Betaine Group Research Articles

Betaine alleviates cerebellar endoplasmic reticulum stress and oxidative imbalance in a cuprizone model of multiple sclerosis in rat.

Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system, especially the cerebellum, with numerous physical and mental symptoms. Oxidative stress caused by inflammation can play a role in the occurrence of this disease. Betaine, a natural methyl donor compound, has potent neuroprotective effects. Here, we investigated the effects of betaine on motor behavior, cerebellar histological changes, oxidative stress response, and endoplasmic reticulum stress in a cuprizone (CPZ)-induced multiple sclerosis model in male rats. Twenty Wistar adult male rats were randomly divided into four groups including control, MS, betaine-treated MS, and betaine groups. MS was induced by feeding animals with rodent chow containing 0.5% CPZ for 12 weeks. Betaine was daily administrated as 1% in drinking water for the last 6 weeks. The motor behavioral performance was evaluated by open field, rotarod, and reverse basket tests. Histological analysis of the cerebellum was performed by hematoxylin and eosin (H&E) and Cresyl violet (Nissl) staining. Oxidative stress factors (GSH, GSSG, GPX, GR, and GT) were assessed in the experimental groups and finally, the expression of ERS-associated proteins was measured using western blot analysis. Data showed that treatment with betaine could effectively prevent and reverse the adverse behavioral manifestation compared with the MS group. Betaine treatment protected cerebellar demyelination and neuron and Purkinje cell degeneration against CPZ-induced demyelination. Betaine attenuated the protein levels of ESR-related proteins in the cerebellum of MS rats and similarly increased the level of enzymes related to antioxidants in the cerebellum. Therefore, our results suggest that oral administration of betaine may be used as a novel adjunct therapy against cerebellar dysfunctions in an animal model of MS.

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.

Betaine supplementation alleviates corticosterone-induced hepatic cholesterol accumulation through epigenetic modulation of HMGCR and CYP7A1 genes in laying hens

Excessive corticosterone (CORT) exposure could cause hepatic cholesterol accumulation in chickens and maternal betaine supplementation could decrease hepatic cholesterol deposition through epigenetic modifications in offspring chickens. Nevertheless, it remains uncertain whether providing betaine to laying hens could protect CORT-induced hepatic cholesterol accumulation via epigenetic mechanisms. This study aimed to examine the effects of dietary betaine on plasma and hepatic cholesterol contents, expression of cholesterol metabolic genes, as well as DNA methylation on their promoters in the liver of laying hens exposed to CORT. A total of 72 laying hens at 130 d of age were randomly divided into 3 groups: control (CON), CORT, and CORT+betaine (CORT+BET) groups. The experiment lasted for 35 d. Chickens in CON and CORT groups were fed a basal diet, whereas the CORT+BET group chickens were fed the basal diet supplemented with 0.1% betaine for 35 d. On d 28 of the experiment, chickens in CORT and CORT+BET groups received daily subcutaneous injections of CORT (4.0 mg/kg body weight), whereas the CON group chickens were injected with an equal volume of solvent for 7 d. The results showed that CORT administration led to a significant increase (P < 0.05) in the contents of cholesterol in plasma and liver, associated with activation (P < 0.05) of sterol regulatory element binding transcription factor 2 (SREBP2), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), lecithin-cholesterol acyltransferase (LCAT) and low-density lipoprotein receptor (LDLR) genes expression, and inhibition of cholesterol-7-alpha hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) genes expression in the liver compared to the CON. In contrast, CORT-induced up-regulation of HMGCR mRNA and protein abundances and downregulation of CYP7A1 mRNA and protein abundances were completely normalized (P < 0.05) by betaine supplementation. Besides, CORT injection led to significant hypomethylation (P < 0.05) on HMGCR promoter and hypermethylation (P < 0.05) on CYP7A1 promoter. Moreover, dietary betaine rescued (P < 0.05) CORT-induced changes in methylation status of HMGCR and CYP7A1 genes promoters. These results indicate that dietary betaine addition protects laying hens from CORT-induced hepatic cholesterol accumulation via epigenetic modulation of HMGCR and CYP7A1 genes.

Protective influence of supplementary betaine against heat stress by regulating intestinal oxidative status and microbiota composition in broiler chickens.

To assess the impact of supplementing betaine (BT) under heat stress (HS) conditions on broiler performance and intestinal health from 21 to 42days of age, a total of 150 male Ross 308 broilers were indiscriminately allotted to 3 treatments with 10 replications of 5 birds each. The control (CON) group was given a basal ration and accommodated at a thermoneutral condition (22 ± 1°C), whereas the HS and HS + BT groups were raised under cyclic HS (33 ± 1°C for 8h and 22 ± 1°C for 16h per day) and received the basal ration without or with 1000mg/kg BT, respectively. The HS reduced average daily gain (ADG); average daily feed intake; villus height (VH); VH to crypt depth (CD) ratio (VCR); activities of trypsin, lipase, glutathione peroxidase (GPX), and catalase; and enumeration of Lactobacillus and Bifidobacterium (P < 0.05) and augmented feed conversion ratio (FCR), CD, malondialdehyde (MDA) accumulation, and enumeration of Escherichia coli, Clostridium, and coliforms (P < 0.05). Conversely, BT supplementation heightened ADG, VH, VCR, trypsin activity, GPX activity, and populations of Lactobacillus and Bifidobacterium (P < 0.05) and lowered FCR, MDA accumulation, and Clostridium population (P < 0.05). Furthermore, the FCR value, trypsin and GPX activities, MDA content, and Bifidobacterium and Clostridium populations in the HS + BT group were nearly equivalent to those in the CON group. To conclude, feeding BT under HS conditions could improve broiler performance through improving intestinal health by specifically mitigating oxidative damage and enhancing the colonization of beneficial bacteria.

Dietary Betaine Supplementation Enhances Colonic Barrier Function through the Nrf2/Keap1 and TLR4-NF-κB/MAPK Signaling Pathways and Alters Colonic Microbiota in Bama Mini-Pigs.

This study evaluated the effects of betaine supplementation in sows and/or their offspring's diets on the redox status, immune and inflammatory levels, colonic barrier function, and colonic microbial community of offspring piglets. Thirty-six Bama mini-sows on day 3 of gestation and their weaned offspring piglets (28 d of age) were randomly allocated to the following treatments: (1) sows and their weaned offspring fed the basal diet (control group, Con group); (2) sows fed the basal diet with 3.50 kg/t betaine, and their weaned offspring fed the basal diet (sows betaine group, SB group); (3) sows fed the basal diet with 3.50 kg/t betaine, and their weaned offspring fed the basal diet with 2.50 kg/t betaine (sow-offspring betaine group, S-OB group). Six offspring piglets from each group were selected to collect plasma and colon samples on d 30, 60, and 90 after weaning. Compared with the Con group, the plasma levels of IgA, IgM, GSH-Px, and SOD during d 30-90 after weaning, IFN-α, T-AOC, and GSH on d 30 and 60 after weaning were increased, while MDA during d 30-90 after weaning was decreased in the SB and S-OB groups (p < 0.05). In addition, the plasma levels of IFN-γ on d 60 and T-AOC on d 30 after weaning were higher in the S-OB group than those in the Con group (p < 0.05). In the colon, betaine supplementation increased plasma T-AOC, GSH, and SOD levels while decreasing MDA concentration (p < 0.05). Betaine supplementation improved the colonic protein abundances of ZO-1, occludin, and claudin in offspring and activated the Nrf2/Keap1 signaling pathway while inhibiting the TLR4-NF-κB/MAPK signaling pathway on d 90 after weaning. The 16S rRNA sequencing results showed that betaine supplementation altered colonic microbiota composition by increasing the relative abundances of Verrucomicrobia and Actinobacteria in the SB group while decreasing proinflammatory-associated microbiota abundances (Tenericutes, Prevotella, and Parabacteroides) (p < 0.05). Collectively, these findings suggest that dietary betaine supplementation in sows and/or their offspring could improve offspring piglets' redox status and immune and anti-inflammatory levels and enhance the colonic barrier function by activating Nrf2/Keap1 and inhibiting TLR4-NF-κB/MAPK signaling pathways.

Effects of Dietary Betaine on the Laying Performance, Antioxidant Capacity, and Uterus and Ovary Function of Laying Hens at the Late Stage of Production.

Betaine has been found to alleviate oxidative stress, inflammation, and apoptosis. However, whether dietary betaine can protect late-laying hens against these adverse effects is unknown. Here, 270 65-week-old Jinghong-1 laying hens were randomly divided into the Control, 0.1% Betaine, and 0.5% Betaine groups and fed a basal diet, 0.1%, and 0.5% betaine supplemented diet, respectively. The trial lasted for seven weeks. Birds that consumed 0.5% betaine laid more eggs with thicker eggshells. Accordingly, uterine reduced glutathione (GSH), glutathione peroxidase (GSH-PX), and ovarian superoxide dismutase (SOD) contents were increased. The uterine calcium ion content and the mRNA expression of ovalbumin, ovotransferrin, and carbonic anhydrase two were increased. Moreover, ovarian IL-1β, Caspase-1, Caspase-8, and Caspase-9 mRNA expressions were decreased; luteinising hormone receptor (LHR) and follicle-stimulating hormone receptor mRNA expressions were increased. Furthermore, dietary betaine decreased the ovaries' mRNA expression of DNA methyltransferase 1 (DNMT)1, DNMT3a, and DNMT3b. The methylation level at the promoter region of ovarian LHR decreased. These results indicated that dietary betaine consumption with a concentration of 0.5% could increase the laying rate and the eggshell thickness during the late-laying period. The underlying mechanism may include antioxidative, anti-apoptosis, and hormone-sensitivity-enhancing properties.

Effect of dietary betaine supplementation on the liver transcriptome profile in broiler chickens under heat stress conditions.

The objective of the present study was to investigate the effect of dietary betaine (BT) supplementation on the hepatic transcriptome profiles in broiler chickens raised under heat stress (HS) conditions. A total of 180 (21-d-old) Ross 308 male broiler chicks were allotted to 1 of 3 treatment groups with 6 replicated cages in a completely randomized design. One group was kept under thermoneutral conditions at all times and was fed a basal diet (PC). Other 2 groups were exposed to a cyclic heat stress condition. One of the 2 groups under heat stress conditions was fed the basal diet as a negative control (NC), whereas the other group was fed the basal diet supplemented with 0.2% BT. All chickens were provided with diets and water ad libitum for 21 d. Following the experiment, the liver samples were collected for RNA sequencing analysis. Broiler chickens in NC and BT group had decreased (p<0.05) growth performance. In the transcriptome analysis, the number of differentially expressed genes were identified in the liver by HS conditions and dietary BT supplementation. In the comparison between NC and PC treatments, genes related to energy and nucleic acid metabolism, amino acid metabolism, and immune system were altered by HS, which support the reason why heat-stressed poultry had decreased growth performance. In the comparison between NC and BT treatments, genes related to lipid metabolism, carbohydrate metabolism, and immune system were differently expressed under HS conditions. HS negatively impacts various physiological processes, including DNA replication, metabolism of amino acids, lipids, and carbohydrates, and cell cycle progression in broiler chickens. Dietary BT supplementation, however, offers potential counteractive effects by modulating liver function, facilitating gluconeogenesis, and enhancing immune systems. These findings provide a basis for understanding molecular responses by HS and the possible benefits of dietary BT supplementation in broiler chickens exposed to HS.

Betaine as an alternative feed additive to choline and its effect on performance, blood parameters, and egg quality in laying hens rations

This research aimed to evaluate how using betaine levels as a choline substitute affects productive performance, egg quality parameters, fatty acids profile, and antioxidant status in laying hens. One hundred and forty brown chickens, 45 wk old, were divided into 4 groups, each group of 7 replicates with 5 chickens per replicate. The first group of diets with choline has control (A) 100% choline, the second group (B) 75% choline+25% betaine, the third group (C) 50% choline+50% betaine, and the fourth group (D) received 100% betaine. No significant effects were observed in final body weight (BW), body weight gain (BWG), egg production (EW), and feed intake (FI) for laying hens. In the diet in which betaine was replaced choline, egg mass (EM) and egg weight (EW) increased compared to the control group (P < 0.05). Also, after 12 wk of feeding, the egg quality parameters were not influenced; however, yolk color was increased significantly compared with the control group. Serum total cholesterol, LDL-lipoprotein, HDL-lipoprotein, triglyceride, glucose, aspartate transaminase (AST), and alanine transaminase (ALT) were not affected by replacing choline with betaine. Furthermore, liver malondialdehyde (MDA) content, yolk vitamin E, and fatty acid levels were not significantly affected by replacing choline with betaine. Moreover, hens fed betaine displayed an increased antibody titer of the Newcastle disease (ND) virus. EW and EM were increased by 3.50% and 5.43% in 100% betaine group (D) when compared to the control group. Isthmus weight was decreased by 48.28 % in 50% choline+50% betaine group (C) when compared to the control group. ND was increased by 26.24% in 100% betaine group when compared to the control group. In conclusion, betaine supplementation positively affected productive performance, egg quality measurements, and immunity response in Bovans brown laying hens.

Effects of different floor spaces and betaine supplementation on performance and physiology of quails

Decreased productive performance due to heat stress in poultry often occurs in tropical environments. This study seeks to see the body temperature and productive performance of quail in different floor spaces and levels of betaine supplementation. The study was designed as a completely randomized design, consisting of two floor spaces (225 and 164 cm2/bird) and supplementation treatment (0% and 0.15% betaine). ANOVA test and DMRT were applied to catch the effect of treatments. Body temperature measurements showed that rectal and wing temperatures in quail with betaine supplementation were lower than in the control treatment (P<0.05). These results correspond with the betaine group’s feed, protein, and energy efficiency, which is better than the control (P<0.05). The egg production at floor spaces 225 cm2 and 164 cm2 supplemented with betaine was higher than the control groups (P<0.05), with values of 69.55% and 66.49%, respectively. Based on this study, we concluded that betaine supplementation to 225 cm2/bird and 164 cm2/bird floor spaces reduced heat stress and improved laying quail performance.

Porous Crosslinked Zwitterionic Microparticles Based on Glycidyl Methacrylate and N-Vinylimidazole as Possible Drug Delivery Systems

Crosslinked porous microparticles have received great attention as drug delivery systems lately due to their unique set of properties: the capability to form various polymer-drug combinations, low immunogenicity, patient compliance and ability to release drugs in a delayed or controlled manner. Moreover, polymers with betaine groups have shown some unique features such as antifouling, antimicrobial activity, biocompatibility and strong hydration properties. Herein, novel porous zwitterionic microparticles were prepared in two stages. The first step involves the synthesis of porous microparticles based on glycidyl methacrylate, N-vinylimidazole and triethyleneglycol dimethacrylate using the suspension polymerization technique, the second step being the synthesis of zwitterionic porous microparticles by polymer-analogous reaction in presence of sodium monochloroacetate as betainization agent. Both types of microparticles were characterized structurally and morphologically by FT-IR spectroscopy, energy dispersive X-ray analysis, scanning electron microscopy, dynamic vapors sorption and mercury porosimetry. The tetracycline loading into crosslinked and zwitterionic microparticles was also performed, the maximum tetracycline loading capacities being 87 mg/g and 135 mg/g, respectively. The drug release mechanism, elucidated by various mathematical models, is controlled by both diffusion and swelling processes as a function of the zwitterionic and/or porous microparticle structure. Both types of microparticles presented antibacterial activity against the two reference strains used in this study: Escherichia coli and Staphylococcus aureus.

Betaine Inhibits NLRP3 Inflammasome Hyperactivation and Regulates Microglial M1/M2 Phenotypic Differentiation, Thereby Attenuating Lipopolysaccharide-Induced Depression-Like Behavior.

Depression is one of the most important mental illnesses and is closely related to inflammation. Betaine is a natural product with an anti-inflammatory and antioxidant activities. However, the mechanism by which betaine ameliorates depression-like behaviors induced by lipopolysaccharide (LPS) is poorly understood. The purpose of this study was to investigate the neuroprotective effect of betaine on LPS-induced depression-like behavior in mice and its mechanism of action. ICR mice were randomly divided into four groups: the control group, the LPS model group (0.83 mg/kg), the positive drug group (MIDO, 50 mg/kg), and the betaine group (5% and 1% in drinking water). The betaine group was administered for 21 days, and on the 22nd day, except for the blank group, LPS (0.83 mg/kg) was intraperitoneally injected to establish a lipopolysaccharide-induced mice depression-like model. Twenty-four hours after LPS injection, the tail suspension test (TST), open field test (OFT), and sucrose preference test (SPT) were performed to evaluate the effect of betaine on LPS-induced depressive behavior in mice. After the behavioral study, the mouse brain, hippocampus, and serum were taken for detection. The expressions of cytokines and inflammatory mediators were detected by ELISA, HE staining, immunofluorescence, immunohistochemistry, and western blotting. Western blotting was used to detect the protein expression levels of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), caspase-1, and ASC, the protein expression levels of the microglial polarization markers COX-2, inducible nitric oxide synthase (iNOS), and CD206. The results showed that betaine significantly ameliorated the depression-like behavior in LPS-induced mice, significantly attenuated the production of proinflammatory cytokines and increased the release of an anti-inflammatory cytokines. Betaine decreased the expression of the NLRP3 inflammasome, decreased the expression of M1 polarization markers, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), COX-2, and iNOS and promoted the expression of M2 polarization marker CD206. Our study suggests that betaine may promote the transition of microglia from the M1 to the M2 phenotype by inhibiting NLRP3 inflammasome activation, thereby attenuating lipopolysaccharide-induced depression-like behavior.

Evaluating the effects of betaine on testicular ischemia/reperfusion injury induced by torsion/detorsion in the rat.

In this research, the effects of betaine on testicular ischemia-reperfusion were evaluated. Forty rats were randomly divided into 4 groups of sham, torsion/detorsion (TD), torsion/detorsion with two different dosage of betaine 200 mg/kg, and 300 mg/kg, respectively. At the end of the experiment, the testosterone concentration, sperm motility, concentration and vitality, oxidative stress biomarkers including Malondialdehyde (MDA), Glutathione peroxidase (GPx), Catalase (CAT), and total antioxidant capacity (TAC) were assessed. Moreover, histopathological parameters including seminiferous tubules diameter (STD), seminiferous epithelium thickness (SET), spermatogonia nuclei diameter (SpND), Sertoli cell nuclei diameter (StND) and miotic index were evaluated. The testosterone concentration altered during torsion/detorsion and betaine could increase slightly the testosterone concentration after 15 days. Sperm motility and vitality significantly increased in the betaine treated groups compared to the TD group on days 3 and 15. Among oxidative stress biomarkers, only CAT on day 3 and GPx on day 15 were significantly higher in the betaine groups compared to the TD group. Among histopathological parameters an increase in the STD and SET in betaine-200 and betaine-300 groups were observed on 15th day of post-surgery, compared to the TD group. These findings indicate that betaine can ameliorate testicular damages triggered by torsion/detorsion.

Effects of 6-Week Betaine Supplementation on Muscular Performance in Male Collegiate Athletes.

Simple SummaryBetaine supplementation has ergogenic potential for exercise performance, but the effect of betaine supplementation in combination with training for 6 weeks is still unclear. The present study aimed to investigate the effects of betaine supplementation on muscular power and maximal strength in collegiate male athletes. The participants in the study received either 5 g/day of betaine or placebo for 6 weeks, during which they maintained their regular exercise training. The overhead medicine-ball throw, countermovement jump, and one repetition-maximum of a bench press, overhead press, half squat, and sumo dead lift by the participants were assessed before and after betaine supplementation. Blood lipids were also analyzed before and after betaine supplementation. We found that receiving 5 g of betaine supplementation daily during the 6-week preparatory period had extra benefits on the power of the upper body and maximal strength on the half squat and overhead press. Betaine seems to be a useful nutritional strategy to improve and maintain performance during 6-week preparatory periods in collegiate athletes.The purpose of this study was to investigate the effects of 6-week betaine supplementation during a preparatory period of collegiate athletes on muscular power and strength. Sixteen male collegiate athletes received 5 g/day of betaine (betaine group, n = 9) or carboxymethyl cellulose (placebo group, n = 7) for 6 weeks. All participants engaged in their regular training during the experimental period. The overhead medicine-ball throw (OMBT), countermovement jump, and maximal strength (one repetition maximum, 1-RM) on the bench press, overhead press, half squat, and sumo dead lift by the participants were assessed before and after betaine supplementation. Blood lipids were also analyzed before and after betaine supplementation. After supplementation, there were no significant differences between betaine and placebo groups on any variables. Compared to presupplementation, the performance of OMBT and 1-RM of overhead press and half squat in the betaine group had significantly improved (p < 0.05). By contrast, no significant differences were observed in the placebo group before and after supplementation. Blood analysis revealed no negative effect on blood lipid profiles. Betaine seems to be a useful nutritional strategy to improve and maintain performance during 6-week preparatory periods in collegiate athletes.

High Betaine and Dynamic Increase of Betaine Levels Are Both Associated With Poor Prognosis of Patients With Pulmonary Hypertension.

Background and ObjectiveThe association between plasma betaine levels and cardiovascular diseases (CVDs) has been revealed except for pulmonary hypertension (PH). In this study, we aimed to explore the role of betaine in patients with PH.MethodsInpatients with PH at Fuwai Hospital were enrolled after excluding relative comorbidities. Each patient received at least one follow-up through a clinical visit, and the fasting blood was obtained both at the first and second hospitalization for betaine detection. The primary endpoint was defined as composite outcome events and the mean duration was 14.3 (6.9, 21.3) months. The associations of betaine and changes of betaine (Δbetaine) with disease severity and prognosis were explored.ResultsFinally, a total of 216 patients with PH were included and the medians for betaine plasma levels in the total patients group, low betaine, and high betaine groups were 49.8 (39.0, 68.3) μM, 39.0 (33.5, 44.7) μM, and 68.1 (57.8, 88.7) μM, respectively. High betaine was associated with poor World Health Organization Functional Class (WHO-FC), increased N-terminal pro-brain natriuretic peptide (NT-proBNP), low tricuspid annular plane systolic excursion (TAPSE), and cardiac output index even after adjusting for confounders. Patients with high betaine were over twice the risk to receive the poor prognosis than those with a low level [hazard ratio (HR) = 2.080, (95% CI: 1.033–4.188)]. Moreover, the decrease of betaine level after further treatment was positively correlated to ΔNT-proBNP indicating Δbetaine might be an effector of disease severity, and dynamic increase of betaine was also associated with poor prognosis in PH.ConclusionBetaine was associated with disease severity and might be an effector in PH. Patients with increased levels or with dynamic rise of betaine heralded a poor prognosis.

In ovo injection of betaine promotes adrenal steroidogenesis in pre-hatched chicken fetuses

Corticosterone is critical for the maturation and survival of chicken fetus around hatching. Betaine is used as a feed additive in poultry industry to promote growth and mitigate stress. However, it remains unknown whether betaine could affect adrenal corticosterone synthesis in pre-hatching chicken fetuses. In this study, betaine (2.5 mg/egg) was injected into developing chicken fetuses at d 11 of incubation (E11) and its impact on adrenal steroidogenesis was investigated at day 19 (E19). Plasma corticosterone concentration was significantly (P < 0.05) elevated in betaine-treated fetuses, together with increased adrenal expression of melanocortin 2 receptor and steroidogenic acute regulatory protein. Accordingly, the corticosterone biosynthetic enzymes, such as cytochrome P450 family 11 subfamily A member 1, 3β-hydroxysteroid dehydrogenase and cytochrome P450 family 21 subfamily A member 2, as well as cholesterol biosynthesis or regulation-related genes, such as sterol regulatory element-binding protein 1, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase and low-density lipoprotein receptor, were all significantly (P < 0.05) upregulated in betaine group. Meanwhile, steroidogenic factor-1 and glucocorticoid receptor were significantly (P < 0.05) enhanced, whereas expression of dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome gene, a nuclear receptor known as a repressor of adrenal steroidogenesis, was significantly (P < 0.05) downregulated. Betaine significantly (P < 0.05) increased adrenal expression of genes involved in one-carbon metabolism and DNA methylation, such as S-adenosyl homocysteine hydrolase, betaine-homocysteine-methyltransferase, methionine adenosyl transferase and DNA methyltransferases, yet the promoter regions of most steroidogenic genes were significantly (P < 0.05) hypomethylated. These results indicate that in ovo injection of betaine promotes adrenal glucocorticoid synthesis in chicken fetuses before hatching, which involves alterations in DNA methylation.

Betaine Supplementation Causes an Increase in Fatty Acid Oxidation and Carbohydrate Metabolism in Livers of Mice Fed a High-Fat Diet: A Proteomic Analysis.

Betaine, a common methyl donor whose methylation is involved in the biosynthesis of carnitine and phospholipids in animals, serves as food and animal feed additive. The present study used liquid chromatography-mass spectrometry (LC-MS) to analyze the liver protein profile of mice on a high fat (HF) diet to investigate the mechanism by which betaine affects hepatic metabolism. Although betaine supplementation had no significant effect on body weight, a total of 103 differentially expressed proteins were identified between HF diet + 1% betaine group (HFB) and HF diet group by LC-MS (fold change > 2, p < 0.05). The addition of 1% betaine had a significant enhancement of the expression of enzymes related to fatty acid oxidation metabolism, such as hydroxyacyl-Coenzyme A dehydrogenase (HADHA), enoyl Coenzyme A hydratase 1 (ECHS1) (p < 0.05) etc., and the expression of apolipoprotein A-II (APOA2) protein was significantly reduced (p < 0.01). Meanwhile, the protein expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and succinate-CoA ligase (SUCLG1) were highly significant (p < 0.01). Pathway enrichment using the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that the functions of differential proteins involved fatty acid catabolism, carbohydrate metabolism, tricarboxylic acid cycle (TCA) and peroxisome proliferator-activated receptor alpha (PPARα) signaling pathway. Protein–protein interaction (PPI) analysis discovered that acetyl-Coenzyme A acetyltransferase 1 (ACAT1), HADHA and ECHS1 were central hubs of hepatic proteomic changes in the HFB group of mice. Betaine alleviates hepatic lipid accumulation by enhancing fatty acid oxidation and accelerating the TCA cycle and glycolytic process in the liver of mice on an HF diet.

Effect of Dietary Betaine on Muscle Protein Deposition, Nucleic Acid and Amino Acid Contents, and Proteomes of Broilers.

Simple SummaryIn animal production, growth trials have shown that betaine has a positive effect on growth performance, especially improving meat yield. Proteins are the largest unit comprising muscle cells except moisture. However, how betaine regulates muscle protein anabolism and abundance levels remains unclear. Therefore, this study was conducted to investigate the effect of dietary betaine on growth performance, muscle protein deposition, and proteome of broilers. The results suggested that betaine could improve growth performance and muscle protein deposition of broilers. Alterations in muscle nucleic acids, amino acids, and protein abundance levels were involved in this process. Proteomic analysis further revealed that 35 proteins in breast muscle were identified as differentially abundant proteins by betaine supplementation, which were mainly related to cell differentiation, small molecule metabolic process, and tissue development.To investigate the effect of betaine supplementation on growth performance, muscle protein deposition, muscle nucleic acid and amino acid contents, and muscle proteome of broilers, 160 one-day-old male partridge shank broiler chickens were randomly divided into 2 groups with 8 replicates of 10 broilers each. Broilers were fed a basal diet alone, or a basal diet supplemented with 1000 mg/kg betaine. Compared with the control group, the betaine group significantly increased (p < 0.05) the broilers average daily gain, the levels of serum insulin-like growth factor-1 (IGF-1), growth hormone (GH), total protein (TP), the contents of muscle absolute protein deposition, RNA, Ser, Glu, Met, and Phe, and the ratio of RNA/DNA, and decreased (p < 0.05) the feed conversion ratio and serum blood urea nitrogen content. Moreover, proteomic analysis revealed 35 differentially abundant proteins (DAPs) in the betaine group compared with the control group, including 27 upregulated proteins and 8 downregulated proteins (p < 0.05). These DAPs were mainly related to cell differentiation, small molecule metabolic process, and tissue development. In conclusion, diets supplemented with 1000 mg/kg betaine improved growth performance and muscle protein deposition of broilers. Increased serum GH, IGF-1, and TP contents, and alterations in muscle nucleic acids, amino acids, and protein abundance levels were involved in this process.

Serial Extraction Technique of Rich Antibacterial Compounds in Sargassum cristaefolium Using Different Solvents and Testing their Activity

Background: Sargassum cristaefolium, as one of the brown seaweeds locally found in Indonesia, is extracted using the serial technique employing different solvents. Methods: S. cristaefolium powder (50 mesh) was extracted with three different solvents, including hexane, ethyl acetate, and methanol. S. cristaefolium powder residue was dried prior to serial re-extraction using different solvents. Three serial extracts were obtained and named as 1-stage extract, 2-stage extract, and 3-stage extract. Besides, a single-step extract (i.e., extraction using only methanol) was produced to be compared with three serial extracts in antibacterial activity tests (against E. coli and S. aureus). The three serial extracts were detected for their antibacterial compounds using GC-MS, LC-HRMS, and FT-IR. Results: The 3-stage extract exhibited the highest extraction yield. On S. aureus, the inhibition zone in all extracts was not significantly different. On E.coli, the highest inhibition zone (5.42±0.14 mm) was of the 3-stage extract; indeed, it was higher than both antibiotic and a single- step extract. Antibacterial compounds, such as phenol, 9-Tricosene(Z)-, palmitic acid, and oleamide, were present in all extracts. Other antibacterial compound types, both the 1-stage and 2-stage extracts, contained 7 types, whilst the 3-stage extract contained the most types (11 types). Particularly, hexyl cinnamic aldehyde, betaine and several cinnamic aldehyde groups were detected only in the 3-stage extract comprising the dominant area. The carboxylic acid groups were detected in all extracts to confirm the fatty acid structure. Conclusions: The serial extraction technique could produce the 3-stage extract which exhibited the strongest antibacterial activity and contained the richest antibacterial compounds.

Betaine downregulates microRNA 34a expression via a p53-dependent manner in cisplatin-induced nephrotoxicity in rats.

Cisplatin-induced nephrotoxicity limits its wide application as a chemotherapeutic drug. Betaine is a natural trimethylglycine compound involved in several biological reactions. In this study, the protective effect of betaine against cisplatin-induced nephrotoxicity through modulating the expression of microRNA 34a (miRNA 34a), p53, apoptosis, and inflammation was investigated. Adult Wistar rats were divided into normal group (received vehicle); betaine group (received 250 mg betaine/kg BW/day via oral gavage from Day 1 to Day 25); cisplatin group (received a single intraperitoneal dose of cisplatin at 5 mg/kg BW on Day 21) and betaine + cisplatin group (received the same doses of betaine and cisplatin). The results demonstrated that the cisplatin group exhibited severe kidney tissue damage and an increase in blood creatinine and urea levels. Furthermore, the cisplatin group showed a significant upregulation of miRNA 34a and higher levels of phospho-p53, caspase 3, cytochrome c, NFk B, and IL-1β compared to the normal group. Remarkably, the betaine + cisplatin group showed significantly decreased blood creatinine and urea concentrations, decreased levels of miRNA 34a, phospho-p53, caspase 3, cytochrome c, NFk B, and IL-1β as well as improved kidney tissue integrity compared to the cisplatin group. In conclusion, cisplatin-induced nephrotoxicity in rats was associated with upregulation of miRNA 34a expression, apoptosis, and inflammation in p53-dependent manner. These effects were reversed by betaine administration that ultimately improved the kidney function and tissue integrity.

Ciprofloxacin conjugated gold nanorods with pH induced surface charge transformable activities to combat drug resistant bacteria and their biofilms

The ever-growing threat of drug-resistant pathogens and their biofilms based persistent, chronic infections has created an urgent call for new strategies to deal with multidrug resistant bacteria (MDR). Near-infrared (NIR) laser-induced photothermal treatment (PTT) of gold nanorods (AuNRs) disinfects microbes by local heating with low possibility to develop resistant. However, PTT disinfection strategy of AuNRs alone shows less efficiency in killing multidrug resistant strains (i.e. Methicillin-resistant Staphylococcus aureus, MRSA) and their matured biofilms. Herein, a novel synergistic chemo-photothermal integrated antimicrobial platform (P(Cip-b-CB)-AuNRs) was fabricated which show enhanced killing efficiency against MRSA in both planktonic and biofilm phenotypes. Polymethacrylate copolymers with pendant ciprofloxacin (Cip) and the carboxyl betaine groups (P(Cip-b-CB)) were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization. P(Cip-b-CB) was decorated onto AuNRs via gold−thiol bond which resulted in AuNRs with acidic-induced surface charge-switchable activities and lipase triggered Cip release properties (P(Cip-b-CB)-AuNRs). The lower pH value and overexpress of lipase are characteristics for microenvironment of microbial infections and their biofilms, which ensure the targeting on, penetration into and on-demand release of Cip from the nanocomposites in bacterial infection sites and their biofilms. The bacterial cell membrane was disrupt by photothermal therapy which could improve its permeability and sensitivity to antibiotics, meanwhile lipase-triggered release of Cip ensures a high concentration of antibiotics at the site of bacterial infection. Besides their NIR induced PTT disinfection activities, the increased local temperature generated by NIR light irradiation accelerated Cip release which further enhanced the antibacterial efficiency, leading to synergistic antibacterial activities of chemo-photothermal therapy. Taken together, the designed synergistic chemo-photothermal integrated antimicrobial platform is a promising antibacterial agent for fighting MDR bacterial infections and their biofilms.