Amino Acids[JOURNAL]
Sun
200 papers
The relationship between dietary branched-chain and aromatic amino acids with the regulation of leptin and FTO genes in adipose tissue of patients undergoing abdominal surgery.
Teymoori F, Farhadnejad H, Norouzzadeh M … +10 more , Jahromi MK, Saber N, Mokhtari E, Asghari G, Yuzbashian E, Mirmiran P, Khalaj A, Zarkesh M, Hedayati M, Vafa M
Amino Acids · 2025 Jan · PMID 39798053 · Full text
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 a...
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/m), 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/m), 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.
Retraction Note: Modulation of mercury-induced mitochondria-dependent apoptosis by glycine in hepatocytes.
Pal PB, Pal S, Das J … +1 more , Sil PC
Amino Acids · 2025 Jan · PMID 39792176 · Full text
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Taurine prevents mitochondrial dysfunction and protects mitochondria from reactive oxygen species and deuterium toxicity.
Seneff S, Kyriakopoulos AM
Amino Acids · 2025 Jan · PMID 39789296 · Full text
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...
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.
Isoaspartate formation and irreversible aggregation of collapsin response mediator protein 2: implications for the etiology of epilepsy and age-related cognitive decline.
Zhu JX, Aswad DW
Amino Acids · 2024 Dec · PMID 39719537 · Full text
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 accu...
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.
Effect of D-amino acid metabolic enzyme deficiency on cancer development-diffuse large B-cell lymphoma onset and gene expression analyses in DASPO-knockout mice.
Nakade Y, Iwata Y, Harada K … +10 more , Sato Y, Mita M, Hamase K, Konno R, Hayashi M, Kobayashi T, Yamamura Y, Toyama T, Tajima A, Wada T
Amino Acids · 2024 Dec · PMID 39718666 · Full text
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 enz...
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.
Comprehensive analysis of peripheral blood free amino acids in MASLD: the impact of glycine-serine-threonine metabolism.
Mino M, Kakazu E, Sano A … +14 more , Tsuruoka M, Matsubara H, Kakisaka K, Kogure T, Sekine K, Aoki Y, Imamura M, Matsuda M, Yamazoe T, Mori T, Yoshio S, Inoue J, Masamune A, Kanto T
Amino Acids · 2024 Dec · PMID 39718621 · Full text
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...
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.
Dipeptides in CSF and plasma: diagnostic and therapeutic potential in neurological diseases.
Küper K, Poschet G, Rossmann J … +7 more , Garbade SF, Spiegelhalter A, Wen D, Hoffmann GF, Schmitt CP, Opladen T, Peters V
Amino Acids · 2024 Dec · PMID 39673003 · Full text
Dipeptides (DPs), composed of two amino acids (AAs), hold significant therapeutic potential but remain underexplored. Given the crucial role of AAs in central nervous system (CNS) function, this study investigated the pr...
Dipeptides (DPs), composed of two amino acids (AAs), hold significant therapeutic potential but remain underexplored. Given the crucial role of AAs in central nervous system (CNS) function, this study investigated the presence of DPs in cerebrospinal fluid (CSF) and their correlation with corresponding AAs, potentially indicating their role as AA donors. Plasma and CSF samples were collected from 43 children with neurological or metabolic conditions of unknown origin, including 23 with epilepsy. A panel of 33 DPs was quantified using UPLC-MS/MS. Out of 33 DPs, 18 were detectable in CSF and 20 in plasma, displaying high inter-individual variance. Gly-Asp, Gly-Pro, and Ala-Glu were consistently found in all CSF samples, while only Gly-Asp was universally detectable in plasma. Anserine and carnosine were prominent in CSF and plasma, respectively, with no other histidine-containing DPs observed. Generally, DP concentrations were higher in plasma than in CSF; however, anserine and Gly-Pro had similar concentrations in both fluids. Significant correlations were observed between specific DPs and their corresponding AAs in CSF (Gly-Glu, Gly-Pro and Ser-Gln) and plasma (Glu-Glu and Glu-Ser). Notably, patients with epilepsy had elevated medium anserine concentrations in CSF. This study is the first to demonstrate the presence of numerous DPs in CSF and plasma. Further research is needed to determine if DP patterns can support the diagnosis of neurological diseases and whether DP administration can modulate amino acid availability in the brain, potentially offering new therapeutic options, such as for defects in the amino acid transporter.
Free amino acids accelerate the time-dependent inactivation of rat liver nucleotide pyrophosphatase/phosphodiesterase Enpp3 elicited by EDTA.
Romero A, Cumplido-Laso G, Fernández A … +7 more , Moreno J, Canales J, Ferreira R, López-Gómez J, Ribeiro JM, Costas MJ, Cameselle JC
Amino Acids · 2024 Dec · PMID 39641818 · Full text
Nucleotide-pyrophosphatases/phosphodiesterases (NPP/PDE) are membrane or secreted Zn-metallohydrolases of nucleoside-5´-monophosphate derivatives. They hydrolyze, for instance, ATP and 4-nitrophenyl-dTMP, and belong to t...
Nucleotide-pyrophosphatases/phosphodiesterases (NPP/PDE) are membrane or secreted Zn-metallohydrolases of nucleoside-5´-monophosphate derivatives. They hydrolyze, for instance, ATP and 4-nitrophenyl-dTMP, and belong to the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family that contains seven members (ENPP1-ENPP7). Earlier we had shown that an NPP/PDE activity solubilized and partially purified from rat liver membranes is inactivated by EDTA in a time-dependent fashion, an effect enhanced by glycine and blocked by the 4-nitrophenyl-dTMP. Here, we extended this observation to other free amino acids. Activity assays started after different incubation lengths with EDTA provided first-order, apparent inactivation constants (k). With the exception of cysteine (a strong inhibitor) and histidine (itself evoking a time-dependent inactivation), free amino acids themselves did not affect activity but increased k. The results are compatible with a conformational change of NPP/PDE evoked by interaction with free amino acids. The enzyme preparation was analyzed to identify what ENPP family members were present. First, the hydrolytic activity on 2´,3´-cGAMP was assayed because until very recently ENPP1 was the only mammalian enzyme known to display it. 2´,3´-cGAMP hydrolase activity was clearly detected, but mass spectrometry data obtained by LC-MS/MS gave evidence that only rat Enpp3, Enpp4 and Enpp5 were present with low abundance. This finding coincided in time with a recent publication claiming that mouse Enpp3 hydrolyzes 2´,3´-cGAMP, and that Enpp1 and Enpp3 account for all the 2´,3´-cGAMP hydrolase activity in mice. So, our results are confirmatory of Enpp3 activity towards 2´,3´-cGAMP. Finally, the effect of amino acids could be relevant to NPP/PDE actions dependent on protein-protein interactions, like the known insulin-related effects of ENPP1 and possibly ENPP3.
The application and prospects of antimicrobial peptides in antiviral therapy.
Yang F, Ma Y
Amino Acids · 2024 Dec · PMID 39630161 · Full text
Antimicrobial peptides (AMPs) have broad-spectrum antimicrobial activity, enabling them to rapidly detect and eliminate targets. In addition, many AMPs are natural peptides, making them promising candidates for therapeut...
Antimicrobial peptides (AMPs) have broad-spectrum antimicrobial activity, enabling them to rapidly detect and eliminate targets. In addition, many AMPs are natural peptides, making them promising candidates for therapeutic drugs. This review discusses the basic properties and mechanisms of action of AMPs, highlighting their ability to disrupt microbial membranes and modulate host immune responses. It also reviews the current state of research into using AMPs against various viral infections, focusing on their therapeutic potential against viruses that contribute to the global health crisis. Despite promising developments, therapies based on AMPs still face challenges such as stability, toxicity, and production costs. In this text, we will discuss these challenges and the latest technological advances aimed at overcoming them. The combination of nanotechnology and bioengineering approaches offers new ways to enhance the delivery, efficacy, and safety of AMPs. We emphasize the importance of further research to fully exploit the potential of AMPs in antiviral therapy, advocating a multifaceted approach that includes optimizing clinical use and exploring synergies with existing antiviral drugs.
Synthesis of enantiomerically enriched β-substituted analogs of (S)-α-alanine containing 1-phenyl-1H-1,2,3-triazole groups.
Poghosyan AS, Khachatryan EA, Mkrtchyan AF … +6 more , Mirzoyan V, Hovhannisyan AM, Ghazaryan KR, Minasyan EV, Langer P, Saghyan AS
Amino Acids · 2024 Dec · PMID 39627616 · Full text
A synthesis of new enantiomerically enriched derivatives of (S)-α-aminopropionic acid, containing in the β-position 1,2,3-triazole groups coupled with a o-, m- and p-substituted phenyl residue, was developed based on Cu(...
A synthesis of new enantiomerically enriched derivatives of (S)-α-aminopropionic acid, containing in the β-position 1,2,3-triazole groups coupled with a o-, m- and p-substituted phenyl residue, was developed based on Cu(I) catalyzed [3 + 2] cycloaddition of azides with alkynes. As the starting materials was used the square-planar Ni(II)complex of the Schiff base of propargylglycine with the chiral auxiliary BPB (Benzylprolylbenzophenone) and 1,4-substituted phenyl azides. The assignment of the (S)-absolute configuration of the α-carbon atom of the amino acid residue of the main diastereomeric complexes of the cycloaddition products was carried out on the basis of positive Cotton effects in the region of 480-580 nm of the circular dichroism spectra. The target amino acids were isolated from acid hydrolysates of diastereomeric complexes using ion-exchange demineralization and crystallization from aqueous ethanol. Additional confirmation of the absolute configuration and determination of the enantiomeric purity of the target amino acids were carried out by chiral HPLC analysis. As a result, seven new non-proteinogenic (S)-α-amino acids, containing in the β-position a 1,2,3-triazole moiety, were synthesized.
Multiple strategies of HSP antimicrobial peptide optimization to enhance antimicrobial activity.
Cheng X, Zhang Y, Zhang Y … +4 more , Chen Y, Chen J, Wang W, Zhu G
Amino Acids · 2024 Nov · PMID 39589573 · Full text
Antimicrobial peptides (AMPs) have caught the attention of researchers over the last couple of years due to their unique membrane lytic mechanism for combating antibiotic resistance, which differs from the molecular targ...
Antimicrobial peptides (AMPs) have caught the attention of researchers over the last couple of years due to their unique membrane lytic mechanism for combating antibiotic resistance, which differs from the molecular targets of traditional antibiotics. Although natural AMPs exhibit potential antimicrobial activity against a wide range of microorganisms, some drawbacks, such as toxicity, low antibacterial activity, and high production costs limit their clinical application. To enhance the antimicrobial activity of a series of HSP peptides derived from the natural peptide HSP-1, this study optimized them using a variety of strategies, including net charge, hydrophobic moment, hydrophobicity, and helicity. Optimizing the antimicrobial action of HSP peptides depended mostly on net charge, hydrophobic moment, and hydrophobicity rather than helicity. HSP-M4 may be designed to combat microbial infections because the antimicrobial activity and cytotoxicity assays showed that they exhibited low cytotoxicity and prominent antimicrobial activity, respectively.
Altered amino acid levels in young hypopituitarism: impact of NAFLD and insulin resistance.
Zhang Y, Qiu J, Sun S … +1 more , Fang X
Amino Acids · 2024 Nov · PMID 39580591 · Full text
Elevated concentrations of amino acids (AAs) are commonly observed in patients with nonalcoholic fatty liver disease (NAFLD). Individuals with hypopituitarism (HP) are at a heightened risk of developing NAFLD due to fact...
Elevated concentrations of amino acids (AAs) are commonly observed in patients with nonalcoholic fatty liver disease (NAFLD). Individuals with hypopituitarism (HP) are at a heightened risk of developing NAFLD due to factors such as visceral obesity, increased insulin resistance (IR), and disturbances in lipid metabolism. However, the changes in AAs concentrations associated with HP remain poorly understood. Therefore, our study aimed to investigate whether individuals with HP, who were not receiving growth hormone replacement therapy (GHRT), exhibited altered AAs compared to controls (CTs), and whether these AAs were associated with IR, the presence of NAFLD, and the Metabolic Syndrome (MetS) score. The AAs profiles of 133 young males with HP (age: 24.5 ± 5.9; 57 with NAFLD and 76 without NAFLD) and 90 age and BMI-matched CTs were analyzed using untargeted metabolomics. The results revealed that most AAs were found to be elevated in subjects with HPs compared to CTs. Glutamate, glutamine, norleucine, and branched-chain amino acids (BCAAs) (leucine and valine) were correlated with the homeostasis model assessment of insulin resistance (HOMA-IR), with glutamate and norleucine showing independent linkage. Glutamate and proline levels were specifically associated with MetS score, while alanine and proline linked to NAFLD. Given that elevated glutamate and BCAAs levels have higher prevalence of NAFLD, we hypothesized that the changes in AAs observed in HPs may be attributed to the impact of NAFLD and IR.
The reverse transsulfuration pathway affects the colonic microbiota and contributes to colitis in mice.
Gobert AP, Latour YL, McNamara KM … +12 more , Hawkins CV, Williams KJ, Asim M, Barry DP, Allaman MM, Delgado AG, Milne GL, Zhao S, Piazuelo MB, Washington MK, Coburn LA, Wilson KT
Amino Acids · 2024 Oct · PMID 39427081 · Full text
Cystathionine γ-lyase (CTH) is a critical enzyme in the reverse transsulfuration pathway, the major route for the metabolism of sulfur-containing amino acids, notably converting cystathionine to cysteine. We reported tha...
Cystathionine γ-lyase (CTH) is a critical enzyme in the reverse transsulfuration pathway, the major route for the metabolism of sulfur-containing amino acids, notably converting cystathionine to cysteine. We reported that CTH supports gastritis induced by the pathogen Helicobacter pylori. Herein our aim was to investigate the role of CTH in colonic inflammation. First, we found that CTH is induced in the colon mucosa in mice with dextran sulfate sodium-induced colitis. Expression of CTH was completely absent in the colon of Cth mice. We observed that clinical and histological parameters are ameliorated in Cth-deficient mice compared to wild-type animals. However, Cth deletion had no effect on tumorigenesis and the level of dysplasia in mice treated with azoxymethane-DSS, as a reliable model of colitis-associated carcinogenesis. Mechanistically, we determined that the deletion of the gene Slc7a11 encoding for solute carrier family 7 member 11, the transporter of the anionic form of cysteine, does not affect DSS colitis. Lastly, we found that the richness and diversity of the fecal microbiota were significantly increased in Cth mice compared to both WT and Slc7a11 mice. In conclusion, our data suggest that the enzyme CTH represents a target for clinical intervention in patients with inflammatory bowel disease, potentially by beneficially reshaping the composition of the gut microbiota.
Structure-activity relationship of amino acid analogs to probe the binding pocket of sodium-coupled neutral amino acid transporter SNAT2.
Jakobsen S, Pedersen M, Nielsen CU
Amino Acids · 2024 Oct · PMID 39427053 · Full text
The sodium-coupled neutral amino acid transporter SNAT2 (SLC38A2) has been shown to have important physiological functions and is implicated in various diseases like cancer. However, few compounds targeting this transpor...
The sodium-coupled neutral amino acid transporter SNAT2 (SLC38A2) has been shown to have important physiological functions and is implicated in various diseases like cancer. However, few compounds targeting this transporter have been identified and little is known about the structural requirements for SNAT2 binding. In this study, the aim was to establish the basic structure-activity relationship for SNAT2 using amino acid analogs. These analogs were first studied for their ability to inhibit SNAT2-mediated H-glycine uptake in hyperosmotically treated PC-3 cells. Then to identify substrates a FLIPR membrane potential assay and o-phthalaldehyde derivatization of intracellular amino with subsequent quantification using HPLC-Fl was used. The results showed that ester derivatives of the C-terminus maintained SNAT2 affinity, suggesting that the negative charge was less important. On the other hand, the positive charge at the N-terminus of the substrate and the ability to donate at least two hydrogen bonds to the binding site appeared important for SNAT2 recognition of the amine. Side chain charged amino acids generally had no affinity for SNAT2, but their non-charged derivatives were able to inhibit SNAT2-mediated H-glycine uptake, while also showing that amino acids of a notable length still had affinity for SNAT2. Several amino acid analogs appeared to be novel substrates of SNAT2, while γ-benzyl L-glutamate seemed to be inefficiently translocated by SNAT2. Elaborating on this structure could lead to the discovery of non-translocated inhibitors of SNAT2. Thus, the present study provides valuable insights into the basic structural binding requirements for SNAT2 and can aid the future discovery of compounds that target SNAT2.
LLM4THP: a computing tool to identify tumor homing peptides by molecular and sequence representation of large language model based on two-layer ensemble model strategy.
Yang S, Xu P
Amino Acids · 2024 Oct · PMID 39404804 · Full text
Tumor homing peptides (THPs) have a distinctive capacity to specifically attach to tumor cells, providing a promising approach for targeted cancer treatment and detection. Although THPs have the potential for significant...
Tumor homing peptides (THPs) have a distinctive capacity to specifically attach to tumor cells, providing a promising approach for targeted cancer treatment and detection. Although THPs have the potential for significant impact, their detection by conventional methods is both time-consuming and expensive. To tackle this issue, we provide LLM4THP, an innovative computational approach that utilizes large language models (LLMs) to quickly and effectively detect THPs. LLM4THP utilizes two protein LLMs, ESM2 and Prot_T5_XL_UniRef50, to encode peptide sequences. This allows for the capture of complex patterns and relationships within the peptide data. In addition, we utilize inherent sequence characteristics such as Amino Acid Composition (AAC), Pseudo Amino Acid Composition (PAAC), Amphiphilic Pseudo Amino Acid Composition (APAAC), and Composition, Transition, and Distribution (CTD) to improve the representation of peptides. The RDKitDescriptors feature representation approach transforms peptide sequences into molecular objects and computes chemical characteristics, resulting in enhanced THP identification. The LLM4THP ensemble strategy incorporates various features into a two-layer learning architecture. The first layer consists of LightGBM, XGBoost, Random Forest, and Extremely Randomized Trees, which generate a set of meta results. The second layer utilizes Logistic Regression to further refine the identification of sequences as either THP or non-THP. LLM4THP exhibits exceptional performance compared to the most advanced methods, showcasing enhancements in accuracy, Matthew's correlation coefficient, F1 score, area under the curve, and average precision. The source code and dataset can be accessed at the following URL: https://github.com/abcair/LLM4THP.
Kinetic analysis of D-Alanine upon oral intake in humans.
Kimura T, Sakai S, Horio M … +11 more , Takahara S, Ishigo S, Nakane M, Negishi E, Imoto H, Mita M, Hamase K, Higa-Maekawa Y, Kakuta Y, Mizui M, Isaka Y
Amino Acids · 2024 Oct · PMID 39400632 · Full text
D-Alanine, a rare enantiomer of alanine, can potentially alleviate the worsening of viral infections and maintain circadian rhythm. This study aimed to analyze the kinetics of D-Alanine upon oral intake. Five healthy vol...
D-Alanine, a rare enantiomer of alanine, can potentially alleviate the worsening of viral infections and maintain circadian rhythm. This study aimed to analyze the kinetics of D-Alanine upon oral intake. Five healthy volunteers were administered D-Alanine as a single oral dose at 11,236 or 33,708 µmoL (1-3 g). Upon intake of the lower dose, the plasma level of D-Alanine reached its peak concentration of 588.4 ± 40.9 µM with a peak time of 0.60 ± 0.06 h. The compartment model estimated the clearance of D-Alanine at 12.5 ± 0.3 L/h, or 208 ± 5 mL/min, distribution volume of 8.3 ± 0.7 L and half-life of 0.46 ± 0.04 h, suggesting a rapid clearance of D-Alanine. The peak concentration and area under the curve increased proportionally upon intake of the higher dose, while the clearance, distribution volume and half-life did not. The urinary ratio of D-Alanine per sum of D- and L-Alanine reached its peak of nearly 100%, followed by a slow decline. The peak time of the urinary ratio was 1.15 ± 0.15 h, showing a time lag of blood to urine excretion. Fractional excretion, a ratio of the clearance of a substance per a standard molecule in kidney, of D-Alanine increased from 14.0 ± 5.8% to 64.5 ± 10.3%; the latter corresponded to the urinary clearance of D-Alanine as about 77 mL/min for an adult, with a peak time of 1.90 ± 0.56 h. D-Alanine was quickly absorbed and appeared in blood, followed by urinary excretion. This kinetic analysis increases our fundamental knowledge of the oral intake of D-Alanine for the chronic dosing. Trial number: #UMIN000050865. Date of registration: 2023/6/30.
A systematic review and meta-analysis of clinical trials on the effects of glutamine supplementation on gut permeability in adults.
Abbasi F, Haghighat Lari MM, Khosravi GR … +3 more , Mansouri E, Payandeh N, Milajerdi A
Amino Acids · 2024 Oct · PMID 39397201 · Full text
The gastrointestinal tract's epithelial barrier plays a crucial role in maintaining health. This study aims to investigate the impact of glutamine supplementation on intestinal permeability, considering its importance fo...
The gastrointestinal tract's epithelial barrier plays a crucial role in maintaining health. This study aims to investigate the impact of glutamine supplementation on intestinal permeability, considering its importance for immune function and nutrient absorption. The study adhered to the PRISMA protocol for systematic reviews and meta-analyses. A systematic search was performed in four databases (PubMed, Scopus, Web of Science, and Google Scholar) until April 2023 to identify clinical trials on glutamine supplementation and gastrointestinal permeability. Eligibility criteria included randomized placebo-controlled trials measuring gut permeability post-glutamine supplementation. Studies were included regardless of language or publication date. Data extraction involved study characteristics, intervention details, and outcomes. Quality assessment was performed using the Cochrane tool, and statistical analysis utilized mean differences and standard deviations with a random effects model. Subgroup analysis was conducted to explore heterogeneity. The systematic review and meta-analysis included 10 studies from 1998 to 2014 with 352 participants. A total of 216 patients were enrolled in the intervention group, and 212 in the control group. The mean participant age was 46.52 years. The participants had different types of diseases in terms of their health status. Overall, glutamine supplementation did not significantly affect intestinal permeability (WMD: -0.00, 95% CI -0.04, 0.03). Subgroup analysis showed a significant reduction in intestinal permeability with doses over 30g/day (WMD: -0.01, 95% CI -0.10, -0.08). The glutamine supplements were administered orally in all included studies. The meta-analysis demonstrated a significant reduction in intestinal permeability with glutamine supplementation exceeding 30 mg/day for durations of less than 2 weeks. Further investigations with varying dosages and patient populations are warranted to enhance understanding and recommendations regarding glutamine supplementation's effects on gut permeability.
Green synthesis of self-oriented flower-like Ag@AgO nanostructures functionalized with L-Tryptophan for colorimetric simultaneous determination of ultra-trace level of thiamin and riboflavin.
Tarighat MA, Khosravani Z, Abdi G
Amino Acids · 2024 Oct · PMID 39395923 · Full text
The study focuses on the green synthesis of Ag@AgO nanostructures using Padina algae extract and functionalizing them with L-tryptophan to enhance their properties as a colorimetric sensor for simultaneous detection of u...
The study focuses on the green synthesis of Ag@AgO nanostructures using Padina algae extract and functionalizing them with L-tryptophan to enhance their properties as a colorimetric sensor for simultaneous detection of ultra-trace levels of thiamin and riboflavin. The nanostructures are characterized using techniques like XRD, FESEM, FTIR, TEM, AFM, and DLS to understand their morphology, structure, and interactions with target molecules. FESEM analysis revealed the hierarchical flower-like Ag@AgO nanostructures. The TEM image shows the formation of core-shell nanostructures. Also, DLS analysis and surface zeta potential spectra illustrated the aggregated nature of fabricated nanocomposites in the presence of vitamins. The study is the first to report simultaneous determination of thiamin and riboflavin using a colorimetric sensor based on Ag@AgO-L-Try nanocomposites using partial leas square (PLS). The dynamic range of thiamin and riboflavin was achieved in 0.1 mol L1 acetate buffer pH 4 and the ratio Ag@AgO: L-try 1:1. The Ag@AgO-L-Try sensor exhibited two linear ranges of 0.1- 1.0 and 3-350 µMol L for riboflavin and a linear range 3.0-60 µMol L for thiamin. Also, low detection limit of 1.92 µMol L and 0.048 µMol L was obtained for riboflavin and thiamin, respectively. The results indicated that the success of the method depends on the selective and sensitive colorimetric assay of the sensor along with the simultaneous determination by the PLS algorithm. Hence, the proposed technique can be used for the accurate and precise determination of vitamins in different pharmaceutical syrup and tablet samples.
Impact of smokeless tobacco on psychological and oxidative stress in unemployed indian youth.
Mishra A, Kumar R, Mishra SN … +3 more , Vijayaraghavalu S, Shukla GC, Kumar M
Amino Acids · 2024 Oct · PMID 39395920 · Full text
In India, tobacco (nicotine) addiction among youth has increased, leading to substantial socioeconomic burdens, mortality, and morbidity. While minimal short-term nicotine consumption may have antioxidant effects, chroni...
In India, tobacco (nicotine) addiction among youth has increased, leading to substantial socioeconomic burdens, mortality, and morbidity. While minimal short-term nicotine consumption may have antioxidant effects, chronic exposure results in various adverse health outcomes. This study examines the impact of chronic nicotine consumption on cellular oxidative stress and psychological stress, and their correlation with Homocysteine (Hcy) levels in unemployed tobacco consumers. This case-control study included 156 healthy, educated, unemployed male volunteers aged 20-40 years, divided into nicotine-addicted (n = 80) and non-addicted (n = 76) groups. Psychological stress was assessed using perceived stress scales (PSS) and coping self-efficacy (CSE) scales. Oxidative stress markers, including Malondialdehyde (MDA), Superoxide Dismutase (SOD), and Catalase, were measured. Hcy levels were quantified using high-performance liquid chromatography (HPLC). Nicotine-addicted participants exhibited significantly higher perceived stress (p = 0.0001) and lower coping self-efficacy (p = 0.0001) compared to non-addicted individuals. MDA levels in erythrocytes were significantly increased (p = 0.0006), while SOD (p = 0.0001) and Catalase (p = 0.02) activities were significantly decreased in the addicted group. Nicotine intake influenced Hcy concentrations, with 55% of addicted individuals falling into moderate, 27.5% into intermediate, and 7.5% into severe Hcy categories. Chronic nicotine intake also reflected the hematological parameters (WBCs, RBCs, HGB, and Platelets). Chronic tobacco consumption induces oxidative stress and perceived psychological stress, leading to elevated Hcy levels in nicotine consumers. The study highlights the detrimental effects of nicotine addiction on cellular defensive mechanisms, emphasizing the need for targeted interventions to address this growing health issue among unemployed Indian youth.
HECTD2 as a target for veratric acid in the regulation of ferroptosis in renal cell carcinoma.
Lv D, Xiang Y, Song T … +4 more , Li J, Chen Y, Huili Y, Shen T
Amino Acids · 2024 Sep · PMID 39343853 · Full text
Function of HECTD2 in renal cell carcinoma malignant progression is undefined. Molecular mechanism behind anti-cancer effects of veratric acid (VA) from traditional Chinese medicine (TCM) is underexplored. The Cancer Gen...
Function of HECTD2 in renal cell carcinoma malignant progression is undefined. Molecular mechanism behind anti-cancer effects of veratric acid (VA) from traditional Chinese medicine (TCM) is underexplored. The Cancer Genome Atlas was leveraged to study HECTD2 expression in renal cell carcinoma and its relationship with histological grading. Kaplan-Meier survival analysis was performed. HECTD2 expression was detected in cancer cells and tissues via qRT-PCR and immunohistochemistry. GPX4 and SLC7A11 expression in tumor samples with high or low HECTD2 expression was examined by immunohistochemistry, cell viability by CCK8, cell proliferation by colony formation assay, lipid ROS and mitochondrial superoxide levels by flow cytometry, Fe and MDA content by assay kits, and GPX4 and SLC7A11 proteins by western blot. SeeSAR software screened TCM small molecule compounds with highest affinity to HECTD2, confirmed with cellular thermal shift assay. VA IC was measured by CCK8. Xenograft model was developed and treated with VA. Tumor size and weight were monitored, with immunohistochemistry to detect HECTD2 expression in tumors and assess ferroptosis-related markers. HECTD2 was overexpressed in tumor tissues and cells, which positively correlated with histological grading. HECTD2 depletion inhibited cell vitality and proliferation, raised intracellular lipid ROS, mitochondrial superoxide, Fe, and MDA. HECTD2 was a target with highest VA affinity. In vitro and vivo experiments concurred that VA treatment hindered malignancy of renal cell carcinoma and enhanced its susceptibility to ferroptosis. HECTD2 supports ferroptosis resistance in renal cell carcinoma, but VA, through its targeting of HECTD2, initiates ferroptosis, showcasing its anti-cancer efficacy.
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