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Journal of Experimental Zoology. Part... Aug 2024Ecological nutrition aims to unravel the extensive web of nutritional links that drives animals in their interactions with their ecological environments. Nutrition plays...
Ecological nutrition aims to unravel the extensive web of nutritional links that drives animals in their interactions with their ecological environments. Nutrition plays a key role in the success of European wild rabbit (Oryctolagus cuniculus) and could be affected by the breeding status of the animals and reflected in the metabolome of this species. As nutritional needs are considerably increased during pregnancy and lactation, the main objective of this work was to determine how the breeding status (pregnant and lactating) of European wild rabbit does affects nutritional requirements and their metabolome (using targeted and untargeted metabolomics), aiming to find a useful biomarker of breeding status and for monitoring nutritional requirements. To address this gap, 60 wild European rabbits were studied. Animals were divided according to their breeding status and only pregnant (n = 18) and lactating (n = 11) rabbit does were used (n = 29 in total). The body weight and length of each animal were analyzed. The relative and absolute chemical composition of the gastric content and whole blood sample were taken, and targeted and untargeted metabolomics were analyzed. As a main result, there were no differences in biometric measurements, gastric content, and targeted metabolomics, except for live weight and nonesterified fatty acids (NEFA), as pregnant animals showed higher live weight (+12%; p = 0.0234) and lower NEFA acid levels (-46%; p = 0.0262) than lactating females. Regarding untargeted metabolomics, a good differentiation of the metabolome of the two breeding groups was confirmed, and it was proven that pregnant animals showed higher plasmatic levels of succinic anhydride (3.48 more times; p = 0.0236), succinic acid (succinate) (3.1 more times; p = 0.0068) and propionic acid (3.98 more times; p = 0.0121) than lactating animals. However, lactating animals showed higher levels of N-[(3a,5b,7b)-7-hydroxy-24-oxo-3-(sulfoxide) cholan-24-yl]-Glycine (cholestadien) (2.4 more times; p < 0.0420), 4-maleyl-acetoacetate (MAA) (3.2 more times; p < 0.0364) and irilone (2.2 more times; p = 0.0451) than pregnant animals, any of these metabolites could be used as a potential biomarker. From these results, it can be concluded that the most notable changes were observed in the metabolome of individuals, with most of the changes observed being due to energy and protein mobilisation.
Topics: Animals; Female; Rabbits; Lactation; Pregnancy; Metabolome; Metabolomics; Animal Nutritional Physiological Phenomena; Animals, Wild
PubMed: 38651595
DOI: 10.1002/jez.2818 -
The Journal of Organic Chemistry Apr 2024The synthesis of cyclohex-2-enone derivatives is a topic of current interest in organic chemistry. A novel three-component cascade reaction of alkynes with ketones and...
The synthesis of cyclohex-2-enone derivatives is a topic of current interest in organic chemistry. A novel three-component cascade reaction of alkynes with ketones and ethyl acetoacetate has been uncovered. This process provides di- and trisubstituted cyclohex-2-enones in good yields with excellent functional group tolerance. A variety of terminal alkynes and a wide range of aryl, alkyl, and cyclic ketones are viable in this transformation. Successful scale-up preparation and synthetic transformations have demonstrated the potential of this simple operating protocol.
PubMed: 38566575
DOI: 10.1021/acs.joc.3c02913 -
Molecules (Basel, Switzerland) Mar 2024Ursodeoxycholic acid (UDCA) and acetoacetate are natural compounds present in the human intestine and blood, respectively. A number of studies highlighted that besides...
Ursodeoxycholic acid (UDCA) and acetoacetate are natural compounds present in the human intestine and blood, respectively. A number of studies highlighted that besides their well-known primary biological roles, both compounds possess the ability to influence a variety of cellular processes involved in the etiology of various diseases. These reasons suggested the potential of acetoacetate-UDCA hybrids as possible therapeutic agents and prompted us to develop a synthetic strategy to selectively derivatize the hydroxyl groups of the bile acid with acetoacetyl moieties. 3α-acetoacetoxy UDCA was obtained (60% isolated yield) via the regioselective transesterification of methyl acetoacetate with UDCA promoted by the lipase B (CAL-B). 3α,7β-bis-acetoacetoxy UDCA was obtained instead by thermal condensation of methyl acetoacetate and UDCA (80% isolated yield). This bis-adduct was finally converted to the 7β-acetoacetoxy UDCA (82% isolated yield) via CAL-B catalyzed regioselective alcoholysis of the ester group on the 3α position. In order to demonstrate the value of the above new hybrids as UDCA-based scaffolds, 3α-acetoacetoxy UDCA was subjected to multicomponent Biginelli reaction with benzaldehyde and urea to obtain the corresponding 4-phenyl-3,4-dihydropyrimidin-2-()-one derivative in 65% isolated yield.
Topics: Humans; Ursodeoxycholic Acid; Acetoacetates; Bile Acids and Salts
PubMed: 38542941
DOI: 10.3390/molecules29061305 -
The Journal of Organic Chemistry Apr 2024Two efficient and convenient methods for the synthesis of 3-alkylideneoxindoles are described in this paper. The InCl/TfOH-mediated tandem Knoevenagel...
Two efficient and convenient methods for the synthesis of 3-alkylideneoxindoles are described in this paper. The InCl/TfOH-mediated tandem Knoevenagel condensation-deacylation sequence of various 2-oxindoles with 1,3-diones or acetoacetate furnished 3-alkylideneoxindoles in satisfactory to excellent yields (up to >99% yield). Employing the reaction system, the condensation of 2-oxindoles with ketones or aldehydes also proceeded smoothly to produce 3-alkylideneoxindoles. This protocol can be amenable to scale up. The effect of acids on this condensation reaction and intermolecular competition experiments were investigated to understand the aspect of the reaction.
PubMed: 38536713
DOI: 10.1021/acs.joc.4c00202 -
Canadian Liver Journal Feb 2024Hepatorenal tyrosinemia type 1 (HT-1) is a rare autosomal recessive disease that results from a deficiency of fumaryl acetoacetate hydrolase (FAH), a critical enzyme in... (Review)
Review
Hepatorenal tyrosinemia type 1 (HT-1) is a rare autosomal recessive disease that results from a deficiency of fumaryl acetoacetate hydrolase (FAH), a critical enzyme in the catabolic pathway for tyrosine. This leads to the accumulation of toxic metabolites such as fumaryl and maleylacetoacetate, which can damage the liver, kidneys, and nervous system. The discovery of 2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione (NTBC or nitisinone) has significantly improved the management of HT-1, particularly when initiated before the onset of symptoms. Therefore, newborn screening for HT-1 is essential for timely diagnosis and prompt treatment. The analysis of succinyl acetone (SA) in dried blood spots of newborns followed by quantification of SA in blood or urine for high-risk neonates has excellent sensitivity and specificity for the diagnosis of HT-1. NTBC combined with dietary therapy, if initiated early, can provide liver transplant (LT) free survival and reduce the risk of hepatocellular carcinoma (HCC). Patients failing medical treatment (eg, due to non-adherence), and who develop acute liver failure (ALF), have HCC or evidence of histologically proven dysplastic liver nodule(s), or experience poor quality of life secondary to severe dietary restrictions are currently indicated for LT. Children with HT-1 require frequent monitoring of liver and renal function to assess disease progression and treatment compliance. They are also at risk of long-term neurocognitive impairment, which highlights the need for neurocognitive assessment and therapy.
PubMed: 38505790
DOI: 10.3138/canlivj-2023-0018 -
Frontiers in Endocrinology 2024Alzheimer's disease (AD) is increasing in prevalence, but effective treatments for its cognitive impairment remain severely limited. This study investigates the impact...
BACKGROUND
Alzheimer's disease (AD) is increasing in prevalence, but effective treatments for its cognitive impairment remain severely limited. This study investigates the impact of ketone body production through dietary manipulation on memory in persons with mild cognitive impairment due to early AD and explores potential mechanisms of action.
METHODS
We conducted a 12-week, parallel-group, controlled feasibility trial of a ketogenic diet, the modified Atkins diet (MAD), compared to a control diet in patients with cognitive impairments attributed to AD. We administered neuropsychological assessments, including memory tests, and collected blood samples at baseline and after 12 weeks of intervention. We performed untargeted lipidomic and targeted metabolomic analyses on plasma samples to detect changes over time.
RESULTS
A total of 839 individuals were screened to yield 38 randomized participants, with 20 assigned to receive MAD and 18 assigned to receive a control diet. Due to attrition, only 13 in the MAD arm and nine in the control arm were assessed for the primary endpoint, with two participants meeting ketosis levels used to define MAD adherence criteria. The average change from baseline in the Memory Composite Score was 1.37 (95% CI: -0.87, 4.90) points higher in the MAD group compared to the control group. The effect size of the intervention on baseline MAD change was moderate (Cohen's = 0.57, 95% CI: -0.67, 1.33). In the 15 participants (nine MAD, six control) assessed for lipidomic and metabolomic-lipidomics and metabolomics, 13 metabolites and 10 lipids showed significant changes from baseline to 12 weeks, including triacylglycerols (TAGs, 50:5, 52:5, and 52:6), sphingomyelins (SM, 44:3, 46:0, 46:3, and 48:1), acetoacetate, fatty acylcarnitines, glycerol-3-phosphate, and hydroxy fatty acids.
CONCLUSIONS
Attrition was greatest between baseline and week 6. All participants retained at week 6 completed the study. Despite low rates of adherence by criteria defined , lipidomic and metabolomic analyses indicate significant changes from baseline in circulating lipids and metabolites between MAD and control participants at 12-week postrandomization, and MAD participants showed greater, albeit nonsignificant, improvement in memory.
Topics: Humans; Aged; Alzheimer Disease; Diet, High-Protein Low-Carbohydrate; Feasibility Studies; Cognitive Dysfunction; Fatty Acids
PubMed: 38505743
DOI: 10.3389/fendo.2024.1182519 -
International Journal of Biological... Apr 2024Efficient and effective use of biopolymers, such as starch, has increasingly prompted interest due to the current environmental challenges. However, starch-based...
Efficient and effective use of biopolymers, such as starch, has increasingly prompted interest due to the current environmental challenges. However, starch-based composites still show poor ductility along with water and oxygen permeability, which may not meet the requirements for food packaging standards. In this study, modified starch (m-St), isolated from the avocado seed and synthesized with tert-butyl acetoacetate (t-BAA), was embedded into polylactic acid (PLA) to design new eco-friendly composites. The developed biocomposites were found to exhibit high performance with outstanding mechanical properties in conjunction with remarkable light, water vapor, and oxygen blocking features for food packaging applications. PLA/m-St(1:6) 20 wt% composites showed a dramatic increase in elongation at break (EB%) from 3.35 to 27.80 % (about 730 % enhancement) and exhibited remarkable UV-blocking performance from 16.21 to 83.86 % for UVB, relative to pure PLA. Equally importantly, these biocomposites revealed significant improvement in oxygen and water vapor barrier performance by reducing their values from 1331 to 32.9 cc m day (indicating a remarkable reduction of 97.53 %) and 61.9 to 28 g m day, respectively. This study can show the great potential of extracting starch from biowaste resources and transforming it into sustainable bio-based composites as a promising solution for food packaging applications.
Topics: Persea; Food Packaging; Starch; Steam; Polyesters; Oxygen
PubMed: 38503372
DOI: 10.1016/j.ijbiomac.2024.130837 -
Angewandte Chemie (International Ed. in... May 2024Vitrimers represent an emerging class of polymeric materials that combine the desirable characteristics of both thermoplastics and thermosets achieved through the design...
Vitrimers represent an emerging class of polymeric materials that combine the desirable characteristics of both thermoplastics and thermosets achieved through the design of dynamic covalent bonds within the polymer networks. However, these materials are prone to creep due to the inherent instability of dynamic covalent bonds. Consequently, there are pressing demands for the development of robust and stable dynamic covalent chemistries. Here, we report a catalyst-free α-acetyl cinnamate/acetoacetate (α-AC/A) exchange reaction to develop vitrimers with remarkable creep resistance. Small-molecule model studies revealed that the α-AC/A exchange occurred at temperatures above 140 °C in bulk, whereas at 120 °C, this reaction was absent. For demonstration in the case of polymers, copolymers derived from common vinyl monomers were crosslinked with terephthalaldehyde to produce α-AC/A vitrimers with tunable thermal and mechanical performance. All resulting α-AC/A vitrimers exhibited high stability, especially in terms of creep resistance at 120 °C, while retaining commendable reprocessability when subjected to high temperatures. This work showcases the α-AC/A exchange reaction as a novel and robust dynamic covalent chemistry capable of imparting both reprocessability and high stability to cross-linked networks.
PubMed: 38489506
DOI: 10.1002/anie.202400955 -
Molecules (Basel, Switzerland) Feb 2024Zinc alumotitanate sorbents with various compositions were prepared through sol-gel synthesis with the use of ethyl acetoacetate as a chelating agent. The formation and...
Zinc alumotitanate sorbents with various compositions were prepared through sol-gel synthesis with the use of ethyl acetoacetate as a chelating agent. The formation and decomposition of chelates, providing insight into sol-gel process advancement, have been successfully monitored via H NMR, C NMR, and FTIR spectroscopy. It has been established that Al(OBu) and Ti(OBu) react completely with Eaa, forming chelates after 1 h, while after 24 h hydrolysis is already advanced. Hydrolysis is accelerated in the presence of Zn(NO)·6HO, supplying the water needed for hydrolysis. In dried gels, the amount of ethyl acetoacetate is greatly reduced, and it is mainly present unbound. According to XRD analysis, samples with none or less titania are composed of layered double hydroxide, while in samples with greater amounts of titania, crystal nitrates are present. In all samples except those without Al, the spinel phase with variable composition crystallizes.
PubMed: 38474477
DOI: 10.3390/molecules29050965 -
Animals : An Open Access Journal From... Mar 2024This review paper provides an in-depth analysis of three critical metabolic diseases affecting dairy cattle such as subacute ruminal acidosis (SARA), ketosis, and... (Review)
Review
This review paper provides an in-depth analysis of three critical metabolic diseases affecting dairy cattle such as subacute ruminal acidosis (SARA), ketosis, and hypocalcemia. SARA represents a disorder of ruminal fermentation that is characterized by extended periods of depressed ruminal pH below 5.5-5.6. In the long term, dairy herds experiencing SARA usually exhibit secondary signs of the disease, such as episodes of laminitis, weight loss and poor body condition despite adequate energy intake, and unexplained abscesses usually 3-6 months after an episode of SARA. Depressed milk-fat content is commonly used as a diagnostic tool for SARA. A normal milk-fat test in Holstein dairy cows is >4%, so a milk-fat test of <3% can indicate SARA. However, bulk tank testing of milk fat is inappropriate to diagnose SARA at the herd level, so when >4 cows out of 12 and <60 days in milk are suspected to have SARA it can be considered that the herd has a problem. The rapid or abrupt introduction of fresh cows to high-concentrate diets is the most common cause of SARA. Changes in ruminal bacterial populations when exposed to higher concentrate rations require at least about 3 weeks, and it is recommended that concentrate levels increase by no more than 400 g/day during this period to avoid SARA. Ketosis, a prevalent metabolic disorder in dairy cattle, is scrutinized with a focus on its etiological factors and the physiological changes leading to elevated ketone bodies. In total mix ration-fed herds, an increased risk of mastitis and reduced fertility are usually the first clinical signs of ketosis. All dairy cows in early lactation are at risk of ketosis, with most cases occurring in the first 2-4 weeks of lactation. Cows with a body condition score ≥3.75 on a 5-point scale at calving are at a greater risk of ketosis than those with lower body condition scores. The determination of serum or whole blood acetone, acetoacetate, beta-hydroxybutyrate (BHB) concentration, non-esterified fatty acids (NEFA), and liver biopsies is considered the best way to detect and monitor subclinical ketosis, while urine or milk cowside tests can also be used in on-farm monitoring programs. Concentrations >1.0 mmol/L or 1.4 mmol/L blood or serum BHB are considered diagnostic of subclinical ketosis. The standard threshold used for blood is 1.2 mmol/L, which corresponds to thresholds of 100 mcmol/L for milk and 15 mg/dL for urine. Oral administration of propylene glycol (250-400 g, every 24 h for 3-5 days) is the standard and most efficacious treatment, as well as additional therapy with bolus glucose treatment. Hypocalcemia is a disease of adult dairy cows in which acute hypocalcemia causes acute to peracute, afebrile, flaccid paralysis that occurs most commonly at or soon after parturition. Dairy cows are at considerable risk for hypocalcemia at the onset of lactation, when daily calcium excretion suddenly increases from about 10 g to 30 g per day. Cows with hypocalcemia have a more profound decrease in blood calcium concentration-typically below 5.5 mg/dL. The prevention of parturient paresis has been historically approached by feeding cows low-calcium diets during the dry period. Negative calcium balance triggers calcium mobilization before calving and better equips the cow to respond to the massive calcium needs at the onset of lactation. Calcium intake must be limited to <20 g per day for calcium restriction to be effective. The most practical and proven method for monitoring hypocalcemia is by feeding cows an acidogenic diet for ~3 weeks before calving. Throughout the review, emphasis is placed on the importance of early diagnosis and proactive management strategies to mitigate the impact of these metabolic diseases on dairy cattle health and productivity. The comprehensive nature of this paper aims to serve as a valuable resource for veterinarians, researchers, and dairy farmers seeking a deeper understanding of these prevalent metabolic disorders in dairy cattle.
PubMed: 38473200
DOI: 10.3390/ani14050816