Amino Acids最新文献

From January 2000 to December 2019, the SEER Plus Database collecting human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR; including estrogen receptor [ER] and progesterone receptor [PR]) status for breast cancer (BC) cases. HER2-positive (HER2+) BC is an aggressive type, and HER2-targeted therapies have significantly improved the therapeutic outcome of patients. However, not every HER2+ BC patient achieves optimal benefits from current HER2-targeted therapies. Here, we conducted a detailed analysis to compare the demographic and clinic-pathological characteristics, survival, differential genes and mutations between HR+ and HR– in HER2+ BC patients. In this retrospective cohort study, Joint HR and HER2 status distributions by more than ten specific clinic-pathological characteristics were evaluated by using Pearson’s chi-squared (χ2) test. The transciptome RNA-seqencing (RNA-seq) expression data together with detailed clinic-pathological information of HER2+ BC were from The Cancer Genome Atlas (TCGA) and UCSC Xena. 30,482 (71.02%) patients were identified as HR+ /HER2+ BC and 12,440 (28.98%) patients were identified as HR−/HER2+ BC. HR+ /HER2+ BC patients were more likely to be younger than 50-year-old, white and infiltrating lobular carcinoma history than patients with HR−/HER2+. Patients with HR+ /HER2+ BC had lower risks of breast cancer-specific death and higher overall survival rates. Mast cells were enriched in the HR+ /HER2+ BC group, while plasma cells were more abundant in the HR–/HER2+ BC group.In conclusion, HER2+ BC patients benefit differently from current HER2-directed therapies, maybe partly due to the HR status and gene mutations, and they may provide potentially prognostic and predictive value and new treatment strategies for clinicians.

Antibiotic resistance is a growing problem in the treatment of life-threatening diseases. Recently, a variety of covalent drugs have emerged. Cysteine ​​is one of the least abundant amino acids in the proteins of many organisms, and the thiol group in its structure makes it unique and has become a common covalent amino acid residue in covalent drug development. Therefore, it is important to conduct research on cysteine ​​derivatives. In this study, the in vitro antibacterial activity of L-cysteine esters were tested against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli using the modified microdilution broth method. In vitro cytotoxic activities of the esters were carried out against the healthy HEK293T cell line and well-differentiated liver cancer cell lines PLC/PRF/5 and HEP3B at different concentrations by using an MTS assay. In addition, molecular docking studies, ADMET properties, and drug-likeness were also reported. The results obtained are new and it is thought that these results of the study will contribute to the development of new synthesizable cysteine-based drugs. In conclusion, a thorough examination of the frontier orbital (HOMO and LUMO) and MEP studies was conducted using quantum chemistry techniques to determine the molecule’s reactivity, electrophilic and nucleophilic sites.

Celiac disease (CD) is a chronic autoimmune disorder characterized by gluten-induced intestinal inflammation, epithelial barrier dysfunction, and malabsorption of nutrients, including amino acids (AAs). While essential AAs have been extensively studied, the roles of conditionally essential amino acids (CEAAs), cysteine (Cys), and tyrosine (Tyr) in CD pathogenesis remain comparatively underexplored. This review synthesizes current evidence on the contributions of these AAs to intestinal barrier integrity, immune regulation, oxidative stress mitigation, and gut microbiota modulation in CD. Key findings indicate that asparagine (Asn), glycine (Gly), Cys, glutamate (Glu), aspartate (Asp), and glutamine (Gln) contribute to the reinforcement of intestinal barrier integrity. In parallel, Cys and Gly, along with Gln and Asp, play important roles in suppressing oxidative stress, while Gln and Asp have been shown to positively influence the composition and function of the gut microbiota. Serine (Ser) may contribute to gliadin-induced epithelial damage but could also have potential protective effects during treatment. Arginine (Arg), through its metabolism via the inducible nitric oxide synthase (iNOS) and arginase pathways, contributes to immune regulation. This review underscores the therapeutic potential of AAs as adjunctive targets to gluten-free diets (GFD), offering avenues for nutritional interventions, enzyme therapies, and biomarker development. A deeper understanding of AA-mediated mechanisms may pave the way for personalized management strategies to improve clinical outcomes in CD.

Among the 20 standard amino acids, aromatic amino acids hold particular importance due to their crucial roles in protein–protein interactions. These residues, including phenylalanine, tyrosine, tryptophan, and histidine, contribute significantly to protein structure and function through their ability to engage in non-covalent interactions, such as π–π stacking and cation–π interactions. In addition, the acid–base duality of aromatic amino acids makes their interactions with metal ions particularly valuable. These interactions are implicated in several essential biological processes, including protein biosynthesis, enzyme catalysis, and molecular recognition. While the interactions between transition metal ions and amino acids have been extensively studied and well-documented, the role of alkali metal ions in similar contexts has received comparatively less attention. However, their influence on amino acid coordination and stability cannot be overlooked, especially given their biological relevance in processes such as ionic regulation, enzyme activation, and membrane transport. The results of this study demonstrate that the complexation of aromatic amino acids with alkali metal ions enhances their acidity. Additionally, we examined the detailed interactions of these metals with the aromatic amino acids.

The design of peptide-based inhibitors targeting cell receptors represents a promising strategy in the development of antiviral agents. In this study, a novel octapeptide containing the RGD sequence was rationally designed to explore its potential interaction with integrins. The peptide was functionalized with a malonic moiety to enhance its binding capabilities and potential bioactivity. Conformational and physicochemical properties were evaluated using DFT-PBEh-3c calculations. Molecular docking studies revealed favorable interactions with the integrin α₅β₁, including coordination with the Mg²⁺ ion at the active site. The peptide was successfully synthesized via Fmoc-based solid-phase peptide synthesis (SPPS) and fully characterized by NMR, IR, MS, and RP-HPLC.

Pressure ulcers (PU) are a major and serious problem affecting millions of people. Malnutrition, frequently co-occurring with PU, is considered modifiable risk factor, and dietary supplements currently recommended for supporting PU healing contain a high amount of protein and some additives (zinc, vitamin C, arginine). Unfortunately, many patients with PU suffer from chronic kidney disease and would not tolerate a high-protein diet. Amino acid profiling of the blood serum of PU patients has shown decreased concentrations of exogenous amino acids histidine, tryptophan and threonine. Their common feature is a low daily requirement, 4 to 15 mg/kg body weight. In animal experiments, various types of stress increase metabolic demand for these amino acids. On the other hand, stress significantly slows down wound healing, both in animals and in humans. Considering these observations, a pilot clinical trial in the quasi-experimental design has been performed to assess the effect of Pellicar-F, a proprietary food composition containing histidine in the form of carnosine, plus tryptophan and threonine on PU control. After six weeks patients receiving daily doses of the aforementioned food composition, compared to control patients, displayed statistically significant reduction of the pressure ulcer area. Further evaluation of this product in pressure ulcers and other chronic wounds is indicated.

This article introduces a mechanistic framework to reclassify suboptimal responses to GLP-1 receptor agonists. It defines three mechanistic subtypes of incretin resistance—receptor-level, post-receptor, and secretory—highlighting their distinct pathways and therapeutic implications. This model promotes personalized care by moving beyond the oversimplified ‘non-responder’ classification.

Rheumatoid arthritis is the most prevalent form of autoimmune arthritis. In modern drug development, computer-aided drug design plays a crucial role not only in discovering new therapeutic compounds but also in assessing their potential efficacy. This study employs ligand-based pharmacophore modeling to identify novel drug candidates without requiring an initial target protein structure. Essential chemical features were extracted from nucleotides, amino acids, and sulfonylaziridine derivatives to construct potential drug scaffolds. Ligands exhibiting similar structural characteristics were then screened for promising chemical interactions. Using MATLAB software, the initial pool of 4,000 candidates was narrowed down to 330, which was further reduced to 58 and finally to 8 through AutoDock screening. These top candidates were further analyzed using molecular docking (static analysis) and molecular dynamics simulations (dynamic analysis). Among them, the compound CPROSCP demonstrated favorable dynamic stability, an appropriate hydrodynamic radius, minimal distortion of protein structure, and advantageous binding energy. The synthesized drug candidate achieved a yield of approximately 92%, with IR and NMR spectroscopy confirming its successful synthesis and high purity.

Stopping then restarting the blood flow to the heart can cause ischaemia reperfusion (IR) injury. This can happen during revascularisation following a myocardial infarction and during on pump cardiac surgery using cardioplegic arrest. Despite extensive studies to identify cardioprotective interventions, the myocardium continues to sustain significant injury. Therefore, there is a need to identify agents that can be used during IR. This review focuses on the potential cardioprotective role for acidic amino acids and natural dipeptides using evidence from experimental studies and clinical trials with particular emphasis on their membrane transport. Acidic amino acids are present at high concentration in the heart with a large tissue to plasma concentration gradient, where they are involved in protein synthesis and intermediary metabolism. During cardiac insults they are lost from heart cells but replenishment leads to cardioprotection through energy provision, protection against the production of reactive oxygen species production and improved calcium homeostasis. One important determinant of the intracellular concentration of acidic amino acids and natural dipeptides is membrane transport. The expression and activity of the acidic amino acids transporters EAAT1-3 and the dipeptide transporter, PEPT2 have been demonstrated in membrane vesicles and isolated cardiomyocytes. Improvements in our understanding of these different transport mechanisms should lead to the maximisation of acidic amino acid and natural dipeptide uptake during IR leading to improved cardioprotection.

Plants are known as a source of different biologically active compounds, which are uncommon for other kingdoms of life. Among them are different amino acid analogues, which are synthesized and accumulated in certain plants as a passive defense mechanism against herbivorous insects and grazing mammals. As a rule, cell protein synthesis machinery of herbivores cannot effectively differentiate between standard proteinogenic amino acids and their specific plant analogues, resulting in misincorporation of the latter into nascent proteins and their malfunctioning, which constitutes a mechanism of plant defense. Examples of such amino acids are analogues of arginine (canavanine, indospicine), proline (azetidine-2-carboxylic acid), and cysteine/lysine (thialyasine). This review summarizes existing knowledge on these and other related amino acids as potential antibacterial and antifungal agents, including their possible targets and known resistance mechanisms. We also discuss the possibility of using amino acid analogues as sole antimicrobial agents or in combination with known antibacterials and antifungals. We also propose a strategy of enhancing the antimicrobial activity of amino acid analogue by concomitant starvation for the corresponding standard amino acid, which has been proven efficient in anticancer studies. Such an approach might potentially help to overcome, at least partially, microbial resistance to known antibiotics, especially when such resistance relies on increased protein synthesis in pathogen cells.