Amino Acids最新文献

L-Arg is a nonessential amino acid but has many physiological roles. Accordingly, L-Arg has been used in various fields, but there is only limited information available about its safety upon overdose. Generally, the no-observed adverse effect level (NOAEL) is used when setting the upper amount for chemical substances. Recently, systematic reviews have been used to assess the safety as well as the effectiveness and usefulness of them. Therefore, we conducted an assessment of the safety of the oral intake of L-Arg in healthy subjects using gastrointestinal symptoms as an index. We limited the study design to only double-blind randomized controlled trials and searched PubMed, Cochrane Library, EBSCOhost, and Ichushi-Web from inception until May 2021. Assessment of the quality of studies was conducted using the Cochrane Collaboration tool and Jadad score, and the random effects model was used for data analysis. Ultimately, 34 studies were selected for inclusion in this work. The dosage of L-Arg used in the studies ranged from 2000 to 30,000 mg/day (or/one-time dose), and the treatment duration was 1–84 days. The increased risk of gastrointestinal symptoms associated with L-Arg intake from 23 studies (647 participants in total) in which such symptoms were reported was 0.01 (95% confidence interval: – 0.02–0.04), which was not significant difference. NOAEL was estimated as 7531 mg/ one-time dose using a weighted change-point regression model (UMIN000046133).

Registration and protocol: Umin.ac.jp as UMIN000046133.

Bioactive peptides consist of small protein fragments, which are inactive in their original conformation, and they become active when released from these through enzymatic hydrolysis or fermentation processes. The bioactivity of such peptides has been extensively reported in the literature as contributors to organic homeostasis processes, as well as in immunomodulation, organism defense against oxidative processes, among others. In this study, reports of the activity of BPs isolated from milk with the potential glycemic control, antihypertensive activity, and inhibitors of uric acid formation were compiled. A systematic literature review and bibliometric analysis were conducted, using the PICO strategy for the research. The temporal analysis of publications revealed a growing interest in the investigation of bioactive peptides with potential antidiabetic, antihypertensive, and xanthine oxidase inhibitory activities, using dairy sources as products for their extraction. The literature analysis also revealed an increase in research involving non-bovine dairy products for bioactive peptide extraction. The collaboration network among authors exhibited weaknesses in scientific cooperation. Regarding the analysis of keywords, the usage of terms such as “bioactive peptides”, “antioxidant”, “antihypertensive”, and “diabetes” was evident, constituting the main research clusters. Peptides with low molecular weight, typically < 10 kDa, of hydrophobic nature with aliphatic and aromatic chains, have significant implications in molecular interactions for the required activities. Although there is a growing interest in the industry regarding the utilization of bioactive peptides as potential drugs, there is a need to address gaps related to elucidating their interactions with cellular targets and their use in human therapy.

Disruptions to iron metabolism and iron homeostasis have emerged as significant contributors to the development and progression of Alzheimer's disease (AD). Human transferrin plays a key part in maintaining iron equilibrium throughout the body, highlighting its importance in AD. Many plant-derived compounds and dietary constituents show promise for preventing AD. Polyphenols that are abundant in fruits, vegetables, teas, coffee, and herbs possess neuroprotective attributes. Resveratrol is a natural polyphenol present in various plant sources like grapes, berries, peanuts, and red wine that has garnered research interest due to its wide range of biological activities. Notably, resveratrol exhibits neuroprotective effects that may help prevent or treat AD through multiple mechanisms. In the present study, we employed a combination of molecular docking and all-atom molecular dynamic simulations (MD) along with experimental approaches to unravel the intricate interactions between transferrin and resveratrol deciphering the binding mechanism. Through molecular docking analysis, it was determined that resveratrol occupies the iron binding pocket of transferrin. Furthermore, MD simulations provided a more profound insight into the stability and conformational dynamics of the complex suggesting that the binding of resveratrol introduced localized flexibility, while maintaining overall stability. The spectroscopic observations yielded clear evidence of substantial binding between resveratrol and transferrin, confirming the computational findings. The identified binding mechanism and conformational stability hold potential for advancing the development of innovative therapeutic approaches targeting AD through resveratrol, particularly concerning iron homeostasis. These insights serve as a platform for considering the natural compounds in the realm of AD therapeutics.

Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by increased release of proinflammatory cytokines that are known to activate the indoleamine 2,3-dioxygenase (IDO-1) enzyme, which catalyzes the rate-limiting step of the kynurenine pathway (KP). This study aimed to measure KP metabolite levels in patients with SLE and investigate the relationship between disease activity, clinical findings, and KP. The study included 100 patients with SLE and 100 healthy controls. Serum tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), quinolinic acid (QA) concentrations were measured with tandem mass spectrometry. Serum KYN, KYNA, 3HAA, 3HK, and QA levels of the patients with SLE were significantly higher than the control group. Serum QA levels were elevated in patients with neurological involvement (four patients with peripheral neuropathy and two patients with mononeuropathy), serum KYN levels and KYN/TRP ratio increased in patients with joint involvement, and serum KYN, 3HK, and 3HAA levels and the KYN/TRP ratio were increased in patients with renal involvement. Moreover, KYN and KYN/TRP ratios were positively correlated with the disease activity score. These findings indicated that imbalances in KP metabolites may be associated with the pathogenesis, activation, and clinical manifestations of SLE.

β-Lactoglobulin is one of the proteins in milk possessing antioxidant activity. The peptides derived from β-Lactoglobulin exhibit higher antioxidant activities than the most commonly used antioxidant. Furthermore, the detailed structure–activity relationship of these antioxidant peptides has not been elucidated. Therefore, in the present work, two-dimensional quantitative structure–activity relationship (2D-QSAR) and three-dimensional quantitative structure–activity relationship (3D-QSAR) models were constructed to investigate the structural factors affecting activities and gave information for the rational design of novel antioxidant peptides. After calculation and screening of molecular descriptors, linear and nonlinear models were developed by multiple linear regression (MLR), partial least squares regression (PLSR) and support vector machines (SVM) approaches. The statistical parameters are as follows: R² = 0.643, Q² = 0.553/MLR, R² = 0.612, Q² = 0.5278/PLSR, R² = 0.7085, Q² = 0.6887/SVM, indicating that the SVM model is superior to the MLR and PLSR models. In addition, in the 3D-QSAR models, the Dragon-CoMFA (R²_cv = 0.537, R²_pred = 0.5201) and Dragon-CoMSIA (R²_cv = 0.665, R²_pred = 0.6489) methods were conducted to predict the antioxidant activities. Comparison of statistical parameters illustrates that the suitability of Dragon-CoMSIA is superior to the Dragon-CoMFA model. The results show the robustness and excellent prediction of the proposed models, and would be applied for modifying and designing novel and potent antioxidant peptides.

Recently, opportunistic pathogens like Acinetobacter baumannii and Pseudomonas aeruginosa have caused concern due to their ability to cause antibiotic resistance in weakened immune systems. As a result, researchers are always seeking efficient antimicrobial agents to tackle this issue. The hypothesis of the recent study was that probiotic products derived from bacteria would be effective in reducing drug resistance in other bacteria. This research aimed to investigate the antimicrobial properties of probiotic products from various bacterial strains, including Lactobacillus rhamnosus, Pediococcus acidilactisi, Bacillus coagulans, Bacillus subtilis, and Bacillus licheniformis. These were tested against multi-drug-resistant (MDR) standard strains A. baumannii and P. aeruginosa. B. licheniformis was found to be the most effective probiotic strain, possessing the LanA and LanM lantibiotic genes. The lipopeptide nature of the probiotic product was confirmed through high-performance liquid chromatography (HPLC) and Fourier-transform infrared spectroscopy (FTIR) techniques. The anti-biofilm and antimicrobial properties of this probiotic were measured using an SEM electron microscope and minimum inhibitory concentration (MIC) test. Real-time PCR (qPCR) was used to compare the expression of bap and luxI genes, which are considered virulence factors of drug-resistant bacteria, before and after treatment with antimicrobial agents. The MIC results showed that the probiotic product prevented the growth of bacteria at lower concentrations compared to antibiotics. In addition, the ΔΔCqs indicated that gene expression was significantly down-regulated following treatment with the obtained probiotic product. It was found that B. licheniformis probiotic products could reduce drug resistance in other bacteria, making it a potential solution to antibiotic resistance.

Alzheimer's disease is characterized by the presence of senile plaques composed of β-amyloid peptide (Aβ) aggregates with toxic effects that are still not fully understood. Recently, it was discovered that Aβ(1–42) fibrils possess catalytic activity on acetylcholine hydrolysis. Catalytic amyloids are an emerging and exciting field of research. In this study, we examined the catalytic activity of the fibrils formed by Aβ(1–40), the most abundant Aβ variant, on acetylcholine hydrolysis. Our findings reveal that Aβ(1–40) fibrils exhibit moderate enzymatic activity, indicating that natural peptide aggregates could serve as biocatalysts and provide new insights into the potential role of Aβ in neurological disorders.

Small neuropeptides from the corpora cardiaca are responsible in cockroaches for the mobilisation of trehalose from the fat body into the haemolymph. Such hypertrehalosaemic hormones (HrTHs) belong to the large family of insect adipokinetic hormones (AKHs); a few HrTHs were previously sequenced from cockroaches, and from genomic and/or transcriptomic information one may predict the genes encoding HrTHs from more species. Definite elucidation of the primary structure of the mature peptide with putative modifications needs analytical chemical methods. In the current study, we use high-resolution mass spectrometry coupled with liquid chromatography to identify unequivocally the HrTHs of 13 cockroach species. Either genomic/transcriptomic information was available for most of the species examined, or from related species. We confirm predicted novel sequences and find hydroxyproline modification for the majority of the peptides. The novel decapeptides are structurally close to Bladi-HrTH, which is found in all seven of the investigated blaberid subfamilies. Bladi-HrTH and all the novel peptides elicit a hypertrehalosaemic response in Periplaneta americana, a blattid cockroach.

The health-improving functions of bioactive flavonoids in vitro and in vivo are often limited by their low stability, which could be counteracted by the application of proteins as carriers of flavonoids. Clarification of the mechanism of protein–ligand interaction is crucial for the encapsulation of bioactive components. Herein, common plasma proteins [i.e., bovine serum albumin (BSA), human serum albumin (HSA), human immunoglobulin G (IgG) and fibrinogen (FG)] were compared for their binding characteristics to quercetin, the main component of flavonoids in human diet, in the absence and presence of free Cu²⁺ (an accelerator for flavonoids’ instability) using multi-spectroscopic and computational methods. As a flexible open structure of proteins, both BSA and HSA were found to be the most promising carriers for quercetin and Cu²⁺ with an affinity on the order of 10⁴ M⁻¹. HSA-diligand complex (i.e., HSA-quercetin-Cu²⁺) was successfully generated when both quercetin and Cu²⁺ were added to the HSA solution. The stability and free radical scavenging activity of bioactive quercetin during incubation was promoted in the HSA-diligand complex relative to quercetin-Cu²⁺ complex. Quercetin/Cu²⁺ system could induce the formation of reactive oxygen species such as hydrogen peroxide (H₂O₂) and hydroxide radical (·OH), which were significantly suppressed upon HSA binding. Consistently, the cytotoxicity of the quercetin/Cu²⁺ system to endothelial cells was reduced in the HSA-diligand complex. These results demonstrate the possibility of developing serum albumin-based carriers for the protection of bioactive flavonoids in their nutritional application.

Bridging the gap between preclinical models of neurological and psychiatric disorders with their human manifestations is necessary to understand their underlying mechanisms, identify biomarkers, and develop novel therapeutics. Cognitive and social impairments underlie multiple neuropsychiatric and neurological disorders and are often comorbid with sleep disturbances, which can exacerbate poor outcomes. Importantly, many symptoms are conserved between vertebrates and invertebrates, although they may have subtle differences. Therefore, it is essential to determine the molecular mechanisms underlying these behaviors across different species and their translatability to humans. Genome-wide association studies have indicated an association between glutamatergic gene variants and both the risk and frequency of psychiatric disorders such as schizophrenia, bipolar disorder, and autism spectrum disorder. For example, changes in glutamatergic neurotransmission, such as glutamate receptor subtype N-methyl-d-aspartate receptor (NMDAR) hypofunction, have been shown to contribute to the pathophysiology of schizophrenia. Furthermore, in neurological disorders, such as traumatic brain injury and Alzheimer’s disease, hyperactivation of NMDARs leads to synaptic damage. In addition to glutamate binding, NMDARs require the binding of a co-agonist d-serine or glycine to the GluN1 subunit to open. d-serine, which is racemized from l-serine by the neuronal enzyme serine racemase (SRR), and both SRR and d-serine are enriched in cortico-limbic brain regions. d-serine is critical for complex behaviors, such as cognition and social behavior, where dysregulation of its synthesis and release has been implicated in many pathological conditions. In this review, we explore the role of d-serine in behaviors that are translationally relevant to multiple psychiatric and neurological disorders in different models across species.