Amino Acids最新文献

{"title":"The reverse transsulfuration pathway affects the colonic microbiota and contributes to colitis in mice","authors":"Alain P. Gobert,&nbsp;Yvonne L. Latour,&nbsp;Kara M. McNamara,&nbsp;Caroline V. Hawkins,&nbsp;Kamery J. Williams,&nbsp;Mohammad Asim,&nbsp;Daniel P. Barry,&nbsp;Margaret M. Allaman,&nbsp;Alberto G. Delgado,&nbsp;Ginger L. Milne,&nbsp;Shilin Zhao,&nbsp;M. Blanca Piazuelo,&nbsp;M. Kay Washington,&nbsp;Lori A. Coburn,&nbsp;Keith T. Wilson","doi":"10.1007/s00726-024-03423-4","DOIUrl":"10.1007/s00726-024-03423-4","url":null,"abstract":"<div><p>Cystathionine γ-lyase (CTH) is a critical enzyme in the reverse transsulfuration pathway, the major route for the metabolism of sulfur-containing amino acids, notably converting cystathionine to cysteine. We reported that CTH supports gastritis induced by the pathogen <i>Helicobacter pylori</i>. Herein our aim was to investigate the role of CTH in colonic inflammation. First, we found that CTH is induced in the colon mucosa in mice with dextran sulfate sodium-induced colitis. Expression of CTH was completely absent in the colon of <i>Cth</i>^–/– mice. We observed that clinical and histological parameters are ameliorated in <i>Cth</i>-deficient mice compared to wild-type animals. However, <i>Cth</i> deletion had no effect on tumorigenesis and the level of dysplasia in mice treated with azoxymethane-DSS, as a reliable model of colitis-associated carcinogenesis. Mechanistically, we determined that the deletion of the gene <i>Slc7a11</i> encoding for solute carrier family 7 member 11, the transporter of the anionic form of cysteine, does not affect DSS colitis. Lastly, we found that the richness and diversity of the fecal microbiota were significantly increased in <i>Cth</i>^–/– mice compared to both WT and <i>Slc7a11</i>^–/– mice. In conclusion, our data suggest that the enzyme CTH represents a target for clinical intervention in patients with inflammatory bowel disease, potentially by beneficially reshaping the composition of the gut microbiota.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03423-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-activity relationship of amino acid analogs to probe the binding pocket of sodium-coupled neutral amino acid transporter SNAT2","authors":"Sebastian Jakobsen,&nbsp;Maria Pedersen,&nbsp;Carsten Uhd Nielsen","doi":"10.1007/s00726-024-03424-3","DOIUrl":"10.1007/s00726-024-03424-3","url":null,"abstract":"<div><p>The sodium-coupled neutral amino acid transporter SNAT2 (SLC38A2) has been shown to have important physiological functions and is implicated in various diseases like cancer. However, few compounds targeting this transporter have been identified and little is known about the structural requirements for SNAT2 binding. In this study, the aim was to establish the basic structure-activity relationship for SNAT2 using amino acid analogs. These analogs were first studied for their ability to inhibit SNAT2-mediated ³H-glycine uptake in hyperosmotically treated PC-3 cells. Then to identify substrates a FLIPR membrane potential assay and o-phthalaldehyde derivatization of intracellular amino with subsequent quantification using HPLC-Fl was used. The results showed that ester derivatives of the C-terminus maintained SNAT2 affinity, suggesting that the negative charge was less important. On the other hand, the positive charge at the N-terminus of the substrate and the ability to donate at least two hydrogen bonds to the binding site appeared important for SNAT2 recognition of the amine. Side chain charged amino acids generally had no affinity for SNAT2, but their non-charged derivatives were able to inhibit SNAT2-mediated ³H-glycine uptake, while also showing that amino acids of a notable length still had affinity for SNAT2. Several amino acid analogs appeared to be novel substrates of SNAT2, while γ-benzyl L-glutamate seemed to be inefficiently translocated by SNAT2. Elaborating on this structure could lead to the discovery of non-translocated inhibitors of SNAT2. Thus, the present study provides valuable insights into the basic structural binding requirements for SNAT2 and can aid the future discovery of compounds that target SNAT2.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03424-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LLM4THP: a computing tool to identify tumor homing peptides by molecular and sequence representation of large language model based on two-layer ensemble model strategy","authors":"Sen Yang,&nbsp;Piao Xu","doi":"10.1007/s00726-024-03422-5","DOIUrl":"10.1007/s00726-024-03422-5","url":null,"abstract":"<div><p>Tumor homing peptides (THPs) have a distinctive capacity to specifically attach to tumor cells, providing a promising approach for targeted cancer treatment and detection. Although THPs have the potential for significant impact, their detection by conventional methods is both time-consuming and expensive. To tackle this issue, we provide LLM4THP, an innovative computational approach that utilizes large language models (LLMs) to quickly and effectively detect THPs. LLM4THP utilizes two protein LLMs, ESM2 and Prot_T5_XL_UniRef50, to encode peptide sequences. This allows for the capture of complex patterns and relationships within the peptide data. In addition, we utilize inherent sequence characteristics such as Amino Acid Composition (AAC), Pseudo Amino Acid Composition (PAAC), Amphiphilic Pseudo Amino Acid Composition (APAAC), and Composition, Transition, and Distribution (CTD) to improve the representation of peptides. The RDKitDescriptors feature representation approach transforms peptide sequences into molecular objects and computes chemical characteristics, resulting in enhanced THP identification. The LLM4THP ensemble strategy incorporates various features into a two-layer learning architecture. The first layer consists of LightGBM, XGBoost, Random Forest, and Extremely Randomized Trees, which generate a set of meta results. The second layer utilizes Logistic Regression to further refine the identification of sequences as either THP or non-THP. LLM4THP exhibits exceptional performance compared to the most advanced methods, showcasing enhancements in accuracy, Matthew’s correlation coefficient, F1 score, area under the curve, and average precision. The source code and dataset can be accessed at the following URL: https://github.com/abcair/LLM4THP.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03422-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinetic analysis of D-Alanine upon oral intake in humans","authors":"Tomonori Kimura,&nbsp;Shinsuke Sakai,&nbsp;Masaru Horio,&nbsp;Shiro Takahara,&nbsp;Shoto Ishigo,&nbsp;Maiko Nakane,&nbsp;Eiichi Negishi,&nbsp;Hiroshi Imoto,&nbsp;Masashi Mita,&nbsp;Kenji Hamase,&nbsp;Yoko Higa-Maekawa,&nbsp;Yoichi Kakuta,&nbsp;Masayuki Mizui,&nbsp;Yoshitaka Isaka","doi":"10.1007/s00726-024-03421-6","DOIUrl":"10.1007/s00726-024-03421-6","url":null,"abstract":"<div><p>D-Alanine, a rare enantiomer of alanine, can potentially alleviate the worsening of viral infections and maintain circadian rhythm. This study aimed to analyze the kinetics of D-Alanine upon oral intake. Five healthy volunteers were administered D-Alanine as a single oral dose at 11,236 or 33,708 µmoL (1–3 g). Upon intake of the lower dose, the plasma level of D-Alanine reached its peak concentration of 588.4 ± 40.9 µM with a peak time of 0.60 ± 0.06 h. The compartment model estimated the clearance of D-Alanine at 12.5 ± 0.3 L/h, or 208 ± 5 mL/min, distribution volume of 8.3 ± 0.7 L and half-life of 0.46 ± 0.04 h, suggesting a rapid clearance of D-Alanine. The peak concentration and area under the curve increased proportionally upon intake of the higher dose, while the clearance, distribution volume and half-life did not. The urinary ratio of D-Alanine per sum of D- and L-Alanine reached its peak of nearly 100%, followed by a slow decline. The peak time of the urinary ratio was 1.15 ± 0.15 h, showing a time lag of blood to urine excretion. Fractional excretion, a ratio of the clearance of a substance per a standard molecule in kidney, of D-Alanine increased from 14.0 ± 5.8% to 64.5 ± 10.3%; the latter corresponded to the urinary clearance of D-Alanine as about 77 mL/min for an adult, with a peak time of 1.90 ± 0.56 h. D-Alanine was quickly absorbed and appeared in blood, followed by urinary excretion. This kinetic analysis increases our fundamental knowledge of the oral intake of D-Alanine for the chronic dosing.</p><p>\u0000 Trial number: #UMIN000050865.</p><p>\u0000 Date of registration: 2023/6/30.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03421-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review and meta-analysis of clinical trials on the effects of glutamine supplementation on gut permeability in adults","authors":"Fatemeh Abbasi,&nbsp;Mohammad Mehdi Haghighat Lari,&nbsp;Gholamreza Reza Khosravi,&nbsp;Elahe Mansouri,&nbsp;Nastaran Payandeh,&nbsp;Alireza Milajerdi","doi":"10.1007/s00726-024-03420-7","DOIUrl":"10.1007/s00726-024-03420-7","url":null,"abstract":"<div><p>The gastrointestinal tract's epithelial barrier plays a crucial role in maintaining health. This study aims to investigate the impact of glutamine supplementation on intestinal permeability, considering its importance for immune function and nutrient absorption. The study adhered to the PRISMA protocol for systematic reviews and meta-analyses. A systematic search was performed in four databases (PubMed, Scopus, Web of Science, and Google Scholar) until April 2023 to identify clinical trials on glutamine supplementation and gastrointestinal permeability. Eligibility criteria included randomized placebo-controlled trials measuring gut permeability post-glutamine supplementation. Studies were included regardless of language or publication date. Data extraction involved study characteristics, intervention details, and outcomes. Quality assessment was performed using the Cochrane tool, and statistical analysis utilized mean differences and standard deviations with a random effects model. Subgroup analysis was conducted to explore heterogeneity. The systematic review and meta-analysis included 10 studies from 1998 to 2014 with 352 participants. A total of 216 patients were enrolled in the intervention group, and 212 in the control group. The mean participant age was 46.52 years. The participants had different types of diseases in terms of their health status. Overall, glutamine supplementation did not significantly affect intestinal permeability (WMD: −0.00, 95% CI −0.04, 0.03). Subgroup analysis showed a significant reduction in intestinal permeability with doses over 30g/day (WMD: −0.01, 95% CI −0.10, −0.08). The glutamine supplements were administered orally in all included studies. The meta-analysis demonstrated a significant reduction in intestinal permeability with glutamine supplementation exceeding 30 mg/day for durations of less than 2 weeks. Further investigations with varying dosages and patient populations are warranted to enhance understanding and recommendations regarding glutamine supplementation's effects on gut permeability.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03420-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green synthesis of self-oriented flower-like Ag@Ag2O nanostructures functionalized with L-Tryptophan for colorimetric simultaneous determination of ultra-trace level of thiamin and riboflavin","authors":"Maryam Abbasi Tarighat,&nbsp;Zahra Khosravani,&nbsp;Gholamreza Abdi","doi":"10.1007/s00726-024-03406-5","DOIUrl":"10.1007/s00726-024-03406-5","url":null,"abstract":"<div><p>The study focuses on the green synthesis of Ag@Ag₂O nanostructures using <i>Padina</i> algae extract and functionalizing them with L-tryptophan to enhance their properties as a colorimetric sensor for simultaneous detection of ultra-trace levels of thiamin and riboflavin. The nanostructures are characterized using techniques like XRD, FESEM, FTIR, TEM, AFM, and DLS to understand their morphology, structure, and interactions with target molecules. FESEM analysis revealed the hierarchical flower-like Ag@Ag₂O nanostructures. The TEM image shows the formation of core-shell nanostructures. Also, DLS analysis and surface zeta potential spectra illustrated the aggregated nature of fabricated nanocomposites in the presence of vitamins. The study is the first to report simultaneous determination of thiamin and riboflavin using a colorimetric sensor based on Ag@Ag₂O-L-Try nanocomposites using partial leas square (PLS). The dynamic range of thiamin and riboflavin was achieved in 0.1 mol L⁻1 acetate buffer pH 4 and the ratio Ag@Ag₂O: L-try 1:1. The Ag@Ag₂O-L-Try sensor exhibited two linear ranges of 0.1- 1.0 and 3-350 µMol L^− 1 for riboflavin and a linear range 3.0–60 µMol L^− 1 for thiamin. Also, low detection limit of 1.92 µMol L^− 1 and 0.048 µMol L^− 1 was obtained for riboflavin and thiamin, respectively. The results indicated that the success of the method depends on the selective and sensitive colorimetric assay of the sensor along with the simultaneous determination by the PLS algorithm. Hence, the proposed technique can be used for the accurate and precise determination of vitamins in different pharmaceutical syrup and tablet samples.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03406-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of smokeless tobacco on psychological and oxidative stress in unemployed indian youth","authors":"Anurag Mishra,&nbsp;Rishabh Kumar,&nbsp;Satya Narayan Mishra,&nbsp;Sivakumar Vijayaraghavalu,&nbsp;Girish C. Shukla,&nbsp;Munish Kumar","doi":"10.1007/s00726-024-03416-3","DOIUrl":"10.1007/s00726-024-03416-3","url":null,"abstract":"<div><p>In India, tobacco (nicotine) addiction among youth has increased, leading to substantial socioeconomic burdens, mortality, and morbidity. While minimal short-term nicotine consumption may have antioxidant effects, chronic exposure results in various adverse health outcomes. This study examines the impact of chronic nicotine consumption on cellular oxidative stress and psychological stress, and their correlation with Homocysteine (Hcy) levels in unemployed tobacco consumers. This case-control study included 156 healthy, educated, unemployed male volunteers aged 20–40 years, divided into nicotine-addicted (n = 80) and non-addicted (n = 76) groups. Psychological stress was assessed using perceived stress scales (PSS) and coping self-efficacy (CSE) scales. Oxidative stress markers, including Malondialdehyde (MDA), Superoxide Dismutase (SOD), and Catalase, were measured. Hcy levels were quantified using high-performance liquid chromatography (HPLC). Nicotine-addicted participants exhibited significantly higher perceived stress (p = 0.0001) and lower coping self-efficacy (p = 0.0001) compared to non-addicted individuals. MDA levels in erythrocytes were significantly increased (p = 0.0006), while SOD (p = 0.0001) and Catalase (p = 0.02) activities were significantly decreased in the addicted group. Nicotine intake influenced Hcy concentrations, with 55% of addicted individuals falling into moderate, 27.5% into intermediate, and 7.5% into severe Hcy categories. Chronic nicotine intake also reflected the hematological parameters (WBCs, RBCs, HGB, and Platelets). Chronic tobacco consumption induces oxidative stress and perceived psychological stress, leading to elevated Hcy levels in nicotine consumers. The study highlights the detrimental effects of nicotine addiction on cellular defensive mechanisms, emphasizing the need for targeted interventions to address this growing health issue among unemployed Indian youth.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03416-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HECTD2 as a target for veratric acid in the regulation of ferroptosis in renal cell carcinoma","authors":"Dong Lv,&nbsp;Ying Xiang,&nbsp;Tao Song,&nbsp;Jinze Li,&nbsp;Yongbo Chen,&nbsp;Youlong Huili,&nbsp;Taimin Shen","doi":"10.1007/s00726-024-03419-0","DOIUrl":"10.1007/s00726-024-03419-0","url":null,"abstract":"<div><p>Function of HECTD2 in renal cell carcinoma malignant progression is undefined. Molecular mechanism behind anti-cancer effects of veratric acid (VA) from traditional Chinese medicine (TCM) is underexplored. The Cancer Genome Atlas was leveraged to study HECTD2 expression in renal cell carcinoma and its relationship with histological grading. Kaplan–Meier survival analysis was performed. HECTD2 expression was detected in cancer cells and tissues via qRT-PCR and immunohistochemistry. GPX4 and SLC7A11 expression in tumor samples with high or low HECTD2 expression was examined by immunohistochemistry, cell viability by CCK8, cell proliferation by colony formation assay, lipid ROS and mitochondrial superoxide levels by flow cytometry, Fe²⁺ and MDA content by assay kits, and GPX4 and SLC7A11 proteins by western blot. SeeSAR software screened TCM small molecule compounds with highest affinity to HECTD2, confirmed with cellular thermal shift assay. VA IC₅₀ was measured by CCK8. Xenograft model was developed and treated with VA. Tumor size and weight were monitored, with immunohistochemistry to detect HECTD2 expression in tumors and assess ferroptosis-related markers. HECTD2 was overexpressed in tumor tissues and cells, which positively correlated with histological grading. HECTD2 depletion inhibited cell vitality and proliferation, raised intracellular lipid ROS, mitochondrial superoxide, Fe²⁺, and MDA. HECTD2 was a target with highest VA affinity. In vitro and <i>vivo</i> experiments concurred that VA treatment hindered malignancy of renal cell carcinoma and enhanced its susceptibility to ferroptosis. HECTD2 supports ferroptosis resistance in renal cell carcinoma, but VA, through its targeting of HECTD2, initiates ferroptosis, showcasing its anti-cancer efficacy.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of amino acids metabolomic profiling in human plasma distinguishes lupus nephritis from systemic lupus erythematosus","authors":"Zui-Shuang Guo,&nbsp;Man-man Lu,&nbsp;Dong-wei Liu,&nbsp;Chun-Yu Zhou,&nbsp;Zhang-suo Liu,&nbsp;Qing Zhang","doi":"10.1007/s00726-024-03418-1","DOIUrl":"10.1007/s00726-024-03418-1","url":null,"abstract":"<div><p>Lupus nephritis (LN) is an immunoinflammatory glomerulonephritis associated with renal involvement in systemic lupus erythematosus (SLE). Given the close relationship between plasma amino acids (AAs) and renal function, this study aimed to elucidate the plasma AA profiles in LN patients and identify key AAs and diagnostic patterns that distinguish LN patients from those with SLE and healthy controls. Participants were categorized into three groups: normal controls (NC), SLE, and LN. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to quantify AA levels in human plasma. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were utilized to identify key AAs. The diagnostic capacity of the models was assessed using receiver operating characteristic (ROC) curve analysis and area under the ROC curve (AUC) values. Significant alterations in plasma AA profiles were observed in LN patients compared to the SLE and NC groups. The OPLS-DA model effectively separated LN patients from the SLE and NC groups. A joint model using histidine (His), lysine (Lys), and tryptophan (Trp) demonstrated exceptional diagnostic performance, achieving an AUC of 1.0 with 100% sensitivity, specificity, and accuracy in predicting LN. Another joint model comprising arginine (Arg), valine (Val), and Trp also exhibited robust predictive performance, with an AUC of 0.998, sensitivity of 93.80%, specificity of 100%, and accuracy of 95.78% in distinguishing between SLE and LN. The joint forecasting models showed excellent predictive capabilities in identifying LN and categorizing lupus disease status. This approach provides a novel perspective for the early identification, prevention, treatment, and management of LN based on variations in plasma AA levels.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03418-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of supplementary carnosine accumulation and distribution: an initial analysis of participants in the Nucleophilic Defense Against PM Toxicity (NEAT) clinical trial","authors":"Shahid P. Baba,&nbsp;Alok R. Amraotkar,&nbsp;David Hoetker,&nbsp;Hong Gao,&nbsp;Daniel Gomes,&nbsp;Jingjing Zhao,&nbsp;Michael F. Wempe,&nbsp;Peter J. Rice,&nbsp;Andrew P. DeFilippis,&nbsp;Shesh N. Rai,&nbsp;C. Arden Pope III,&nbsp;Aruni Bhatnagar,&nbsp;Timothy E. O’Toole","doi":"10.1007/s00726-024-03414-5","DOIUrl":"10.1007/s00726-024-03414-5","url":null,"abstract":"<div><p>Carnosine is an endogenous dipeptide that buffers intracellular pH and quenches toxic products of lipid peroxidation. Used as a dietary supplement, it also supports exercise endurance. However, the accumulation and distribution of carnosine after supplementation has not been rigorously evaluated. To do this, we randomized a cohort to receive daily supplements of either placebo or carnosine (2 g/day). Blood and urine samples were collected twice over the subsequent 12 week supplementation period and we measured levels of red blood cell (RBC) carnosine, urinary carnosine, and urinary carnosine-propanol and carnosine-propanal conjugates by LC/MS–MS. We found that, when compared with placebo, supplementation with carnosine for 6 or 12 weeks led to an approximate twofold increase in RBC carnosine, while levels of urinary carnosine increased nearly sevenfold. Although there were no changes in the urinary levels of carnosine propanol, carnosine propanal increased nearly twofold. RBC carnosine levels were positively associated with urinary carnosine and carnosine propanal levels. No adverse reactions were reported by those in the carnosine or placebo arms, nor did carnosine supplementation have any effect on kidney, liver, and cardiac function or blood electrolytes. In conclusion<i>,</i> irrespective of age, sex, or BMI, oral carnosine supplementation in humans leads to its increase in RBC and urine, as well as an increase in urinary carnosine-propanal. RBC carnosine may be a readily accessible pool to estimate carnosine levels. <b>Clinical trial registration:</b> This study is registered with ClinicalTrials.gov (Nucleophilic Defense Against PM Toxicity (NEAT Trial)—Full Text View—ClinicalTrials.gov), under the registration: NCT03314987.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}