Tyrosine Levels Research Articles

Identification of region-specific amino acid signatures for doxorubicin-induced chemo brain.

Doxorubicin (DOX) is a cornerstone of chemotherapy for solid tumors and leukemias. DOX-induced cognitive impairment, termed chemo brain, has been reported in cancer survivors, whereas its mechanism remains poorly understood. Here we initially evaluated the cognitive impairments of mice treated with clinically relevant, long-term, low-dosage of DOX. Using HILIC-MS/MS-based targeted metabolomics, we presented the changes of 21 amino acids across six anatomical brain regions of mice with DOX-induced chemo brain. By mapping the altered amino acids to the human metabolic network, we constructed an amino acid-based network module for each brain region. We identified phenylalanine, tyrosine, methionine, and γ-aminobutyric acid as putative signatures of three regions (hippocampus, prefrontal cortex, and neocortex) highly associated with cognition. Relying on the reported mouse brain metabolome atlas, we found that DOX might perturb the amino acid homeostasis in multiple brain regions, similar to the changes in the aging brain. Correlation analysis suggested the possible indirect neurotoxicity of DOX that altered the brain levels of phenylalanine, tyrosine, and methionine by causing metabolic disorders in the liver and kidney. In summary, we revealed the region-specific amino acid signatures as actionable targets for DOX-induced chemo brain, which might provide safer treatment and improve the quality of life among cancer survivors.

A Compound Heterozygous HPD Mutation in an Iranian Patient with Hypertyrosinemia Type III

Background and Aims: Hypertyrosinemia type 3 (HT3) is an inherited error in tyrosine metabolism caused by a mutation in the 4-hydroxyphenylpyruvate dioxygenase (HPD) gene. Here we report a one and half-year-old girl infant who was diagnosed based on increased serum tyrosine levels and increased urinary excretion of p-hydroxyphenyl derivatives.
 Materials and Methods: The proband was one and half-year-old Iranian girl who was diagnosed based on increased serum tyrosine levels and increased urinary excretion of p-hydroxyphenyl derivatives. In this study, we used Whole-Exome Sequencing to identify the genetic reason for the disease and the funded mutation confirmed by Sanger sequencing.
 Results and Conclusion: Through whole-exome sequencing screening of heterozygotes c.413C>T (p.T138M) and c.75G.A (p.W25Ter) in the HPD gene and genetically confirmed by Sanger sequencing. There were heterozygous conditions c.413C>T (p.T138M) and c.75G.A (p.W25Ter) in father and mother respectively. This mutation in her parents was also confirmed by Sanger sequencing.

Pharmacokinetics of some newly synthesized 1, 5- benzothiazepine scaffolds: A molecular docking and molecular dynamics simulation approach

A highly efficient in silico pharmacokinetics was studied for some newly synthesized 1, 5- benzothiazepine derivatives. A total of fourteen title moieties were prepared by the condensation of substituted chalcones and 2- aminothiophenol that led to ring expansion in the presence of CuO nanocatalytic framework. The reported synthetic route is advantageous due to shorter reaction time and enhanced yield. The drug-target binding analysis revealed the potential therapeutic targets against 1,5- benzothiazepine derivatives using auto in silico consensus inverse docking (ACID) server. Among the seven selected 1,5- benzothiazepine derivatives, consensus inverse docking (CID) against PDB-binding database identified potential therapeutic targets using structure-based screening. The comparative analysis predicted 4-hydroxyphenylpyruvate dioxygenase (HPPD) (Uniprot ID: P32754), involved in the regulation of blood tyrosine levels by catalyzing the reaction of HPPD to homogentisic acid in tyrosine catabolism pathway. Dimethylglycine dehydrogenase (DMGDH) (Uniprot ID: Q9AGP8), a flavin adenine dinucleotide (FAD)‐ and tetrahydrofolate (THF)‐dependent, mitochondrial matrix enzyme that degrades choline and transfers electrons to the respiratory chain, one‐carbon metabolism, and folate receptor beta (Uniprot ID: P14207), which is a glycosylphosphatidylinositol-linked protein capturing ligandsfrom the extracellular matrix and passages them inside the cell throughendosomalpathway and recognized as an emerging biomarker for cancer and chronic inflammatory diseases, as potential targets for the selected derivatives. These findings warrant for in vitro cell-based experimental validation of the currently identified actives.

Homocysteine and methylmalonic acid in Phenylketonuria patients.

Hyperhomocysteinemia and vitamin B12 deficiency have been reported in patients with phenylketonuria. In this study, total homocysteine (tHcy) and methylmalonic acid (MMA) levels were analyzed in samples from 25 phenylketonuria (PKU) patients. Comparisons were made between pre- and post-treatment values (n= 3); on treatment values, between periods with high and normal/low phenylalanine (Phe) levels (n= 20); and in women before, during and after pregnancy (n= 3). THcy levels decreased after treating PKU with metabolic formula (p=0.014). Except for a pregnant woman before pregnancy, none of the patients had tHcy values above the normal range. In fact, tHcy was < 5 μmol/L in 34% of the samples. We observed a decrease in Phe, tHcy, and tyrosine levels during pregnancy. MMA levels did not differ significantly, with values remaining in the normal range. These data indicate that there was no B12 deficiency in patients who adhere to the diet. In conclusion, in PKU patients treated with metabolic formula, tHcy is frequently not elevated, remaining even in the lower normal range in some patients. Thus, clinical follow-up and adherence to dietary treatment are crucial to prevent B12 deficiency.

Metabolite variations in the sera of HIV+ patients after an oral administration of effervescent glutamine and in comparison to non-HIV individuals by NMR.

It was demonstrated that effervescent glutamine supplementation in HIV+ individuals treated with antiretroviral therapy (ART) increased CD4+ T lymphocytes, decreased inflammation biomarkers, and brought health benefits. This pilot study aimed to explore serum metabolite variations in the HIV+ group under ART after 30 days of supplementation with glutamine, and in comparison to the matched HIV- group. The group of HIV+ showed lower levels of choline, creatine, pyruvate, glutamate, lysine, and tyrosine when compared to the HIV- group. Glucose, lipids, lactate, glutamine, phenylalanine, threonine, and phenylalanine/tyrosine were higher in HIV+ patients under long ART. Serum metabolome variations were shown to be consistent with the health improvements observed in the HIV+ group after effervescent glutamine supplementation, which might aid in ART in HIV+ individuals.

Inducible chemical defenses in wild mungbean confer resistance to Spodoptera litura and possibly at the expense of drought tolerance

Mungbean ( Vigna radiata ) is susceptible to many insect pests, but genotypes resistant to the common cutworm ( Spodoptera litura ) have yet to be identified. We screened for natural variants among wild mungbean populations and identified resistant (R1) and susceptible (S1) accessions. RNA-Seq data from R1 leaves exposed to larval feeding for 0, 2, 6 and 24 h suggested the involvement of CaMK, MAPK and jasmonic acid (JA) signaling, which diverts resources from primary metabolism to the biosynthesis of defense-related proteins and secondary metabolites. We compared the temporal expression of candidate genes in R1 and S1 plants exposed to larval feeding and observed the stronger induction of CAMK, MAPK, JA signaling, terpene and flavonoid biosynthesis genes in R1 plants. Accordingly, higher levels of JA accumulated in R1 leaves after larval feeding for 24 h, and metabolic profiling revealed elevated levels of tryptophan and tyrosine in R1 plants, possibly triggering the accumulation of glucosylated kaempferols and the emission of the volatile (E)-β-ocimene. Drought stress experiments showed that the inducible chemical defense system in accession R1 may come at the expense of drought tolerance. This potential trade-off between abiotic and biotic stress tolerance may reflect the lower levels of endogenous proline in R1 plants. • The wild mungbean accession CQ3114 (R1) have greater resistance against S. litura . • The resistant R1 plants have a robust jasmonate-induced chemical defenses. • The roles of β-ocimene in indirect defense/defense activation warrant more studies. • A trade-off between pest resistance and drought tolerance in wild mungbeans.

DRIVERS OF HYPERFERREMIA IN CHILDREN LIVING ON RADIOLOGICALLY CONTAMINATED TERRITORIES AFTER THE CHNPP ACCIDENT IN UKRAINE.

assessment of clinical-hematological and metabolic-biochemical parameters of the of bone tissue and hormonal regulation depending on the serum iron content and radiation dose values in children living on radiologically contaminated territories after the ChNPP accident in Ukraine. Children (n = 271) living on radiologically contaminated territories (RCT) of Ukraine were involved in the study. Three study groups were formed according to the serum iron level (SIL), namely group I with SIL 10.0-22.0 μmol/l (n = 92), group II with SIL 23.0-34.0 μmol/l (n = 144), and group III with SIL above 35.0 μmol/l (n = 35). Diseases in the family tree, bodyweight at birth, complaints on osalgia, bone fractures, jaw anomalies, dental caries, and obesity were accounted. Morphometric parameters of erythrocytes and hemogram elements were analyzed. Creatinine, alkaline phosphatase, calcium, total protein, iron, cholesterol, bilirubin, and transaminases were assayed in blood serum. The urine content of the 19 free amino acids, serum content of the free thyroxine (FT4), pituitary thyroid-stimulating hormone (TSH), and cortisol were assayed both with bone tissue density. Individual radiation doses were calculated. In 12.9 % of cases the SIL was > 35.0 μmol/l. Relatives with endocrine diseases were often present in the family tree of children with SIL > 23.0 μmol/l. There were increased urine content of the free amino acids (p < 0.05) and signs of protein degradation under high SIL. Contents of amino acids involved in collagen synthesis and antioxidant status (alanine, serine, glutamine, aspartic acid) and iron metabolism (arginine, leucine) were assayed at the highest levels (p < 0.05). Urinary levels of valine, lysine, and methionine, which are associated with iron metabolism, were decreased (p < 0.05). An inverse correlation (rs = -0.58; p < 0.01) was established between the serum TSH and cortisol levels regardless of the SIL. Serum TSH level directly correlated with urine content of amino acids involved in collagen synthesis. An inverse correlation (rs = -0.55; p < 0.001) was established between the serum TSH level and urine content of tyrosine that is essential for the thyroid hormone (triiodothyronine and thyroxine) synthesis.Cortisol was found having a negative effect on protein synthesis. Inverse correlation was established between the serum cortisol level and urine content of the free amino acids essential for collagen synthesis. There was no dependence of the average radiation dose values on the SIL. An inverse correlation was determined between the patient's radiation dose and SIL > 35.0 μmol/l (rs = -0.29; p < 0.05). The increased SIL in children living on RCT may occur due to both a genetic predisposition and the acquired factors driving protein and mineral metabolism of bone and their hormonal regulation.

Central Interaction Between L-Ornithine and Neuropeptide Y in the Regulation of Feeding Behavior of Neonatal Chicks.

Ornithine has been identified as a potential satiety signal in the brains of neonatal chicks. We hypothesized that brain nutrient signals such as amino acids and appetite-related neuropeptides synergistically regulate food intake. To test this hypothesis, we investigated the interaction between neuropeptide Y (NPY) and ornithine in the control of feeding behavior in chicks and the associated central and peripheral amino acid metabolic processes. Five-day-old chicks were intracerebroventricularly injected with saline, NPY (375 pmol), or NPY plus ornithine (2 or 4 μmol) at 10 μl per chick, and then subjected to ad libitum feeding conditions; food intake was monitored for 30 min after injection. Brain and plasma samples were collected after the experiment to determine free amino acid concentrations. Co-injection of NPY and ornithine significantly attenuated the orexigenic effect induced by NPY in a dose-dependent manner. Central NPY significantly decreased amino adipic acid, asparagine, γ-aminobutyric acid, leucine, phenylalanine, tyrosine, and isoleucine levels, but significantly increased lysine levels in the brain. Co-injection of NPY and ornithine significantly increased ornithine and proline levels in all examined brain regions, but decreased diencephalic tryptophan and glycine levels compared with those of the control and NPY-alone groups. Co-injection of NPY and high-dose ornithine significantly decreased methionine levels in all brain regions. Central NPY significantly suppressed the plasma concentrations of amino acids, including proline, asparagine, methionine, phenylalanine, tyrosine, leucine, isoleucine, glycine, glutamine, alanine, arginine, and valine, and this reduction was greater when NPY was co-injected with ornithine. These results suggest that brain ornithine interacts with NPY to regulate food intake in neonatal chicks. Furthermore, central NPY may induce an anabolic effect that is modified by co-injection with ornithine.

Plasma amino acids by age and gender in Hangzhou, Eastern China.

Amino acids (AAs) are crucial nutrients and fundamental building blocks of organisms that can be utilized to assess nutritional status and detect diseases. However, insufficient information has been reported on plasma AA in the Eastern Chinese population. 1859 persons who underwent physical examination in our hospital from January to December 2020 were enrolled. Plasma AA levels were determined by ultra-performance liquid chromatography mass spectrometry (UPLC-MS/MS.), and the effects of age and sex on 19 plasma AA profiles were analyzed. The Python language was used for data analysis and graphic visualization. Plasma arginine, proline, threonine, as-paragine, phenylalanine, and glycine in males, and plasma lysine, leucine, proline, valine, isoleucine, alanine, tyrosine, phenylalanine, and hydroxyproline levels in females increased with age. The 2-aminobutyric acid and serine levels in both sexes, and isoleucine, valine, leucine, and histidine levels in males decreased with age. Glycine level was higher in females than in males, and other 17 AAs except arginine and aspartate were higher in males than in females. Our study indicated that plasma AA levels can reflect the nutritional status and dietary structure of the population, with high obesity rate and high incidence of chronic diseases in eastern China. Age has certain effects on plasma AA levels, especially compared with sex.

Evaluation of Attention-deficit/Hyperactivity Disorder in Referred Patients to the PKU Clinic in Yazd, Iran.

The imbalance of phenylalanine (PA) to tyrosine level and decreased dopamine brain level in patients with phenylketonuria (PKU) may have a role in their susceptibility of them to attention-deficit/hyperactivity disorder (ADHD). This study aimed to evaluate the frequency of ADHD in referred patients to PKU Clinic in Yazd, Iran. In this cross-sectional analytical study, all patients older than three years with PKU who were referred to the PKU Clinic of Shahid Sadoughi Hospital, Yazd, Iran, in 2018 were evaluated, and ADHD symptoms in them were assessed via parent face-to-face interview. The patients were diagnosed with ADHD if they scored at least of 20 on ADHD diagnostic rating scale via parent interview based on DSM-VI criteria. Fourteen boys and 21girls with a mean age of 9.55±1.8 years were evaluated. 51.5% of those diagnosed with PKU had ADHD. Accordingly, ADHD was more frequent in girls (77.8% vs. 41% in boys, P=0.03). The mean age of diagnosis of PKU was significantly higher in patients with ADHD (52.54±15.65 months vs. 29.75±9.65 months, P = 0.03). The mean of PA level in the last six months (15.59±5.95 vs. 8.72+5.18, P= 0.005) and mean of the last six PA levels (14.76±4.71 vs. 8.96±3.86, P= 0.03) were significantly higher in ADHD group. The prevalence of ADHD in phenylketonuria patients in the present study was much more than in other studies. Late diagnosis of PKU and long-term high PA blood and brain level might be associated with increased neonatal screening. Hence, regular follow-up and continuous evaluation of patients with PKU for ADHD symptoms should be performed.

Untargeted 1 H-NMR Metabolome of Celery During Fusarium Wilt: Implications for Vegetable Quality.

Celery is a vegetable widely consumed as a condiment to prepare diverse dishes around the world. Nevertheless, this plant is susceptible to the attack of several phytopathogens including those of the Fusarium genus which is translated into devastating losses for the production chain. Herein we report on the metabolic changes produced during the celery wilt caused by Fusarium oxysporum which was determined through untargeted 1 H-NMR metabolomics. The changes in the metabolite content of celery were measured at 16, 24, and 32 days post-inoculation using viable conidia obtained from the native F. oxysporum strain FO3. Our results demonstrated that the parasitic activity of the fungus reduced the endogenous levels of free sugars (fructose, galactose, glucose isomers, mannose, Myo-inositol, mannitol, and sucrose) amino acids (alanine, aspartate GABA, glutamate, glutamine, histidine, isoleucine, leucine, methionine, proline, threonine, tyrosine, and valine), nucleosides (adenosine, cytidine, guanosine, and uridine) and organic acids (citric acid, fumaric acid, malic acid, and succinic acid). Interestingly, the levels of tyrosine and tryptophan were triggered as a consequence of F. oxysporum infection. This tendency was correlated with an increase in the levels of chlorogenic acid, apiin, and apigenin derivatives, suggesting their involvement in the chemical defense of celery against fungal colonization. According to principal component analysis (PCA) and Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) methanol was the main differential metabolite and it was considered as a new chemical marker associated with F. oxysporum infection. Our results demonstrate that infected celery plants dramatically reduced their nutritional and nutraceutical contents during Fusarium wilt after 32 days post-inoculation. However, these findings also suggest that the phenylpropanoid pathway is strongly related with the chemical defense of celery against F. oxysporum.

The Clostridium Metabolite P-Cresol Sulfate Relieves Inflammation of Primary Biliary Cholangitis by Regulating Kupffer Cells

To study the effect and mechanism of the Clostridium metabolite p-Cresol sulfate (PCS) in primary biliary cholangitis (PBC). Gas chromatography-mass spectrometry (GC-MS) was used to detect differences in tyrosine, phenylalanine, tryptophan, PCS, and p-Cresyl glucuronide (PCG) between the serum of PBC patients and healthy controls. In vivo experiments, mice were divided into the normal control, PBC group, and PBC tyrosine group. GC-MS was used to detect PCS and PCG. Serum and liver inflammatory factors were compared between groups along with the polarization of liver Kupffer cells. Additionally, PCS was cultured with normal bile duct epithelial cells and Kupffer cells, respectively. PCS-stimulated Kupffer cells were co-cultured with lipopolysaccharide-injured bile duct epithelial cells to detect changes in inflammatory factors. Levels of tyrosine and phenylalanine were increased, but PCS level was reduced in PBC patients, with PCG showing a lower concentration distribution in both groups. PCS in PBC mice was also lower than those in normal control mice. After oral administration of tyrosine feed to PBC mice, PCS increased, liver inflammatory factors were decreased, and anti-inflammatory factors were increased. Furthermore, Kupffer cells in the liver polarized form M1 transitioned to M2. PCS can damage normal bile duct epithelial cells and suppress the immune response of Kupffer cells. But PCS protects bile duct epithelial cells damaged by LPS through Kupffer cells. PCS produced by Clostridium-metabolized tyrosine reduced PBC inflammation, suggesting that intervention by food, or supplementation with PCS might represent an effective clinical strategy for treating PBC.

SCIATIC DENERVATION-INDUCED SKELETAL MUSCLE ATROPHY IS ASSOCIATED WITH PERSISTENT INFLAMMATION AND INCREASED MORTALITY DURING SEPSIS.

Background: Patients with underlying skeletal muscle atrophy are likely to develop aggravated sepsis. However, no study has experimentally verified the association between the prognosis of sepsis and muscle atrophy, and the mechanism of aggravation of sepsis under muscle atrophy remains unclear. In this study, we investigated the effect of skeletal muscle atrophy induced by sciatic denervation (DN), an experimental muscle atrophy model, on sepsis prognosis. Methods: Skeletal muscle atrophy was induced by DN of the sciatic nerve in C57BL/6J male mice. Cecal ligation and puncture (CLP) was performed to induce sepsis. Results: The survival rates of the sham and DN groups 7 days after CLP were 63% and 35%, respectively, wherein an approximately 30% reduction was observed in the DN group ( P < 0.05, vs. sham-CLP). The DN group had a higher bacterial count in the blood 48 h after CLP ( P < 0.05, vs. sham-CLP). Notably, NOx (a metabolite of nitric oxide) concentrations in DN mice were higher than those in sham mice after CLP ( P < 0.05, vs. sham-CLP), whereas serum platelet levels were lower 48 h after CLP ( P < 0.05, vs. sham-CLP). In organ damage analysis, DN mice presented increased protein expression of the kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), a kidney injury marker, after CLP (NGAL 48 h after CLP, P < 0.05, vs. sham-CLP; KIM-1 24 h after CLP, P < 0.01, vs. sham-CLP). Furthermore, nitro tyrosine levels in the kidneys of DN mice were higher 48 h after CLP compared with those in sham-CLP mice, indicating the accumulation of nitrative stress ( P < 0.05, vs. sham-CLP). Serum cytokine levels were increased in both groups after CLP, but decreased in the sham group 48 h after CLP and remained consistently higher in the DN group (tumor necrosis factor [TNF]-α: P < 0.05, sham-CLP vs. DN-CLP; interleukin (IL)-1β: P < 0.01, sham-CLP vs. DN-CLP; IL-6: P < 0.05, DN vs. DN-CLP; IL-10: P < 0.05, sham-CLP vs. DN-CLP). Conclusions: We verified that skeletal muscle atrophy induced by DN is associated with poor prognosis after CLP-induced sepsis. Importantly, mice with skeletal muscle atrophy presented worsening sepsis prognosis at late onset, including prolonged infection, persistent inflammation, and kidney damage accumulation, resulting in delayed recovery.

1H NMR metabolic profiling of Staphylococcus pseudintermedius isolated from canine uroliths.

Staphylococcus pseudintermedius is a urease-producing bacteria which is a major cause of magnesium ammonium phosphate (MAP) urolithiasis in canine. A positive urolith culture is an important risk factor for MAP urolithiasis in canine. The mechanism underlying the metabolic changes of S. pseudintermedius after crystallization in artificial urine (AU) needs more defined baseline metabolic information. Therefore, we extensively investigated the metabolic changes of S. pseudintermedius extensively after crystallization in AU. A high urease activity and positive biofilm formation strain, entitled the S. pseudintermedius (SPMAP09) strain, was isolated from canine MAP uroliths, and analyzed using nuclear magnetic resonance (NMR) spectroscopy-based metabolomics. The molecular mechanism-specific metabolic phenotypes were clearly observed after crystallization in AU at day 3. The crystals induced by SPMAP09 were also confirmed and the major chemical composition identified as struvite. Interestingly, our findings demonstrated that a total of 11 identified metabolites were significantly changed. The levels of formate, homocarnosine, tyrosine, cis-aconitate, glycolate, ethyl malonate, valine and acetate level were significantly higher, accompanied with decreased levels of inosine, glucose, and threonine at day 3 compared with the initial time-point (day 0). In addition, our results exhibited that the glyoxylate and dicarboxylate metabolism was significantly related to the SPMAP09 strain at day 3 in AU. Thus, metabolic changes of the SPMAP09 strain after crystallization in AU potentially helps to explain the preliminary molecular mechanism for the crystals induced by S. pseudintermedius.

Growth and Nutritional Status of Phenylketonuric Children and Adolescents

BackgroundThe goal of this study was to assess the anthropometric and biochemical parameters of children and adolescents with phenylketonuria (PKU).MethodsThe participants in this cross-sectional study ranged in age from four to 18 years old. Biochemical markers such as vitamin B12, folic acid, iron, ferritin, calcium, 25-hydroxy vitamin D3, zinc, plasma phenylalanine (Phe) and tyrosine (Tyr) levels in blood were evaluated, as well as demographics and anthropometric measurements. A three-day dietary recall questionnaire was completed by all individuals.Results80% (64) of the 80 patients (42 females, 52.5%) had typical PKU. Consanguineous marriages were found in 57.5% (46) of the patients’ parents. According to the height for age index, 17.5% of the study group (n = 14) were short or very short. According to age-related weight and body mass index (BMI), 37.5% (n = 30) and 43.8% (n = 35) of people are obese or overweight, respectively. Biochemical tests revealed increased vitamin B12 levels and 25-hydroxy vitamin D3 deficiency in 35% (n = 28) of the patients, insufficient folic acid in 12.5% (n = 10), and elevated phenylalanine levels in 70.3% (n = 45) of children under 12 years old, and adolescents 62.5% (n = 10). A high Phe intake (OR = 4.44, CI %95 = 1.27–15.57) is a risk factor for obesity and overweight.ConclusionPatients with PKU had a high rate of overweight and obesity. PKU patients who are overweight or obese do not differ from normal-weight patients in terms of dietary intake or laboratory findings (except for serum iron levels). One-third of patients with phenylketonuria were vitamin D deficient and had a BMI/A index of overweight/obese. It is recommended to use special medical food to help solve energy and nutrient deficiencies.

Higher Concentration of Dietary Selenium, Zinc, and Copper Complex Reduces Heat Stress-Associated Oxidative Stress and Metabolic Alteration in the Blood of Holstein and Jersey Steers.

This study investigated the influence of high concentrations of dietary minerals on reducing heat stress (HS)-associated oxidative stress and metabolic alterations in the blood of Holstein and Jersey steers. Holstein steers and Jersey steers were separately maintained under a 3 × 3 Latin square design during the summer conditions. For each trial, the treatments included Control (Con; fed basal TMR without additional mineral supplementation), NM (NRC recommended mineral supplementation group; [basal TMR + (Se 0.1 ppm + Zn 30 ppm + Cu 10 ppm) as DM basis]), and HM (higher than NRC recommended mineral supplementation group; [basal TMR + (Se 3.5 ppm + Zn 350 ppm + Cu 28 ppm) as DM basis]). Blood samples were collected at the end of each 20-day feeding trial. In both breeds, a higher superoxide dismutase concentration (U/mL) along with lower HSP27 (μg/L) and HSP70 (μg/L) concentrations were observed in both mineral-supplemented groups compared to the Con group (p &lt; 0.05). The HM group had significantly higher lactic acid levels in Jersey steers (p &lt; 0.05), and tended to have higher alanine levels in Holstein steers (p = 0.051). Based on star pattern recognition analysis, the levels of succinic acid, malic acid, γ-linolenic acid, 13-methyltetradecanoic acid, and tyrosine decreased, whereas palmitoleic acid increased with increasing mineral concentrations in both breeds. Different treatment groups of both breeds were separated according to the VIP scores of the top 15 metabolites through PLS-DA analysis; however, their metabolic trend was mostly associated with the glucose homeostasis. Overall, the results suggested that supplementation with a higher-than-recommended concentration of dietary minerals rich in organic Se, as was the case in the HM group, would help to prevent HS-associated oxidative stress and metabolic alterations in Holstein and Jersey steers.

Manganese (Mn) in Drinking Water From Gravity Feed System: A Literature Review

Manganese (Mn) is an element of metals that exists in a huge number of metals in the Earth’s crust. Mn is not naturally found in its pure form; instead, it is usually forming a compound with iron. Mn is an important element that has a function in both animals and humans [1]. Mn is commonly used in the manufacture and as an ingredient in several products such as batteries, glass and fireworks. Besides, Mn compounds are also present in surface waters in dissolved and suspended forms [2]. Besides ores and rocks, Mn can also be found in groundwater and surface water due to reducing conditions in soils and rocks that contain Mn, which may erode and turn it into a soluble form that then enters the water naturally [3]. Thus, high levels of Mn are found in groundwater and some lakes as well as reservoirs due to these conditions. Mn can also be present in water in the environment through human activities such as mining and landfill leaching near the water [4]. Health Canada stated the prevalence of Mn in ground waters is higher than that of surface waters [5].&#x0D; &#x0D; Inhalation and ingestion are the main routes of exposure, with inhalation mostly happening in workers due to occupational factors, and those who consume food or drinking water that contains high amounts of Mn are exposed through ingestion [4]. However, Mn is easily absorbed into the body when consumed with drinking water as compared to ingestion with food. Mn levels in drinking water should not be more than 0.1 mg/L, based on the Drinking Water Quality Standard [6]. Many enzymes including manganese superoxide dismutase arginase and pyruvate carboxylase require Mn as a cofactor; while in combination with vitamin K, Mn can aid in blood coagulation and hemostasis [7]. In addition, Mn is involved in the metabolism of amino acids, cholesterol, glucose and carbohydrates as well as bone formation, reproduction and immune response [8]. However, problems with memory, attention and motor skills exist when children and adults alike consume high levels of Mn for extended durations including consumption of drinking water [9]. There are no strong studies that show the results of the health effects of Mn in drinking water for adults. However, many studies have shown evidence of adverse health effects of Mn exposure on children especially in term of neurobehavioral effect.&#x0D; &#x0D; A review was conducted on the literature on Mn exposure from drinking water, concentrating on the World Health Organization's health-based Mn guideline value [10]. There is no study that has determined a lethal threshold of Mn for children and newborns, although data suggest that youngsters are more susceptible to poisoning than adults. Another study reported the association between Mn and arsenic exposure in drinking water among academic achievement of children in Bangladesh. It showed a significant association between water containing more than 400µg/L and decreased mathematical scores observed after adjusting the confounders [8]. There is a significant decrease in IQ scores of children that were exposed to higher levels of Mn from the earlier study [11]. Changes in the neurotransmitter system were shown to vary with the period of exposure during Mn intoxication in mice exposed to manganese chloride (MnCl2) through lactation and drinking water containing 3 mg/L Mn for 180 days, and male rats given 1000 mg/L water for 360 days. The studies also showed that Mn exposure increased the levels of dopamine, norepinephrine and tyrosine in the corpus striatum [5].&#x0D; &#x0D; The gravity feed system (GFS) is a downstream distribution system that is powered by gravity to supply water to households without the need to use electricity [12]. It is commonly used by populations living in hilly areas. These include the Orang Asli communities which usually live in areas which cannot be supplied with centralized water supply system. GFS is suitable in areas with a continuous supply of spring water. In Malaysia, gravity feed system is a type of water delivery system that includes a secure catchment area, a weir or sluice, and a piped water supply network (Figure 1). Since the majority of the systems generate untreated but healthy water, rural residents are recommended to boil the water [13].

Effect of dietary protein content shift on aging in elderly rats by comprehensive quantitative score and metabolomics analysis.

In the protein nutrition strategy of middle-aged and elderly people, some believe that low protein is good for health, while others believe high protein is good for health. Facing the contradictory situation, the following hypothesis is proposed. There is a process of change from lower to higher ratio of protein nutritional requirements that are good for health in the human body after about 50 years of age, and the age at which the switch occurs is around 65 years of age. Hence, in this study, 50, 25-month-old male rats were randomly divided into five groups: Control (basal diet), LP (low-protein diet with a 30% decrease in protein content compared to the basal diet), HP (high-protein diet with a 30% increase in protein content compared to the basal diet), Model 1 (switched from LP to HP feed at week 4), and Model 2 (switched from LP to HP feed at week 7). After a total of 10 weeks intervention, the liver and serum samples were examined for aging-related indicators, and a newly comprehensive quantitative score was generated using principal component analysis (PCA). The effects of the five protein nutritional modalities were quantified in descending order: Model 1 > HP > LP > Control > Model 2. Furthermore, the differential metabolites in serum and feces were determined by orthogonal partial least squares discriminant analysis, and 15 differential metabolites, significantly associated with protein intake, were identified by Spearman's correlation analysis (p < 0.05). Among the fecal metabolites, 10 were positively correlated and 3 were negatively correlated. In the serum, tyrosine and lactate levels were positively correlated, and acetate levels were negatively correlated. MetaboAnalyst analysis identified that the metabolic pathways influenced by protein intake were mainly related to amino acid and carbohydrate metabolism. The results of metabolomic analysis elucidate the mechanisms underlying the preceding effects to some degree. These efforts not only contribute to a unified protein nutrition strategy but also positively impact the building of a wiser approach to protein nutrition, thereby helping middle-aged and older populations achieve healthy aging.

Plasma amino acids levels in 1859 physical examination subjects in Hangzhou City in 2020

To study the relationship between fasting plasma amino acids and obesity in the physical examination population. A total of 1859 persons who underwent physical examination in the Second Affiliated Hospital Zhejiang University School of Medicine from January to December 2020 were enrolled. Fasting plasma amino acids concentrations and body fat ratio(BFR) were respectively determined by ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS) and Inbody instrument. According to body mass index and gender grouping, Python language was used for data analysis and graphic visualization to explore the relationship between body mass index, gender and plasma amino acids levels. The plasma levels of glycine, serine and asparagine in the overweight and obesity groups were significantly lower than those in the normal group, especially the levels in the obesity group were lower than those in the overweight group in males(P&lt;0.05). There was no significant difference in plasma levels of lysine, tryptophan, arginine and hydroxyproline among normal, overweight and obesity groups(P&gt;0.05). The plasma levels of leucine, valine, tyrosine, phenylalanine(in males), isoleucine(in females) and alanine in the overweight and obesity groups were significantly higher than those in the normal group, and the levels in the obesity group were higher than those in the overweight group except alanine(P&lt;0.05). BFR was positively correlated with body mass index. BFR in females increased significantly with age after 50 years old(P&lt;0.05). The rate of overweight and obesity among the health screening population is high.

Postprandial Metabolome Following a Low Glycaemic Index Meal-Challenge Test: A Narrative Review.

The Identifying the dynamic metabolome of the individual in response to a particular stimulus using a metabolomic approach is an emerging research area. Measuring the postprandial metabolite response utilising a meal-challenge test (MCT) provides information beyond the fasting state, which is especially important since human beings spend most of their time in the postprandial state. This is pertinent as an excessive rise in postprandial glycaemia is common in individuals with type 2 diabetes mellitus (T2DM), which puts them at a high risk of developing cardiovascular disease (CVD). While a low glycaemic index (GI) meal improves postprandial glycaemia and insulin levels in MCT studies among individuals with T2DM, its effect on metabolite changes in the postprandial state is unclear. This review summarises the perturbation in postprandial metabolites following a low GI meal in comparison to that following a usual or high GI meal and maps the metabolites in their metabolic pathways. We undertook a literature review using electronic databases, with the Medical Subject Headings (MeSH) terms, to retrieve relevant studies based on specific criteria. A total of seven related studies were documented. For the majority of metabolites studied, it was identified that metabolic regulation following an MCT extends beyond the glucose pathway. Altered metabolic pathways after the consumption of a low GI meal include: i) essential amino acid metabolism by altering the levels of plasma phenylalanine, tyrosine, lysine, leucine, isoleucine and valine; ii) glycolysis and tricarboxylic acid (TCA) metabolism by altering citrate and alanine, and iii) gut microbiota metabolism by altering betaine and acetate. The altered metabolites regulated the pancreatic insulin secretion and related to other dietary factors beyond GI modifications. These metabolomics data need to be interpreted cautiously because the metabolic changes analysed might not be due to the beneficial effects of a low GI meal. Validation of the putative metabolomic biomarkers following a dietary intervention MCT is suggested because researchers need to fully understand the kinetics and metabolism of individuals metabolite before reaching a solid conclusion. Further research characterising the metabotype based on habitual dietary patterns is warranted.