In ovo betaine injection improves breast muscle growth in newly hatched goslings through FXR/IGF-2 pathway.

Betaine has been shown to enhance growth performance and increase breast muscle yield in ducks and broilers through various mechanisms, including the modification of DNA methylation. However, the impact of in ovo betaine injection on muscle growth in newly hatched goslings remains unclear. In this study, fifty eggs were injected with saline or betaine at 7.5 mg/egg prior to incubation, and the subsequent effects on breast muscle growth in the newly hatched goslings were investigated. Betaine significantly increased (P < 0.05) the hatch weight, breast muscle weight, and breast muscle index, accompanied by an augmentation in muscle bundle cross-sectional area. Concurrently, betaine significantly upregulated (P < 0.05) the expression levels of myogenic regulatory factors, including myogenin (MyoG) and paired box 7 (Pax7) both mRNA and protein, while downregulating (P < 0.05) the mRNA and protein levels of myostatin (MSTN). Histological analysis revealed a higher abundance of proliferating cell nuclear antigen (PCNA) and Pax7 immune-positive cells in the breast muscle of the betaine group, consistent with elevated PCNA and Pax7 mRNA and protein levels. Additionally, significantly increased (P < 0.05) contents of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2) were observed in the breast muscle of the betaine group, so was mRNA expression of IGF-1, IGF-2, and insulin-like growth factor 1 receptor (IGF-1R). Betaine also significantly in8creased (P < 0.05) global DNA methylation of the breast muscle, accompanied by enhanced mRNA and protein levels of methionine cycle and DNA methylation-related enzymes, Interestingly, the promoter regions of IGF-1, IGF-2, and IGF-1R genes were significantly hypomethylated (P < 0.05). Moreover, in ovo betaine injection significantly upregulated (P < 0.05) the protein level of farnesoid X receptor (FXR) in breast muscle and FXR binding to the promoter of IGF-2 gene. These findings suggest that in ovo betaine injection promotes breast muscle growth during embryonic development in goslings through the FXR-mediated IGF-2 pathway, ultimately improving hatch weight and breast muscle weight.

Metabolome analysis revealed the critical role of betaine for arsenobetaine biosynthesis in the marine medaka (Oryzias melastigma).

Arsenobetaine (AsB), a non-toxic arsenic (As) compound found in marine fish, structurally resembles betaine (GB), a common methyl donor in organisms. This study investigates the potential role of GB in AsB synthesis in marine medaka (Oryzias melastigma) using metabolomic analysis. Dietary exposure to arsenate (As(V)) and varying GB concentrations (0.05% and 0.1% in diets) increased total As and AsB bioaccumulation, particularly in marine medaka muscle. Metabolomic analysis revealed that GB played a crucial role in promoting up-regulation in methylthioadenosine (MTA) by modulating the methionine cycle and down-regulation in glutathione (GSH) by modulating the glutathione cycle. Methionine metabolism and GSH, potentially binding again to exogenous GB, could synchronously produce more non-toxic AsB. Combining verification experiments of differential metabolites of Escherichia coli in vitro, GB, GSH, S-adenosylmethionine (SAM), and arsenocholine (AsC) entered methionine and glutathione metabolism pathways to generate more AsB. These findings underscore the GB's crucial regulatory role in modulating the synthesis of AsB. This study provides vital insights into the interplay between the structural analogs GB and AsB, offering specific strategies to enhance the detoxification mechanisms of marine fish in As-contaminated environments.

SLC25A48 influences plasma levels of choline and localizes to the inner mitochondrial membrane.

Choline contributes to the biogenesis of methyl groups, neurotransmitters, and cell membranes. Our genome-wide association study (GWAS) of circulating choline in 2228 college students found that alleles in SLC25A48 (rs6596270) influence choline concentrations in men (p = 9.6 × 10-8), but not women. Previously, the subcellular location and function of SLC25A48 were unknown. Using super-resolution immunofluorescence microscopy, we localized SLC25A48 to the inner mitochondrial membrane. Our results suggest that SLC25A48 transports choline across the inner mitochondrial membrane.

Structural insights into the molecular effects of the anthelmintics monepantel and betaine on the Caenorhabditis elegans acetylcholine receptor ACR-23.

Anthelmintics are drugs used for controlling pathogenic helminths in animals and plants. The natural compound betaine and the recently developed synthetic compound monepantel are both anthelmintics that target the acetylcholine receptor ACR-23 and its homologs in nematodes. Here, we present cryo-electron microscopy structures of ACR-23 in apo, betaine-bound, and betaine- and monepantel-bound states. We show that ACR-23 forms a homo-pentameric channel, similar to some other pentameric ligand-gated ion channels (pLGICs). While betaine molecules are bound to the classical neurotransmitter sites in the inter-subunit interfaces in the extracellular domain, monepantel molecules are bound to allosteric sites formed in the inter-subunit interfaces in the transmembrane domain of the receptor. Although the pore remains closed in betaine-bound state, monepantel binding results in an open channel by wedging into the cleft between the transmembrane domains of two neighboring subunits, which causes dilation of the ion conduction pore. By combining structural analyses with site-directed mutagenesis, electrophysiology and in vivo locomotion assays, we provide insights into the mechanism of action of the anthelmintics monepantel and betaine.

Tetrel bond affects the self-assembly of acetylcholine and its analogues and is an ancillary interaction in protein binding.

The -N+(CH3)3 residue is present in acetylcholine (ACh) and in many of its analogues which are used as selective ACh agonist or antagonists for human therapy.  The X-ray structures of four ACh derivatives show the presence of short and linear contacts between the C atoms of -N+(CH3)3 groups and lone pair possessing atoms.  These contacts can be rationalized as tetrel bonds (TtBs) thanks to their geometric features.  Interrogation of the Protein Data Bank suggests that similar -N+‒C···nucleophile contacts affect the details of the binding of ACh and its derivatives to proteins.  Quantum theory of atoms in molecules, noncovalent interaction plot, and natural bond orbital analyses consistently confirm that the -N+‒C···nucleophile contacts observed in small molecule crystals and in substrate/protein complexes are attractive in nature and can be rationalized as TtBs.  TtBs involving methyl groups of the -N+(CH3)3 moiety can be proposed as a new item in the palette of interactions allowing the compounds containing this pharmacophoric unit to bind to their target protein and/or to express their biological/pharmacological properties.

Betaine improves METH-induced depressive-like behavior and cognitive impairment by alleviating neuroinflammation via NLRP3 inflammasome inhibotion.

Methamphetamine abuse has been associated with central nervous system damage, contributing to the development of neuropsychiatric disorders such as depressive-like behavior and cognitive impairment. With the escalating prevalence of METH abuse, there is a pressing need to explore effective therapeutic interventions. Thus, the objective of this research was to investigate whether betaine can protect against depressive-like behavior and cognitive impairment induced by METH. Following intraperitoneal injections of METH in mice, varying doses of betaine were administered. Subsequently, the behavioral responses of mice and the impact of betaine intervention on METH-induced neural damage, synaptic plasticity, microglial activation, and NLRP3 inflammatory pathway activation were assessed. Administration 30 mg/kg and 100 mg/kg of betaine ameliorated METH-induced depressive-like behaviors in the open field test, tail suspension test, forced swimming test, and sucrose preference test and cognitive impairment in the novel object recognition test and Barnes maze test. Moreover, betaine exerted protective effects against METH-induced neural damage and reversed the reduced synaptic plasticity, including the decline in dendritic spine density, as well as alterations in the expression of hippocampal PSD95 and Synapsin-1. Additionally, betaine treatment suppressed hippocampal microglial activation induced by METH. Likewise, it also inhibited the activation of the hippocampal NLRP3 inflammasome pathway and reduced IL-1ß and TNF-α release. These results collectively suggest that betaine's significant role in mitigating depressive-like behavior and cognitive impairment resulting from METH abuse, presenting potential applications in the prevention and treatment of substance addiction.

Unraveling the neutral and polar lipidome of Nordic brown macroalgae: A sustainable source of functional lipids.

Brown macroalgae represent a sustainable and abundant source of lipids with acknowledged functional and health benefits. Nonetheless, macroalgae lipidome has been poorly unraveled due to lipids complex structural and chemical diversity. In this study, a comprehensive lipidomic analysis was performed in four macroalgae: Saccharina latissima, Fucus vesiculosus, Fucus serratus and the invasive Sargassum muticum, using HILIC-C30RP-HRMS. Neutral lipids (tri-, di-glycerides) comprised 72-82% of total lipids (TL) with a highly unsaturation profile (27-49% depending on species). The polar lipidome comprised glycolipids, phospholipids, betaine lipids and sphingolipids with varied content among macroalgae. S. latissima displayed the greatest level of glycolipids (23% of TL), by contrast with the dominance of long-chain polyunsaturated betaine lipids (10-18% of TL) in the other species, particularly in S. muticum. Phospholipids and sphingolipids were detected in low abundance (<1.7% of TL). This study elevated the potential of brown macroalgae as an emerging reservoir of bioactive lipids with nutritional relevance.

Multiomics reveals the ameliorating effect and underlying mechanism of aqueous extracts of polygonatum sibiricum rhizome on obesity and liver fat accumulation in high-fat diet-fed mice.

BACKGROUND: Polygonatum sibiricum polysaccharides protect against obesity and NAFLD. However, the potential effects of PS rhizome aqueous extracts (PSRwe) on adiposity and hepatic lipid accumulation remains unexplored. PURPOSE: Elucidating the impact and underlying mechanism of PSRwe on HFD-induced obesity and liver fat depostition. STUDY DESIGN: 56 male mice, aged eight weeks, were divided into seven groups: Positive, four doses of PSRwe, Model, and Control. HFD was fed for eight weeks, followed by alternate-day gavage of orlistat and PSRwe for an additional eight-week period. Integrative analysis encompassing multiomics, physiological and histopathological, and biochemical indexes was employed. METHODS: Body weight (BW); liver, fat and Lee's indexes; TC, TG, LDL-C, HDL-C, AST, ALT, FFA, leptin, and adiponectin in the liver and blood; TNFα, IL-6, and LPS in the colon, plasma, and liver; H&E, PAS and oil red O staining on adipose and liver samples were examined. OGTT and ITT were conducted The gut microbiome, microbial metabolome, colonic and liver transcriptome, plasma and liver metabolites were investigated. RESULTS: PSRwe at the dosage of 7.5 mg/kg demonstrated significant and consistent reduction in BW and hepatic fat deposition than orlistat. PSRwe significantly decreased TC, TG, LDL-C, LEP, FFA levels in blood and liver. PSRwe significantly enhanced the relative abundance of probiotics including Akkermansia muciniphila, Bifidobacterium pseudolongum, Lactobacillus reuteri, and metabolic pathways including glycolysis and fatty acids ß-oxidation. The 70 up-regulated microbial metabolites in PSRwe-treated mice mainly involved in nucleotides and amino acids metabolism, while 40 decreased metabolites primarily associated with lipid metabolism. The up-regulated colonic differentially expressed genes (DEGs) participate in JAK-STAT/PI3K-Akt/FoxO signaling pathway, serotonergic/cholinergic/glutamatergic synapses, while the down-regulated DEGs predominantly focused on fat absorption and transport. The up-regulated liver DEGs mainly concentrated on fatty acid oxidation and metabolism. Liver metabolisms revealed 131 differential metabolites, among which carnitine and oxidized lipids significantly increased in PSRwe-treated mice. In plasma, the 58 up-regulated metabolites mainly participate in co-factors/vitamins metabolism while 154 down-regulated ones in fatty acids biosynthesis. Comprehensive multiomics association analysis revealed significant associations between gut microbiota and colonic/liver gene expression, and suggested exogenous and endogenous betaine may be active compound in alleviating HFD-induced symptoms. CONCLUSION: PSRwe effectively mitigate HFD-induced obesity and hepatic steatosis by increasing beneficial bacteria, reducing colonic fat digestion/absorption, increasing hepatic lipid metabolism, and elevating betaine levels.

Unravelling the impact of RNA methylation genetic and epigenetic machinery in the treatment of cardiomyopathy.

Cardiomyopathy (CM) represents a heterogeneous group of diseases primarily affecting cardiac structure and function, with genetic and epigenetic dysregulation playing a pivotal role in its pathogenesis. Emerging evidence from the burgeoning field of epitranscriptomics has brought to light the significant impact of various RNA modifications, notably N6-methyladenosine (m6A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), N1-methyladenosine (m1A), 2'-O-methylation (Nm), and 6,2'-O-dimethyladenosine (m6Am), on cardiomyocyte function and the broader processes of cardiac and vascular remodelling. These modifications have been shown to influence key pathological mechanisms including mitochondrial dysfunction, oxidative stress, cardiomyocyte apoptosis, inflammation, immune response, and myocardial fibrosis. Importantly, aberrations in the RNA methylation machinery have been observed in human CM cases and animal models, highlighting the critical role of RNA methylating enzymes and their potential as therapeutic targets or biomarkers for CM. This review underscores the necessity for a deeper understanding of RNA methylation processes in the context of CM, to illuminate novel therapeutic avenues and diagnostic tools, thereby addressing a significant gap in the current management strategies for this complex disease.

Unraveling the metabolomic architecture of autism in a large Danish population-based cohort.

BACKGROUND: The prevalence of autism in Denmark has been increasing, reaching 1.65% among 10-year-old children, and similar trends are seen elsewhere. Although there are several factors associated with autism, including genetic, environmental, and prenatal factors, the molecular etiology of autism is largely unknown. Here, we use untargeted metabolomics to characterize the neonatal metabolome from dried blood spots collected shortly after birth. METHODS: We analyze the metabolomic profiles of a subset of a large Danish population-based cohort (iPSYCH2015) consisting of over 1400 newborns, who later are diagnosed with autism and matching controls and in two Swedish population-based cohorts comprising over 7000 adult participants. Mass spectrometry analysis was performed by a timsTOF Pro operated in QTOF mode, using data-dependent acquisition. By applying an untargeted metabolomics approach, we could reproducibly measure over 800 metabolite features. RESULTS: We detected underlying molecular perturbations across several metabolite classes that precede autism. In particular, the cyclic dipeptide cyclo-leucine-proline (FDR-adjusted p = 0.003) and the carnitine-related 5-aminovaleric acid betaine (5-AVAB) (FDR-adjusted p = 0.03), were associated with an increased probability for autism, independently of known prenatal and genetic risk factors. Analysis of genetic and dietary data in adults revealed that 5-AVAB was associated with increased habitual dietary intake of dairy (FDR-adjusted p < 0.05) and with variants near SLC22A4 and SLC22A5 (p < 5.0e - 8), coding for a transmembrane carnitine transporter protein involved in controlling intracellular carnitine levels. CONCLUSIONS: Cyclo-leucine-proline and 5-AVAB are associated with future diagnosis of autism in Danish neonates, both representing novel early biomarkers for autism. 5-AVAB is potentially modifiable and may influence carnitine homeostasis.

Heat Production of Iberian Pig Exposed to High Temperature and Effect of Dietary Supplementation with Betaine or Zinc.

The effect of heat, and dietary betaine or zinc on the heat production (HP) of Iberian pigs was studied. Thirty barrows (44 kg) were individually housed for 28 days and assigned to one of five treatments: (1) thermoneutrality (20 °C) and fed a control diet (TN-CON) ad libitum; (2) hot (30 °C) and fed a control diet (HT-CON) ad libitum; (3) thermoneutrality and pair fed a control diet (TN-CON-PF) to HT-CON; (4) hot and fed a betaine-supplemented (0.5%) diet (HT-BET) ad libitum; and (5) hot and fed a zinc-supplemented (0.012%) diet (HT-ZN) ad libitum. On the 18th day, pigs were moved to a respirometry chamber (two chambers) under their respective treatment. The metabolizable energy (ME) intake, HP and respiratory quotient (RQ) were measured over 24 h. No differences (p > 0.05) were found in HP and RE between treatments. For RQ, TN-CON was greater (p < 0.01) than HT treatments, except for HT-BET. All RQs indicated an overall lipogenesis where betaine supplementation showed an intermediate value, indicating that it may have a positive effect on lipogenesis and overall growth. At 30 °C, betaine or zinc had no effect on HP and RE; ME intake was not reduced, indicating a genetic adaptation of Iberian pigs to heat.

Extremozymes and compatible solute production potential of halophilic and halotolerant bacteria isolated from crop rhizospheric soils of Southwest Saurashtra Gujarat.

Halophiles are one of the classes of extremophilic microorganisms that can flourish in environments with very high salt concentrations. In this study, fifteen bacterial strains isolated from various crop rhizospheric soils of agricultural fields along the Southwest coastline of Saurashtra, Gujarat, and identified by 16S rRNA gene sequencing as Halomonas pacifica, H. stenophila, H. salifodinae, H. binhaiensis, Oceanobacillus oncorhynchi, and Bacillus paralicheniformis were investigated for their potentiality to produce extremozymes and compatible solute. The isolates showed the production of halophilic protease, cellulase, and chitinase enzymes ranging from 6.90 to 35.38, 0.004-0.042, and 0.097-0.550 U ml-1, respectively. The production of ectoine-compatible solute ranged from 0.01 to 3.17 mg l-1. Furthermore, the investigation of the ectoine-compatible solute production at the molecular level by PCR showed the presence of the ectoine synthase gene responsible for its biosynthesis in the isolates. Besides, it also showed the presence of glycine betaine biosynthetic gene betaine aldehyde dehydrogenase in the isolates. The compatible solute production by these isolates may be linked to their ability to produce extremozymes under saline conditions, which could protect them from salt-induced denaturation, potentially enhancing their stability and activity. This correlation warrants further investigation.

Betaine alleviates doxorubicin-related cardiotoxicity via suppressing oxidative stress and inflammation via the NLRP3/SIRT1 pathway.

Cardiotoxicity is one of the side effects of the anti-cancer drug doxorubicin (DOX) that limits its clinical application. Betaine (BT) is a natural agent with promising useful effects against inflammation and oxidative stress (OS). We assessed the effects of BT on DOX-induced cardiotoxicity in mice. Forty-two male NMRI mice were assigned to six groups: I: control; II: BT (200 mg/kg; orally, alone); III: DOX (2.5 mg/kg; six injections (ip)) for two weeks; IV, V, VI: BT (50 mg/kg, 100 mg/kg, and 200 mg/kg; orally, once a day for two weeks, respectively) plus DOX administration. The cardiac enzymes like cardiac troponin-I (cTn-I), lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB) were assessed in serum. Oxidative/inflammatory markers like nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reduced glutathione level (GSH), and glutathione peroxidase (GPx) activities were determined in cardiac tissue. The expressions of NOD-like receptor protein 3 (NLRP3), caspase-1, interleukin (IL)-1ß, and silent information regulator 1 (SIRT1) proteins were also evaluated in cardiac tissue. The results indicated that DOX significantly increased LDH, CK-MB, cTn-I, MDA, and NO levels and also the caspase-1, NLRP3, and IL-1ß expression. Furthermore, DOX caused a significant reduction in the GSH levels and SOD, CAT, GPX activities, and the expression of SIRT1 protein in heart tissue. However, BT significantly improved all studied parameters. The findings were confirmed by histopathological assessments of the heart. BT can protect against DOX-induced cardiotoxicity by suppressing the activation of NLRP3 and OS by stimulating the SIRT1 pathway.

Analysis of volatile compounds, betaine, and antioxidant effect in goji berry (Lycium barbarum L.) powder extracted by various drying methods and extraction solvents.

Goji berry (Lycium barbarum L.), a deciduous solanaceous shrub, were subjected to extraction using five solvents (water, 50% and 70% ethanol, and 50% and 70% methanol) and dried using two methods: freeze drying (FD) and spray drying (SD). To investigate the chemical properties of these various goji berry powders, an examination was conducted on the content of volatile compounds, betaine, antioxidant effect, total phenolic content (TPC), and total flavonoid compounds (TFC) (p < 0.05). The total volatile compound content was highest in SD powder with 50% ethanol extract, showing a 66.7% increase over the control. The betaine content was in the range of 9.25-31.9 mg/g dry weight, and it exhibited a significant increase with higher water concentration in the extraction solvent. Betaine, total phenolic compounds and total flavonoid compounds showed a significant increase in the sequence of SD followed by FD (p < 0.05). Overall, the SD sample showed superior benefits when evaluating volatile compounds, betaine, and antioxidant effect. SD was more suitable for drying goji berry, as it retains its appearance and biological activity.

Oral Supplementation with Betaine Powder Ameliorated High Blood Pressure in Spontaneously Hypertensive Rats.

Supplementation of betaine is associated with improved cardiac health, potentially due to its function in re-methylation of homocysteine, an independent risk factor for cardiovascular diseases. We investigated the effects of oral betaine supplementation on blood pressure homeostasis in spontaneously hypertensive (SHR) rats and Wistar Kyoto (WKY) rats in an 8 week-feeding trial with control (SHR-con and WKY-con) and 1% betaine supplemented (SHR-b and WKY-b) diets. Systolic, diastolic, and mean blood pressure in the SHR-b group were significantly lower at week 8 (p = 0.013, p = 0.011, p = 0.010, respectively). Furthermore, serum nitric oxide (NO) levels were significantly (p < 0.05) improved in the WKY-b and SHR-b groups, suggesting a healthy endothelial function. Additionally, the serum angiotensin I converting enzyme level in SHR-b rats was also significantly lowered, which may have been another reason for lower blood pressure. A significantly higher non-HDL level in the SHR-b group might reflect enhanced lipid secretion into the circulation in the form of very-low-density lipoprotein (VLDL). Betaine is known for its effect on the synthesis of phosphatidylcholine, a key component of VLDL. However, the long-term net outcomes of both blood pressure lowering and serum lipid increment should be further studied.

Longitudinal Analysis of One-Carbon Metabolism-Related Metabolites in Maternal and Cord Blood of Japanese Pregnant Women.

One-carbon metabolism (OCM) is a complex and interconnected network that undergoes drastic changes during pregnancy. In this study, we investigated the longitudinal distribution of OCM-related metabolites in maternal and cord blood and explored their relationships. Additionally, we conducted cross-sectional analyses to examine the interrelationships among these metabolites. This study included 146 healthy pregnant women who participated in the Chiba Study of Mother and Child Health. Maternal blood samples were collected during early pregnancy, late pregnancy, and delivery, along with cord blood samples. We analyzed 18 OCM-related metabolites in serum using stable isotope dilution liquid chromatography/tandem mass spectrometry. We found that serum S-adenosylmethionine (SAM) concentrations in maternal blood remained stable throughout pregnancy. Conversely, S-adenosylhomocysteine (SAH) concentrations increased, and the total homocysteine/total cysteine ratio significantly increased with advancing gestational age. The betaine/dimethylglycine ratio was negatively correlated with total homocysteine in maternal blood for all sampling periods, and this correlation strengthened with advances in gestational age. Most OCM-related metabolites measured in this study showed significant positive correlations between maternal blood at delivery and cord blood. These findings suggest that maternal OCM status may impact fetal development and indicate the need for comprehensive and longitudinal evaluations of OCM during pregnancy.

Effect of dietary treatments on performance, oocysts shedding and lesion scores in broiler chickens experimentally challenged with Eimeria infection.

Although anticoccidials effectively control coccidiosis, a needed reduction in the reliance on antimicrobials in animal production leads to the exploration of alternative compounds. The present study aimed to test five different dietary treatments to counteract the negative impact of coccidiosis on broiler chickens' health and performance. 1-day-old male Ross 308 broilers (n = 960) were randomly assigned to one of eight treatments, with six cages per treatment (20 birds/cage). To the diet of the broiler chickens of treatments (Trt) 1-5, a synbiotic was added from d0-10. From d10-28, birds of Trt1 and Trt2 were fed synbiotics, whereas birds of Trt3 were fed diets with glutamine, and birds of Trt4 and Trt5 were fed diets with a combination of ß-glucans and betaine. From d28-35 onwards, birds of Trt1 were fed a diet with a synbiotic, whereas birds of Trt2-4 received diets with glutamine, and birds of Trt5 were fed a non-supplemented diet. Birds of the positive control group (PC; Trt6) were fed a standard diet supplemented with an anticoccidial (Decoquinate). The challenged negative control (NCchall; Trt7) and non-challenged negative control (NC) Trt8 were fed a standard diet without anticoccidial or other dietary treatment. At 7 days (d) of age, all birds were inoculated with 1 023, 115, and 512 sporulated oocysts of E. acervulina, E. maxima, and E. tenella, respectively, except for Trt8. Body weight gain (BWG), feed intake, and feed conversion ratio were assessed for each feeding phase (d0-10, d10-28 and d28-35) and overall experimental period (d0-35). Oocyst shedding, Eimeria lesion scores, cecal length, and relative weight were assessed at d13, d22, d28 and d35. Additionally, oocyst shedding was determined at d9 and d17. Litter quality was evaluated at d27 and d34, and footpad lesions at d34. During the starter (d0-10) and finisher (d28-35) periods, performance did not differ between the treatments. During the grower period (d10-28), Trt6 (PC) and Trt8 (NC) chickens had the highest BWG of all treatments (P < 0.001). Dietary treatment had no effect on litter quality and severity of footpad lesions. In the PC group (Trt6), low oocyst excretion and lesion scores were found. When comparing Trt1-5 with NCchall (Trt7), none of the treatments significantly reduced oocyst output or lesion scores. In conclusion, in this experiment, none of the dietary treatments performed similar or better compared to the PC group (Trt6) regarding performance or reducing Eimeria oocyst shedding or lesion scores.

Optimizing growth and antioxidant function in heat-stressed broilers with vitamin C and betaine supplementation.

This study investigates the potential of vitamin C (VC) and/or betaine (Bet) to enhance growth performance, regulate serum metabolism, and bolster antioxidant function aiming to mitigate the impact of heat stress (HS) on broilers. Two hundred Ross 308 broilers at 28 days of age were randomly assigned to five groups. The control group, housed at 24 ± 1℃, was fed a basal diet. High-temperature treatment groups, housed at 32 ± 1℃, received a basal diet with 0 (HS group), 250 mg/kg VC (HSVC group), 1000 mg/kg Bet (HSBe group), and 250 mg/kg VC + 1000 mg/kg Bet (HSVCBe group). On day 42, assessments were made on growth performance, muscle quality, serum biochemistry, and antioxidant function. Results revealed that HS significantly lowered (P < 0.05) average daily feed intake (ADFI), the degree of redness (a*) in muscles, and serum total superoxide dismutase (T-SOD) level. It also reduced (P < 0.01) average daily gain (ADG), and serum total antioxidant capacity (T-AOC) level, while increasing (P < 0.05) shear force, serum direct bilirubin (D-BIL), uric acid (UA), and malondialdehyde (MDA) levels compared with the control group. Dietary supplementation of VC and Bet, either alone or in combination, significantly decreased shear force and serum UA level, while increasing ADG and serum T-AOC, T-SOD level compared with the HS group (P < 0.05). In conclusion, the addition of VC and/or Bet to the diet proves effective in enhancing the growth performance of HS-exposed broilers through the positive regulation of serum chemical metabolism and the alleviation of oxidative damage.

Effects of guanidino acetic acid and betaine supplementation on growth, dietary nutrient digestion and intestinal creatine metabolism in sheep.

BACKGROUND: The intestine of young ruminants is in the developmental stage and has weaker resistance to the changes of external environment. Improving intestinal health is vital to promoting growth of young ruminants. This study investigated effects of guanidino acetic acid (GAA) and rumen-protected betaine (RPB) supplementation on growth, dietary nutrient digestion and GAA metabolism in the small intestine of sheep. METHODS: Eighteen healthy Kazakh rams (27.46 ± 0.10 kg of body weight and 3-month old) were categorized into control, test group I and test group II, which were fed a basal diet, 1500 mg/kg GAA and 1500 mg/kg GAA + 600 mg/kg RPB, respectively. RESULTS: Compared with control group, test group II had increased (p < 0.05) average daily gain, plasma creatine level, ether extract (EE) and phosphorus digestibility on day 30. On day 60, the EE apparent digestibility, jugular venous plasma GAA, GAA content in the duodenal mucosa and GAA content in the jejunal and ileal mucosa of test group II were higher (p < 0.05) than other groups. Transcriptome analysis revealed that the differentially expressed genes (DEGs) involved in the duodenal pathways of oxidative phosphorylation and non-alcoholic fatty liver disease were significantly altered in test group II versus test group I (p < 0.05). Moreover, in the jejunum, the MAPK signalling pathway, complement and coagulation cascade and B-cell receptor signalling pathway were significantly enriched, with ATPase, solute carrier transporter protein, DHFR, SI, GCK, ACACA and FASN being the significantly DEGs (p < 0.05). CONCLUSION: Dietary supplementation of RPB on top of GAA in sheep diets may promote sheep growth and development by improving the body's energy, amino acid, glucose and lipid metabolism capacity.

The Role of Macrophage Inhibitory Factor in TAA-Induced Liver Fibrosis in Mice: Modulatory Effects of Betaine.

Macrophage inhibitory factor (MIF) is a multipotent cytokine, involved in the inflammatory response to infections or injuries. This study investigates the role of MIF in liver fibrosis and the modulating effect of betaine on MIF in thioacetamide (TAA)-induced liver fibrosis. The wild-type and knockout MIF-/- C57BL/6 mice were divided into the following groups: control; Bet group, which received betaine; MIF-/-; MIF-/-+Bet; TAA group, which received TAA; TAA+Bet; MIF-/-+TAA; and MIF-/-+TAA+Bet group. After eight weeks of treatment, liver tissue was collected for further analysis. The results revealed that TAA-treated MIF-deficient mice had elevated levels of hepatic TGF-ß1 and PDGF-BB, as well as MMP-2, MMP-9, and TIMP-1 compared to TAA-treated wild-type mice. However, the administration of betaine to TAA-treated MIF-deficient mice reduced hepatic TGF-ß1 and PDGF-BB levels and also the relative activities of MMP-2, MMP-9 and TIMP-1, albeit less effectively than in TAA-treated mice without MIF deficiency. Furthermore, the antifibrogenic effect of MIF was demonstrated by an increase in MMP2/TIMP1 and MMP9/TIMP1 ratios. The changes in the hepatic levels of fibrogenic factors were confirmed by a histological examination of liver tissue. Overall, the dual nature of MIF highlights its involvement in the progression of liver fibrosis. Its prooxidant and proinflammatory effects may exacerbate tissue damage and inflammation initially, but its antifibrogenic activity suggests a potential protective role against fibrosis development. The study showed that betaine modulates the antifibrogenic effects of MIF in TAA-induced liver fibrosis, by decreasing TGF-ß1, PDGF-BB, MMP-2, MMP-9, TIMP-1, and the deposition of ECM (Coll1 and Coll3) in the liver.