Asparagine Levels Research Articles

EVALUATION OF THE EFFICACY OF ASPARAGINASE ADDED TO CHEMOTHERAPEUTIC DRUG REGIMEN IN ACUTE LYMPHOBLASTIC LEUKEMIA BY MINIMAL RESIDUAL DISEASE MEASUREMENT

B-ALL is the most common subtype of childhood Acute Lymphoblastic Leukemia (ALL), affecting approximately 85% of children worldwide. Minimal Residual Disease (MRD) monitoring during treatment of ALL is important for the prognosis of the disease. MRD monitoring, which enables early detection of relapse, determination of risk percentage and understanding the effectiveness of treatment, can be performed with multiple methods such as flow cytometry, qRT-PCR and NGS. Asparaginase is an enzyme that has been used in the treatment of ALL since the 1960s, converting asparagine to ammonia and aspartic acid, lowering serum asparagine levels and causing the death of malignant cells. In this study, we investigated the effect of asparaginase added to the ALL IC BFM 2009 treatment protocol in 62 B-ALL patients aged 0-18 years with MRD monitoring by flow cytometry. In our study, Escherichia Coli (E.Coli.) asparaginase was used primarily and PEG-asparaginase was used after allergy development. The effect of asparaginase on treatment was evaluated by evaluating asparagine concentration and asparaginase activity measured at TP1 (4th week after induction treatment) together with MRD levels. As a result of the study, it was observed that the added asparaginase positively affected the treatment and increased the negativity in MRD levels.

Identifying targetable metabolic dependencies across colorectal cancer progression

Colorectal cancer (CRC) is a multi-stage process initiated through the formation of a benign adenoma, progressing to an invasive carcinoma and finally metastatic spread. Tumour cells must adapt their metabolism to support the energetic and biosynthetic demands associated with disease progression. As such, targeting cancer cell metabolism is a promising therapeutic avenue in CRC. However, to identify tractable nodes of metabolic vulnerability specific to CRC stage, we must understand how metabolism changes during CRC development. Here, we use a unique model system – comprising human early adenoma to late adenocarcinoma. We show that adenoma cells transition to elevated glycolysis at the early stages of tumour progression but maintain oxidative metabolism. Progressed adenocarcinoma cells rely more on glutamine-derived carbon to fuel the TCA cycle, whereas glycolysis and TCA cycle activity remain tightly coupled in early adenoma cells. Adenocarcinoma cells are more flexible with respect to fuel source, enabling them to proliferate in nutrient-poor environments. Despite this plasticity, we identify asparagine (ASN) synthesis as a node of metabolic vulnerability in late-stage adenocarcinoma cells. We show that loss of asparagine synthetase (ASNS) blocks their proliferation, whereas early adenoma cells are largely resistant to ASN deprivation. Mechanistically, we show that late-stage adenocarcinoma cells are dependent on ASNS to support mTORC1 signalling and maximal glycolytic and oxidative capacity. Resistance to ASNS loss in early adenoma cells is likely due to a feedback loop, absent in late-stage cells, allowing them to sense and regulate ASN levels and supplement ASN by autophagy. Together, our study defines metabolic changes during CRC development and highlights ASN synthesis as a targetable metabolic vulnerability in later stage disease.

Study on the difference and clinical value of serum amino acids in patients with laryngeal squamous cell carcinoma

Objective:To detect the differences in types and levels of amino acids in the peripheral serum of patients with laryngeal squamous cell carcinoma and non-tumor patients, and explore their relationship with clinical parameters of laryngeal squamous cell carcinoma as well as their clinical value in diagnosis. Methods:High-performance liquid chromatography-tandem mass spectrometry（HPLC-MS） was employed to detect the serum amino acid contents and levels of 62 patients diagnosed with laryngeal carcinoma and 141 non-tumor patients at the First Affiliated Hospital of Jinzhou Medical University between September 2018 and February 2021. The study compared the differences in 22 non-essential and essential amino acids found in the serum between the experimental group and the control group. An ROC curve and risk scoring formula of multivariate linear logic regression model was utilized to evaluate the efficiency of serum amino acids in the early diagnosis of laryngeal carcinoma. Results:There were significant differences in the contents of fourteen types of amino acids between the experimental and control groups, with thirteen amino acids showing higher levels in the experimental group（P<0.05）. Seven of these amino acids were essential, including phenylalanine, threonine, leucine, valine, histidine, tyrosine, and citrulline. The other six amino acids were non-essential, including arginine, asparagine, cysteine, glycine, ornithine, and proline. Interestingly, the content of homocysteine in the experimental group was lower than that in the control group（P=0.024）. Further analysis showed that patients with laryngeal squamous cell carcinoma in TNM stage Ⅰ and Ⅱ had higher serum methionine levels compared to those in stages Ⅲ and Ⅳ（P=0.026）. In addition, the content of serum histidine was higher in patients with poorly differentiated squamous cell carcinoma compared to those with well-differentiated squamous cell carcinoma（P=0.041）. The level of asparagine in the serum of patients with laryngeal squamous cell carcinoma older than 64 years old was lower than that in patients younger than 64 years old（P=0.033）. The level of tryptophan in the serum of patients with a smoking history was lower than that in patients without a smoking history（P=0.033）. The level of citrulline in the serum of patients with a history of alcohol consumption was higher than that in patients with no history of alcohol consumption（P=0.003）. ROC curve analysis showed that out of the 14 different amino acids between the experimental and control groups, citrulline and cysteine were relatively effective as independent factors in the diagnosis of laryngeal squamous cell carcinoma, with an AUC of 0.856 and 0.850, respectively. Arginine was the most sensitive factor in the diagnosis of laryngeal squamous cell carcinoma（AUC=0.855）. However, citrulline alone had the highest specificity（0.830） in the diagnosis of laryngeal squamous cell carcinoma, and the combination of 12 amino acids significantly improved the diagnostic efficiency of laryngeal squamous cell carcinoma, with an AUC of 0.946, sensitivity of 0.887, and specificity of 0.894. A risk score formula for a multivariate logistic regression model was established based on the differential amino acid content in the serum. The risk score of laryngeal squamous cell carcinoma group was higher than that of the non-tumor group（P<0.001）. The AUC of risk score in the diagnosis of laryngeal squamous cell carcinoma was 0.953 with sensitivity and specificity of 0.957 and 0.855. Conclusion:This study found that there are differences in the contents of 14 amino acids among which 13 amino acids were increased in serum of patients with laryngeal squamous cell carcinoma, and were associated with age, clinical stage, pathological differentiation, smoking, and drinking. Combined detection of 12 amino acids can improve the diagnostic efficiency of laryngeal squamous cell carcinoma and serve as potential markers for the auxiliary diagnosis of laryngeal squamous cell carcinoma using peripheral blood samples. Additionally, the established risk score model was found to be more effective in the diagnosis of laryngeal squamous cell carcinoma, indicating its important potential value as an auxiliary diagnostic tool.

Nitrate Inhibits Nodule Nitrogen Fixation by Accumulating Ureide in Soybean Plants.

The mechanism by which nitrate inhibits nitrogen fixation in soybean (Glycine max L.) is not fully understood. Accumulation of ureide in soybean plant tissues may regulate the nitrogen fixation capacity through a feedback pathway. In this study, unilaterally nodulated dual-root soybeans prepared by grafting were grown in sand culture. They were subjected to the removal of the nodulated side roots, and were given either nitrate supply or no supply to the non-nodulated side roots for 3 days (experiment I). Additionally, they received nitrate supply to the non-nodulated side roots for 1-14 days (experiment II). The results showed that nitrate supply increased the levels of asparagine and ureide in soybean shoots (Experiment I). In Experiment II, nodule dry weight, nodule number, nodule nitrogenase activity, and nodule urate oxidase activity decreased significantly after 3, 7, and 14 days of nitrate supply. Ureide content in the shoots and nodules increased after 1, 3, and 7 days of nitrate supply, but decreased after 14 days of nitrate supply. There was a significant positive correlation between urate oxidase activity and nitrogenase activity. Hence, we deduced that nitrate supply increased the asparagine content in soybean shoots, likely inhibiting ureide degradation, which induced the accumulation of ureide in soybean shoots and nodules, and, in turn, feedback inhibited the nodule nitrogen fixation. In addition, urate oxidase activity can be used to assess the nitrogen fixation capacity of nodules.

Revealing metabolic alterations in brucellosis patients by targeted metabolomics

Brucellosis, a zoonotic disease caused by brucella infection, presents metabolic profile changes in patients that have not been extensively explored. This study utilized an ultra-high performance liquid chromatography tandem mass spectrometry based targeted metabolomic approach to comprehensively investigated metabolic changes in Brucella patients. Serum samples of brucellosis 50 patients and 50 well-matched healthy controls were analyzed for 228 metabolites, revealing significant alterations in 83 metabolites in brucellosis patients. Notably, disruptions were observed in key metabolite pathways, such as amino acid metabolism, urea cycle, tricarboxylic acid cycle (TCA), and fatty acid metabolism. Patients diagnosed with Brucellosis exhibited distinct differences in the levels of aspartate, glutamate, β-alanine, and asparagine when compared to controls. Within the urea cycle, a significant downregulation of arginine was observed, whereas ornithine levels were considerably upregulated. In the TCA cycle, concentrations of 2-oxoglutarate, succinate, and malate were significantly elevated, while citrate levels demonstrated a notable decrease. Due to the interruption of the TCA cycle, glycolysis was accelerated to compensate for the resultant energy deficit in Brucella patients. Concurrently, there was a significant increase in the levels of short and medium-chain fatty acids, while long-chain fatty acids showed a marked decrease. The study systematically revealed significant metabolic alterations in Brucellosis patients and further explored the potential correlation between these changes and clinic symptoms, including fatigue, muscle soreness and prolonged fever. The results enhanced our understanding of Brucellosis, offering valuable insights potentially beneficial in formulating more effective treatment strategies and improving prognostic approaches.

Influence of Controlled Condition Ice Encasement of Creeping Bentgrass and Annual Bluegrass on Plant Recovery, Gas Evolution, and Metabolites

Two cool-season putting green turfgrass species, annual bluegrass and creeping bentgrass, are differential in ice encasement tolerance. Physiological mechanisms associated with creeping bentgrass ice encasement tolerance and annual bluegrass susceptibility are not understood. The objectives were to evaluate oxygen, ethylene, and CO2 content within the upper soil space of the plants while frozen and immediately after ice melt after 0, 5, 10, 20, and 28 days of ice encasement (2.54 cm of ice) in growth chamber conditions. Following ice melt, plant samples were separated into leaf, crown, and root tissues and used to evaluate carbohydrate and amino acid content. Annual bluegrass exhibited higher damage (slower recovery rates) on most sampling days compared with creeping bentgrass. The organs that were most damaged and exhibited a differential principal component analysis snapshot, were the leaf and crown tissues. Creeping bentgrass may preserve leaf and crown tissues for postwinter recovery whereas significant metabolic changes occur in annual bluegrass leaves and crowns. Creeping bentgrass retained total amino acids in leaves following ice encasement whereas total leaf amino acid levels declined in annual bluegrass. Specific carbohydrates and amino acids such as the ability to maintain high levels of fructose, asparagine, and proline may be important indicators of the tolerance to ice encasement stress. On the basis of more prominent carbohydrate and amino acid loss in leaves and crowns and higher levels of CO2 evolution, annual bluegrass may exhibit a higher metabolism and/or tissue damage during ice encasement compared with creeping bentgrass, which could reduce spring recuperative potential.

Carrot strips of various origins: Impact on acrylamide formation in baked goods

The study explored the effects of varied qualities of carrot strips (Q1, Q2) with similar market specification, water addition (56.5–67.8 g/100 g flour) and carrot quantities (7.5–22.5 g/100 g flour) on AA concentrations in wheat bread crumb and crust and baking quality. Analyses included reducing sugars (HPAEC–PAD) and free asparagine (HPLC) levels in doughs as well as acrylamide (HPLC-MS/MS) in crumbs and crusts and baking quality measures. Bread crusts with Q1 reached AA levels of 142 ± 13 μg/kg and significant values in the crumbs (40.8 ± 6.7 μg/kg), whereas bread crusts with Q2 reached up to 274 ± 10 μg/kg and crumbs did not contain AA. With increasing dough water addition, a significant reduction in AA was visible in the case of carrots Q1 and a significant increase in crust AA for carrots Q2. Significant and positive correlation was observed between AA levels in crusts and the addition of carrot strips (rQ1 = 0.93, p < 0.001), whereas for the crust moisture and AA a significant and negative correlation was observed (rQ1 = −0.73, p < 0.01). The precursors in the dough were significantly influenced by the quantities and qualities of ingredients, while the AA formation depended on the quality of the carrot strips and the amount of water added.

Long-acting Erwinia chrysanthemi, Pegcrisantaspase, induces alternate amino acid biosynthetic pathways in a preclinical model of pancreatic ductal adenocarcinoma

BackgroundPancreatic ductal adenocarcinoma (PDAC) is an aggressive disease without meaningful therapeutic options beyond the first salvage therapy. Targeting PDAC metabolism through amino acid restriction has emerged as a promising new strategy, with asparaginases, enzymes that deplete plasma glutamine and asparagine, reaching clinical trials. In this study, we investigated the anti-PDAC activity of the asparaginase formulation Pegcrisantaspase (PegC) alone and in combination with standard-of-care chemotherapeutics.MethodsUsing mouse and human PDAC cell lines, we assessed the impact of PegC on cell proliferation, cell death, and cell cycle progression. We further characterized the in vitro effect of PegC on protein synthesis as well as the generation of reactive oxygen species and levels of glutathione, a major cellular antioxidant. Additional cell line studies examined the effect of the combination of PegC with standard-of-care chemotherapeutics. In vivo, the tolerability and efficacy of PegC, as well as the impact on plasma amino acid levels, was assessed using the C57BL/6-derived KPC syngeneic mouse model.ResultsHere we report that PegC demonstrated potent anti-proliferative activity in a panel of human and murine PDAC cell lines. This decrease in proliferation was accompanied by inhibited protein synthesis and decreased levels of glutathione. In vivo, PegC was tolerable and effectively reduced plasma levels of glutamine and asparagine, leading to a statistically significant inhibition of tumor growth in a syngeneic mouse model of PDAC. There was no observable in vitro or in vivo benefit to combining PegC with standard-of-care chemotherapeutics, including oxaliplatin, irinotecan, 5-fluorouracil, paclitaxel, and gemcitabine. Notably, PegC treatment increased tumor expression of asparagine and serine biosynthetic enzymes.ConclusionsTaken together, our results demonstrate the potential therapeutic use of PegC in PDAC and highlight the importance of identifying candidates for combination regimens that could improve cytotoxicity and/or reduce the induction of resistance pathways.

Acrylamide formation in air-fryer roasted legumes as affected by legume species and roasting degree: the correlation of acrylamide with asparagine and free sugars.

Acrylamide is a well-recognized hazardous compound with known carcinogenic, genotoxic, neurotoxic, and reproductive toxic effects. This research aimed to investigate how different legume species and roasting durations influence acrylamide formation during air-fryer roasting. The study also examined the relationship between acrylamide formation and the levels of free asparagine and free sugars in different bean species. Asparagine content varies substantially across different bean species. Sucrose was the predominant sugar across all bean species, with smaller amounts of galactose and glucose. Air-fryer-roasted Wandu kong (garden pea) showed the highest acrylamide formation, followed by Ultari kong (kidney bean) and Heoktae (black soybean), in that order. Beans roasted for longer periods in an air fryer contained significantly higher levels of acrylamide. This study revealed a strong positive correlation between acrylamide formation and the level of free asparagine in the beans, highlighting the risks associated with certain legume species and air-fryer roasting durations.

An observational and Mendelian randomization study of the associations of body mass index with plasma amino acids and acylcarnitines in Chinese adults

Objective: To explore the relationship between BMI and levels of plasma amino acids and acylcarnitines in Chinese adults. Methods: Based on 2 182 individuals with targeted mass spectrometry metabolomic measurements from the first resurvey of the China Kadoorie Biobank, we assessed the linear and nonlinear associations between BMI and plasma levels of 20 amino acids and 40 acylcarnitines using linear regression models and restricted cubic spline models, and identified BMI-related metabolic pathways. We conducted one-sample Mendelian randomization (MR) with BMI genetic risk scores as the instrumental variable further to explore the potential causal relationships between BMI and 20 amino acids and 40 acylcarnitines, and tested for horizontal pleiotropy using the MR-Egger method. Results: Observational analyses found that BMI was associated with increased plasma levels of 3 branched-chain amino acids (isoleucine, leucine, and valine), 2 aromatic amino acids (phenylalanine and tyrosine), 3 other amino acids (cysteine, glutamate, lysine), and 7 acylcarnitines (C3, C4, C5, C10, C10:1, C14, and C16), and with decreased circulating levels of asparagine, serine, and glycine. Pathway analysis identified 7 BMI-related amino acids metabolic pathways (false discovery rate corrected all P<0.05), including branched-chain amino acids and aromatic amino acids biosynthesis, glutathione metabolism, etc. BMI showed a nonlinear relationship with leucine, valine, and threonine, and a linear relationship with other amino acids and acylcarnitines. One-sample MR analyses revealed that BMI was associated with elevated levels of tyrosine and 4 acylcarnitines [C5-DC(C6-OH), C5-M-DC, C12-DC, and C14], with tyrosine and acylcarnitine C14 positively correlated with BMI in both observational [the β values (95%CIs) were 0.057 (0.044-0.070) and 0.018 (0.005-0.032), respectively] and One-sample MR analyses [the β values (95%CIs) were 0.102 (0.035-0.169) and 0.104 (0.036-0.173), respectively]. The MR analyses of the current study satisfied the 3 core assumptions of instrumental variable. Conclusions: BMI was associated with circulating 11 amino acids and 7 acylcarnitines in Chinese adults, involving several pathways such as branched-chain amino acid and aromatic amino acid metabolism, fatty acid metabolism, and oxidative stress. There may be a causal relationship between BMI and tyrosine and acylcarnitine C14.

Evaluation of Deficient Nutrients in Infants and Toddlers Mainly Taking Amino Acid-Based Elemental Formulas: An Exploratory Study

Introduction: This study evaluated nutrient deficiencies in infants and toddlers with inflammatory bowel disease (IBD) and eosinophilic gastrointestinal disorders (EGIDs), whose primary nutritional source is elemental formulas (EFs). Methods: The nutrient status of children with IBD and EGID aged 6 months to 6 years was evaluated. Results: Twenty-one children fed with EFs (EF group) and 25 controls (CL group) were enrolled. The selenium level in the EF group was lower than that in the CL group (2.2 μg/dL vs. 9.3 μg/dL; p < 0.01). Although fat-soluble vitamins were deficient in some EF group participants, no significant differences were observed in their concentration and insufficiency proportion. However, ascorbic acid deficiency was more frequent in the EF group, with significantly lower levels (8.6 μg/mL vs. 12.0 μg/mL; p < 0.01). The triene:tetraene ratio was significantly higher in the EF group (0.046 vs. 0.010; p < 0.01). Asparagine and taurine levels were significantly lower in the EF group (asparagine: p < 0.01; taurine: p < 0.01) and tyrosine and phenylalanine levels were higher in the EF group, resulting in a lower Fisher’s ratio (p < 0.01). Conclusion: Long-term feeding with EFs can cause deficiencies in essential fatty acids, selenium, and ascorbic acid and also carries a risk of amino acid imbalance in infants and toddlers.

Polybrominated diphenyl ethers (PBDEs) decreased the protein quality of rice grains by disturbing amino acid metabolism

Polybrominated diphenyl ethers (PBDEs) in soils posed potential risks to crop growth and food safety due to their prevalence and persistence. PBDEs were capable of being absorbed and accumulated into crops, impacting their growth, whereas the interference on metabolic components and nutritional composition deserves further elucidation. This study integrated a combined non-targeted and targeted metabolomics method to explore the influences of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), 2,2′,4,4′,5-pentabromodiphenyl ether (BDE-99) and decabromodiphenyl ether (BDE-209) on the metabolic responses of rice (Oryza sativa). Metabolic pathways, which were associated with sugars, organic acids, and amino acids, were significantly disturbed under PBDE stresses. Particularly, 75% of the marked altered pathways belonged to amino acid metabolism, with alanine/aspartate/glutamate metabolism being commonly enhanced. The degradation of aspartic acid promoted the formation of downstream amino acids, among which the levels of lysine, methionine, isoleucine, and asparagine were increased by 1.31–3.15 folds compared to the control. Thus, the antioxidant capacity in rice plants was enhanced, particularly through the significant promotion of ascorbic acid-glutathione (AsA-GSH) cycle in rice leaves. The amino acids were promoted to resist reactive oxygen species (ROS) efficiently, thus were deficient for nutrient storage. When exposed to 4 μmol/kg PBDEs, the contents of amino acids and proteins in grains decreased by 9.1–32.1% and 8.6–34.8%, respectively. In particular, glutelin level was decreased by 5.6–41.2%, resulting in a decline in nutritional quality. This study demonstrated that PBDEs deteriorated the protein nutrition in rice grains by affecting amino acid metabolism, providing a new perspective for evaluating the ecological risks of PBDEs and securing agricultural products.

Special bakery products - Acrylamide formation and bread quality are influenced by potato addition

Especially high levels of asparagine, like those present in potatoes, combined with reducing sugars, lead to increased acrylamide formation. As the influence of potato addition on acrylamide and baking quality in breads has not been examined yet, we aimed to investigate this area and prepared breads with potato flakes (7.5–22.5 g/100 g flour) at different moisture levels as a common mitigation approach (56.5–79.1 g/100 g flour). Analyses included reducing sugars (HPAEC–PAD), asparagine (HPLC) in dough, acrylamide (HPLC-MS/MS) in crumbs and crusts and baking quality measures (dimensions, baking yield, specific volume, lightness, browning index, firmness, crumb and crust moisture, crust-to-crumb ratio, crust thickness, pore analysis). High acrylamide concentrations were measured in crusts, reaching 292.3 ± 16.2 μg/kg, or 91.8 ± 5.3 μg/kg in bread. Significant (p < 0.001) linear correlations were identified between crust acrylamide and asparagine (r = 0.97), glucose (r = 0.85) and maltose (r = 0.92) in doughs, and also potato flakes addition (r = 0.95), surface browning index (r = 0.90) and bread lightness (r = −0.97). Summarizing, potato flakes addition led to higher precursor levels, while water addition influenced the reaction kinetics. Both parameters affected the quality of the bread significantly.

Asparagine reduces the risk of schizophrenia: a bidirectional two-sample mendelian randomization study of aspartate, asparagine and schizophrenia

BackgroundDespite ongoing research, the underlying causes of schizophrenia remain unclear. Aspartate and asparagine, essential amino acids, have been linked to schizophrenia in recent studies, but their causal relationship is still unclear. This study used a bidirectional two-sample Mendelian randomization (MR) method to explore the causal relationship between aspartate and asparagine with schizophrenia.MethodsThis study employed summary data from genome-wide association studies (GWAS) conducted on European populations to examine the correlation between aspartate and asparagine with schizophrenia. In order to investigate the causal effects of aspartate and asparagine on schizophrenia, this study conducted a two-sample bidirectional MR analysis using genetic factors as instrumental variables.ResultsNo causal relationship was found between aspartate and schizophrenia, with an odds ratio (OR) of 1.221 (95%CI: 0.483–3.088, P-value = 0.674). Reverse MR analysis also indicated that no causal effects were found between schizophrenia and aspartate, with an OR of 0.999 (95%CI: 0.987–1.010, P-value = 0.841). There is a negative causal relationship between asparagine and schizophrenia, with an OR of 0.485 (95%CI: 0.262-0.900, P-value = 0.020). Reverse MR analysis indicates that there is no causal effect between schizophrenia and asparagine, with an OR of 1.005(95%CI: 0.999–1.011, P-value = 0.132).ConclusionThis study suggests that there may be a potential risk reduction for schizophrenia with increased levels of asparagine, while also indicating the absence of a causal link between elevated or diminished levels of asparagine in individuals diagnosed with schizophrenia. There is no potential causal relationship between aspartate and schizophrenia, whether prospective or reverse MR. However, it is important to note that these associations necessitate additional research for further validation.

Allantoate Amidohydrolase OsAAH is Essential for Preharvest Sprouting Resistance in Rice

Preharvest sprouting (PHS) is an undesirable trait that decreases yield and quality in rice production. Understanding the genes and regulatory mechanisms underlying PHS is of great significance for breeding PHS-resistant rice. In this study, we identified a mutant, preharvest sprouting 39 (phs39), that exhibited an obvious PHS phenotype in the field. MutMap+ analysis and transgenic experiments demonstrated that OsAAH, which encodes allantoate amidohydrolase, is the causal gene of phs39 and is essential for PHS resistance. OsAAH was highly expressed in roots and leaves at the heading stage and gradually increased and then weakly declined in the seed developmental stage. OsAAH protein was localized to the endoplasmic reticulum, with a function of hydrolyzing allantoate in vitro. Disruption of OsAAH increased the levels of ureides (allantoate and allantoin) and activated the tricarboxylic acid (TCA) cycle, and thus increased energy levels in developing seeds. Additionally, the disruption of OsAAH significantly increased asparagine, arginine, and lysine levels, decreased tryptophan levels, and decreased levels of indole-3-acetic acid (IAA) and abscisic acid (ABA). Our findings revealed that the OsAAH of ureide catabolism is involved in the regulation of rice PHS via energy and hormone metabolisms, which will help to facilitate the breeding of rice PHS-resistant varieties.

The osmoregulatory mechanism in response to hypoosmotic stress and the key role of ABCC1 in osmoregulation in the mud crab, Scylla paramamosain

Scylla paramamosain is an important mariculture animal. In the present study, we examined the physiological and biochemical characteristics of juvenile S. paramamosain under hypoosmotic stress and further verified the function of ABCC1, a key transport protein in gill tissue. The results showed that Na+/K+-ATPase, Ca2+-ATPase, and Na+/K+/2Cl- cotransporter in gill tissues increased first and then decreased. In addition, SOD and CAT activities also began to gradually increase, protecting gill tissues from oxidative damage. The hemolymph osmolarity decreased rapidly from 792 mOsm/kg to 560 mOsm/kg within 6 h, and then rose to 626.25 mOsm/kg at 48 h, and then remained stable. At the same time, Na+, Cl-, K+, and Ca2+ concentrations were decreased to varying degrees. There were significant changes in free amino acids such as aspartic acid, glutamic acid, and asparagine in hemolymph in response to acute salt depletion. By injection of ABCC1 inhibitor/activator, it was found that while ABCC1 transporter activity in the MK-571 group showed a decreasing trend at 9 h, Na+/K+ -ATPase activity began to increase and reached a peak at 48 h. Compared with the control group, the levels of aspartic acid, glutamic acid, asparagine, glycine, arginine, alanine, lysine, and proline in the MK-571 group showed significant differences at 6 h; Significant differences in glutamate, asparagine, arginine, alanine, lysine, and proline appeared at 12 h in the Thiethylperazine group. These results suggested that the dynamic changes of gill ion transport enzymes, antioxidant enzymes, inorganic ions, and free amino acids in hemolymph occurred in S. paramamosain under hypoosmotic stress, and the ABCC1 transporter played an important role in this regulatory process.

Glutamine transporter SLC38A3 promotes breast cancer metastasis via Gsk3β/β-catenin/EMT pathway

Breast cancer is the leading cancer-related cause of death in women. Here we show that solute carrier family 38-member 3 (SLC38A3) is overexpressed in breast cancer, particularly in triple-negative breast cancer (TNBC) cells and tissues. Our study reveals that SLC38A3 regulates cellular glutamine, glutamate, asparagine, aspartate, alanine, and glutathione (GSH) levels in breast cancer cells. Our data demonstrate that SLC38A3 enhances cell viability, cell migration and invasion in vitro, and promotes tumor growth and metastasis in vivo, while reducing apoptosis and oxidative stress. Mechanistically, we show that SLC38A3 suppresses the activity of glycogen synthase kinase 3-β (Gsk3β), a negative regulator of β-catenin, and increases protein levels of β-catenin, leading to the upregulation of epithelial-to-mesenchymal-transition (EMT)-inducing transcription factors and EMT markers in breast cancer. In summary, we show that SLC38A3 is overexpressed in breast cancer and promotes breast cancer metastasis via the GSK3β/β-catenin/EMT pathway, presenting a novel therapeutic target to explore for breast cancer.

Metabolomics Reveals Rubiadin Accumulation and the Effects of Methyl Jasmonate Elicitation in Damnacanthus major Calli.

Callus suspension techniques have been considered attractive for improving bioactive metabolite productivity; methyl jasmonate (MeJA) is a widely used elicitor for stimulating synthetic pathways. In this study, a multivariate analysis-based metabolomics approach was employed to investigate the primary and specialized metabolites in the leaves, unelicited calli, and 100 or 200 μM MeJA elicited calli of Damnacanthus major. Rubiadin, a powerful anthraquinone with various therapeutic properties, was only identified in D. major calli, accumulating in a MeJA elicitation concentration-dependent manner. Callus cultures also contained high levels of amino acids, sugars, and phenolic compounds, indicating energy metabolism and metabolic adaptation responses for proliferation and stabilization. Regarding MeJA application, elicited calli contained higher amounts of quinic acid, kaempferol, and glucose with lower amounts of sucrose and raffinose than those in the unelicited control, which were closely related to protective mechanisms against MeJA. Moreover, excessive elicitation increased the asparagine, fructose, and raffinose levels and decreased the glucose and sucrose levels, which was ascribed to increased activation of the aminoacyl-tRNA biosynthesis pathway and wider utilization of glucose than of fructose after sucrose degradation. These results will be useful for optimizing plant cell culture techniques to achieve high production rates for valuable specialized metabolites.

Comparison of efficacy and safety of different asparaginases in adult acute lymphoblastic leukemia based on nano-magnetic beads immunoassay.

To compare the efficacy and safety of different asparaginase formulations in the treatment of acute lymphoblastic leukemia (ALL) based on nano-magnetic bead immunoassay. Retrospective analysis of adult ALL patients' clinical data who admitted to The Affiliated Hospital of Changsha Health Vocational College from August 2020 to August 2023. Finally, 65 adult ALL patients were included in this study, including the polyethylene glycol conjugated asparaginase (PEG-ASNase) group (n = 32) and the L-asparaginase (L-ASNase) group (n = 33). Enzyme-linked immunosorbent assay (ELISA) based on magnetic nanoparticles was used to determine the activity of ASNase in both groups. The levels of asparagine or glutamine in two groups were detected by automatic biochemical analyzer during induction therapy, and the adverse events of the two groups were observed during the treatment. PEG-ASNase demonstrated a slower decrease in enzyme activity, longer action duration, and higher safety profile compared to L-ASNase. PEG-ASNase group and L-ASNase group demonstrated a similar complete remission rate (71.88% vs. 60.61%). Event-free survival was higher in patients receiving PEG-ASNase than those receiving L-ASNase (42.4% and 18.7%). The observed adverse reactions included allergic reactions, pancreatic lesions, gastrointestinal reactions and liver function damage. The incidence of gastrointestinal reactions and liver function damage was higher in the L-ASNase group than that in PEG-ASNase group (45.45% and 33.33%). This study provides valuable insights into the asparaginase treatments in clinical, highlighting the importance of PEG-ASNase for improving treatment protocols in adult ALL patients.

Aldehyde-mediated inhibition of asparagine biosynthesis has implications for diabetes and alcoholism.

Patients with alcoholism and type 2 diabetes manifest altered metabolism, including elevated aldehyde levels and unusually low asparagine levels. We show that asparagine synthetase B (ASNS), the only human asparagine-forming enzyme, is inhibited by disease-relevant reactive aldehydes, including formaldehyde and acetaldehyde. Cellular studies show non-cytotoxic amounts of reactive aldehydes induce a decrease in asparagine levels. Biochemical analyses reveal inhibition results from reaction of the aldehydes with the catalytically important N-terminal cysteine of ASNS. The combined cellular and biochemical results suggest a possible mechanism underlying the low asparagine levels in alcoholism and diabetes. The results will stimulate research on the biological consequences of the reactions of aldehydes with nucleophilic residues.