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Targeted metabolomics studies on organic acids (OAs) and amino acids (AAs) were performed to search for biomarkers for ovarian cancer progression. Simultaneous AA profiling analysis method was developed through LC-MS/MS. Under optimal conditions, method showed good linearity (r ≥ 0.998) with limits of detection (LOD) ≤ 0.22 ng/mL and limits of quantification (LOQ) of ≤0.72 ng/mL. Repeatability varied from 1.4 to 17.3 relative standard deviation (%RSD) and accuracy varied from −20.6% to 12.1% relative error (% RE). Twenty-six AAs and 13 OAs were detected in the analyses of ovarian tissue from patients with benign ovarian tumors (BOT), borderline tumors (BT), and ovarian serous carcinoma (OSC). Star pattern recognition analysis was performed by normalizing each group to the BOT group. The star symbol plots in the BT and OSC groups were distinct and easily distinguished from those in the BOT group. The BT and the OSC groups exhibited higher 3-hydroxybutyric acid and lactic acid levels, lower pyruvic acid and OA levels in the TCA cycle, and alterations in AA metabolic patterns in comparison to the BOT group. Especially, citrulline and leucine were significantly reduced, while fumaric acid and malic acid significantly increased in the OSC group compared to the BT group. The BT and the OSC groups were completely separated in orthogonal partial least squares-discriminant analysis (OPLS-DA) and heatmap analysis. These findings, elevated ketone body levels, increased anaerobic glycolysis, reduced energy production related to mitochondrial dysfunction in the TCA cycle, and AA metabolic patterns associated with the impaired antioxidant system, may explain the characteristic metabolic reprogramming and Warburg effect related to the progression of the OSC into malignancy. [ABSTRACT FROM AUTHOR]

The main objective of this experiment was to study the metabolism of arginine in juvenile largemouth bass (Micropterus salmoides). A total of 300 healthy fish (average weight of 25 ± 0.5 g) were randomly assigned to ten groups. Experimental fish were orally administered or intraperitoneally injected with 0.9% sodium chloride, arginine, arginine-aspartate, citrulline, and glutamate solutions, respectively. They were euthanized at 10, 30, 60, 120, and 240 min after oral administration or intraperitoneal injection, and various tissue samples were subsequently collected for analysis. The results revealed that serum ornithine and citrulline concentrations of largemouth bass were significantly increased by oral administration of arginine or arginine-aspartate (P < 0.05). Intraperitoneal injection of arginine or arginine-aspartate solution significantly elevated the concentrations of ornithine and citrulline in the serum, liver, kidney, and muscles (P < 0.05). The concentrations of citrulline, ornithine, and arginine in serum and muscle increased significantly at 4 h after intraperitoneal injection of glutamate (P < 0.05). Intraperitoneal injection of citrulline significantly increased the concentrations of ornithine and arginine in the serum and muscles (P < 0.05). The research findings demonstrate that both free and small peptide forms of arginine were rapidly degraded to ornithine due to the high arginase activity in various tissues of largemouth bass. Additionally, the pathway of synthesizing citrulline from glutamate and then arginine from citrulline may exist in largemouth bass, but the exact location of this synthesis process may differ from that found in mammals. [ABSTRACT FROM AUTHOR]

Mutations in CHRNE encoding the epsilon subunit of acetylcholine receptor result in impaired neuromuscular transmission and congenital myasthenic syndrome (CMS) with variying severity of symptoms. Although the pathophysiology is well-known, blood biomarker signatures enabling a patient-stratification are lacking. This retrospective two-center-study includes 19 recessive CHRNE-patients (AChR deficiency; mean age 14.8 years) from 13 families which were clinically characterized according to disease severity. 15 patients were classified as mildly and 4 patients as moderate to severely affected. Seven known pathogenic and one unreported variant (c.1032 + 2_1032 + 3delinsGT) were identified. Biomarker discovery was carried out on blood samples: proteomics was performed on white blood cells (WBC; n = 12) and on extracellular vesicles (EV) purified from serum samples (n = 7) in addition to amino acid profiling (n = 9) and miRNA screening (n = 18). For miRNA studies, 7 patients with other CMS-subtypes were moreover included. WBC-proteomics unveiled a significant increase of 7 and a decrease of 36 proteins. In silico studies of these proteins indicated affection of secretory granules and the extracellular space. Comparison across patients unveiled increase of two vesicular transport proteins (SCAMP2 and SNX2) in severely affected patients and indeed EV-proteomics revealed increase of 7 and decrease of 13 proteins. Three of these proteins (TARSH, ATRN & PLEC) are known to be important for synaptogenesis and synaptic function. Metabolomics showed decrease of seven amino acids/ amino acid metabolites (aspartic and glutamic acids, phosphoserine, amino adipate, citrulline, ornithine, and 1-methyhistidine). miRNA-profiling showed increase miR − 483 − 3p, miR-365a-3p, miR − 365b − 3p and miR-99a, and decrease of miR-4433b-3p, miR-6873-3p, miR-182-5p and let-7b-5p in CHRNE-patients whereas a comparison with other CMS subtypes showed increase of miR − 205 − 5p, miR − 10b − 5p, miR-125a-5p, miR-499-5p, miR-3120-5p and miR − 483 − 5p and decrease of miR − 1290. Our combined data introduce a molecular fingerprint on protein, metabolic and miRNA level with some of those playing different roles along the neuromuscular axis. [ABSTRACT FROM AUTHOR]

The main purpose of this study was to optimize the L-citrulline production process using Plackett-Burman and Box-Behnken designs. L-citrulline-producing bacterium BH-01 was isolated from raw buffalo milk. The isolate was tested for probiotic activities such as tolerance to simulated gastric and intestinal juices, antagonistic activity against six antibiotic-resistant bacteria, and temperature tolerance. L-citrulline production and arginine deiminase (ADI) activity were optimized using statistical designs. The bacterial isolate was molecularly identified as Bacillus subtilis strain AUMC B-498 (accession number PP574248.1). The strain exhibited resistance at pH 2.0 and bile salt 0.5% for a two-hour exposure period. It could inhibit the growth of Escherichia coli, Klebsiella pneumonia, Serratia sp., Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus pneumoniae. From the results of statistical optimization, the Plackett-Burman design identified temperature, L-arginine, incubation period, and peptone as the most effective factors among the eight selected variables. Based on these, the Box-Behnken design was used to optimize the factors required to maximize citrulline production. The maximum L-citrulline was 632.5 µg/L, and ADI activity was 1.42 U/mL. Therefore, BH-01 isolated from Buffalo milk might be a promising candidate in food, biotechnological, and pharmaceutical applications due to its dual functionality for citrulline production and probiotic characteristics. [ABSTRACT FROM AUTHOR]

Purpose: To enhance the detection rate of Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD) through newborn screening (NBS), we analyzed the metabolic profiles of missed patients and proposed a more reliable method for early diagnosis. Methods: In this retrospective study, NICCD patients were classified into "Newborn Screening" (64 individuals) and "Missed Screening" (52 individuals) groups. Metabolic profiles were analyzed using the non-derivatized MS/MS Kit, and genetic mutations were identified via next-generation sequencing and confirmed by Sanger sequencing. Receiver Operating Characteristic (ROC) analysis evaluated the predictive value of amino acids and acylcarnitines in dried blood spots (DBS) for identifying missed patients including 40 missed patients and 17,269 healthy individuals, with additional validation using 12 missed patients and 454 healthy controls. Results: The age of diagnosis was significantly higher in the "Missed Screening" group compared to the "Newborn Screening" group (74.50 vs. 18.00 days, P < 0.001). ROC analysis revealed that citrulline had excellent diagnostic accuracy for missed patients, with an AUC of 0.970 and a cut-off value of 17.57 µmol/L. Additionally, glycine, phenylalanine, ornithine, and C8 were significant markers, each with an AUC greater than 0.70. A combination of these markers achieved an AUC of 0.996 with a cut-off value of 0.00195. Validation demonstrated a true positive rate of 91.67% and a true negative rate of 96.48%. Common SLC25A13 mutations in both groups were c.852_855del, IVS16ins3kb, and c.615 + 5G > A. Conclusions: Combining multiple metabolic markers during NBS significantly improves sensitivity and specificity for detecting missed NICCD cases. However, the relationship between genetic mutations and missed cases remains unclear. [ABSTRACT FROM AUTHOR]

Background: Ornithine transcarbamylase deficiency exhibits a high degree of clinical heterogeneity, making its screening and classification challenging in some instances. In this study, we first established a simple and stable method for testing ornithine transcarbamylase activity using micro blood from newborns, rather than relying on venous blood. Methods: The activity of ornithine transcarbamylase was assessed by measuring the concentration of citrulline produced in the reaction with carbamoyl phosphate and ornithine, using serum, plasma or micro blood. Correlation analysis was evaluated using Sangerbox Tools. The Receiver Operating Characteristic curve was used in SPSS Statistics 17.0 to evaluate the diagnostic efficiency of Ornithine transcarbamylase deficiency. Results: A strong linear relationship was observed between ornithine transcarbamylase activity and both micro blood volume and reaction time (R2 = 0.9793, 0.9922 respectively). The intra-coefficient variation and inter-coefficient variation were 11% and 12.5% with a 1-h reaction time, and 6.77% and 9.58% with a 3-h reaction time, respectively. And the inter-coefficient variation was lower than the most widely used colorimetry method (5.1–21.1%). The Limit of Blank was 0.57 nmol/mL/h. The reference interval for normal newborn population is greater than or equal to 39.6 nmol/mL/h. Notably, the method exhibited a 100% sensitivity, surpassing the sensitivity of colorimetry method (94.3%), along with and a specificity of 96.9% for diagnosing ornithine transcarbamylase deficiency. Conclusions: We pioneered a method for testing OTC activity that normally carried on venous blood can be effectively performed on microblood heel samples. Meanwhile, our method presents a simpler, more stable and reproducible approach compared to colorimetry. [ABSTRACT FROM AUTHOR]

Background: Meat goat production is a worldwide industry with products such as meat, milk, soap, and fiber being produced. There are approximately 2.6 million meat goats in the United States. For breeding female ruminants, early pregnancy loss is estimated to be 30% within the first month of gestation. Extracellular L-citrulline (a precursor to L-arginine) is not degraded by ruminal microbes due to the lack of uptake. L-Arginine and thus L-citrulline, have beneficial impacts on placentation and, subsequently, fetal-placental development and survival. This study aimed to determine the impact of feeding L-citrulline to meat goats during gestation to improve reproductive success. Meat goats were fed either a control (CON) or L-citrulline (CIT) supplemented diet from d 12 to 82 of gestation. Blood samples were collected and sera were subjected to high-performance liquid chromatography analyses to quantify the abundance of amino acids. Pregnancy rates were determined on d 30, 61, and 90 of gestation, and litter weight, individual birth weights, and 90 d adjusted weaning weights were collected. Results: The concentrations of citrulline, ornithine, and arginine were greater in CIT does compared to CON does, but there was no difference in pregnancy rates between CON and CIT does. Birth weight was greater for male kids born as singles when compared to females, but this phenotype was not observed for kids born as twins or triplets. Further, males born to CON does had greater 90 d adjusted weaning weights than females, but this was not observed in the CIT group. Female kids born to CON and CIT Boer goats had heavier 90 d adjusted weaning weights than those born to Spanish or F1 Boer-Spanish does. Conclusion: This study provides proof of concept that feeding dietary L-citrulline increases concentrations of citrulline and arginine in blood of gestating meat goats. However, further studies are needed to understand the cellular mechanisms impacted by feeding this supplement. Regardless, this study demonstrated that feeding L-citrulline has the potential to increase reproductive performance in gestating ruminants. [ABSTRACT FROM AUTHOR]

Citrulline is a natural antioxidant and an amino acid found in watermelon, which is eaten for its fruit flesh. In this study, citrulline content was determined in different parts of the fruit flesh and rind of four watermelon lines with varying skin colors. The fruits were divided into six parts, and samples were taken from the rind and fruit pulp for the citrulline in each part. The highest value of citrulline was obtained for the genotype with a very light green ground skin color (3.37 g kg-1), while the lowest value was obtained from the genotype with a very dark green ground skin color (2.0 g kg-1). Regarding the fruit parts, the highest value was in the third part (3.72 g kg-1), while the lowest value belonged to the second part (2.00 g kg-1). Higher citrulline values were found in the fruit flesh (3.10 g kg-1) than in the fruit rind (2.40 g kg-1). [ABSTRACT FROM AUTHOR]

Severe intestinal mucositis (IM) increases the risk of bloodstream infections (BSI) and inflammatory toxicity during acute lymphoblastic leukaemia (ALL) induction treatment. However, the implications of IM in subsequent ALL therapy phases after achieving remission remain unknown. This study investigated the relationship between IM (measured by plasma citrulline and the chemokine CCL20) and the development of BSI and systemic inflammation (reflected by C‐reactive protein, CRP) in children with ALL during high‐dose methotrexate (HDMTX) treatment, an important part of ALL consolidation therapy. The study compared patients treated according to the NOPHO ALL 2008 protocol (n = 52) and the ALLTogether1 protocol (n = 42), both with identical HDMTX procedures but different scheduling. One week post‐HDMTX, citrulline dropped to median levels of 14.5 and 16.9 μM for patients treated according to the NOPHO ALL 2008 and ALLTogether1 protocols, respectively (p = 0.11). In a protocol and neutrophil count‐adjusted analysis, hypocitrullinaemia (<10 μmol/L) was associated with increased odds of BSI within 3 weeks from HDMTX (OR = 26.2, p = 0.0074). Patients treated according to the NOPHO ALL 2008 protocol exhibited increased mucosal‐ and systemic inflammation post‐HDMTX compared to patients treated according to ALLTogether1, with increased CCL20 (14.6 vs. 3.7 pg/mL, p < 0.0001) and CRP levels (10.0 vs. 1.0 mg/L, p < 0.0001). Both citrulline and CCL20 correlated with CRP for these patients (rs = −0.44, p = 0.0016 and rs = 0.35, p = 0.016, respectively). These results suggest that hypocitrullinaemia following HDMTX increases the risk of BSI, confirming previous observations from more intensive treatments. Moreover, these data indicate that the patients' vulnerability to mucositis and inflammatory toxicity after chemotherapy varies with treatment protocol. [ABSTRACT FROM AUTHOR]

Background/Objectives: Citrulline, an amino acid produced by small bowel enterocytes, has been proposed as a potential marker of intestinal absorptive capacity. The aim of this study is to evaluate whether measuring citrulline levels could be useful for celiac disease (CD) patients, both at the time of diagnosis and during follow-up. Methods: A multicenter prospective study was conducted. Citrulline levels were measured and compared in 93 pediatric patients classified into three groups. Group A: 28 patients with newly diagnosed CD. In this group, an additional measurement was performed after 3–6 months on a gluten-free diet (GFD). Group B: 32 patients with a prior CD diagnosis and on a GFD for at least 6 months. Group C: 33 healthy controls. Citrulline levels were correlated with clinical and laboratory variables, including serological markers. Statistical analysis: t-tests for paired groups and independent groups, Pearson and Spearman correlation tests. Results: Newly diagnosed CD patients had lower citrulline levels compared to those on a GFD for more than 6 months (27.13 vs. 32.42 µmol/L; p > 0.05). Citrulline levels were nearly identical between healthy controls and CD patients on a GFD for more than 6 months (32.48 vs. 32.42 µmol/L; p > 0.05). Starting a GFD led to a significant increase in citrulline levels in group A (from 27.13 to 37.43 µmol/L, p < 0.001). Conclusions: Plasma citrulline could serve as a valuable marker for mucosal recovery in the follow-up of diagnosed celiac patients adhering to a GFD. [ABSTRACT FROM AUTHOR]

In the present study, nutraceutical citrulline was produced using immobilization of permeabilized whole cells of Pseudomonas furukawaii , an efficient producer of ADI. Since arginine deiminase (ADI) is intracellularly localized, various additives such as SDS (Sodium dodecyl sulfate), Triton X-100, and EDTA (Ethylenediaminetetraacetic Acid) were used to permeabilize the cell to improve substrate accessibility and ADI activity. The maximum ADI activity was observed with 0.25 mg ml−1 biomass concentration treated with 0.5 mmol l−1 EDTA for 15 min using OFAT (One factor at a time) approach. Optimization of permeabilization conditions of P. furukawaii cells using novel neural networks and particle swarm optimization led to maximum ADI activity with 0.10 mmol l−1 EDTA and 0.30 mg ml−1 biomass. Further, the morphological characterization of immobilized cells was assessed by field emission scanning electron microscopy and FTIR (Fourier transform infrared spectroscopy). An optimal citrulline production of 1.19 mmol l−1 was achieved at 2.5% sodium alginate with 20 mmol l−1 arginine at 38°C, and 180 min of incubation. The immobilized cells retained 90.3% productivity after seven reuse cycles. Thus, the formulated immobilized whole-cell biocatalyst, with higher stability offers cost-effective methods of citrulline production. [ABSTRACT FROM AUTHOR]

Background/Objectives: The prevalence of cardiovascular-kidney-metabolic (CKM) syndrome is increasing rapidly, and cardiovascular complications pose significant risks in individuals with kidney disease and metabolic dysfunction. Understanding the mechanisms of CKM disorders is crucial, as is the discovery of novel preventive treatments. This study aimed to examine the therapeutic effects of a specially formulated nitric oxide-enhancing food additive in a mouse model of CKM syndrome induced by unilateral nephrectomy (UNX) in combination with chronic Western diet (WD) feeding. Methods: C57BL/6J mice underwent UNX and were fed a WD high in salt, sugar, and fat for 12 weeks, compared to sham-operated mice on standard chow. One group of UNX+WD mice received Flexovital (FLX), a food additive containing extracts of Rhodiola rosea and beetroot, and the amino acids L-arginine and L-citrulline. CKM parameters were assessed both in vivo and ex vivo alongside histological and biochemical analyses. Results: The UNX+WD mice showed an increase in body fat mass, the fat/lean mass ratio, and adipocyte area, of which most were significantly reduced by FLX. Elevated fasting glucose levels were also reduced by FLX, which tended towards improving glucose clearance. Elevated arterial blood pressure and endothelial dysfunction in UNX+WD mice were significantly reduced by FLX. FLX improved GFR and reduced glomerular and tubular injuries in UNX+WD mice. Additionally, FLX increased the P/O ratios of oxidative phosphorylation in the isolated renal mitochondria of UNX+WD mice. Conclusions: In this model of CKM syndrome, FLX effectively prevented the onset and progression of CKM dysfunctions induced by UNX+WD, as well as the associated organ injuries. These promising results highlight the need for validation in upcoming human trials. [ABSTRACT FROM AUTHOR]

Watermelon is a rich natural source of Citrulline, an amino acid with potential antioxidant and vasodilation effects in the human body. An efficient Microwave-assisted aqueous two-phase extraction (MA-ATPE) technique was developed to extract and enrich L-Citrulline from watermelon rind in a one-step procedure. The aqueous two-phase system (ATPS) consisted of the ionic liquid 1-Butyl-3-methylimidazolium bromide [C4mim] [Br], and the salt dipotassium hydrogen phosphate (K2HPO4) was used as the extracting solvent. MA-ATPE conditions, such as the compositions of ATPS, particle size, liquid-solid ratio, irradiation power, and extraction time were investigated. The results indicated that the optimal conditions were as follows: salt concentration 35%, ionic liquid concentration 1.6 M, particle sizes 60 mesh, irradiation power 300 W, and extraction time 10 min. Under the optimized conditions, the extraction yields of L-Citrulline reached 87.74%. According to the DPPH results, at a concentration of 2 mg/mL, the DPPH radical-scavenging activity of the MA-ATPE extract from watermelon rind (0.388 mg/ml) was greater than that of the MAE (Microwave-assisted extraction) extract (0.456 mg/ml) and the conventional extract (0.468 mg/ml). DLS and TEM were used together to examine the microstructure of the top phase and explore the potential extraction mechanism. The findings revealed that the aggregation and embrace phenomenon were the primary driving forces for the separation. Compared with the conventional method and regular MAE, MA-ATPE exhibited a higher extraction yield and a shorter extraction time. In conclusion, MA-ATPE is an efficient, rapid, eco-friendly, and economical technique, representing an excellent alternative for the extraction of bioactive compounds. [ABSTRACT FROM AUTHOR]

Vine decline (VD) is a recalcitrant syndrome of watermelon, melon, and other cucurbits, often associated with soil-borne pathogens such as Monosporascus cannonballus and characterized by root necrosis, leaf chlorosis, and wilting at the later stage of fruit maturation. The present study examined VD's effects on watermelon fruits' metabolism. The VD-affected watermelon fruits had significantly lower lycopene and total solid contents. Still, polyphenols content and total antioxidant activities were comparable with the controls, suggesting that VD inhibited the ripening processes but maintained defensive processes in the fruits. The VD fruits showed a lower calcium level than the controls, while the contents of other major nutrition minerals were not significantly altered. The VD fruits had a lower content of total amino acids, and their composition was characterized by an increase in the percentage fractions for several amino acids, including citrulline, which may reflect the physiological response to the VD-related water deficit condition. The principal component analysis distinguished amino acid profiles between the VD and control fruits, demonstrating that VD significantly influenced their amino acid metabolisms. The present study revealed that VD imposed characteristic impacts on the biochemical behaviors in the watermelon fruits. [ABSTRACT FROM AUTHOR]

Human sepsis is characterized by increased protein breakdown and changes in arginine and citrulline metabolism. However, it is unclear whether this is caused by changes in transorgan metabolism. We therefore studied the changes in protein and arginine-related metabolism on the whole body (Wb) and transorgan levels in a Pseudomonas aeruginosa-induced pig sepsis model. We studied 22 conscious pigs for 18 h during sepsis induced by infusing live bacteria (Pseudomonas aeruginosa) or after placebo infusion (Control). We used stable isotope tracers to measure Wb and skeletal muscle protein synthesis and breakdown, as well as Wb, splanchnic, skeletal muscle, hepatic, and portal-drained viscera (PDV) arginine and citrulline disposal and production rates. During sepsis, arginine Wb production (P = 0.0146), skeletal muscle release (P = 0.0035), and liver arginine uptake were elevated (P = 0.0031). Wb de novo arginine synthesis, citrulline production, and transorgan PDV release of citrulline, glutamine, and arginine did not differ between Sepsis and Control pigs. However, Wb (P < 0.0001) and muscle (P < 0.001) protein breakdown were increased, suggesting that the enhanced arginine production is predominantly derived from muscle breakdown in sepsis. In conclusion, live bacterium sepsis increases muscle arginine release and liver uptake, mirroring previous pig endotoxemia studies. In contrast to observations in humans, acute live bacterium sepsis in pigs does not change citrulline production or arterial arginine concentration. We therefore conclude that the arginine dysregulation observed in human sepsis is possibly initiated by enhanced protein catabolism and splanchnic arginine catabolism, whereas decreased arterial arginine concentration and citrulline metabolism may require more time to fully manifest in patients. NEW & NOTEWORTHY: Our work highlights that arginine availability may be largely determined by muscle breakdown and hepatic extraction in early sepsis, while citrulline production appears maintained. Additionally, our work highlights a novel ANCOVA approach for transorgan analysis to control for inherent variation in transorgan data and increase statistical sensitivity. [ABSTRACT FROM AUTHOR]

L‐citrulline (referred to hereafter as citrulline), a non‐essential amino acid and an intermediate in the urea cycle, is widely recognized for its role in managing genetic urea cycle disorders (UCDs). Recent studies, however, suggest that citrulline's therapeutic potential extends beyond UCDs, particularly in conditions associated with nitric oxide (NO) deficiency, endothelial dysfunction, and oxidative stress. This review explores citrulline's emerging applications in sickle cell disease (SCD), post‐operative pulmonary hypertension (PH), hepatic veno‐occlusive disease (HVOD), and bronchopulmonary dysplasia (BPD), as well as its speculative use in asthma and acute respiratory distress syndrome (ARDS). In SCD, citrulline may restore NO bioavailability, potentially reducing the incidence and severity of vaso‐occlusive crises and preventing complications like pulmonary hypertension. In the context of post‐operative PH, citrulline's capacity to enhance NO production can improve pulmonary vascular resistance, decrease right ventricular strain, and reduce the need for mechanical ventilation. Citrulline's protective effects on endothelial function and its ability to mitigate oxidative stress offer promising adjunctive therapy for HVOD, particularly in patients undergoing bone marrow transplantation. In BPD, citrulline could promote alveolar development, reduce inflammation, and improve long‐term respiratory outcomes. Despite these promising findings, further research is necessary to determine optimal dosing strategies and to evaluate long‐term efficacy and safety. The potential role of citrulline in modulating NO production in conditions like asthma and ARDS also warrants further investigation. This review underscores the versatile therapeutic potential of citrulline and highlights the need for continued research into its applications across various conditions associated with NO deficiency and endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Citrin deficiency is an autosomal recessive disorder caused by a defect of citrin resulting from mutations in the SLC25A13 gene. Intrahepatic cholestasis and various metabolic abnormalities, including hypoglycemia, galactosemia, citrullinemia, and hyperammonemia may be present in neonates or infants in the "neonatal intrahepatic cholestasis caused by citrin deficiency" (NICCD) form of the disease. Because at present, newborn screening (NBS) for citrin deficiency using citrulline levels in dried blood spots (DBS) can only detect some of the patients, we tried to develop a new evaluation system to more reliably detect newborns with citrin deficiency utilizing parameters already in place in present NBS methods. To achieve this goal, we re‐analyzed NBS profiles of amino acids and acylcarnitines in 96 NICCD patients, who were diagnosed through selective screening or positive family history. Hereby, we identified the combined evaluation of arginine (Arg), citrulline (Cit), isoleucine+leucine (Ile + Leu), tyrosine (Tyr), free carnitine (C0) / glutarylcarnitine (C5‐DC) ratio in DBS as potentially sensitive to diagnose citrin deficiency in pre‐symptomatic newborns. In particular, a scoring system using threshold levels for Arg (≥9 μmol/L), Cit (≥ 39 μmol/L), Ile + Leu (≥ 99 μmol/L), Tyr (≥ 96 μmol/L) and C0/C5‐DC ratio (≥327) was significantly effective to detect newborns who later developed NICCD, and could thus be implemented in existing NBS programs at no extra analytical costs whenever citrin deficiency is considered to become a novel target disease. [ABSTRACT FROM AUTHOR]

Increasing global life expectancy motivates investigations of molecular mechanisms of aging and age‐related diseases. This study examines age‐associated changes in red blood cells (RBCs), the most numerous host cell in humans. Four cohorts, including healthy individuals and patients with sickle cell disease, were analyzed to define age‐dependent changes in RBC metabolism. Over 15,700 specimens from 13,757 humans were examined, a major expansion over previous studies of RBCs in aging. Multi‐omics approaches identified chronological age‐related alterations in the arginine pathway with increased arginine utilization in RBCs from older individuals. These changes were consistent across healthy and sickle cell disease cohorts and were influenced by genetic variation, sex, and body mass index. Integrating multi‐omics data and metabolite quantitative trait loci (mQTL) in humans and 525 diversity outbred mice functionally linked metabolism of arginine during RBC storage to increased vesiculation—a hallmark of RBC aging—and lower post‐transfusion hemoglobin increments. Thus, arginine metabolism is a biomarker of RBC and organismal aging, suggesting potential new targets for addressing sequelae of aging. [ABSTRACT FROM AUTHOR]

The primary objective of this study was to evaluate the effects of liquid (Fructose-added lactic acid bacteria, F-LAB) and commercial (Commercial LAB, C-LAB) probiotics sourced from Rye-Grass Lactic Acid Bacteria (LAB) on broiler chickens experiencing heat stress (HS). The research involved 240 broiler chicks, divided into six groups: control, F-LAB, C-LAB (raised at 24 °C), HS, F-LAB/HS, and C-LAB/HS (exposed to 5–7 h of 34–36 °C daily). The study followed a randomized complete block design, with each group consisting of 40 chicks. F-LAB and HS/F-LAB groups received a natural probiotic added to their drinking water at a rate of 0.5 ml/L, while C-LAB and HS/C-LAB groups were supplemented with a commercial probiotic at the same dosage. Control and HS groups received no probiotic supplementation. The duration of the study was 42 days, with data collected on growth performance, feed intake, feed conversion ratio, and health parameters. Statistical analyses were performed using ANOVA, and significant differences between groups were determined using post hoc tests. The results revealed that without probiotic supplementation, heat stress led to a decrease in body weight gain, T3 levels, citrulline, and growth hormone levels, along with an increase in the feed conversion ratio, serum corticosterone, HSP70, ALT, AST, and leptin levels (p < 0.05 for all). Heat stress also adversely affected cecal microbiota, reducing lactic acid bacteria count (LABC) while increasing Escherichia coli and coliform bacteria (CBC) counts. However, in the groups receiving probiotic supplementation under heat stress (F-LAB/HS and C-LAB/HS), these effects were alleviated (p < 0.05 for all). Particularly noteworthy was the observation that broiler chickens supplemented with natural lactic acid bacteria (F-LAB) exhibited greater resilience to heat stress compared to those receiving the commercial probiotic, as evidenced by improvements in growth, liver function, hormonal balance, intestinal health, and cecal microbiome ecology (p < 0.05). These findings suggest that the supplementation of naturally sourced probiotics (F-LAB) may positively impact the intestinal health of broiler chickens exposed to heat stress, potentially supporting growth and health parameters. [ABSTRACT FROM AUTHOR]

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Introduction: L-citrulline, a non-proteinogenic amino acid, is predominantly synthesized in the enterocytes of the small intestine, with smaller amounts produced in the kidneys, which plays a critical role in the detoxification of ammonia in the urea cycle, and serves as a precursor for nitric oxide (NO). Recent studies have highlighted citrulline's potential benefits in diverse physiological and pathological contexts, ranging from enhancing physical performance and muscle recovery to supporting cardiovascular health, mitigating endothelial dysfunction, and acting as a therapeutic agent in various health conditions. Aim of study: The study aims to provide a comprehensive summary of current knowledge on the biochemical characteristics, physiological functions, and therapeutic potential of citrulline. Materials and methods: A comprehensive scientific literature review was conducted using the PubMed database, focusing on studies published up to 2024, reporting experimental, clinical, or in vivo data related to citrulline's synthesis, biological functions, and therapeutic applications. Conclusion: Emerging evidence highlights citrulline's potential in treating various health conditions, such as erectile dysfunction, neurodegenerative diseases, and intestinal barrier dysfunction, as well as its protective effects in hepatic failure, wound healing, and oxidative stress-related damage. These findings suggest that citrulline may serve as a multifaceted therapeutic agent, meriting further research to optimize its clinical use.

Citrulline, a non-essential amino acid and precursor to L-arginine, plays a pivotal role in nitric oxide (NO) synthesis, with profound implications for vascular health and neuroprotection. By enhancing NO production, citrulline supports endothelial function, vasodilation, and cerebral circulation, thereby mitigating cognitive decline associated with aging and neurodegenerative diseases. Unlike direct arginine supplementation, citrulline offers superior bioavailability, bypassing first-pass metabolism and achieving sustained plasma levels of arginine. Furthermore, citrulline's antioxidant properties counteract oxidative stress by modulating reactive oxygen species (ROS), reducing lipid peroxidation, and protecting neuronal integrity. Emerging evidence suggests its potential in delaying endothelial senescence and preventing ferroptosis, establishing its role in vascular and neuroprotective strategies. Dietary sources, such as watermelon juice, further enhance citrulline’s accessibility, combining its bioactivity with additional antioxidants like lycopene. While existing studies underscore its promise, targeted research is needed to confirm its direct impact on cognitive function and explore its application in neurodegenerative populations. This review synthesizes current knowledge on citrulline's mechanisms, therapeutic potential, and broader implications for aging and vascular health.

This article presents a study on the use of urinary guanidino compounds (GCs) and ureido compounds (UCs) as biomarkers for cardiac surgery-associated acute kidney injury (CSA-AKI). The study utilized a benzylic rearrangement reaction and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to analyze the concentrations of GCs/UCs in urine samples from patients with CSA-AKI at different stages. The findings suggest that certain GC/UC metabolites show significant changes in concentration during CSA-AKI and could potentially serve as biomarkers for different stages of AKI. This research provides valuable resources and new therapeutic targets for further study on CSA-AKI. [Extracted from the article]

Using a new red blood cell (RBC) metabolite extraction protocol, we performed a metabolomic analysis on RBCs in rheumatoid arthritis (RA) patients treated or not with methotrexate (MTX), with the two following objectives: to compare the RBC metabolic profiles of MTX-naïve RA patients and healthy controls (HC), and to investigate whether RBC profiles before and after MTX treatment in RA differed between responders and non-responders. Plasma analysis was performed in parallel. Metabolites were extracted and identified in RBCs and plasma by liquid chromatography-mass spectrometry. We compared the metabolomic fingerprints of 31 DMARD-naïve RA patients and 39 HCs. We also compared the RBC and plasma metabolomes of 25 RA patients who responded or not to MTX therapy before (M0) and after a 3-month treatment period (M3). Significance was determined by Storey's false discovery rate (FDR) q-values to correct for multiple testing. RA patients and HCs differed in the metabolomic signature of RBCs. The signature mainly contained amino acids (AA). Eleven metabolites, including 4 metabolites belonging to the carbohydrate subclass and 2 amino acids (creatine and valine) showed accumulation in RBCs from RA patients. Conversely, citrulline (fold change = 0.83; q = 0.025), histidine (fold change = 0.86; q = 0.014) and ergothioneine (EGT) (fold change = 0.66; q = 0.024), were lower in RBC of RA patients. Five plasma metabolites, including succinic acid and hydroxyproline, were higher in RA patients, and 7 metabolites, including DHEA sulfate, alanine, threonine and ornithine, were lower. Among RA patients undergoing MTX treatment pre-treatment (M0), EGT values were significantly lower in non-responders. In conclusion, low RBC levels of EGT, a food-derived AA barely detectable in plasma, characterize DMARD naïve RA patients and lack of response to MTX treatment. [ABSTRACT FROM AUTHOR]

The treatment of childhood cancer is challenged by toxic side effects mainly due to chemotherapy-induced organ damage and infections, which are accompanied by severe systemic inflammation. Insulin-like growth factor I (IGF-I) is a key regulating factor in tissue repair. This study investigated associations between the circulating IGF-I levels and chemotherapy-related toxicity in pediatric acute lymphoblastic leukemia (ALL). In this prospective study, we included 114 patients (age: 1–17 years) with newly diagnosed ALL treated according to The Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol between 2013 and 2018. The patients' plasma levels of IGF-I, and the primary binding protein, IGFBP-3, were measured weekly during the first six weeks of treatment, including the induction therapy. The patients' systemic inflammation was monitored by their C-reactive protein (CRP) and interleukin (IL)-6 levels and their intestinal epithelial damage by their plasma citrulline levels. IGF-I and IGFBP-3 were converted into sex-and age-adjusted standard deviation scores (SDS) using 1621 healthy children as reference. At ALL diagnosis, IGF-I levels were decreased (median (quartiles): −1.2 SDS (−1.9 to −0.5), p = 0.001), but increased significantly following the initiation of chemotherapy, peaking on day 8 (0.0 SDS (from −0.8 to 0.7), p < 0.001). This increase correlated with the levels of CRP (rho = 0.37, p < 0.001) and IL-6 (rho = 0.39, p = 0.03) on day 15, when these markers reached maximum levels. A larger IGF-I increase from day 1 to 15 correlated with a slower recovery rate of the intestinal damage marker citrulline from day 15 to 29 (rho = −0.28, p = 0.01). Likewise, IGFBP-3 was reduced at diagnosis, followed by an increase after treatment initiation, and was highly correlated with same-day IGF-I levels. This study demonstrates a chemotherapy-induced increase in IGF-I, with a response that appears to reflect the severity of tissue damage and systemic inflammation, preceding CRP and IL-6 increases. IGF-I may have potential as an early reactive biomarker for acute toxicity in patients with ALL. [ABSTRACT FROM AUTHOR]

Background/Objectives: Free amino acids substantially contribute to energy metabolism. Also, their profile may identify (over)training status and effectiveness. The long-term effects of speed-power training on plasma free amino acid (PFAA) profiles are not known. We aimed to observe variations in PFAA levels in high-performance sprinters in a six-month training cycle. Methods: Ten male athletes (24.6 ± 3.3 years) were examined during four training phases: transition (1 month), general preparation (2 months), specific preparation (1 month), and pre-competition/competition (2 months). Venous blood was collected at rest, after exhaustive exercise, and recovery. Forty-two PFAAs were analyzed by the LC-ESI-MS/MS method. Results: Significant decreases in resting concentrations were observed between the transition and competition phases for glutamine (762 ± 117 vs. 623 ± 53 μmol∙L−1; p < 0.001, η2 = 0.47) and histidine (89 ± 15 vs. 75 ± 10 μmol∙L−1; p = 0.010, η2 = 0.27), whereas β-alanine (30 ± 7 vs. 41 ± 9 μmol∙L−1; p = 0.024, η2 = 016) and sarcosine (3.6 ± 0.4 vs. 4.8 ± 0.6 μmol∙L−1; p = 0.006, η2 = 0.188) levels increased. Between the specific and competition phases, significant decreases in the resting levels of 1-methylhistidine (22.1 ± 19.4 vs. 9.6 ± 8.8 μmol∙L−1; p = 0.14, η2 = 0.19), 3-methylhistidine (7.1 ± 1.5 vs. 6.5 ± 1.6 μmol∙L−1; p = 0.009, η2 = 0.18), citrulline (40 ± 10 vs. 29 ± 4 μmol∙L−1; p = 0.05, η2 = 0.29), and ornithine (74 ± 15 vs. 56 ± 10 μmol∙L−1; p = 0.015, η2 = 185) were noticed. Also, for β-alanine and sarcosine, the pattern of response to exercise strongly changed between the training phases. Blood ammonia levels at exhaustion decreased between the transition and competition phases (32 ± 4 vs. 23 ± 5 μmol∙L−1; p < 0.001, η2 = 0.67), while lactate, the phenylalanine–tyrosine ratio, the glutamine–glutamate ratio, hematological parameters, and cardiorespiratory indices remained at similar levels. Conclusions: Speed-power training seems to affect PFAAs involved in skeletal muscle metabolic pathways responsible for neutralizing toxic ammonia (glutamine, arginine, citrulline, ornithine), attenuating the deleterious effects of H+ ions (histidine, β-alanine), and reducing exercise-induced protein breakdown (1- and 3-methylhistidine). Our findings suggest that sprint-oriented training supports metabolic pathways that are responsible for the removal of harmful metabolites produced during exercise. [ABSTRACT FROM AUTHOR]

The influence of molasses (M) and Lactobacillus rhamnosus (LR) on fermentation products, microbial communities, and metabolites in big-bale alfalfa silage was investigated. Alfalfa (Medicago sativa L.) was harvested at the third growth stage during the flowering stage in the experimental field of Linhui Grass Company from Tongliao City, Inner Mongolia. An alfalfa sample without additives was used as a control (C). M (20 g/kg) and LR (106 cfu/g) were added either alone or in combination. Alfalfa was fermented for 7, 14, and 56 d. Lactic acid content in the M, LR, and MLR groups increased, whereas the pH value and butyric acid, 2,3-butanediol, and ethanol contents decreased compared to those of C group after 7, 14, and 56 d of fermentation. A two-way analysis of variance (ANOVA) was performed to estimate the results. The LR group exhibited increased Lactobacillus abundance, whereas the M and MLR groups showed increased Weissella abundance compared to the C group. The relative contents of amino acids (tyrosine, isoleucine, threonine, arginine, valine, and citrulline) in the M and MLR groups were higher than those in the C group. During fermentation, the M, LR, and MLR groups showed decreased phenylalanine, isoleucine, and ferulic acid contents. Amino acids such as isoleucine and L-aspartic acid were positively correlated with Lactobacillus but negatively correlated with Weissella. In conclusion, combining high-throughput sequencing and liquid chromatography–mass spectrometry during anaerobic alfalfa fermentation can reveal new microbial community compositions and metabolite profiles, supporting the application of M, LR, and MLR as feed fermentation agents. [ABSTRACT FROM AUTHOR]

Lung cancer (LC) is one of the major malignant diseases threatening human health. The study aimed to identify the effect of citrulline on the malignant phenotype of LC cells and to further disclose the potential molecular mechanism of citrulline in regulating the development of LC, providing a novel molecular biological basis for the clinical treatment of LC. The effects of citrulline on the viability, proliferation, migration, and invasion of LC cells (A549, H1299) were validated by CCK‐8, colony formation, EdU, and transwell assays. The cell glycolysis was assessed via determining the glucose uptake, lactate production, ATP levels, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR). RNA‐seq and molecular docking were performed to screen for citrulline‐binding target proteins. Western blotting experiments were conducted to examine the expression of related signaling pathway molecules. In addition, the impacts of citrulline on LC growth in vivo were investigated by constructing mouse models. Citrulline augmented the viability of LC cells in a concentration and time‐dependent manner. The proliferation, migration, invasion, glycolysis, and EMT processes of LC cells were substantially enhanced after citrulline treatment. Bioinformatics analysis indicated that citrulline could bind to RAB3C protein. Western blotting results indicated that citrulline activated the IL‐6/STAT3 pathway by binding to RAB3C. In addition, animal experiments disclosed that citrulline promoted tumor growth in mice. Citrulline accelerated the glycolysis and activated the IL6/STAT3 pathway through the RAB3C protein, consequently facilitating the development of LC. [ABSTRACT FROM AUTHOR]

Endurance athletes often aim to improve their aerobic metabolism. The aim of this pilot study was to examine if malic acid and L-citrulline supplementation can improve aerobic metabolism and lactate elimination. Nine young (23.9 ± 1.9 years) recreational male athletes participated in this study. Following a standardised breakfast and a body composition analysis (InBody720), 6000 mg of citrulline and 3000 mg of malic acid or a placebo of 300 mL of water were consumed on three separate days in a cross-over design using a double-blind method. Sixty minutes after the supplementation, participants completed a ramp bicycle spiroergometer protocol (35 W/3 min) until reaching a respiratory exchange ratio (RER) of 1.1, followed by a 9 min active recovery. Cadence, heart rate (HR), rate of perceived exertion (RPE), respiratory parameters and lactate levels were registered. The RPExHR value was calculated to accurately characterise exhaustion. During the exercise protocol, citrulline supplementation induced significantly lower RER values at 70-105-140 W compared to malic acid and the placebo, respectively. There was no difference in lactate levels neither during rest nor at RER 1.1. RPExHR rate values were significantly lower after malic acid supplementation compared to placebo at 175 and 210 W. Power at RER 1.1 was higher after malic acid (+4 W) and citrulline (+5 W) supplementation. Although the supplementation failed to decrease lactate levels, lower RER and RPE values may indicate a performance-enhancing benefit. [ABSTRACT FROM AUTHOR]

Background: Arginine is a conditionally essential amino acid that is depleted in critically ill or surgical patients. In pediatric and adult patients, sepsis results in an arginine-deficient state, and the depletion of plasma arginine is associated with greater mortality. However, direct supplementation of arginine can result in the excessive production of nitric oxide (NO), which can contribute to the hypotension and macrovascular hypo-reactivity observed in septic shock. Pegylated arginine deiminase (ADI-PEG20, pegargiminase) reduces plasma arginine and generates citrulline that can be transported intracellularly to generate local arginine and NO, without resulting in hypotension, while maintaining microvascular patency. The objective of this study was to assess the efficacy of ADI-PEG20 with and without supplemental intravenous citrulline in mitigating hypovolemic shock, maintaining tissue levels of arginine, and reducing systemic inflammation in an endotoxemic pediatric pig model. Methods: Twenty 3-week-old crossbred piglets were implanted with jugular and carotid catheters as well as telemetry devices in the femoral artery to measure blood pressure, body temperature, heart rate, and respiration rate. The piglets were assigned to one of three treatments before undergoing a 5 h lipopolysaccharide (LPS) infusion protocol. Twenty-four hours before LPS infusion, control pigs (LPS; n=6) received saline, ADI-PEG20 pigs (n=7) received an injection of ADI-PEG20, and seven pigs (ADI-PEG20 + CIT pigs [n=7]) received ADI-PEG20 and 250 mg/kg citrulline intravenously. Pigs were monitored throughout LPS infusion and tissue was harvested at the end of the protocol. Results: Plasma arginine levels decreased and remained low in ADI-PEG20 + CIT and ADI-PEG20 pigs compared with LPS pigs but tissue arginine levels in the liver and kidney were similar across all treatments. Mean arterial pressure in all groups decreased from 90 mmHg to 60 mmHg within 1 h of LPS infusion but there were no significant differences between treatment groups. ADI-PEG20 and ADIPEG20 + CIT pigs had less CD45+ infiltrate in the liver and lung and lower levels of pro-inflammatory cytokines in the plasma. Conclusion: ADI-PEG20 and citrulline supplementation failed to ameliorate the hypotension associated with acute endotoxic sepsis in pigs but reduced systemic and local inflammation in the lung and liver. [ABSTRACT FROM AUTHOR]

Simple Summary: L-citrulline, as a non-essential amino acid, is recognized for its effectiveness in enhancing arginine bioavailability and nitric oxide (NO) synthesis, drawing significant attention from the scientific community for its potential to improve athletic performance. This study investigated the effects of L-citrulline supplementation on the racing performance of Yili horses as well as on the blood acid–base balance, physiological and biochemical blood indices, and antioxidant markers before and after an exercise. Additionally, changes in the plasma amino acid metabolism and polyamine levels were examined. The results indicate that the supplementation of 50 g of L-citrulline to the horses' diet significantly increased the plasma concentrations of citrulline and arginine and provided a certain improvement in the athletic performance of the Yili horses. Additionally, compared to a control group, the total protein and lactate dehydrogenase levels were significantly elevated 2 h before and 2 h after the race, while the lactate concentration immediately post-race was significantly reduced. The objective of this study was to evaluate the effects of pre-exercise L-citrulline supplementation on the athletic performance of Yili speed-racing horses during a high-intensity exercise. On the 20th day of the experiment, blood samples were collected at 3 h and 6 h post-supplementation to measure the amino acid and polyamine concentrations. On the 38th day of the experiment, the horses participated in a 2000 m speed race, and three distinct blood samples were gathered for assessing blood gases, hematological parameters, the plasma biochemistry, antioxidant parameters, and NO concentrations. The results indicate that the L-citrulline group showed a significant increase in the plasma citrulline and arginine concentrations. Conversely, the concentrations of alanine, serine, and threonine were significantly decreased. The glycine concentration decreased significantly, while there was a trend towards an increase in the glutamine concentration. Additionally, the levels of putrescine and spermidine in the plasma of the L-citrulline group were significantly increased. In terms of exercise performance, L-citrulline can improve the exercise performance of sport horses, significantly reduce the immediate post-race lactate levels in Yili horses, and accelerate the recovery of blood gas levels after an exercise. Furthermore, in the L-citrulline group of Yili horses, The levels of the total protein of plasma, superoxide dismutase, catalase, and lactate dehydrogenase were significantly increased both 2 h before and 2 h after the race. The total antioxidant capacity showed a highly significant increase, while the malondialdehyde content significantly decreased. In the immediate post-race period, the creatinine content in the L-citrulline group significantly increased. In conclusion, this study demonstrates that L-citrulline supplementation can influence the circulating concentrations of L-citrulline and arginine in Yili horses, enhance the antioxidant capacity, reduce lactate levels, and improve physiological and biochemical blood parameters, thereby having a beneficial effect on the exercise performance of athletic horses. [ABSTRACT FROM AUTHOR]

Pseudomonas fragi (P. fragi) is usually detected in low-temperature meat products, and seriously threatens food safety and human health. Therefore, the study investigated the antibacterial mechanism of linalool against P. fragi from membrane damage and metabolic disruption. Results from field-emission transmission electron microscopy (FETEM) and atomic force microscopy (AFM) showed that linalool damage membrane integrity increases surface shrinkage and roughness. According to Fourier transform infrared (FTIR) spectra results, the components in the membrane underwent significant changes, including nucleic acid leakage, carbohydrate production, protein denaturation and modification, and fatty acid content reduction. The data obtained from amino acid metabolomics indicated that linalool caused excessive synthesis and metabolism of specific amino acids, particularly tryptophan metabolism and arginine biosynthesis. The reduced activities of glucose 6-phosphate dehydrogenase (G6PDH), malate dehydrogenase (MDH), and phosphofructokinase (PFK) suggested that linalool impair the respiratory chain and energy metabolism. Meanwhile, genes encoding the above enzymes were differentially expressed, with pfkB overexpression and zwf and mqo downregulation. Furthermore, molecular docking revealed that linalool can interact with the amino acid residues of G6DPH, MDH and PFK through hydrogen bonds. Therefore, it is hypothesized that the mechanism of linalool against P. fragi may involve cell membrane damage (structure and morphology), disturbance of energy metabolism (TCA cycle, EMP and HMP pathway) and amino acid metabolism (cysteine, glutamic acid and citrulline). These findings contribute to the development of linalool as a promising antibacterial agent in response to the food security challenge. [ABSTRACT FROM AUTHOR]

This study investigated the correlation between oxidative stress and blood amino acids associated with nitric oxide metabolism in adult patients with coronavirus disease (COVID-19) pneumonia. Clinical data and serum samples were prospectively collected from 100 adult patients hospitalized for COVID-19 between July 2020 and August 2021. Patients with COVID-19 were categorized into three groups for analysis based on lung infiltrates, oxygen inhalation upon admission, and the initiation of oxygen therapy after admission. Blood data, oxidative stress-related biomarkers, and serum amino acid levels upon admission were compared in these groups. Patients with lung infiltrations requiring oxygen therapy upon admission or starting oxygen post-admission exhibited higher serum levels of hydroperoxides and lower levels of citrulline compared to the control group. No remarkable differences were observed in nitrite/nitrate, asymmetric dimethylarginine, and arginine levels. Serum citrulline levels correlated significantly with serum lactate dehydrogenase and C-reactive protein levels. A significant negative correlation was found between serum levels of citrulline and hydroperoxides. Levels of hydroperoxides decreased, and citrulline levels increased during the recovery period compared to admission. Patients with COVID-19 with extensive pneumonia or poor oxygenation showed increased oxidative stress and reduced citrulline levels in the blood compared to those with fewer pulmonary complications. These findings suggest that combined oxidative stress and abnormal citrulline metabolism may play a role in the pathogenesis of COVID-19 pneumonia. [ABSTRACT FROM AUTHOR]

This research is to determine the effect of citrulline malate supplement applied in addition to fitness training on the hormonal metabolism of athletes. 30 male athletes (15 Control group, 15 Experimental group) who are in the fitness branch and regularly participate in the research group voluntarily participated. A four-week, ninety-minute fitness training program three days a week was applied to the research group. Blood samples were taken from the athletes in the research group twice, before the start of the training program and at the end of the training. ACTH, Cortisol and Total Testosterone levels were determined in the blood samples taken. SPSS package program was used in the analysis of the data. Significance was accepted as p<0.05. According to the research results; It was determined that there was a statistically significant difference between the pretestposttest values of the experimental group's ACTH, cortisol and total testosterone levels (p<0.05), while it was determined that there was a statistically significant difference between the pretest-posttest values of the control group's total testosterone levels (p<0.05), there was no statistically significant difference between the pretest-posttest values of ACTH and cortisol levels (p>0.05). According to the comparisons between the groups; It was seen that there was a significant difference between the cortisol and total testosterone levels post-test values of the control and experimental groups (p<0.05), there was no significant difference between the pre-test values of ACTH pre-post-test, cortisol and total testosterone levels (p>0.05). In conclusion; It has been observed that the citrulline malate supplement group applied in addition to the fitness training has a significant effect on the hormone metabolism and provides a greater increase compared to the group in which the fitness training is applied. In this context, we believe that the supplements to be applied in addition to routine training will contribute positively to the performance of the athletes. [ABSTRACT FROM AUTHOR]

Background: Testicular torsion is a critical urological emergency that can lead to testicular ischemia and significant tissue damage. Citrulline, a supplement known for enhancing cellular metabolism and mitigating oxidative stress and inflammation, has been explored for its protective effects against testicular injury resulting from torsion and detorsion in rat models. Methods: This study involved 42 Wistar rats, divided into six groups: Sham, torsion/detorsion (T/D), and four groups receiving varying doses of Citrulline (300, 600, 900 mg/kg) and vitamin E (20 mg/kg). A surgical procedure was performed to induce torsion by rotating the left testicle for 4 hr, followed by reperfusion. Daily oral administration of the supplements continued for one week post-surgery. Assessments included oxidative stress markers, apoptosis, inflammation, pathology, and sperm parameters. Statistical analysis was conducted using GraphPad Prism. Results: Citrulline administration at doses of 600 and 900 mg/kg significantly reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels. Additionally, it increased glutathione (GSH) levels and decreased protein carbonyl levels at the 900 mg/kg dose. The expression of interleukin-6 (IL-6) decreased at 900 mg/ kg, tumor necrosis factor-alpha (TNF-α) levels dropped at 600 and 900 mg/kg, and the pro-apoptotic factor Bax was reduced at all doses. Sperm analysis showed improved sperm count and motility at the 900 mg/kg dose. Histological examination revealed significant positive effects of Citrulline on testicular tissue. Conclusion: Citrulline effectively lowers oxidative stress, inflammation, while enhancing sperm quality and pathological outcomes. These results indicate that Citrulline has potential as a therapeutic agent for testicular torsion. [ABSTRACT FROM AUTHOR]

Canine parvovirus (CPV) poses a significant threat to dogs globally, leading to both illness and death. Examining biomarkers may enhance early detection of the disease, gauge hospital stay duration, increase disease severity, and estimate patient prognosis. The purpose of this study was to examine the influence of diagnostic (hematological and biochemical) and prognostic biomarkers (Citrulline, serum amyloid A (SAA), thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD), interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), and interferon (IFN)) in CPV infection. Blood samples were collected from CPV-positive dogs (Experimental Group, n=20) and healthy dogs (Control Group, n=20) included in the study. Consequently of laboratory analyses, it was observed that citrulline, TNF-α, and SOD levels were significantly increased in CPV-positive animals compared to healthy animals, while IL-6 and SAA levels decreased. Also, leukocyte (WBC), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), thrombocyte (THR), pH, chloride (Cl), lactate (Lac), glucose, sO2, and HCO3 levels were lower in CPV-positive dogs compared to the healthy ones (P<0.05). As a result, it was interpreted that the inflammatory and oxidative response changes can be measured with the investigated parameters and thus the animals can be in the recovery period despite the clinical symptoms. It was concluded that the measured biomarkers can provide important information in terms of the prognosis of CPV infection when measuring in different periods of the disease or in experimental infection model studies. [ABSTRACT FROM AUTHOR]

Patients with phenylketonuria (PKU) must restrict their intake of phenylalanine, which can also affect the levels of other essential and non-essential amino acids due to inadequate supply. Therefore, our objective was to assess amino acids in serum samples from 20 PKU patients and compare them with results from 51 healthy subjects. A sample analysis was conducted using liquid chromatography–tandem mass spectrometry. We obtained levels of 28 substances, including amino acids, biogenic amines, carnitine, and acetylcarnitine. Kynurenine (p = 0.000001), tyrosine (p = 0.0002), asparagine (p = 0.001), proline (p = 0.012), and the kynurenine/tryptophan ratio (p < 0.000001) were identified as features that differed between the studied groups, being significantly lower in patients with PKU. Glycine (p = 0.000012), putrescine (p = 0.0055), asymmetric dimethylarginine (p = 0.01), creatinine (p = 0.035) levels, as well as the total level of glucogenic amino acids (p = 0.0018), and the ratios of putrescine/ornithine (p = 0.003) and citrulline/ornithine (p = 0.0043) were significantly higher in the PKU group. In conclusion, the amino acid profiles in patients with PKU differ significantly from those in healthy peers, with potential clinical implications. These findings confirm the importance of metabolic testing in clinical practice and highlight the necessity for adequate dietary monitoring and adjustment. [ABSTRACT FROM AUTHOR]

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This article provides information on superficial necrolytic dermatitis (SND), a dermatologic condition that affects humans, dogs, and rarely cats. SND is often associated with metabolic disturbances and can be caused by glucagon-secreting tumors or hepatopathy. It is characterized by cutaneous lesions and is most commonly found in older, smaller-breed dogs. Diagnostic findings include increased alkaline phosphatase and alanine aminotransferase levels, as well as hypoaminoacidemia. The article discusses the cause, diagnosis, and treatment options for SND, emphasizing the importance of early recognition and treatment to improve survival times. The optimal treatment involves a combination of intravenous amino acid infusions, enteral supplements, and high-protein home-cooked diets. [Extracted from the article]