Methionine Deficiency Research Articles

End-of-season supplementary feeding in European carp ponds with appropriate plant protein and carbohydrate combinations to ecologically boost productivity: Lupine, rapeseed and, triticale

The present study investigated end-of-season (July–September) supplementary feeding strategies for European fishponds (carp farming), which suffer from collapsed natural food base (protein availability). Treatment ponds receiving white lupine (Lupinus albus), resulted in higher polyunsaturated fatty acids (PUFA) content (276.1 mg n − 3 PUFA 100 g−1) in skinless fillet of Cyprinus carpio than control ponds receiving triticale (179.5 mg n − 3 PUFA 100 g−1). Despite lupine being richer in nitrogen (N) and phosphorus (P) than triticale, eutrophication was likely suppressed in treatment ponds. Treatment ponds (∼120 g acid detergent fiber, ADF kg−1 lupine) had higher water transparency and lower water column P than control ponds (∼31 g ADF kg−1 triticale). Surprisingly, triticale (8.5% digestible protein; low DIAASLYS 36%) resulted in similar yield (∼1 ton ha−1) as lupine (26.5% digestible protein; higher DIAASLYS 52%, but low DIAASMET 32%). Therefore, protein quality (methionine) deficiency in lupine was investigated. It was balanced iso‑nitrogenously (38% crude protein) with rapeseed expeller meal (Brassica napus): diets T1 (only lupine; Met 0.9% of protein) → T2 (75% lupine: 25% rapeseed; Met 1.2% of protein) → diet T3 (50% lupine: 50% rapeseed; Met 1.4% of protein). A gradual improvement in yield, N and P retention values was observed from T1 to T3 but it did not exceed a low protein (16% crude protein) ‘control’ diet (only triticale; Met 1.9% of protein). Nutrient conversion to fish biomass (protein efficiency ratio and P: N retention ratio) seemed highest in ‘control’ followed by ‘T3’. This could be attributed to starch-mediated protein sparing effect or high organic matter digestibility of triticale (ADCNFE 76%; ADCOM 72%). Which is lacking in either lupine or rapeseed (ADCNFE ≤ 1%; ADCOM ≤ 34%) due to predominance of fibrous carbohydrates (non-starch polysaccharides, NSP). However, in ponds, they may still enhance the food web. In absence of starch, higher ADF influx in pond carp gut may halve absorption of n-3 PUFA from zooplankton. The study concludes end-of-season supplementary feeding with high DIAASMET, LYS protein combinations (e.g., lupine-rapeseed) and inclusion of starch sources (e.g., triticale) could achieve higher yield and nutrient efficiency in ponds. Most proteinaceous plant feedstuff are rich in NSP or ADF and may contribute to improving pond water quality or food web. Balanced supplementary feeds (e.g., 50% triticale +25% lupine +25% rapeseed expeller), that feed both fish (starch, optimum DIAASprotein) and pond (NSP, ADF) are suggested.

Elevated sea temperature combined with dietary methionine levels affect feed intake and appetite-related neuropeptide expression in the brains of juvenile cobia (Rachycentron canadum)

This study aimed to determine the impact of elevated temperature combined with different levels of dietary methionine concentrations on feed intake (FI) and brain expression of selected neuropeptides and one receptor involved in appetite control in juvenile cobia (approximately 3.7 g body weight). The genes studies were neuropeptide y, npy; agouti-related protein, agrp; cocaine- and amphetamine-regulated transcript, cart; cholecystokinin, cck and melanocortin 4 receptor; mc4r. The cobia were reared at typical sea water temperature in Vietnam (30 °C) and elevated temperature (34°C; selected as one of the predicted scenarios of climate change). The fish were fed diets with different levels of methionine: deficient (M9; 9.1 g/kg), sufficient (M12; 12.8 g/kg) and surplus (M16, 16.8 g/kg) for 6 weeks (triplicate tanks per treatment). Both dietary methionine concentration and temperature affected FI in cobia. Dietary methionine deficiency (i.e., M9) and elevated temperature reduced FI in cobia. Temperature significantly influenced the mRNA expression of agrp, cart, cck and mc4r. Expression of the orexigenic neuropeptide npy was consistently higher before the meal than after the meal for all diets and at both temperatures. At 30°C, prefeeding levels of npy correlated with both increased methionine levels and FI. The interaction between dietary methionine and temperature on the levels of brain npy expression was significant (P<0.05). There was higher brain expression of agrp, cart and cck in cobia at 34°C than in fish at 30°C, which was correlated with a lower FI. In conclusion, both feeding, temperature and/or dietary methionine levels affected the brain expression of npy and agrp, cart, cck and mc4r. This suggests that these neuropeptides as well as the mc4r receptor are actively involved in adjusting feed intake to compensate for changing energetic demands, as well as metabolic adjustments due to the variable availability of methionine at elevated temperature.

P16-034-23 The Level of Methionine Deficiency Determines Its Effects on Energy Metabolism in Growing Rats

P16-034-23 The Level of Methionine Deficiency Determines Its Effects on Energy Metabolism in Growing Rats

Methionine restriction improve insulin resistance by reducingmitochondria oxidative stress

Type 2 diabetes is a chronic metabolic disorder whose prevalence has been increasing steadily worldwide and is closelylinked to the epidemic of obesity. The most common features of Type 2 Diabetes are hyperglycemia, insulin resistance,and relative insulin deficiency. Insulin resistance refers to incorrect responses to insulin among cells whose physiologydepends on insulin, such as adipocytes and cardiomyocytes. Methionine is an essential amino acid, so it must beconsumed in the diet to avoid neurological impairment and visual symptoms caused by methionine deficiency. Thisprovides a potential explanation that methionine restriction can alleviate insulin resistance by regulating mTORC1. Thisstudy aims to investigate the effect of methionine restriction on insulin resistance and mitochondria oxidative stress.

Safety and feasibility of the addition of a radiosensitizing methionine-restricted diet to radiation therapy.

e15087 Background: Methionine is an amino acid necessary for cell growth and survival. Normal cells can tolerate methionine deficiency, but most cancer cells are methionine auxotrophs, requiring dietary intake since they cannot synthesize it. In vitro, methionine deficiency causes cancer cells to undergo cell cycle arrest and cell death, and in vivo a methionine restricted diet (MRD) enhances radiosensitization without significant adverse effects. Combining a MRD and radiation therapy (RT) for human malignancies has never been evaluated. The hypothesis of this Phase I study was that a MRD would be safe, and feasible to administer concurrently with curative-intent RT. Methods: Eligible patients included adults with any non-skin cancer malignancy undergoing standard RT without concurrent cytotoxic chemotherapy. The MRD consisted of low-protein cereals, grains, and breads; fruits; vegetables; margarines and oils; and simple carbohydrates. A clinical dietician developed a personalized meal plan with each subject to reduce methionine consumption to 5-10 mg/kg body weight/day, while maintaining adequate protein and caloric intake. An unlimited supply of a commercially available methionine-free protein supplement was provided to minimize hunger and weight loss. The MRD extended from 2 weeks before initiation of RT, through 2 weeks beyond completion of RT. The primary endpoint for safety was the rate of grade 3 or higher acute and late toxicities per CTCAE, over 12 months follow-up. Feasibility was assessed with a biweekly quantitative plasma amino acid panel during the MRD. The target accrual was 15 subjects. Results: Over two years, 53 patients were offered enrollment, 9 subjects enrolled, 5 completed the MRD and RT, and 4 withdrew during the MRD. The table summarizes subjects’ characteristics and outcomes. There was no grade 3 or higher adverse events attributable to the MRD. Methionine plasma levels varied over the course of treatment, and while no subject achieved the target of 13 μM, two nadired at 14 μM. The trial was closed early due to slow accrual and subjects’ difficulty maintaining the diet. Clinical trial information: NCT03574194 .Conclusions: This study suggests a MRD is safe with thoracic or abdominopelvic RT, with toxicities comparable to those expected with RT alone. However, the diet was challenging, and unacceptable to most patients with cancer. [Table: see text]

Arsenophonus Interacts with Buchnera to Improve Growth Performance of Aphids under Amino Acid Stress.

Amino acids play a crucial role in the growth and development of insects. Aphids cannot ingest enough amino acids in plant phloem to meet their requirements, and therefore, they are mainly dependent on the obligate symbiont Buchnera aphidicola to synthesize essential amino acids. Besides Buchnera, aphids may harbor another facultative symbiont, Arsenophonus, which alters the requirement of the cotton-melon aphid Aphis gossypii for amino acid. However, it is unclear how Arsenophonus regulates the requirement. Here, we found that Arsenophonus ameliorated growth performance of A. gossypii on an amino acid-deficient diet. A deficiency in lysine (Lys) or methionine (Met) led to changes in the abundance of Arsenophonus. Arsenophonus suppressed the abundance of Buchnera when aphids were fed a normal amino acid diet, but this suppression was eliminated or reversed when aphids were on a Lys- or Met-deficient diet. The relative abundance of Arsenophonus was positively correlated with that of Buchnera, but neither of them was correlated with the body weight of aphids. The relative expression levels of Lys and Met synthase genes of Buchnera were affected by the interaction between Arsenophonus infections and Buchnera abundance, especially in aphids reared on a Lys- or Met-deficient diet. Arsenophonus coexisted with Buchnera in bacteriocytes, which strengthens the interaction. IMPORTANCE The obligate symbiont Buchnera can synthesize amino acids for aphids. In this study, we found that a facultative symbiont, Arsenophonus, can help improve aphids' growth performance under amino acid deficiency stress by changing the relative abundance of Buchnera and the expression levels of amino acid synthase genes. This study highlights the interaction between Arsenophonus and Buchnera to ameliorate aphid growth under amino acid stress.

Methionine-Mediated Regulation of Intestinal Lipid Transportation Induced by High-Fat Diet in Rice Field Eel (Monopterus Albus).

An eight-week feeding trial explored the mechanism that supplemented methionine (0 g/kg, 4 g/kg, 8 g/kg, and 12 g/kg) in a high-fat diet (120 g/kg fat) on intestinal lipid transportation and gut microbiota of M. Albus (initial weight 25.03 ± 0.13 g) based on the diet (60 g/kg fat), named as Con, HFD+M0, HFD+M4, HFD+M8, and HFD+M12, respectively. Compared with Con, gastric amylase, lipase, trypsin (P < 0.05), and intestinal lipase, amylase, trypsin, Na+/K+ -Adenosinetriphosphatase, depth of gastric fovea, and the number of intestinal villus goblet cells of HFD+M0 were markedly declined (P < 0.05), while intestinal high-density lipoprotein-cholesterol, very low-density lipoprotein-cholesterol and microsomal triglyceride transfer protein of HFD+M0 were markedly enhanced (P < 0.05); compared with HFD+M0, gastric lipase, amylase, trypsin, and intestinal lipase, trypsin, Na+/K+ -Adenosinetriphosphatase, microsomal triglyceride transfer protein, very low-density lipoprotein-cholesterol, and apolipoprotein -A, the height of intestinal villus and the number of intestinal villus goblet cells of HFD+M8 were remarkably enhanced (P < 0.05). Compared with Con, intestinal occ, cl12, cl15, zo-1, zo-2 of HFD + M0 were markedly down-regulated (P <0.05), while intestinal vldlr, npc1l1, cd36, fatp1, fatp2, fatp6, fatp7, apo, apoa, apob, apof, apoo, mct1, mct2, mct4, mct7, mct12, lpl, mttp, moat2, dgat2 of HFD M0 were remarkably upregulated (P < 0.05); compared with HFD+M0, intestinal gcn2 and eif2α of HFD+M8 were remarkably downregulated (P < 0.05), intestinal occ, cl12, cl15, zo-1, zo-2, hdlbp, ldlrap, vldlr, cd36, fatp1, fatp2, fatp6, apo, apoa, apob, apof, apoo, mct1, mct2, mct8, mct12, lpl, mttp, moat2, and dgat2 were remarkably upregulated (P < 0.05). Compared with Con, the diversity of gut microbiota of HFD+M0 was significantly declined (P < 0.05), while the diversity of gut microbiota in HFD+M8 was significantly higher than that in HFD+M0 (P < 0.05). In conclusion, a high-fat methionine deficiency diet destroyed the intestinal barrier, reduced the capacity of intestinal digestion and absorption, and disrupted the balance of gut microbiota; supplemented methionine promoted the digestion and absorption of lipids, and also improved the balance of gut microbiota.

Effect of Methionine and Choline Deficiency on Liver Choline Oxidase Activity in Young Rats

Young male Sprague-Dawley rats were fed a water-soluble chemically defined diet containing 0.06, 0.12, 0.24 or 0.60% methionine with or without 0.25% choline for 10 to 42 days. Liver choline oxidase activity decreased in rats that ingested the choline-deficient diets (devoid of choline and low (0.06 or 0.12%) in methionine). These animals developed pathologic changes in the liver and kidney characteristic of acute choline deficiency. Liver choline oxidase activity remained normal in rats that were fed the methionine-deficient diets (low in methionine but supplemented with 0.25% choline).

Methionine Deficiency Decreases Protein Accretion and Synthesis but Not tRNA Acylation in Muscles of Chicks

The effect of supplementing a methionine-deficient, isolated soy protein diet (0.5% total sulfur amino acids) with 0.2% D,L-methionine (DL-MET) or a molar equivalent of D,L-2-hydroxy-4-(methylthio)butanoic acid (DL-HMB) was assessed in chicks over an 8-d feeding study. Chicks consumed DL-HMB diet ad libitum (HIGH) or were restricted to the level consumed ad libitum by chicks fed the basal diet. The DL-MET diet was fed at the same two levels as the DL-HMB diet. Supplementing with either methionine source resulted in significantly greater growth rate, efficiency of feed conversion, and accretion and synthesis of protein in the gastrocnemius and pectoralis muscles. These increases were greater for chicks consuming feed ad libitum as compared with feed-restricted chicks and were not affected by methionine source. Rate of muscle protein degradation appeared to increase with supplementation of either methionine source, but only when feed intake was permitted to increase. The relative in vivo conversion of DL-HMB vs. D-MET to L-MET was similar in all groups as indicated by pool sizes of methionine, tRNAmet, and tRNAcys, and rates of protein accretion and synthesis. These data demonstrate that dietary DL-HMB and DL-MET are used with similar efficacy to support skeletal muscle protein accretion and rates of protein synthesis when feed intake is equalized.

Effects of levels of methionine supplementations in forms of L- or DL-methionine on the performance, intestinal development, immune response, and antioxidant system in broilers challenged with Eimeria spp.

The study was conducted to investigate the effects of 2 isoforms of methionine on growth performance and intestinal health induced by methionine (Met) deficiency and Eimeria infection in broilers. A total of 720 one-day old male chicks (Cobb500) were randomly allocated to 10 groups in a 2×5 factorial arrangement (6 reps/group, 12 birds/cage) with diets and Eimeria challenge as the main factors. Hundred percent DL-Met, 100% L-Met, 80% DL-Met, and 80% L-Met diets were formulated to meet approximately 100 or 80% of the total sulfur amino acid (TSAA) requirement with DL-Met or L-Met as Met supplementation sources. The 60% TSAA basal diet (60% Met) was formulated without Met supplementation. At d14, the challenge groups were gavaged with mixed Eimeria spp. Growth performance was recorded on d7, 14, 20 (6-day postinfection [DPI]), and 26 (12 DPI). The gut permeability was measured on 5 and 11 DPI. Antioxidant status and gene expression of immune cytokines and tight junction proteins were measured on 6 and 12 DPI. Data were analyzed by 1-way and 2-way ANOVA before and after the challenge, respectively. Orthogonal polynomial contrasts were used for post hoc comparison. Overall, the Eimeria challenge and 60% Met diet significantly reduced growth performance, antioxidant status, and mRNA expression of tight junction genes and immune cytokines. For other Met treatments, the L-Met groups had significantly higher BWG and lower FCR than the DL-Met group from d 1 to 20. The L-Met groups had less gut permeability than the DL-Met groups on 5 DPI. Compared to the 80% Met groups, the 100% Met groups reduced gut permeability. At 6 DPI, the 80% Met groups showed higher ZO1 expression than the 100% Met groups. The challenge groups had higher Muc2 expression and GSH/GSSG compared to the nonchallenge groups, and SOD activity was lower in the L-Met groups compared to the DL-Met groups at 6 DPI. The 100% Met groups had higher GPx activity than the 80% Met groups at 12 DPI. In conclusion, during coccidiosis, the 100% Met groups had better gut integrity and antioxidant status. Met supplementation in the form of L-Met improved growth performance in the starter phase and gut permeability in the challenge phase.

Ginsenoside Rg1 attenuates the NASH phenotype by regulating the miR-375-3p/ATG2B/PTEN-AKT axis to mediate autophagy and pyroptosis

BackgroundNonalcoholic steatohepatitis (NASH) is one of the most frequent liver diseases at present, and there is no radical treatment. The consequences of a variety of ginsenoside compounds on this situation have before been reported, however, the specific effect on the monomeric ginsenoside Rg1 (Rg1) and its associated underlying molecular mechanism stay unknown.Material and methodsIn vitro, the cell models were constructed by exposing free fatty acids (FFAs) to HepG2 cells. A methionine and choline deficiency (MCD)-induced NASH mouse model was also established over 5–6 weeks of treatment. Rg1 is a traditional Chinese medicine monomer. These NASH models were treated with Rg1 and analyzed by qRT-PCR, Western Blot, sequencing, Oil red O staining, immunofluorescence, enzyme activity, HE staining, ELISA, double luciferase reporter assay, and immunohistochemistry.ResultsOverexpression of ATG2B, an autophagy-related protein, attenuated lipid droplet accumulation and reduces ALT, AST, inflammatory cytokines, hydrogen peroxide, and pyroptosis in established mouse and cellular models of NASH and increased levels of ATP and autophagy. The binding sites of miR-375-3p and ATG2B were verified by bioinformatic prediction and a dual-luciferase reporter gene. Knockdown of miR-375-3p promoted autophagy and inhibited pyroptosis. ATG2B knockdown substantially attenuated the impact of miR-375-3p on NASH. Rg1 appears to regulate the occurrence and development of NASH inflammation through miR-375-3p and ATG2B in vitro and in vivo, and is regulated by PTEN-AKT pathway.ConclusionsThis study showed that Rg1 participates in autophagy and pyroptosis through the miR-375-3p/ATG2B/PTEN-AKT pathway, thereby alleviating the occurrence and development of NASH, for that reason revealing Rg1 as a candidate drug for NASH.

Cholestyramine Modulates Non-Alcoholic Steatohepatitis Induced by Methionine and Choline Deficiency in Rats: Cross-linking AGEs, MIP2, EMR1 and Adiponectin.

Cholestyramine Modulates Non-Alcoholic Steatohepatitis Induced by Methionine and Choline Deficiency in Rats: Cross-linking AGEs, MIP2, EMR1 and Adiponectin.

Plasma Methionine and Clinical Severity in Nitrous Oxide Consumption.

In the last few years, there has been an increase in the recreational use of nitrous oxide (N2O), which can lead to neurological symptoms such as sensory or motor disorders. The literature links these symptoms to a functional inactivation of vitamin B12 by oxidation of its cobalt ion, which prevents the vitamin B12 from acting as a cofactor for methionine synthase. Thus, demyelination related to methionine deficiency could be responsible for the neurological disorders associated with N2O consumption, including the combined sclerosis of the spinal cord. We aimed to study the correlation between the plasma methionine levels and clinical severity observed in N2O users. We retrospectively collected clinical and biological data from 93 patients who chronically consumed N2O. The patients were divided into four groups based of the severity of their clinical symptoms (based on their Peripheral Neuropathy Disability (PND) score). The plasma amino acids measurement, including methionine, were performed systematically by liquid chromatography coupled with mass spectrometry. Plasma methionine is significantly correlated with the clinical severity (Spearman coefficient: −0.42; p-value < 10−5), however, the average methionine level in the four groups is within the physiological values (N: 16−23 µmol/L). There is a significant inverse correlation between plasma methionine and homocysteine (Spearman coefficient: −0.57; p-value < 10−9), which confirms the action of nitrous oxide on the methionine synthase. A decrease in plasma methionine cannot be imputed as the only mechanism involved in the pathophysiology of the neurological disorders in nitrous oxide consumption. In addition, there are few therapeutic indications for the use of methionine. Thus, we should be careful concerning the potential use of methionine in nitrous oxide consumption. As a consequence, other pathophysiological mechanisms probably need to be identified in order to find potential therapeutic targets.

Discovery of Betulinic Acid Derivatives as Potent Intestinal Farnesoid X Receptor Antagonists to Ameliorate Nonalcoholic Steatohepatitis.

Farnesoid X receptor (FXR) has emerged as a promising therapeutic target for nonalcoholic steatohepatitis (NASH) because of its tightly interwoven relationship with bile acid homeostasis, inflammation, fibrosis, and glucose and lipid metabolism. Evidence showed that intestinal FXR antagonism exhibited remarkable metabolic improvements in mice. Herein, we developed a series of betulinic acid derivatives as potent intestinal FXR antagonists, and F6 was identified as the most potent one with an IC50 at 2.1 μM. F6 selectively inhibited intestinal FXR signaling and ameliorated the hepatic steatosis, inflammation, and fibrosis in Gubra-amylin NASH (GAN) and high-fat with methionine and choline deficiency (HFMCD) diet-induced NASH models. The beneficial effects were achieved by direct antagonism of intestinal FXR and feedback activation of hepatic FXR, thereby decreasing ceramides and repressing inflammasome activation in the liver. Collectively, our work substantially supports F6 as a promising drug candidate against NASH and demonstrates that antagonism of intestinal FXR signaling is a practical strategy for treating metabolic diseases.

Plant‐based diets fed to juvenile meagre Argyrosomus regius with low methionine and taurine supplementation led to an overall reduction in fish performance and to an increase in muscle fibre recruitment

Methionine and taurine are amino acids (AA) that are usually deficient when fish meal is replaced by plant proteins. In this study, three diets were tested in juvenile meagre (initial weight: 13.4 g) for 8 weeks. The D1 diet had 0.2% methionine and 1% taurine supplementation; the D2 and D3 diets had 0.6% methionine and 1% and 2% taurine supplementation, respectively. The results showed that meagre fed the D1 diet had lower specific growth rate (2.2 to 2.5), lower feed efficiency (0.9 to 1.2) and higher food conversion rate (FCR, 1.1 to 0.8) as well as a lower activity of the alanine aminotransferase (ALAT) enzyme. Furthermore, a higher recruitment of muscle fibres (46% compared to 36%) as well as a higher fibre density was observed (1019 compared to 870 fibres mm-2 ). This study shows that meagre requires a sufficient quantity of methionine in plant-based diets to avoid a reduction in fish performance. Furthermore, taurine supplementation in the D1 diet was not able to mitigate the effects of methionine deficiency. A higher taurine supplementation did not improve meagre performance.

Methionine deficiency facilitates antitumour immunity by altering m6A methylation of immune checkpoint transcripts

ObjectiveMethionine metabolism is involved in a myriad of cellular functions, including methylation reactions and redox maintenance. Nevertheless, it remains unclear whether methionine metabolism, RNA methylation and antitumour immunity are molecularly...

The Self-Bleaching Process of Microcystis aeruginosa is Delayed by a Symbiotic Bacterium Pseudomonas sp. MAE1-K and Promoted by Methionine Deficiency.

ABSTRACTVarious interactions between marine cyanobacteria and heterotrophic bacteria have been known, but the symbiotic relationships between Microcystis and heterotrophic bacteria remain unclear. An axenic M. aeruginosa culture (NIES-298) was quickly bleached after exponential growth, whereas a xenic M. aeruginosa culture (KW) showed a normal growth curve, suggesting that some symbiotic bacteria may delay this bleaching. The bleaching process of M. aeruginosa was distinguished from the phenomena of previously proposed chlorosis and programmed cell death in various characteristics. Bleached cultures of NIES-298 quickly bleached actively growing M. aeruginosa cultures, suggesting that M. aeruginosa itself produces bleach-causing compounds. Pseudomonas sp. MAE1-K delaying the bleaching of NIES-298 cultures was isolated from the KW culture. Bleached cultures of NIES-298 treated with strain MAE1-K lost their bleaching ability, suggesting that strain MAE1-K rescues M. aeruginosa from bleaching via inactivation of bleaching compounds. From Tn5 transposon mutant screening, a metZ mutant of strain MAE1-K (F-D3) unable to synthesize methionine, promoting the bleaching of NIES-298 cultures but capable of inactivating bleaching compounds, was obtained. The bleaching process of NIES-298 cultures was promoted with the coculture of mutant F-D3 and delayed by methionine supplementation, suggesting that the bleaching process of M. aeruginosa is promoted by methionine deficiency.IMPORTANCE Cyanobacterial blooms in freshwaters represent serious global concerns for the ecosystem and human health. In this study, we found that one of the major species in cyanobacterial blooms, Microcystis aeruginosa, was quickly collapsed after exponential growth by producing self-bleaching compounds and that a symbiotic bacterium, Pseudomonas sp. MAE1-K delayed the bleaching process via the inactivation of bleaching compounds. In addition, we found that a metZ mutant of strain MAE1-K (F-D3) causing methionine deficiency promoted the bleaching process of M. aeruginosa, suggesting that methionine deficiency may induce the production of bleaching compounds. These results will provide insights into the symbiotic relationships between M. aeruginosa and heterotrophic bacteria that will contribute to developing novel strategies to control cyanobacterial blooms.

Rhubarb free anthraquinones improved mice nonalcoholic fatty liver disease by inhibiting NLRP3 inflammasome

BackgroundNonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and has become a huge public health issue worldwide. Inhibition of nucleotide oligomerization domain-like receptors containing pyrin domain 3 (NLRP3) inflammasome is a potential therapeutic strategy for NAFLD. Currently, there are no drugs targeting NLRP3 inflammasome for clinical treatment of NAFLD. In this study, we explored the efficacy and mechanism of rhubarb free anthraquinones (RFAs) in treating NAFLD by inhibiting NLRP3 inflammasome.MethodsFirst, NLRP3 inflammasome was established in mouse bone marrow-derived macrophages (BMDMs), Kuffer cells and primary hepatocytes stimulated by lipopolysaccharide (LPS) and inflammasome inducers to evaluate the effect of RFAs on inhibiting NLRP3 inflammasome and explore the possible mechanism. Further, Mice NAFLD were established by methionine and choline deficiency diet (MCD) to verify the effect of RFAs on ameliorating NAFLD by inhibiting NLRP3 inflammasome.ResultsOur results demonstrated that RFAs including rhein/diacerein, emodin, aloe emodin and 1,8-dihydroxyanthraquinone inhibited interleukin-1 beta (IL-1β) but had no effect on tumor necrosis factor-alpha (TNF-α). Similar results were also showed in mouse primary hepatocytes and Kuffer cells. RFAs inhibited cleavage of caspase-1, formation of apoptosis-associated speck-like protein containing a CARD (ASC) speck, and the combination between NLRP3 and ASC. Moreover, RFAs improved liver function, serum inflammation, histopathological inflammation score and liver fibrosis.ConclusionsRFAs including rhein/diacerein, emodin, aloe emodin and 1,8-dihydroxyanthraquinone ameliorated NAFLD by inhibiting NLRP3 inflammasome. RFAs might be a potential therapeutic agent for NAFLD.Graphical

Cost Effective Electrochemical Sensor for L‐Methionine Based on Graphitic Carbon Nitride Sheets Modified Electrode

AbstractL‐methionine (L−Me) deficiency in human body leads to several complications. In the present work, graphitic carbon nitride nanosheets (GCN−S) modified glassy carbon electrode (GC/GCN−S) was developed as a cost effective electrochemical sensor for L−Me. The oxidation of L−Me at bare GC electrode shows an ill‐defined peak and it was unstable whereas a well‐defined stable oxidation peak was obtained at GC/GCN−S electrode. While increasing L−Me concentration from 100 nM to 0.2 mM, the amperometric current increases linearly with R2=0.9901 and LOD was found to be 0.32 nM (S/N=3). Finally, GC/GCN−S electrode was used to determine L−Me in blood serum samples.

The Role of GCN2 Kinase in Mediating the Effects of Amino Acids on Longevity and Feeding Behaviour in Drosophila.

Restriction of amino acids in the diet can extend lifespan in diverse species ranging from flies to mammals. However, the role of individual amino acids and the underlying molecular mechanisms are only partially understood. The evolutionarily conserved serine/threonine kinase General Control Nonderepressible 2 (GCN2) is a key sensor of amino acid deficiency and has been implicated in the response of lifespan to dietary restriction (DR). Here, we generated a novel Drosophila GCN2 null mutant and analyzed its response to individual amino acid deficiency. We show that GCN2 function is essential for fly development, longevity and feeding behaviour under long-term, but not short-term, deprivation of all individual essential amino acids (EAAs) except for methionine. GCN2 mutants were longer-lived than control flies and showed normal feeding behaviour under methionine restriction. Thus, in flies at least two systems regulate these responses to amino acid deprivation. Methionine deprivation acts via a GCN2-independent mechanism, while all other EAA are sensed by GCN2. Combined deficiency of methionine and a second EAA blocked the response of GCN2 mutants to methionine, suggesting that these two pathways are interconnected. Wild type flies showed a short-term rejection of food lacking individual EAA, followed by a long-term compensatory increase in food uptake. GCN2 mutants also showed a short-term rejection of food deprived of individual EAA, but were unable to mount the compensatory long-term increase in food uptake. Over-expression of the downstream transcription factor ATF4 partially rescued the response of feeding behaviour in GCN2 mutants to amino acid deficiency. Phenotypes of GCN2 mutants induced by leucine and tryptophan, but not isoleucine, deficiency were partially rescued by ATF4 over-expression. The exact function of GCN2 as an amino acid sensor in vivo and the downstream action of its transcription factor effector ATF4 are thus context-specific with respect to the EAA involved.