and NO production in human cardiac microvascular endothelial. Furthermore, SCFA-propionate can inhibit ox-LDL-induced eNOS phosphorylation reduction and raise NO production; the mechanism is related to the inhibition of ER stress and downstream signaling pathways PERK/eIF2a, IRE1/JNK, and ATF6. In summary, we demonstrate that ox-LDL induced CMD by activating ER stress, propionate can effectively counteract the adverse effects of ox-LDL and protect coronary microcirculation function via inhibiting ER stress.
Topics: Humans; Endoplasmic Reticulum Stress; Lipoproteins, LDL; Nitric Oxide Synthase Type III; Endoplasmic Reticulum Chaperone BiP; Propionates; Nitric Oxide; Signal Transduction; Phosphorylation; Endothelial Cells; Coronary Vessels; Fatty Acids, Volatile; eIF-2 Kinase; Activating Transcription Factor 6; Microcirculation; Heat-Shock Proteins
PubMed: 38814895
DOI: 10.1371/journal.pone.0304551 -
Communications Biology May 2024Propionic acidemia (PA), resulting from Pcca or Pccb gene mutations, impairs propionyl-CoA metabolism and induces metabolic alterations. While speculation exists that...
Propionic acidemia (PA), resulting from Pcca or Pccb gene mutations, impairs propionyl-CoA metabolism and induces metabolic alterations. While speculation exists that fasting might exacerbate metabolic crises in PA patients by accelerating the breakdown of odd-chain fatty acids and amino acids into propionyl-CoA, direct evidence is lacking. Our investigation into the metabolic effects of fasting in Pcca(A138T) mice, a PA model, reveals surprising outcomes. Propionylcarnitine, a PA biomarker, decreases during fasting, along with the C3/C2 (propionylcarnitine/acetylcarnitine) ratio, ammonia, and methylcitrate. Although moderate amino acid catabolism to propionyl-CoA occurs with a 23-h fasting, a significant reduction in microbiome-produced propionate and increased fatty acid oxidation mitigate metabolic alterations by decreasing propionyl-CoA synthesis and enhancing acetyl-CoA synthesis. Fasting-induced gluconeogenesis further facilitates propionyl-CoA catabolism without changing propionyl-CoA carboxylase activity. These findings suggest that fasting may alleviate metabolic alterations in Pcca(A138T) mice, prompting the need for clinical evaluation of its potential impact on PA patients.
Topics: Animals; Mice; Fasting; Methylmalonyl-CoA Decarboxylase; Mutation; Propionic Acidemia; Male; Mice, Knockout; Disease Models, Animal; Mice, Inbred C57BL; Acyl Coenzyme A
PubMed: 38811689
DOI: 10.1038/s42003-024-06362-8 -
Anais Da Academia Brasileira de Ciencias 2024In the present study, the effect of xanthan gum was evaluated on the metabolic activity and survival of two probiotic strains, namely B. lactis and L. casei using in...
In the present study, the effect of xanthan gum was evaluated on the metabolic activity and survival of two probiotic strains, namely B. lactis and L. casei using in vitro assay and skim milk model system. In vitro assay was carried out identifying by pH, optical cell density (OD), and formation of postbiotics (lactic, acetic, propionic, and butyric acids) in different basal media including glucose, inulin, and xanthan gum as carbon source. The highest pH values were recorded for control (without carbon source) and media with xanthan gum, whereas the media with glucose and xanthan gum had the highest OD values. In comparison to strains, B. lactis had higher pH and lower OD values than L. casei. It was found that xanthan gum supported the formation of postbiotics as a result of bacterial fermentation. In the skim milk model system, xanthan gum did not negatively affect probiotic viability, and the counts of both strains were above the required level for health benefits (8 log cfu g-1) after 28-day storage. The use of xanthan gum in skim milk matrix positively affected techno-functional properties such as syneresis, color, and textural parameters of samples.
Topics: Polysaccharides, Bacterial; Probiotics; Animals; Milk; Lacticaseibacillus casei; Bifidobacterium animalis; Hydrogen-Ion Concentration; Fermentation
PubMed: 38808815
DOI: 10.1590/0001-3765202420230658 -
PloS One 2024In this investigation, we explore the harnessing of bamboo shoot residues (BSR) as a viable source for ruminant feed through fungal treatment, with the overarching...
In this investigation, we explore the harnessing of bamboo shoot residues (BSR) as a viable source for ruminant feed through fungal treatment, with the overarching objective of elevating feed quality and optimizing bamboo shoot utilization. The white-rot fungi (Wr.fungi), Aspergillus niger (A.niger), and its co-cultures (A.niger&Wr.fungi) were employed to ferment BSR. And the impact of different fermentation methods and culture time on the chemical composition (Crude protein Ash, neutral detergent fibre and acid detergent fibers), enzyme activity (Cellulase, Laccase, Filter paperase and Lignin peroxidase activities), and rumen digestibility in vitro were assessed. The findings reveal a nota ble 30.39% increase in crude protein in fermented BSR, accompanied by respective decreases of 13.02% and 17.31% in acid detergent fiber and neutral detergent fibre content. Enzyme activities experienced augmentation post-fermentation with A.niger&Wr.fungi. Specifically, the peak Cellulase, Laccase, and Lignin peroxidase activities for BSR with Wr.fungi treatment reached 748.4 U/g, 156.92 U/g, and 291.61 U/g, respectively, on the sixth day of fermentation. Concurrently, NH3-N concentration exhibited an upward trend with prolonged fermentation time. Total volatile fatty acids registered a decline, and the Acetate/Propionate ratio reached its nadir after 6 days of fermentation under the A.niger&Wr.fungi treatment. These outcomes furnish a theoretical foundation for the development of ruminant feeds treated via fungal co-culture.
Topics: Animals; Animal Feed; Fermentation; Ruminants; Aspergillus niger; Plant Shoots; Rumen; Fungi
PubMed: 38805421
DOI: 10.1371/journal.pone.0302185 -
Frontiers in Microbiology 2024Medicinal plants, rich in phytochemicals like phenolic acids, flavonoids, and tannins, offer potential benefits in enhancing productivity, quality, and animal health....
INTRODUCTION
Medicinal plants, rich in phytochemicals like phenolic acids, flavonoids, and tannins, offer potential benefits in enhancing productivity, quality, and animal health. Amla fruit () is one such plant with promising attributes. This study aimed to investigate the impact of fresh Amla fruit (FAF) supplementation on ruminal microbial composition and its correlation with rumen fermentation in lactating dairy cows.
METHODS
The study employed a repeated crossover design involving eight ruminally cannulated mid-lactation Holstein dairy cows. Animals received varying levels of fresh Amla fruit supplementation (0, 200, 400, and 600 g/d).
RESULTS
When 400 g/d of FAF was added to the diet, there was a significant increase in the relative abundance of Firmicutes ( = 0.02). However, at 200 g/d, the relative abundance of ruminal Bacteroidota was higher than the 0 and 400 g/d FAF supplementation ( < 0.01). LEfSe analysis identified distinct taxa, such as in the 200 g/d group, in the 400 g/d group, and in the 600 g/d group. Notably, the random forest species abundance statistics identified as a biomarker related to milk yield. , and were positively correlated with ruminal total VFA and molar proportion of propionate, while gut group and were negatively correlated.
DISCUSSION
FAF supplementation affects the abundance of beneficial microbes in a dose-dependent manner, which can improve milk yield, efficiency, rumen health, desirable fatty acids, and animal health.
PubMed: 38803380
DOI: 10.3389/fmicb.2024.1365681 -
Microbial Biotechnology May 2024The human gut hosts numerous ecological niches for microbe-microbe and host-microbe interactions. Gut lactate homeostasis in humans is crucial and relies on various...
Mutualistic interactions of lactate-producing lactobacilli and lactate-utilizing Veillonella dispar: Lactate and glutamate cross-feeding for the enhanced growth and short-chain fatty acid production.
The human gut hosts numerous ecological niches for microbe-microbe and host-microbe interactions. Gut lactate homeostasis in humans is crucial and relies on various bacteria. Veillonella spp., gut lactate-utilizing bacteria, and lactate-producing bacteria were frequently co-isolated. A recent clinical trial has revealed that lactate-producing bacteria in humans cross-feed lactate to Veillonella spp.; however, their interspecies interaction mechanisms remain unclear. Veillonella dispar, an obligate anaerobe commonly found in the human gut and oral cavity, ferments lactate into acetate and propionate. In our study, we investigated the interaction between V. dispar ATCC 17748 and three representative phylogenetically distant strains of lactic acid bacteria, Lactobacillus acidophilus ATCC 4356, Lacticaseibacillus paracasei subsp. paracasei ATCC 27216, and Lactiplantibacillus plantarum ATCC 10241. Bacterial growth, viability, metabolism and gene level adaptations during bacterial interaction were examined. V. dispar exhibited the highest degree of mutualism with L. acidophilus. During co-culture of V. dispar with L. acidophilus, both bacteria exhibited enhanced growth and increased viability. V. dispar demonstrated an upregulation of amino acid biosynthesis pathways and the aspartate catabolic pathway. L. acidophilus also showed a considerable number of upregulated genes related to growth and lactate fermentation. Our results support that V. dispar is able to enhance the fermentative capability of L. acidophilus by presumably consuming the produced lactate, and that L. acidophilus cross-feed not only lactate, but also glutamate, to V. dispar during co-culture. The cross-fed glutamate enters the central carbon metabolism in V. dispar. These findings highlight an intricate metabolic relationship characterized by cross-feeding of lactate and glutamate in parallel with considerable gene regulation within both L. acidophilus (lactate-producing) and V. dispar (lactate-utilizing). The mechanisms of mutualistic interactions between a traditional probiotic bacterium and a potential next-generation probiotic bacterium were elucidated in the production of short-chain fatty acids.
Topics: Lactic Acid; Fatty Acids, Volatile; Glutamic Acid; Veillonella; Symbiosis; Microbial Interactions; Humans; Lactobacillus acidophilus; Lactobacillus; Microbial Viability; Fermentation
PubMed: 38801349
DOI: 10.1111/1751-7915.14484 -
Phytotoxicity and hormesis in common mobile organic compounds in leachates of wood-derived biochars.Biochar 2024Although addition of pyrolyzed organic materials (biochars) to soil generally results in increased growth and physiological performance of plants, neutral and negative...
UNLABELLED
Although addition of pyrolyzed organic materials (biochars) to soil generally results in increased growth and physiological performance of plants, neutral and negative responses have also commonly been detected. Toxicity of organic compounds generated during pyrolysis, sorbed by biochars, and then released into the soil solution, has been implicated as a possible mechanism for such negative effects. Conversely, water-soluble biochar constituents have also been suggested to have "hormetic" effects (positive effects on plants at low concentrations); however, no specific compounds responsible have been identified. We investigated the relative phytotoxicity-and possible hormetic effects-of 14 organic compounds common in aqueous extracts of freshly produced lignocellulosic biochars, using seed germination bioassays. Of the compounds examined, volatile fatty acids (VFAs: acetic, propionic, butyric, valeric, caproic, and 2-ethylbutyric acids) and phenol, showed acute phytotoxicity, with germination-based ED50 values of 1-30 mmol L, and 2-ethylbutyric acid showed ED50 values of 0.1-1.0 mmol L. Other compounds (benzene, benzoic acid, butanone, methyl salicylate, toluene, and 2,4-di-tert-butylphenol) showed toxic effects only at high concentrations close to solubility limits. Although phytotoxic at high concentrations, valeric and caproic acid also showed detectable hormetic effects on seedlings, increasing radicle extension by 5-15% at concentrations of ~ 0.01-0.1 mmol L. These data support the hypothesis that VFAs are the main agents responsible for phytotoxic effects of lignocellulosic biochar leachates, but that certain VFAs also have hormetic effects at low concentrations and may contribute to positive effects of biochar leachates on early plant development in some cases.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s42773-024-00339-w.
PubMed: 38799720
DOI: 10.1007/s42773-024-00339-w