Reduction Of Acids Research Articles

Abstract 1711: Rearranged active enhancers and promoter-enhancer contacts promote lipid metabolic reprogramming during secondary trastuzumab adaptation of HER2 positive breast cancer

Abstract Background: The development of secondary trastuzumab resistance signifies an evolutionary adaptation within HER2-positive breast cancer during anti-HER2 treatment. Our research reveals a comprehensive metabolic reprogramming, with a particular emphasis on the synthesis of unsaturated fatty acids and the degradation of arachidonic acid, accompanying this adaptation. Non-mutational epigenetic variations, particularly alterations in active enhancers, coupled with the rearrangement of enhancer-promoter contacts, demonstrate robust correlations with lipid metabolic reprogramming. These findings suggest that non-mutational epigenetic variations play a crucial role in driving the adaptation to trastuzumab. Materials and Methods: In a prior investigation, we successfully generated secondary trastuzumab-resistant SKBR3_HR cells. In our current study, total RNA was extracted from both trastuzumab-resistant SKBR3_HR and trastuzumab-sensitive SKBR3 cells for transcriptome analysis. Additionally, mass spectrometry was employed to analyze cellular metabolism in both resistant and sensitive cell populations. Simultaneously, we utilized the CUT&Tag kit with an anti-H3K27ac antibody to create a sequencing library for active enhancer measurement. Furthermore, the Micro-C kit was applied to generate a sequencing library for genome contact measurement. Results: In our study, secondary trastuzumab-adaptive SKBR3_HR cells demonstrated a reduction in cellular unsaturated fatty acids, with more than 110 UFAs or UFA-containing lipids showing decreases, while only 36 exhibited increases. This phenomenon may be attributed to the downregulation of SCD, FADS2, and HACD2. Simultaneously, the upregulation of PTGS1 and PTGES may contribute to a higher conversion of arachidonic acid to prostaglandin E2 (PGE2), resulting in immune inhibition. In SKBR3 and SKBR3_HR cells, 10,955 and 10,889 non-promoter H3K27me3 peaks, respectively, were identified as active enhancer regions. Among them, 379 enhancers became silent, and 313 transitioned into an active state during the formation of trastuzumab adaptation. Trastuzumab adaptation led to an increase in intra-chromosomal interactions, particularly short-distance contacts (< 1MB). By employing the activity-by-contact (ABC) algorithm, we observed significant variant contacts between PTGES and SCD promoters and enhancers within 1MB genomic regions in SKBR3_HR cells compared to SKBR3 cells. Conclusion: The formation of secondary trastuzumab adaptation involves the rearrangement of active enhancers and promoter-enhancer contacts, serving as an effective force to drive lipid metabolic reprogramming, especially the synthesis of unsaturated fatty acids and PGE2 production, reshaping the cellular fatty acid composition and anti-tumor immunity. Citation Format: Ningjun Duan, Yijia Hua, Yongmei Yin. Rearranged active enhancers and promoter-enhancer contacts promote lipid metabolic reprogramming during secondary trastuzumab adaptation of HER2 positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1711.

Gestational testosterone excess early to mid-pregnancy disrupts maternal lipid homeostasis and activates biosynthesis of phosphoinositides and phosphatidylethanolamines in sheep

Gestational hyperandrogenism is a risk factor for adverse maternal and offspring outcomes with effects likely mediated in part via disruptions in maternal lipid homeostasis. Using a translationally relevant sheep model of gestational testosterone (T) excess that manifests maternal hyperinsulinemia, intrauterine growth restriction (IUGR), and adverse offspring cardiometabolic outcomes, we tested if gestational T excess disrupts maternal lipidome. Dimensionality reduction models following shotgun lipidomics of gestational day 127.1 ± 5.3 (term 147 days) plasma revealed clear differences between control and T-treated sheep. Lipid signatures of gestational T-treated sheep included higher phosphoinositides (PI 36:2, 39:4) and lower acylcarnitines (CAR 16:0, 18:0, 18:1), phosphatidylcholines (PC 38:4, 40:5) and fatty acids (linoleic, arachidonic, Oleic). Gestational T excess activated phosphatidylethanolamines (PE) and PI biosynthesis. The reduction in key fatty acids may underlie IUGR and activated PI for the maternal hyperinsulinemia evidenced in this model. Maternal circulatory lipids contributing to adverse cardiometabolic outcomes are modifiable by dietary interventions.

Unlocking the potential of oil by-products: Investigating the influence of co-culture fermentation on phenolic acid degradation in side stream blends from oil and dairy industry

According to the newest trends in food waste management, the priority for valorisation of oil and dairy industry by-products was recognised. New approach of blending side streams of plant and animal origin has been proposed for obtaining future foods with improved nutritional value. Major obstacle in valorising sunflower seed cake (SSC) and whey (W) is their perishability and a relatively high content of phenolics contributing to, among others, protein indigestibility. In the study, a new approach of microwave pre-treatment applied for SSC and W blends was used. Its influence on phenolic acids and antioxidant properties after fermentation with co-culture of lactic acid bacteria and yeast was examined. Microwave drying of blends was longer than that of SSC affecting phenolic acids content. Fermentation by L. lactis and K. lactis caused pH decrease and increase in total acidity in 48 h effectively limiting the growth of bacterial contaminants. Fermentation decreased the content of phenolic acids, especially in blend composed of SSC and W (8.75:1; w/w) with the highest content of these constituents (from 1611.3 down to 838.8 mg/100 g dry matter). The study showed the synergistic effect of pre-treatment method and fermentation in terms of reduction in phenolic acids in new food matrices.

Altered microbial bile acid metabolism exacerbates T cell-driven inflammation during graft-versus-host disease.

Microbial transformation of bile acids affects intestinal immune homoeostasis but its impact on inflammatory pathologies remains largely unknown. Using a mouse model of graft-versus-host disease (GVHD), we found that T cell-driven inflammation decreased the abundance of microbiome-encoded bile salt hydrolase (BSH) genes and reduced the levels of unconjugated and microbe-derived bile acids. Several microbe-derived bile acids attenuated farnesoid X receptor (FXR) activation, suggesting that loss of these metabolites during inflammation may increase FXR activity and exacerbate the course of disease. Indeed, mortality increased with pharmacological activation of FXR and decreased with its genetic ablation in donor T cells during mouse GVHD. Furthermore, patients with GVHD after allogeneic hematopoietic cell transplantation showed similar loss of BSH and the associated reduction in unconjugated and microbe-derived bile acids. In addition, the FXR antagonist ursodeoxycholic acid reduced the proliferation of human T cells and was associated with a lower risk of GVHD-related mortality in patients. We propose that dysbiosis and loss of microbe-derived bile acids during inflammation may be an important mechanism to amplify T cell-mediated diseases.

Effects of atrazine and S-metolachlor on stream periphyton taxonomic and fatty acid compositions.

Extensive pesticide use for agriculture can diffusely pollute aquatic ecosystems through leaching and runoff events and has the potential to negatively affect non-target organisms. Atrazine and S-metolachlor are two widely used herbicides often detected in high concentrations in rivers that drain nearby agricultural lands. Previous studies focused on concentration-response exposure of algal monospecific cultures, over a short exposure period, with classical descriptors such as cell density, mortality or photosynthetic efficiency as response variables. In this study, we exposed algal biofilms (periphyton) to a concentration gradient of atrazine and S-metolachlor for 14 days. We focused on fatty acid composition as the main concentration-response descriptor, and we also measured chlorophyll a fluorescence. Results showed that atrazine increased cyanobacteria and diatom chlorophyll a fluorescence. Both herbicides caused dissimilarities in fatty acid profiles between control and high exposure concentrations, but S-metolachlor had a stronger effect than atrazine on the observed increase or reduction in saturated fatty acids (SFAs) and very long-chain fatty acids (VLCFAs), respectively. Our study demonstrates that two commonly used herbicides, atrazine and S-metolachlor, can negatively affect the taxonomic composition and fatty acid profiles of stream periphyton, thereby altering the nutritional quality of this resource for primary consumers.

Establishing the processing factor and degradation kinetics of hexaconazole residues in vinification and its residual impact on wine quality and aroma characteristics by GCxGC-ToF/MS analysis

Hexaconazole (HX), a triazole fungicide, is widely used for controlling mildews in commercial viticulture, and residues at harvest are a challenge. The pesticide residues in the harvested grapes may impact the grape and wine quality. In this study, we have investigated the fate of HX residues in the vinification with wine aroma and quality. HX was applied at the recommended dose (RD) and 10 times RD (10 RD). The HX residue dissipation exhibited first-order kinetics with a half-life of 3.5 and 2.5 days for RD and 10 RD, respectively. The processing factor from grape to wine ranged from 0.04 to 0.09, the transfer rate ranged from 2.46% to 6.47%. The HS-SPME-GCxGC-ToF/MS analysis revealed a significant impact on volatile organic compounds (VOCs). The concentration of key VOCs varied in control as esters (147.62 μg L−1), alcohols (144.81 μg L−1), acids (82.92 μg L−1) and in HX RD treated wines showed reduction in alcohols (111.32 μg L−1), esters (91.57 μg L−1) and acids (67.10 μg L−1). In 10 RD, alcohols, esters, acids were declined as 131.42 μg L−1, 118.65 μg L−1, and 75.73 μg L−1 respectively. In HX RD, 28 were up and 58 VOCs were down-regulated. 40 VOCs were up and 46 were down-regulated in HX 10 RD wine. The pathway enrichment analysis revealed impact of HX residues on glycolysis and pyruvate metabolism. Quality analysis showed variation in total flavonoids, phenols, and anthocyanin content. The results revealed that HX residues have a negative impact on wine aroma and metabolism during vinification.

Interaction of Fe2O3 nanoparticles with marine microalga Chlorella sorokiniana: Analysis of growth, morphological changes and biochemical composition

The wide utilization of iron-based nanoparticles (NPs) based on their preferential properties has led to the discharge and accumulation of these materials into the aquatic environment. In this regard, a comparative study of different concentrations of α-Fe2O3 NPs and their micro form was conducted using microalga Chlorella sorokiniana up to the stationary growth phase. This study revealed that high concentrations of NPs (100 and 200 mg L−1) imposed a stressful condition on algal cells documented by a reduction in microalga growth, including cell number and specific growth rate. The physical contact between the algal cells and NPs resulted in a shading effect as well as morphological changes validated by scanning electron microscope results. The biochemical composition of C. sorokiniana exposed to high levels of Fe2O3 NPs was also evaluated. The increase in total carbohydrate content of algal cells along with a significant reduction in unsaturated fatty acids was found. Moreover, Fe2O3 NPs exposure induced oxidative stress evidenced by an increase in lipid peroxidation. To cope with oxidative stress, superoxide dismutase activity and antioxidant potential of microalga as defensive mechanisms increased in the culture with high concentrations of NPs. Besides, due to the interactions, microalga tended to form a protective layer from further cell-NP interactions through the secretion of extracellular polymeric substances. Nonetheless, the nano form of Fe2O3 was more toxic than its micro form due to its small size. Overall, this trial may provide additional insight into the toxicological mechanism and safety assessments of Fe2O3 NPs in the aquatic environment.

Enhancing milk quality and modulating rectal microbiota of dairy goats in starch-rich diet: the role of bile acid supplementation.

Diets rich in starch have been shown to increase a risk of reducing milk fat content in dairy goats. While bile acids (BAs) have been used as a lipid emulsifier in monogastric and aquatic animals, their effect on ruminants is not well understood. This study aimed to investigate the impact of BAs supplementation on various aspects of dairy goat physiology, including milk composition, rumen fermentation, gut microbiota, and BA metabolism. We randomly divided eighteen healthy primiparity lactating dairy goats (days in milk = 100 ± 6 d) into two groups and supplemented them with 0 or 4g/d of BAs undergoing 5weeks of feeding on a starch-rich diet. The results showed that BAs supplementation positively influenced milk yield and improved the quality of fatty acids in goat milk. BAs supplementation led to a reduction in saturated fatty acids (C16:0) and an increase in monounsaturated fatty acids (cis-9 C18:1), resulting in a healthier milk fatty acid profile. We observed a significant increase in plasma total bile acid concentration while the proportion of rumen short-chain fatty acids was not affected. Furthermore, BAs supplementation induced significant changes in the composition of the gut microbiota, favoring the enrichment of specific bacterial groups and altering the balance of microbial populations. Correlation analysis revealed associations between specific bacterial groups (Bacillus and ChristensenellaceaeR-7group) and BA types, suggesting a role for the gut microbiota in BA metabolism. Functional prediction analysis revealed notable changes in pathways associated with lipid metabolism, suggesting that BAs supplementation has the potential to modulate lipid-related processes. These findings highlight the potential benefits of BAs supplementation in enhancing milk production, improving milk quality, and influencing metabolic pathways in dairy goats. Further research is warranted to elucidate the underlying mechanisms and explore the broader implications of these findings.

Cell-free reduction of carboxylic acids with secreted carboxylic acid reductase

Mycobacterium marinum CAR (MmCAR) is one of the most widely used CARs as the key enzyme for the synthesis of aldehydes, alcohols and further products from the respective carboxylic acids. Herein, we describe the first functionally secreted 131 kDa CAR and its isolated A-domain using Komagataella phaffii and a methanol-free constitutive expression strategy. Precipitated and lyophilized MmCAR (500 µg) was isolated from the culture supernatant and showed no decrease in activity for piperonylic acid (80% conversion), even when stored for up to 3 weeks at 4°C. Lyophilized MmCAR precipitate gave 48% yield of E/Z-nonanal-4-nitrobenzoyloxime from the reduction of nonanoic acid and in-situ derivatization with O-4-nitrobenzoyl-hydroxylamine. Furthermore, K. phaffii could successfully secrete the MmCAR adenylation domain. Its activity was confirmed by the amidation of benzoic acid with n-hexylamine. Neither enzyme variant was glycosylated by the yeast. In summary, functional CAR can be secreted by K. phaffii and used for cell free conversion of carboxylic acids to various products.

Fructose dose-dependently influences colon barrier function by regulation of some main physical, immune, and biological factors in rats

Little is known about the effects of fructose on colonic function. Here, forty-eight 7-week-old male SD rats were randomly divided into four groups and given 0, 7.5%, 12.75%, and 35% fructose in diet for 8 weeks respectively to investigate the regulatory influence of fructose on colonic barrier function. The exact amount of fructose intake was tracked and recorded. We showed that fructose affects colonic barrier function in a dose-dependent manner. High-fructose at a dose of 1.69±0.23 g/kg/day could damage the physical barrier function of the colon by down-regulating expression of tight junction proteins (ZO-1 and occludin) and mucus layer biomarkers (MUC2 and TFF3). High fructose reduced sIgA and the anti-inflammatory cytokine (IL-10), induced abdominal fat accumulation and pro-inflammatory cytokines (IL-6 and IL-8), leading to colon inflammation and immune barrier dysfunction. In addition, high-fructose altered the biological barrier of the colon by decreasing the abundance of Blautia, Ruminococcus, and Lactobacillius, and increasing the abundance of Allobaculum at the genus level, leading to a reduction in short-chain fatty acids (SCFAs), amino acids, and carbohydrates, etc. Low fructose at a dose of 0.31±0.05 g/kg/day showed no adverse effects on the colonic barrier. The ability of fructose to affect the colonic barrier through physical, immune, and biological pathways provides additional insight into the intestinal disorders caused by high-fructose diets.

A Versatile Aldehyde: Ferredoxin Oxidoreductase from the Organic Acid Reducing Thermoanaerobacter sp. Strain X514.

Aldehyde:ferredoxin oxidoreductases (AORs) have been isolated and biochemically-characterized from a handful of anaerobic or facultative aerobic archaea and bacteria. They catalyze the ferredoxin (Fd)-dependent oxidation of aldehydes to acids. Recently, the involvement of AOR in the reduction of organic acids to alcohols with electrons derived from sugar or synthesis gas was demonstrated, with alcohol dehydrogenases (ADHs) carrying out the reduction of the aldehyde to the alcohol (AOR-ADH pathway). Here, we describe the biochemical characterization of an AOR of the thermophilic fermentative bacterium Thermoanaerobacter sp. strain X514 (AORX514). The putative aor gene (Teth514_1380) including a 6x-His-tag was introduced into the genome of the genetically-accessible, related species Thermoanaerobacter kivui. The protein was purified to apparent homogeneity, and indeed revealed AOR activity, as measured by acetaldehyde-dependent ferredoxin reduction. AORX514 was active over a wide temperature (10 to 95 °C) and pH (5.5 to 11.5) range, utilized a wide variety of aldehydes (short and branched-chained, aliphatic, aromatic) and resembles archaeal sensu stricto AORs, as the protein is active in a homodimeric form. The successful, recombinant production of AORX514 in a related, well-characterized and likewise strict anaerobe paves the road towards structure-function analyses of this enzyme and possibly similar oxygen-sensitive or W/Mo-dependent proteins in the future.

The role of empagliflozin-induced metabolic changes for cardiac function in patients with type 2 diabetes. A randomized cross-over magnetic resonance imaging study with insulin as comparator

BackgroundMetabolic effects of empagliflozin treatment include lowered glucose and insulin concentrations, elevated free fatty acids and ketone bodies and have been suggested to contribute to the cardiovascular benefits of empagliflozin treatment, possibly through an improved cardiac function. We aimed to evaluate the influence of these metabolic changes on cardiac function in patients with T2D.MethodsIn a randomized cross-over design, the SGLT2 inhibitor empagliflozin (E) was compared with insulin (I) treatment titrated to the same level of glycemic control in 17 patients with type 2 diabetes, BMI of > 28 kg/m2, C-peptide > 500 pM. Treatments lasted 5 weeks and were preceded by 3-week washouts (WO). At the end of treatments and washouts, cardiac diastolic function was determined with magnetic resonance imaging from left ventricle early peak-filling rate and left atrial passive emptying fraction (primary and key secondary endpoints); systolic function from left ventricle ejection fraction (secondary endpoint). Coupling between cardiac function and fatty acid concentrations, was studied on a separate day with a second scan after reduction of plasma fatty acids with acipimox. Data are Mean ± standard error. Between treatment difference (ΔT: E–I) and treatments effects (ΔE: E-WO or ΔI: I -WO) were evaluated using Students’ t-test or Wilcoxon signed rank test as appropriate.ResultsGlucose concentrations were similar, fatty acids, ketone bodies and lipid oxidation increased while insulin concentrations decreased on empagliflozin compared with insulin treatment. Cardiac diastolic and systolic function were unchanged by either treatment. Acipimox decreased fatty acids with 35% at all visits, and this led to reduced cardiac diastolic (ΔT: −51 ± 22 ml/s (p < 0.05); ΔE: −33 ± 26 ml/s (ns); ΔI: 37 ± 26 (ns, p < 0.05 vs ΔE)) and systolic function (ΔT: -3 ± 1% (p < 0.05); ΔE: −3 ± 1% (p < 0.05): ΔI: 1 ± 2 (ns, ns vs ΔE)) under chronotropic stress during empagliflozin compared to insulin treatment.ConclusionsDespite significant metabolic differences, cardiac function did not differ on empagliflozin compared with insulin treatment. Impaired cardiac function during acipimox treatment, could suggest greater cardiac reliance on lipid metabolism for proper function during empagliflozin treatment in patients with type 2 diabetes.Trial registration: EudraCT 2017-002101-35, August 2017.

Differential content of leaf and fruit pigment in tomatoes culminate in a complex metabolic reprogramming without growth impacts

Although significant efforts to produce carotenoid-enriched foods either by biotechnology or traditional breeding strategies have been carried out, our understanding of how changes in the carotenoid biosynthesis might affect overall plant performance remains limited. Here, we investigate how the metabolic machinery of well characterized tomato carotenoid mutant plants [namely crimson (old gold-og), Delta carotene (Del) and tangerine (t)] adjusts itself to varying carotenoid biosynthesis and whether these adjustments are supported by a reprogramming of photosynthetic and central metabolism in the source organs (leaves). We observed that mutations og, Del and t did not greatly affect vegetative growth, leaf anatomy and gas exchange parameters. However, an exquisite metabolic reprogramming was recorded on the leaves, with an increase in levels of amino acids and reduction of organic acids. Taken together, our results show that despite minor impacts on growth and gas exchange, carbon flux is extensively affected, leading to adjustments in tomato leaves metabolism to support changes in carotenoid biosynthesis on fruits (sinks). We discuss these data in the context of our current understanding of metabolic adjustments and carotenoid biosynthesis as well as regarding to improving human nutrition.

A Comprehensive Exploration of the Fatty Acids Profile, Cholesterol, and Tocopherols Levels in Liver from Laying Hens Fed Diets Containing Nonindustrial Hemp Seed.

This study investigates the impact of dietary nonindustrial Moroccan hemp seed (HS) on the fatty acid profile, cholesterol, and tocopherol levels, in the liver of 120 Lohmann brown laying hens aged 22 weeks during 12 weeks of treatment. The hens are randomly allocated into four treatment groups, each subdivided into six replicates with five birds in each replicate. The dietary treatments consist of 0% HS (control), 10% HS, 20% HS, and 30% HS. Results indicate a substantial increase (p < 0.01) in polyunsaturated fatty acids, including omega 3 (n-3) and omega 6 (n-6) types, with the inclusion of HS in the diet. The n-6/n-3 ratio is significantly reduced (p < 0.01), and there is a significant reduction (p < 0.01) in saturated fatty acids only for the 30% HS treatment, indicating a more favorable fatty acid composition. Cholesterol levels remain largely unaffected by HS inclusion, except for the 10% HS group, which shows a significant decrease (p < 0.05). Moreover, hepatic tocopherol levels are significantly elevated (p < 0.01) in subjects receiving the HS diet, with the 30% HS group exhibiting the highest tocopherol content. In summary, incorporating HS into the diet up to 30% appears to offer promising benefits for hepatic lipid composition, particularly in terms of n-3 polyunsaturated fatty acids, the n-6/n-3 ratio, and tocopherol levels, while having minimal impact on cholesterol levels.

Refined diet consumption increases neuroinflammatory signalling through bile acid dysmetabolism

ABSTRACT Over recent decades, dietary patterns have changed significantly due to the increasing availability of convenient, ultra-processed refined foods. Refined foods are commonly depleted of key bioactive compounds, which have been associated with several deleterious health conditions. As the gut microbiome can influence the brain through a bidirectional communication system known as the ‘microbiota-gut-brain axis’, the consumption of refined foods has the potential to affect cognitive health. In this study, multi-omics approaches were employed to assess the effect of a refined diet on the microbiota-gut-brain axis, with a particular focus on bile acid metabolism. Mice maintained on a refined low-fat diet (rLFD), consisting of high sucrose, processed carbohydrates and low fibre content, for eight weeks displayed significant gut microbial dysbiosis, as indicated by diminished alpha diversity metrics (p < 0.05) and altered beta diversity (p < 0.05) when compared to mice receiving a chow diet. Changes in gut microbiota composition paralleled modulation of the metabolome, including a significant reduction in short-chain fatty acids (acetate, propionate and n-butyrate; p < 0.001) and alterations in bile acid concentrations. Interestingly, the rLFD led to dysregulated bile acid concentrations across both the colon (p < 0.05) and the brain (p < 0.05) which coincided with altered neuroinflammatory gene expression. In particular, the concentration of TCA, TDCA and T-α-MCA was inversely correlated with the expression of NF-κB1, a key transcription factor in neuroinflammation. Overall, our results suggest a novel link between a refined low-fat diet and detrimental neuronal processes, likely in part through modulation of the microbiota-gut-brain axis and bile acid dysmetabolism.

The effect of reducing starch bioavailability using organic acids on rumen fermentation and ruminant performance: A meta-analysis

Starch is an important nutrient in ruminants as an energy source. Utilizing organic acids to reduce starch bioavailability offers a safer approach to sustainable ruminant health and productivity. However, the inconsistent results obtained from published studies necessitate integration through meta-analysis to determine the actual effects. This study aimed to evaluate the effect of reducing starch bioavailability using organic acids on rumen fermentation and ruminant performance by meta-analysis. Hedges’ meta-analysis was conducted by using a random effect. A total of 14 articles were selected from the Scopus platform, with 23 comparative studies. This meta-analysis revealed that starch modification using organic acids influenced rumen fermentation. In vitro studies demonstrated a significant increase (p<0.01) in rumen pH and a reduction in ammonia (NH3) and total volatile fatty acids (VFA) levels (p<0.01). Partial VFA components, including butyrate, iso-butyrate, valerate, and iso-valerate, also showed significant decreases (p<0.01). Total protozoa also obtained a significant decrease (p<0.001). Moreover, in vivo trials indicated ruminant performance with increased milk fat content (p<0.05). In conclusion, the intervention of organic acids for reducing the bioavailability starch in rumen is effectively optimizes rumen health by maintaining fermented products within the normal range and increasing ruminant productivity.

Synthesis of S,S-Di(pyridin-2-yl)carbonodithioate (DPDTC) for the Reduction of Carboxylic Acids

Synthesis of S,S-Di(pyridin-2-yl)carbonodithioate (DPDTC) for the Reduction of Carboxylic Acids

Effect of Lactobacillus plantarum BFS1243 on a female frailty model induced by fecal microbiota transplantation in germ-free mice.

Frailty, a complex geriatric syndrome, significantly impedes the goal of achieving 'healthy aging'. Increasing evidence suggests a connection between gut microbiota, systemic inflammation, and disease. However, it remains to be determined whether interventions targeting the intestinal flora can effectively ameliorate frailty. Our research involved fecal microbiota transplantation (FMT) experiments on germ-free (GF) mice, dividing these mice into three groups: a group receiving transplants from healthy elderly individuals (HF group), a group of frailty patients (FF group), and the FF group supplemented with Lactobacillus plantarum BFS1243 (FFL group). Our findings indicated a significant shift in the gut microbiota of the FF group, in contrast to the HF group, characterized by decreased Akkermansia and increased Enterocloster, Parabacteroides, and Eisenbergiella. Concurrently, there was a reduction in amino acids and SCFAs, with BFS1243 partially mitigating these changes. The FF group exhibited an upregulation of inflammatory markers, including PGE2, CRP, and TNF-α, and a downregulation of irisin, all of which were moderated by BFS1243 treatment. Furthermore, BFS1243 improved intestinal barrier integrity and physical endurance in the FF mice. Correlation analysis revealed a negative association between SCFA-producing species and metabolites like lysine and butyric acid with pro-inflammatory factors. In conclusion, our study conclusively demonstrated that alterations in the gut microbiota of elderly individuals can lead to physical frailty, likely due to detrimental effects on the intestinal barrier and a pro-inflammatory state. These findings underscore the potential of gut microbiome modulation as a clinical strategy for treating frailty.

Humic substances as electron acceptor for anaerobic oxidation of methane (AOM) and electron shuttle in Mn (IV)-dependent AOM

Anaerobic methanotrophic archaea (ANME) belonging to the family Methanoperedenaceae are crucial for the global carbon cycle and different biogeochemical processes, owing to their metabolic versatility to couple anaerobic oxidation of methane (AOM) with different electron acceptors. A universal feature of Methanoperedenaceae is the abundant genes encoded in their genomes associated with extracellular electron transfer (EET) pathways. Candidatus. ‘Methanoperedens manganicus’, an archaeon belonging to the family Methanoperedenaceae, was recently enriched in a bioreactor performing AOM coupled with Mn (IV) reduction. Using this EET-capable ANME, we tested the hypothesis in this study that ANME can catalyse the humic-dependent AOM for growth. A two-year incubation showed that AOM activity can be sustained by Ca. ‘M. manganicus’ consortium in a bioreactor fed only with humic acids and methane. An isotopic mass balance batch test confirmed that the observed AOM was coupled to the reduction of humic acids. The increase of relative abundance of Ca. ‘M. manganicus’, and the total archaea population in the microbial community suggested that Ca. ‘M. manganicus’ can grow on methane and humic acids. The observation of humic-dependent AOM led to a subsequent hypothesis that humic acids could be used as the electron shuttle to mediate the EET in dissimilatory Mn (IV) reduction by Ca. ‘M. manganicus’. We tested this hypothesis by adding humic acids to a Ca. ‘M. manganicus’ dominated-culture, which showed that the AOM rate was doubled by the addition of humic acids. X-ray photoelectron spectroscopy (XPS) showed that quinone moieties were consumed when humic acids worked as electron acceptors while remaining stable when functioning as a shuttle for electron transfer. The results of our study suggest that humic acids may serve as electron shuttles to allow ANME to access more electron acceptors through long-range EET.

Cholestasis gravidarum in women in the second and third trimester of gestation, clinical and specific pharmacological treatment and its benefits

Introduction: cholestasis gravidarum is a syndrome that usually occurs in pregnant women in the second or third trimester of pregnancy and ends in the puerperium. It is clinically characterized by the presence of predominantly nocturnal pruritus that is palmoplantar at first and then generalized. Alterations in liver function with or without jaundice and elevated serum bile acid levels, biochemical cholestasis is classified as mild to moderate in severity.This pathology does not have significant consequences for the mother, but it is associated with a high risk of affecting the newborn, such as premature delivery, fetal distress, fetal arrhythmias and intrauterine death. Objective: diagnostic methods and behaviors in their pharmacological treatments that provide the best results for those patients. Methods: systematic review with qualitative database from the PUBMED platform. The articles were downloaded from the PUBMED platform and Zotero was used to make the proper citations and references. In the investigation, the population will be composed of adult female patients who were admitted to any health care unit during the second and third trimesters. Results: the PUBMED database was used with the following MESH terms (cholestasis of pregnancy) that generated 2 597 results. 28 articles were analyzed in more depth, of which 12 articles were finally selected for the final analysis. Ursodeoxycholic acid (UDCA), a beta epimer of chenodeoxycholic acid, is a more polar bile acid than primary bile acids, with substantial choleretic and multiple other chemoprotective effects. The mechanism of action is not fully understood, but studies have shown that after treatment there is a reduction in total serum bile acids in both maternal and umbilical cord serum and a qualitative change in bile acid pool. serum. When compared to all controls, UDCA was also found to be associated with a decreased incidence of preterm birth, neonatal respiratory distress, and the number of neonatal intensive care unit admissions