Amino Acids最新文献

In recent years, the use of cationic peptides as alternative drugs with anticancer activity has received attention. In this study, the targeted release of curcumin (Cur) and CM11 peptide alone and together against hepatocellular carcinoma (HCC) was evaluated using chitosan nanoparticles (CS NPs) coated with Pres1 that target the SB3 antigen of HCC cells (PreS1-Cur-CM11-CS NPs). SB3 protein is the specific antigen of HCC and the PreS1 peptide is a part of the hepatitis B antigen, which can specifically bind to the SB3 protein. Chitosan was used to prepare NPs. To Cur and CM11 loading, drugs were added to the CS solution in appropriate concentrations. Pres1 was coupled to the surface of the NPs using EDC catalyst to target NPs against HepG2 cells. SEM and DLS analysis confirmed that the PreS1-Cur-CM11-CS NPs had a size of about 132 nm, the ideal size for penetrating the cell membrane. The loading of Cur and CM11 was equal to 87% and 65%, respectively, which had a sustained and better release in the acidic environment than in the physiological environment. The MTT assay showed that PreS1-Cur-CM11-CS NPs act in a targeted and specific manner with the highest toxicity on the HepG2 cells compared to the control by a decrease in viability of about 26% after 48 h based on cell apoptosis. The results showed that PreS1-Cur-CM11-CS NPs are capable of targeted and specific drug release against HepG2 cancer cells and have significant potential to fight this cancer.

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Four aliphatic amino acids—α-aminobutyric acid (AABA), β-aminobutyric acid (BABA), α-aminoisobutyric acid (AAIBA) and β-aminoisobutyric acid (BAIBA) were investigated in water as a solvent by two quantum chemical methods. B3LYP hybrid version of DFT was used for geometry optimization and a full vibrational analysis of neutral molecules, their cations and anions in the canonical and zwitterionic forms (6 forms for each species). Ab initio DLPNO-CCSD(T) method was applied in the geometry pre-optimized by B3LYP. Calculated molecular descriptors involve dipole moment, quadrupole moment, dipole polarizability, energy of zero-point vibration and total entropic term which enter the standard Gibbs energy. In addition, a set of collective electronic and thermodynamic properties associated with redox process were evaluated: ionization energy, electron affinity, chemical hardness, molecular electronegativity, electrophilicity index, absolute oxidation and reduction potentials. A mutual comparison of these structural isomers including γ-aminobutyric acid (GABA) shows high degree of similarity in molecular descriptors. However, cluster analysis of 12 electro neutral, linear and branched amino acids with 2 – 6 carbon atoms discriminates them into five clusters. It is found that the electrophilicity index correlates with the absolute reduction potential along a straight line (24 items). The reduction potential for canonical structure varies between 1.21 V (glycine) and 1.45 V (AABA) whereas for the zwitterionic form it is visibly lower 0.52–1.11 V. The highest absolute reduction potential > 1.43 V is shown by α-amino acids: α-alanine, AABA (homoalanine) and AAIBA having 2-methyl or 2-ethyl functional group. The calculated absolute oxidation potential correlates with the adiabatic ionization energy and can be used as a criterion of the antioxidant capacity. According to thermodynamic data, the SPLET mechanism of the electron-proton coupled transfer is favored over the alternative SET-PT mechanism. This work contributes to the creation of a database of molecular properties of amino acids based on the same method and basis set.

Metabolomics provide a promising tool for understanding dementia pathogenesis and identifying novel biomarkers. This study aimed to identify amino acid biomarkers for Alzheimer’s Disease (AD) and Vascular Dementia (VD). By amino acid metabolomics, the concentrations of amino acids were determined in the serum of AD and VD patients as well as age-matched healthy controls. Several differences in the concentration of amino acids were observed in AD patients compared to both healthy controls and VD patients. However, no significant distinction was found between healthy controls and VD patients. Considering comorbidities, cystine levels were higher in AD than in VD among non-diabetic patients, but not in those with diabetes. Notably, creatine, spermidine, cystine, and tyrosine demonstrated favorable results in decision curve analyses and good discriminative performances, suggesting their potential for clinical application. These fundings give novel perspectives of serum amino acids for predicting metabolic pathways in AD and VD pathogenesis.

In recent years, it was found that lysine malonylation modification can affect biological metabolism and play an important role in plant life activities. Platycodon grandiflorus, an economic crop and medicinal plant, had no reports on malonylation in the related literature. This study qualitatively introduces lysine malonylation in P. grandiflorus. A total of 888 lysine malonylation-modified proteins in P. grandiflorus were identified, with a total of 1755 modification sites. According to the functional annotation, malonylated proteins were closely related to catalysis, binding, and other reactions. Subcellular localization showed that related proteins were enriched in chloroplasts, cytoplasm, and nuclei, indicating that this modification could regulate various metabolic processes. Motif analysis showed the enrichment of Alanine (A), Cysteine (C), Glycine (G), and Valine (V) amino acids surrounding malonylated lysine residues. Metabolic pathway and protein-protein interaction network analyses suggested these modifications are mainly involved in plant photosynthesis. Moreover, malonylated proteins are also involved in stress and defense responses. This study shows that lysine malonylation can affect a variety of biological processes and metabolic pathways, and the contents are reported for the first time in P. grandiflorus, which can provide important information for further research on P. grandiflorus and lysine malonylation’s role in environment stress, photosynthesis, and secondary metabolites enrichment.

Recent studies have suggested that the interaction between diet and an individual’s genetic predisposition can determine the likelihood of obesity and various metabolic disorders. The current study aimed to examine the association of dietary branched-chain amino acids(BCAAs) and aromatic amino acids(AAAs) with the expression of the leptin and FTO genes in the visceral and subcutaneous adipose tissues of individuals undergoing surgery. This cross-sectional study was conducted on 136 Iranian adults, both men and women, aged ≥18 years. The samples were selected from patients admitted for abdominal surgeries. The dietary intake of BCAAs and AAAs was determined using a valid and reliable 168-item food frequency questionnaire. Using the quantitative PCR method, leptin and FTO mRNA expression was measured in both visceral and subcutaneous fat tissues. The mean age of the participants was 39.8 ± 12.7 years, and the mean intake of BCAAs and AAAs was 17.7 ± 0.9 and 9.3 ± 0.3% of protein per day, respectively. In overweight-obese patients(body mass index = 25–34.9 kg/m²), the intake of BCAAs(β:-0.75,95%CI:-1.47,-0.03), valine(β:-0.78,95%CI:-1.51,-0.05), and tyrosine(β:-0.81,95%CI:-1.55,-0.06) was inversely associated with FTO gene expression in subcutaneous fat tissue in adjusted model. In morbidly obese patients(body mass index ≥ 35 kg/m²), a higher intake of total BCAAs(β:1.10,95%CI:0.07–2.13), leucine(β:1.07,95%CI:0.03–2.13), and isoleucine(β:1.49,95%CI:0.46–2.52) was associated with an increase of leptin gene expression in subcutaneous fat tissue. Our findings suggest that dietary BCAA may associated with gene expression in adipose tissues, potentially influencing obesity-related metabolic pathways. Further prospective studies are warranted to validate results and elucidate the potential for dietary interventions targeting amino acids intake in obesity management.

Taurine, although not a coding amino acid, is the most common free amino acid in the body. Taurine has multiple and complex functions in protecting mitochondria against oxidative-nitrosative stress. In this comprehensive review paper, we introduce a novel potential role for taurine in protecting from deuterium (heavy hydrogen) toxicity. This can be of crucial impact to either normal or cancer cells that have highly different mitochondrial redox status. Deuterium is an isotope of hydrogen with a neutron as well as a proton, making it about twice as heavy as hydrogen. We first explain the important role that the gut microbiome and the gut sulfomucin barrier play in deuterium management. We describe the synergistic effects of taurine in the gut to protect against the deleterious accumulation of deuterium in the mitochondria, which disrupts ATP synthesis by ATPase pumps. Moreover, taurine’s derivatives, N-chlorotaurine (NCT) and N-bromotaurine (NBrT), produced through spontaneous reaction of taurine with hypochlorite and hypobromite, have fascinating regulatory roles to protect from oxidative stress and beyond. We describe how taurine could potentially alleviate deuterium stress, primarily through metabolic collaboration among various gut microflora to produce deuterium depleted nutrients and deuterium depleted water, and in this way protect against leaky gut barrier, inflammatory bowel disease, and colon cancer.

Collapsin response mediator protein 2 (CRMP2) functions in the genesis and activity of neuronal connections in mammalian brain. We previously reported that a protein coincident with CRMP2 on 2D-gels undergoes marked accumulation of abnormal L-isoaspartyl sites in brain extracts of mice missing the repair enzyme, protein L-isoaspartyl methyltransferase (PIMT). To confirm and explore the significance of isoaspartyl damage in CRMP2, we expressed and purified recombinant mouse CRMP2 (rCRMP2). A polyclonal antibody made against the recombinant protein precipitated CRMP2 from brain extracts of PIMT-KO mice, but not from WT mice, suggesting that (1) the rCRMP2 antigen underwent significant isoAsp formation in the process of antibody production and (2) the isoAsp form of CRMP2 is considerably more immunogenic than the native protein. In vitro aging of rCRMP2 at pH 7.4, 37 °C for 0–28 days led to robust accumulation of isoAsp sites that were repairable by PIMT, and also induced a progressive accumulation of apparent dimers and higher-mass oligomers as judged by SDS-PAGE. A similar pattern of CRMP2 aggregation was observed in mice, with levels increasing throughout the lifespan. We conclude that CRMP2 is indeed a major target of PIMT-mediated protein repair in the brain; that isoAsp forms of CRMP2 are highly immunogenic; and that CRMP2 dysfunction makes a significant contribution to neuropathology in the PIMT-KO mouse.

Little is known about how blood free amino acids (FAAs) change in metabolic dysfunction-associated steatotic liver disease (MASLD). This study aims to identify the imbalance of FAAs in MASLD and explore its correction as a potential therapeutic target. We analyzed plasma FAAs data from 23,036 individuals with steatosis information from a biobank in Japan, and 310 patients with MASLD were enrolled. According to diagnostic criteria for steatotic liver disease (SLD) or cardiometabolic criteria (CC), we divided the subjects into five groups: MASLD, metabolic dysfunction and alcohol-associated liver disease (MetALD), CC-SLD-, CC + SLD-, and CC-SLD + . Twenty FAAs were compared among these groups and among MASLD patients with pathological information. Among the 20 FAAs, the levels of 16 FAAs increased in CC + SLD- according to the number of matches with CC items associated with insulin resistance (IR). Steatosis enhanced most of these changes but serine (Ser) and threonine (Thr) were unaffected. Glycine (Gly), Ser and Thr were significantly decreased in patients according to steatosis grade. We investigated the association between these FAAs imbalances and pathogenesis using MASLD mouse models. In mice fed a high-fat, fructose, and cholesterol (FFC) diet, metabolomics and RNA sequencing analyses indicated that abnormality in Gly, Ser, and Thr metabolism in the liver was associated with mitochondrial dysfunction and enhanced glycolysis via pyruvate. High-Gly, Ser, and Thr diet ameliorated pathogenesis of MASLD in leptin-deficient mice. Most FAAs increase due to cardiometabolic abnormalities, particularly IR. However, interventions targeting the metabolism of Gly, Ser, and Thr have the potential to improve MASLD.

The relationship between D-AA metabolic enzymes and cancer development remains unclear. We aimed to investigate this relationship using mice deficient in D-AA-related metabolic enzymes. We examined mice lacking these enzymes for approximately 900 days and the effects of altered D-AA metabolism on cancer development based on lifespan, pathological findings, and gene expression. The lifespan of female DASPO -knockout (DASPO^−/−) mice was shorter than that of the other group mice; furthermore, these mice showed tumor-like masses in the liver, spleen, and small intestine. A pathological diagnosis of diffuse large B-cell lymphoma (DLBCL) was made. RNA sequencing of the liver samples showed specific alterations in the expression of 71 genes in DASPO^−/− mice compared with that in wild-type B6 mice; RGS 1, MTSS1, and SMARCD 1 were identified as DLBCL-related genes. Patients with DLBCL exhibiting low DASPO expression demonstrated a shorter survival period than those showing high expression. However, the role of DASPO in DLBCL development is unclear. Therefore, future research should focus on B cells. DASPO may serve as novel biomarkers and therapeutic targets in cancer.

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