The multidrug resistance protein 4 is expressed and functionally active in isolated bladder from pig.

Multidrug resistance proteins type 4 (MRP4) and 5 (MRP5) play pivotal roles in the transport of cyclic nucleotides in various tissues. However, their specific functions within the lower urinary tract remain relatively unexplored. This study aimed to investigate the effect of pharmacological inhibition of MRPs on cyclic nucleotide signaling in isolated pig bladder. The relaxation responses of the bladder were assessed in the presence of the MRP inhibitor, MK571. The temporal changes in intra- and extracellular levels of cAMP and cGMP in stimulated tissues were determined by mass spectrometry. The gene (ABCC4) and protein (MRP4) expression were also determined. MK571 administration resulted in a modest relaxation effect of approximately 26% in carbachol-precontracted bladders. The relaxation induced by phosphodiesterase inhibitors such as cilostazol, tadalafil, and sildenafil was significantly potentiated in the presence of MK571. In contrast, no significant potentiation was observed in the relaxation induced by substances elevating cAMP levels or stimulators of soluble guanylate cyclase. Following forskolin stimulation, both intracellular and extracellular cAMP concentrations increased by approximately 15.8-fold and 12-fold, respectively. Similarly, stimulation with tadalafil + BAY 41-2272 resulted in roughly 8.2-fold and 3.4-fold increases in intracellular and extracellular cGMP concentrations, respectively. The presence of MK571 reduced only the extracellular levels of cGMP. This study reveals the presence and function of MRP4 transporters within the porcine bladder and paves the way for future research exploring the role of this transporter in both underactive and overactive bladder disorders.NEW & NOTEWORTHY This study investigates the impact of pharmacological inhibition of MRP4 and MRP5 transporters on cyclic nucleotide signaling in isolated pig bladders. MK571 administration led to modest relaxation, with enhanced effects observed in the presence of phosphodiesterase inhibitors. However, substances elevating cAMP levels remained unaffected. MK571 selectively reduced extracellular cGMP levels. These findings shed light on the role of MRP4 transporters in the porcine bladder, opening avenues for further research into bladder disorders.

Hypogammaglobulinemia Class G Is Present in Compensated and Decompensated Patients with Propionate Defects, Independent of Their Nutritional Status.

Propionate defects (PDs) mainly include methylmalonic (MMA) and propionic acidemia (PA) defects. Lifelong PD patients progress from the compensated to the decompensated stages, the latter of which are characterized by life-threatening acidemia and hyperammonemia crises. PD patients can suffer immunocompromise, especially during the decompensation stage. There is a significant gap in the research regarding the humoral immune response in PD patients. Here, we analyzed serum immunoglobulin concentrations and hemograms across compensated and decompensated stages in PD patients. Nutritional status and crisis triggers of decompensation were also explored. Twenty patients were studied, and 25 decompensation events (DE) and 8 compensation events (CE) were recorded. Compared with those in the CE group, the IgG levels in the DE group (513.4 ± 244.5 mg/dL) were significantly lower than those in the CE group (860.8 ± 456.5 mg/dL) (p < 0.0087). The mean hemoglobin concentration was significantly lower in the DE group (11.8 g/dL) than in the CE group (13.4 g/dL) (p < 0.05). The most frequent (48%) possible decompensation trigger factor was infection. Most of the events were registered in eutrophic patients (87.9%), despite which 65.2% and 50% of patients who experienced decompensated and compensated events, respectively, presented with hypogammaglobulinemia G. These findings provide evidence of the immunodeficiency of PD patients, independent of their nutritional status. We suggest that PD patients be managed as immunocompromised independently of their nutritional status or metabolic state (compensated or decompensated).

Oleic acid reduces oxidative stress in rat brain induced by some anticancer drugs.

Oleic acid (OA) is a monounsaturated compound with many health-benefitting properties such as obesity prevention, increased insulin sensitivity, antihypertensive and immune-boosting properties, etc. The aim of this study was to analyze the effect of oleic acid (OA) and some anticancer drugs against oxidative damage induced by nitropropionic acid (NPA) in rat brain. Six groups of Wistar rats were treated as follows: Group 1, (control); group 2, OA; group 3, NPA + OA; group 4, cyclophosphamide (CPP) + OA; group 5, daunorubicin (DRB) + OA; and group 6, dexrazoxane (DXZ) + OA. All compounds were administered intraperitoneally route, every 24 h for 5 days. Their brains were extracted to measure lipoperoxidation (TBARS), H2O2, Ca+2, Mg+2 ATPase activity, glutathione (GSH) and dopamine. Glucose, hemoglobin and triglycerides were measured in blood. In cortex GSH increased in all groups, except in group 2, the group 4 showed the highest increase of this biomarker. TBARS decrease, and dopamine increase in all regions of groups 4, 5 and 6. H2O2 increased only in cerebellum/medulla oblongata of group 5 and 6. ATPase expression decreased in striatum of group 4. Glucose increased in group 6, and hemoglobin increased in groups 4 and 5. These results suggest that the increase of dopamine and the antioxidant effect of oleic acid administration during treatment with oncologic agents could result in less brain injury.

Resmetirom, the long-awaited first treatment for metabolic dysfunction-associated steatohepatitis and liver fibrosis?

The most important factor associated with liver-related mortality in NAFLD is liver fibrosis. There is no approved treatment for metabolic dysfunction-associated steatohepatitis (MASH) or liver fibrosis. In the MAESTRO-NASH trial, Harrison et al.1 demonstrated the efficacy of resmetirom, a selective THR-ß agonist, for the treatment of MASH and liver fibrosis at 52 weeks.

A novel arylpiperazine derivative (LQFM181) protects against neurotoxicity induced by 3- nitropropionic acid in in vitro and in vivo models.

In the pursuit of novel antioxidant therapies for the prevention and treatment of neurodegenerative diseases, three new arylpiperazine derivatives (LQFM181, LQFM276, and LQFM277) were synthesized through a molecular hybridization approach involving piribedil and butylated hydroxytoluene lead compounds. To evaluate the antioxidant and neuroprotective activities of the arylpiperazine derivatives, we employed an integrated approach using both in vitro (SH-SY5Y cells) and in vivo (neurotoxicity induced by 3-nitropropionic acid in Swiss mice) models. In the in vitro tests, LQFM181 showed the most promising antioxidant activity at the neuronal membrane and cytoplasmic levels, and significant neuroprotective activity against the neurotoxicity induced by 3-nitropropionic acid. Hence, this compound was further subjected to in vivo evaluation, which demonstrated remarkable antioxidant capacity such as reduction of MDA and carbonyl protein levels, increased activities of succinate dehydrogenase, catalase, and superoxide dismutase. Interestingly, using the same in vivo model, LQFM181 also reduced locomotor behavior and memory dysfunction through its ability to decrease cholinesterase activity. Consequently, LQFM181 emerges as a promising candidate for further investigation into its neuroprotective potential, positioning it as a new therapeutic agent for neuroprotection.

Exploring the effects of the acaricide cyflumetofen on the vital organs of the honey bee Apis mellifera (Hymenoptera: Apidae) workers.

Bees are important for maintaining ecosystems, pollinating crops and producing marketable products. In recent years, a decline in bee populations has been reported, with multifactorial causes, including the intensification of pesticide use in agriculture. Among pesticides, cyflumetofen is an insecticide and acaricide used in apple, coffee and citrus crops, whose main pollinator is the honey bee Apis mellifera. Therefore, this bee is a potential target of cyflumetofen during foraging. This study evaluated the histopathological and cytological damage in the midgut, hypopharyngeal glands and fat body of A. mellifera workers exposed to LC50 of cyflumetofen. The midgut epithelium of exposed bees presented cytoplasmic vacuolization, release of vesicles and cell fragments, which indicate autophagy, increased production of digestive enzymes and cell death, respectively. The cytological analysis of the midgut revealed the dilation of the basal labyrinth and the presence of spherocrystals in the digestive cells. The hypopharyngeal glands produced greater amounts of secretion in treated bees, whereas no changes were observed in the fat body. The results indicate that acute exposure to cyflumetofen negatively affect A. mellifera, causing damage to the midgut and changes in the hypopharyngeal glands, which may compromise the survival and foraging of this pollinator.

In vitro Evaluation of the Antileishmanial and Antischistosomal Activities of p-Coumaric Acid Prenylated Derivatives.

We have evaluated eight p-coumaric acid prenylated derivatives in vitro for their antileishmanial activity against Leishmania amazonensis promastigotes and their antischistosomal activity against Schistosoma mansoni adult worms. Compound 7 ((E)-3,4-diprenyl-4-isoprenyloxycinnamic alcohol) was the most active against L. amazonensis (IC50=45.92 µM) and S. mansoni (IC50=64.25 µM). Data indicated that the number of prenyl groups, the presence of hydroxyl at C9, and a single bond between C7 and C8 are important structural features for the antileishmanial activity of p-coumaric acid prenylated derivatives.

Modeling the influence of propionic acid concentration and pH on the kinetics of Salmonella Typhimurium.

Salmonella Typhimurium is a foodborne pathogen often found in the poultry production chain. Antibiotics have been used to reduce S. Typhimurium contamination in poultry aviaries and improve chicken growth. However, antibiotics were banned in several countries. Alternatively, organic acids, such as propionic acid (PA), can control pathogens. This study determined the PA minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and mathematically modeled S. Typhimurium growth/inactivation kinetics under the influence of PA at different pH values (4.5, 5.5, and 6.5) which are within the pH range of the chicken gastrointestinal tract. The PA MIC against S. Typhimurium was pH-dependent, resulting in 5.0, 3.5 and 9.0 mM undissociated PA at pH 4.5, 5.5, and 6.5, respectively. The Baranyi and Roberts and the Weibull model fit growth and inactivation data well, respectively. Secondary models were proposed. The validated model predicted 3-log reduction of S. Typhimurium in 3 h at 68.2 mM of undissociated PA and pH 4.5. The models presented a good capacity to describe the kinetics of S. Typhimurium subjected to PA, representing a useful tool to predict PA antibacterial action depending on the pH.

Anandamide and WIN 55212-2 Afford Protection in Rat Brain Mitochondria in a Toxic Model Induced by 3-Nitropropionic Acid: an In Vitro Study.

Mitochondrial dysfunction plays a key role in the development of neurodegenerative disorders. In contrast, the regulation of the endocannabinoid system has been shown to promote neuroprotection in different neurotoxic paradigms. The existence of an active form of the cannabinoid receptor 1 (CB1R) in mitochondrial membranes (mitCB1R), which might exert its effects through the same signaling mechanisms as the cell membrane CB1R, has been shown to regulate mitochondrial activity. Although there is evidence suggesting that some cannabinoids may induce protective effects on isolated mitochondria, substantial evidence on the role of cannabinoids in mitochondria remains to be explored. In this work, we developed a toxic model of mitochondrial dysfunction induced by exposure of brain mitochondria to the succinate dehydrogenase inhibitor 3-nitropropionic acid (3-NP). Mitochondria were also pre-incubated with the endogenous agonist anandamide (AEA) and the synthetic CB1R agonist WIN 55212-2 to evaluate their protective effects. Mitochondrial reduction capacity, reactive oxygen species (ROS) formation, and mitochondrial swelling were assessed as toxic markers. While 3-NP decreased the mitochondrial reduction capacity and augmented mitochondrial ROS formation and swelling, both AEA and WIN 55212-2 ameliorated these toxic effects. To explore the possible involvement of mitCB1R activation on the protective effects of AEA and WIN 55212-2, mitochondria were also pre-incubated in the presence of the selective CB1R antagonist AM281, which completely reverted the protective effects of the cannabinoids to levels similar to those evoked by 3-NP. These results show partial protective effects of cannabinoids, suggesting that mitCB1R activation may be involved in the recovery of compromised mitochondrial activity, related to reduction of ROS formation and further prevention of mitochondrial swelling.

Locomotor Behavior and Memory Dysfunction Induced by 3-Nitropropionic Acid in Adult Zebrafish: Modulation of Dopaminergic Signaling.

Huntington's disease (HD) is a progressive neurodegenerative disease characterized by neuropsychiatric disturbance, cognitive impairment, and locomotor dysfunction. In the early stage (chorea) of HD, expression of dopamine D2 receptors (D2R) is reduced, whereas dopamine (DA) levels are increased. Contrary, in the late stage (bradykinesia), DA levels and the expression of D2R and dopamine D1 receptors (D1R) are reduced. 3-Nitropropionic acid (3-NPA) is a toxin that may replicate HD behavioral phenotypes and biochemical aspects. This study assessed the neurotransmitter levels, dopamine receptor gene expression, and the effect of acute exposure to quinpirole (D2R agonist) and eticlopride (D2R antagonist) in an HD model induced by 3-NPA in adult zebrafish. Quinpirole and eticlopride were acutely applied by i.p. injection in adult zebrafish after chronic treatment of 3-NPA (60 mg/kg). 3-NPA treatment caused a reduction in DA, glutamate, and serotonin levels. Quinpirole reversed the bradykinesia and memory loss induced by 3-NPA. Together, these data showed that 3-NPA acts on the dopaminergic system and causes biochemical alterations similar to late-stage HD. These data reinforce the hypothesis that DA levels are linked with locomotor and memory deficits. Thus, these findings may suggest that the use of DA agonists could be a pharmacological strategy to improve the bradykinesia and memory deficits in the late-stage HD.

Revealing the beneficial effects of a dairy infant formula on the gut microbiota of early childhood children with autistic spectrum disorder using static and SHIME® fermentation models.

This study evaluated the impact of the Milnutri Profutura® (MNP) dairy infant formula on the gut microbiota of early childhood children (three to five years) with Autistic Spectrum Disorder (ASD) using static fermentation (time zero, 24, and 48 h) and the Simulator of the Human Intestinal Microbiol Ecosystem (SHIME®) (time zero, 72 h, and 7 days). The relative abundance of selected intestinal bacterial groups, pH values, organic acids, and sugars were verified at time zero, 24, and 48 h using flow cytometry and measurements. In addition, the diversity and changes in the gut microbiota, and the amounts of acetic, butyric, and propionic acids and ammonium ions (NH4+) in fermentation using the SHIME® were measured at time zero, 72 h, and 7 days. MNP increased Lactobacillus/Enterococcus and Bifidobacterium populations and decreased Bacteroides/Prevotella, Clostridium histolyticum and Eubacterium rectale/Clostridium coccoides populations (p < 0.05) at 24 and 48 h of static fermentation, showing a positive prebiotic activity score (65.18 ± 0.07). The pH, fructose and glucose decreased, while lactic, butyric, and propionic acids increased (p < 0.05) at 48 h of static fermentation. MNP increased (p < 0.05) the Firmicutes phylum during the fermentation in SHIME®. MNP decreased the diversity at 72 h of fermentation, mostly by the increase (p < 0.05) in the Lactobacillus genus. Microbial groups considered harmful such as Lachnospiraceae, Negativicoccus, and Lachnoclostridium were inhibited after administration with MNP. Propionic and butyric acids increased at 72 h and NH4+ decreased (p < 0.05) at the end of fermentation with MNP. The results indicate MNP as an infant formula which may benefit the gut microbiota of children with ASD.

Metabolomic profile of seminal plasma from Guzerá bulls (Bos indicus) with contrasting sperm freezability phenotypes.

The present study evaluated the seminal plasma metabolome of Bos indicus Guzerá bulls with good (n = 4) and poor (n = 5) sperm freezability. Animals were raised in natural pasture of a 'Caatinga' ecosystem, in the semi-arid region of Brazil. Seminal plasma samples were subjected to gas chromatography coupled to mass spectrometry and data, analysed using bioinformatics tools (Cytoscape with the MetScape plug-in). Sixty-two metabolites were identified in the bovine seminal plasma. Fatty acids and conjugates and organic compounds were the predominant seminal fluid metabolites, followed by carboxylic acids and derivatives, amino acids, benzenes and steroids and derivatives, carbohydrates and carbohydrate conjugates and prenol lipids. Multivariate analysis indicated a distinct separation of seminal plasma metabolomes from bulls with contrasting sperm freezability. Abundances of propanoic acid, d-ribose and glycine were greater in the seminal plasma of bulls with good sperm freezability. Heptadecanoic acid and undecanoic acid were the predominant in bulls of poor sperm freezability. Propanoic acid is an energy source for spermatozoa and may act as an antimicrobial component in semen. Glycine acts against oxidizing and denaturing reactions. d-ribose is also an energy source and reduces apoptosis and oxidative stress. Undecanoic acid may protect sperm against fungal damage. This study provides fundamental information approximately the seminal plasma metabolome of tropically adapted bulls and its association with sperm freezability. However, further studies with larger groups of animals are needed to validate those metabolites as markers of sperm freezability. This strategy could support the selection of sires with superior sperm cryoresistance.

Chia flour combined with a high fat diet increases propionic acid production and improves the microbial richness and diversity in female Wistar rats.

Chia is a functional food because of its positive impact on reducing the risk of metabolic diseases. These benefits are due to its nutritional composition as a source of dietary fiber and bioactive compounds. In our previous study, chia consumption increased the richness of the microbiota and the production of short chain fatty acids (SCFAs) when consumed by male Wistar rats, so, the objective of this study was to assess the effects of the consumption of chia with a high fat diet on gut health in female Wistar rats. 32 adult female Wistar rats were allocated into four groups and received one of the following diets: standard diet (SD), standard diet + chia (SDC), high fat diet (HFD) or high fat diet + chia (HFDC) for 8 weeks. At the end of the study, the intestinal microbiota, SCFA content, cecum content pH, immunoglobulin A (IgA) quantification and brush border membrane functionality were evaluated. There was no difference in the relative abundance of the gut microbiota, but chia consumption increased the microbial richness and diversity, increased the production of acetic and butyric acids in the SDC group and propionic acid in the HFD group, and decreased the pH of cecal content. The HFDC group demonstrated a lower IgA concentration compared to the HFD group. The SDC group increased SI and AP gene expression and decreased SGLT1 and PepT1 compared to the SD group. The consumption of chia can be beneficial for the functionality of the microbiota, improving SCFAs and intestinal pH, and the effects of chia in the microbiota can be more pronounced in HFD.

Mitochondrial dysfunction, oxidative stress, ER stress and mitochondria-ER crosstalk alterations in a chemical rat model of Huntington's disease: Potential benefits of bezafibrate.

Redox homeostasis, mitochondrial functions, and mitochondria-endoplasmic reticulum (ER) communication were evaluated in the striatum of rats after 3-nitropropionic acid (3-NP) administration, a recognized chemical model of Huntington's disease (HD). 3-NP impaired redox homeostasis by increasing malondialdehyde levels at 28 days, decreasing glutathione (GSH) concentrations at 21 and 28 days, and the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione S-transferase at 7, 21, and 28 days, catalase at 21 days, and glutathione reductase at 21 and 28 days. Impairment of mitochondrial respiration at 7 and 28 days after 3-NP administration was also observed, as well as reduced activities of succinate dehydrogenase (SDH) and respiratory chain complexes. 3-NP also impaired mitochondrial dynamics and the interactions between ER and mitochondria and induced ER-stress by increasing the levels of mitofusin-1, and of DRP1, VDAC1, Grp75 and Grp78. Synaptophysin levels were augmented at 7 days but reduced at 28 days after 3-NP injection. Finally, bezafibrate prevented 3-NP-induced alterations of the activities of SOD, GPx, SDH and respiratory chain complexes, DCFH oxidation and on the levels of GSH, VDAC1 and synaptophysin. Mitochondrial dysfunction and synaptic disruption may contribute to the pathophysiology of HD and bezafibrate may be considered as an adjuvant therapy for this disorder.

Effect of low dietary concentrations of Acacia mearnsii tannin extract on chewing, ruminal fermentation, digestibility, nitrogen partition, and performance of dairy cows.

The supplementation of dairy cows with tannins can reduce the ruminal degradation of dietary protein and urine N excretion, but high concentration in the diet can impair ruminal function, diet digestibility, feed intake, and milk yield. This study evaluated the effect of low concentrations (0, 0.14, 0.29, or 0.43% of diet in DM basis) of a tannin extract from the bark of Acacia mearnsii (TA) on milking performance, dry matter intake (DMI), digestibility, chewing behavior, ruminal fermentation, and N partition of dairy cows. Twenty Holstein cows (34.7 ± 4.8 kg/d, 590 ± 89 kg, and 78 ± 33 d in lactation) were individually fed a sequence of 4 treatments in 5, 4 × 4 Latin squares (with 21-d treatment periods, each with a 14-d adaptation period). The TA replaced citrus pulp in the total mixed ration and other feed ingredients were kept constant. Diets had 17.1% crude protein, mostly from soybean meal and alfalfa haylage. The TA had no detected effect on DMI (22.1 kg/d), milk yield (33.5 kg/d), and milk components. The proportions in milk fat of mixed origin fatty acids (16C and 17C) and the daily secretion of unsaturated fatty acids were linearly reduced and the proportion of de novo fatty acids was increased by TA. Cows fed TA had linear increase in the molar proportion of butyrate and linear reduction in propionate in ruminal fluid, whereas acetate did not differ. There was a tendency for the ratio of acetate to propionate to be linearly increased by TA. Cows fed TA had a linear reduction in the relative ruminal microbial yield, estimated by the concentrations of allantoin and creatinine in urine and body weight. The total-tract apparent digestibility of neutral detergent fiber, starch, and crude protein also did not differ. The TA induced a linear increase in meal size and duration of the first daily meal and reduced meal frequency. Rumination behavior did not differ with treatment. Cows fed 0.43% TA selected against feed particles >19 mm in the morning. There were tendencies for linear decreases in milk urea N (16.1-17.3 mg/dL), urine N (153-168 g/d and 25.5-28.7% of N intake), and plasma urea N at 6, 18, and 21 h postmorning feeding, and plasma urea N 12 h postfeeding was reduced by TA. The proportion of N intake in milk (27.1%) and feces (21.4%) did not differ with treatment. Reductions in urine N excretion and milk and plasma urea N suggest that TA reduced ruminal AA deamination, whereas lactation performance did not differ. Overall, TA up to 0.43% of DM did not affect DMI and lactation performance, while there was a tendency to reduce urine N excretion.

Effects of lasalocid, narasin, or virginiamycin supplementation on rumen parameters and performance of beef cattle fed forage-based diet.

Two experiments were designed to evaluate the impacts of supplementing lasalocid (LAS), narasin (NAR), or virginiamycin (VRM) on rumen fermentation parameters, apparent nutrient digestibility, and blood parameters (Exp. 1), as well as feed intake and performance (Exp. 2) of Nellore cattle consuming a forage-based diet. In Exp. 1, 32 rumen-fistulated Nellore steers (initial shrunk body weight [BW] = 355 ± 4.4 kg) were assigned to a randomized complete block design. Within block, animals were randomly assigned to one of four treatments: 1) forage-based diet without feed additives (CON), 2) CON diet plus 13 mg/kg of dry matter (DM) of NAR, 3) CON diet plus 20 mg/kg of DM of sodium LAS, or 4) CON diet plus 20 mg/kg of DM of VRM. No treatment effects were detected (P ≥ 0.32) for intake and apparent digestibility of nutrients. Steers fed NAR had the lowest (P ≤ 0.01) molar proportion of acetate on day 28, 56, and 112 vs. CON, LAS, and VRM steers, whereas acetate did not differ (P ≥ 0.25) between LAS, VRM, and CON steers from day 28 to 84. On day 112, steers fed LAS had a lower (P < 0.02) molar proportion of acetate vs. VRM and CON, whereas it did not differ between CON and VRM (P > 0.33). Steers receiving NAR had a greater (P ≤ 0.04) ruminal propionate vs. CON, LAS, and VRM, whereas LAS steers had greater (P < 0.04) propionate vs. CON and VRM steers on day 28 and 112, and it did not differ (P > 0.22) between CON and VRM. In Exp. 2, 160 Nellore bulls were blocked by initial shrunk BW (212 ± 3.1 kg) in a 140-d feedlot trial. Diets contained the same treatments used in Exp. 1. Bulls fed NAR had greater (P < 0.02) average daily gain (ADG) vs. CON and VRM, and similar (P = 0.17) ADG between NAR and LAS, whereas ADG did not differ (P > 0.28) between LAS, VRM, and CON bulls. A treatment effect was detected (P = 0.03) for dry matter intake, being greater in NAR vs. CON, LAS, and VRM bulls, and similar (P > 0.48) between CON, LAS, and VRM bulls. A tendency was detected (P = 0.09) for feed efficiency, which was greater (P < 0.02) in NAR bulls vs. CON and VRM, and similar (P = 0.36) between NAR and LAS bulls. From day 112 to 140, bulls receiving NAR were heavier (P < 0.03) vs. CON, LAS, and VRM bulls, but no differences were observed (P > 0.51) between CON, LAS, and VRM bulls. Collectively, ruminal fermentation profile and intake were impacted by NAR supplementation, which partially contributed to the enhanced performance of Nellore bulls receiving a forage-based diet.

Feed additives are nutritional tools that benefit dietary digestibility and nutrient utilization, alter ruminal fermentation routes, and improve cattle growth and efficiency, thus increasing productivity and profitability in beef cattle systems. Nonetheless, most of the current research focuses on supplementing feed additives in high-concentrate diets. Leaving a significant gap in understanding the influence of feed additives in cattle consuming forage-based diets, especially molecules capable of altering the fermentation process and, consequently, beef cattle performance. Therefore, this experiment aimed to evaluate the impacts of supplementing narasin (NAR), lasalocid (LAS), or virginiamycin (VRM) on rumen fermentation parameters, apparent nutrient digestibility, feed intake, and performance of Bos indicus Nellore cattle consuming a forage-based diet. Including commercially available feed additives into forage-based diets did not impact nutrient intake and digestibility of nutrients. The inclusion of NAR affected ruminal fermentation parameters toward propionate production, positively contributing to animal performance. Ruminal fermentation characteristics and animal growth were not impacted by dietary LAS and VRM, which could be attributed to the dose used in the current experiment, despite the manufacturer's recommendation. This research provides insights into NAR as an important feed additive for forage-based beef cattle diets.

Short-chain fatty acids are associated with adiposity, energy and glucose homeostasis among different metabolic phenotypes in the Nutritionists' Health Study.

BACKGROUND AND AIMS: The gut microbiome is associated with obesity, mainly mediated by bacteria-produced short-chain fatty acids (SCFAs). It is unknown how SCFA concentrations are associated with the phenotypes metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy obese/overweight (MHO), and metabolically unhealthy obese/overweight (MUO). We compared plasma and fecal SCFA concentrations among adult women categorized according to the metabolic phenotypes mentioned above and examined associations between SCFA and adiposity and components of energy and glucose homeostasis. METHODS: This was a cross-sectional study involving 111 participants. Body composition was assessed by DEXA. Energy and glycemic homeostasis were assessed by the standard mixed-meal tolerance test coupled with indirect calorimetry. SCFAs were quantified by gas chromatography and mass spectrometry. RESULTS: Only plasma propionate was increased in the MHNW phenotype compared to the MHO and MUO phenotypes [p < 0.05]. Fecal propionate and butyrate concentrations and plasma propionate concentrations were inversely associated with total and visceral adiposity [p < 0.05]. Fecal and plasma SCFA concentrations were associated with reduced glucose, insulin and HbA1c levels, increased fasting and postprandial GLP-1 levels; and more preserved beta-cell function [p < 0.05]. Fecal and plasma SCFA concentrations were positively correlated with resting energy expenditure and lipid oxidation rate and inversely correlated with the oxidation rate of carbohydrates [p < 0.05]. CONCLUSION: These findings reinforce the concept that fecal and plasma SCFA concentrations are linked to specific components of energy and glucose homeostasis; and body adiposity. However, it was not possible to discriminate the different metabolic phenotypes of adiposity based on the determination of fecal SCFA concentrations.

Agave fructans enhance the effects of fermented milk products on obesity biomarkers: a randomised trial.

Dysbiosis has been implicated in childhood obesity. Oral intake of fermented milk containing Lacticaseibacillus casei strain Shirota preserves gut microbiota (GM) diversity in children and adults. This study was a double-blind trial involving 37 overweight or obese children aged 6-10 years. Children were followed over a 6-week intervention period in which they received different fermented milk products containing L. casei Shirota: 10 in the first group received just L. casei Shirota; 13 received L. casei Shirota with 3 g/day of inulin (L. casei+inulin); and 14 received L. casei Shirota with 3 g/day of fructans from Agave salmiana (L. casei+fructans). Principal component analysis showed the relationship between microbial abundance, GM metabolites, and other obesity-related markers. Supplementation with probiotics and synbiotics improved the HDL-cholesterol levels of overweight and obese children, although no changes in body composition were detected. We observed an increase in butyrate or propionate concentrations in the L. casei+fructans group compared to the end of the intervention (P<0.03). A diminished level of ANGPTL4 within the L. casei+fructans group (P=0.04) was also found, but no differences when lipopolysaccharide-binding protein was evaluated. The FFAR2+ cell frequency decreased between baseline and at the end of 6-week intervention in L. casei+inulin (P=0.02) and L. casei+fructans groups (P=0.04). In contrast, the percentage of CD14+FFAR3+ frequency increased in the same groups (P=0.04). The L. casei Shirota with inulin or fructans modulates GM, which improves the lipid profile and changes at a molecular level, such as expression of FFAR3 and FFAR2, ANGPTL4, propionate, and butyrate. It, therefore, could be considered an interesting therapeutic possibility for treating childhood overweight and obesity. The study was registered at ClinicalTrials.gov (ID: NCT05423015).

Effect of propionate, monensin, and saccharomyces cerevisiae or their combination on production and rumen fermentation of holstein steers.

This study aimed to evaluate the effects of calcium propionate (PrCa), PrCa + monensin sodium (PrCa + Mon), and PrCa + Saccharomyces cerevisiae (PrCa + Sc) on the productive performance of Holstein steers. Twenty-four Holstein steers (270.0 ± 25.85 kg) were distributed individually into four treatments of six replicates. The treatments were control (no additives), PrCa (10 g/kg), PrCa + Mon (10 g/kg + 30 mg/kg), and PrCa + Sc (10 g/kg + 12.8 × 109 cfu). The steers were fed for 43 days, and afterwards, nutrient intake and digestibility as well as volatile fatty acids were determined, while the weight gained, feed efficiency, and CH4 production were calculated. Diet of PrCa + Sc had the highest (P < 0.0001) acid detergent fiber intake and propionate acid as well as the nutrient digestibility, with lowest (P < 0.0001) rumen acetic acid, methane, and protozoa concentration versus other diets. In conclusion, dietary inclusion of PrCa + Sc (10 g/kg + 12.8 × 109 cfu) improved nutrient digestibility, rumen fermentation, and reduced methane emission, thereby enhancing the possibility of ecofriendly ruminant farming.

Feeding amylolytic and proteolytic exogenous enzymes: Effects on nutrient digestibility, ruminal fermentation, and performance in dairy cows.

Exogenous enzymes are added to diets to improve nutrient utilization and feed efficiency. A study was conducted to evaluate the effects of dietary exogenous enzyme products with amylolytic (Amaize, Alltech) and proteolytic (Vegpro, Alltech) activity on performance, excretion of purine derivatives, and ruminal fermentation of dairy cows. A total of 24 Holstein cows, 4 of which were ruminally cannulated (161 ± 88 d in milk, 681 ± 96 body weight, and 35.2 ± 5.2 kg/d of milk yield), were blocked by milk yield, days in milk, and body weight, and then distributed in a replicated 4 × 4 Latin square design. Experimental periods lasted 21 d, of which the first 14 d were allowed for treatment adaptation and the last 7 d were used for data collection. Treatments were as follows: (1) control (CON) with no feed additives, (2) amylolytic enzyme product added at 0.5 g/kg diet dry matter (DM; AML), (3) amylolytic enzyme product at 0.5 g/kg of diet DM and proteolytic enzyme product at 0.2 g/kg of diet DM (low level; APL), and (4) amylolytic enzyme products added at 0.5 g/kg diet DM and proteolytic enzyme product at 0.4 g/kg of diet DM (high level; APH). Data were analyzed using the mixed procedure of SAS (version 9.4; SAS Institute Inc.). Differences between treatments were analyzed by orthogonal contrasts: CON versus all enzyme groups (ENZ); AML versus APL+APH; and APL versus APH. Dry matter intake was not affected by treatments. Sorting index for feed particles with size <4 mm was lower for ENZ group than for CON. Total-tract apparent digestibility of DM and nutrients (organic matter, starch, neutral detergent fiber, crude protein, and ether extract) were similar between CON and ENZ. Starch digestibility was greater in cows fed APL and APH treatments (86.3%) compared with those in the AML group (83.6%). Neutral detergent fiber digestibility was greater in APH cows compared with those in the APL group (58.1 and 55.2%, respectively). Ruminal pH and NH3-N concentration were not affected by treatments. Molar percentage of propionate tended to be greater in cows fed ENZ treatments than in those fed CON. Molar percentage of propionate was greater in cows fed AML than those fed the blends of amylase and protease (19.2 and 18.5%, respectively). Purine derivative excretions in urine and milk were similar in cows fed ENZ and CON. Uric acid excretion tended to be greater in cows consuming APL and APH than in those in the AML group. Serum urea N concentration tended to be greater in cows fed ENZ than in those fed CON. Milk yield was greater in cows fed ENZ treatments compared with CON (32.0, 33.1, 33.1, and 33.3 kg/d for CON, AML, APL, and APH, respectively). Fat-corrected milk and lactose yields were higher when feeding ENZ. Feed efficiency tended to be greater in cows fed ENZ than in those fed CON. Feeding ENZ benefited cows' performance, whereas the effects on nutrient digestibility were more pronounced when the combination of amylase and protease was fed at the highest dose.