Amino Acids[JOURNAL]
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200 papers
Author Correction: Novel octapeptide containing the RGD sequence as a potential anti-SARS-CoV-2 agent: design, synthesis, and theoretical studies.
Lemos R, Ortiz O, Almagro L … +4 more , Makowski K, Rodríguez H, Albericio F, Suárez M
Amino Acids · 2026 Jul · PMID 42400866 · Publisher ↗
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Polyamines in CNS malignancies: positively charged culprits in the hijacking of neural and immune signaling pathways.
Rana AB, Welford SM
Amino Acids · 2026 Jul · PMID 42400668 · Publisher ↗
The mammalian polyamines (putrescine, spermidine and spermine) are ubiquitous polycations, long recognized for their indispensable roles in maintaining cell proliferation, differentiation and survival. Traditionally view...
The mammalian polyamines (putrescine, spermidine and spermine) are ubiquitous polycations, long recognized for their indispensable roles in maintaining cell proliferation, differentiation and survival. Traditionally viewed as metabolic supporters of growth, polyamines have recently emerged as active regulators of cell-cell signaling in diverse physiological and pathological settings. Through intercellular polyamine transfer, modulation of ion channels and interactions with cell-surface receptors, polyamines orchestrate intricate signaling networks, from neurotransmission in the nervous system to cytokine signaling in the immune compartment. Many cancers, though most clearly, central nervous systems (CNS) cancers, exploit neuro- and immunomodulatory circuits, effectively hijacking neural and immune signaling pathways to sustain growth and evade surveillance. Thus, an integrated, multi-disciplinary perspective is required to overcome hurdles in the treatment of these aggressive malignancies. In light of ongoing clinical trials aimed at disrupting polyamine synthesis and transport in brain tumors, better defining the role of polyamines in mediating tumor-host interactions is essential for maximizing anti-tumor efficacy while minimizing normal tissue toxicity. This review integrates advances from cancer biology, immunology and neuroscience to comprehensively discuss the mechanisms through which polyamines regulate cell-cell signaling, the role of these pathways in brain tumor progression and the diagnostic and therapeutic opportunities that arise from this knowledge.
The effects of glutamine supplementation on inflammatory and oxidative stress indices in chronic diseases: a systematic review.
Movahed S, Bahadorkhan A, Malov V … +2 more , Emadzadeh M, Pahlavani N
Amino Acids · 2026 Jun · PMID 42366260 · Publisher ↗
Chronic diseases are often associated with increased inflammation and oxidative stress, which contribute to disease progression. Glutamine, a conditionally essential amino acid, has been studied for its potential anti-in...
Chronic diseases are often associated with increased inflammation and oxidative stress, which contribute to disease progression. Glutamine, a conditionally essential amino acid, has been studied for its potential anti-inflammatory and antioxidant properties in various chronic conditions. The present systematic review evaluates the effects of glutamine supplementation on inflammatory markers and oxidative stress indices in patients with chronic diseases. Systematic searches were performed in web databases; Web of Science, Scopus, and PubMed/Medline until May 2025, to identify related randomized controlled trials (RCTs) according to the Cochrane Library and PICOS criteria (population: individuals > 18 years, intervention: glutamine, Comparison: placebo or control, Outcomes: inflammatory and oxidative stress markers in chronic diseases). The Cochrane collaboration tool was used to assess the risk of bias in clinical trials. Six RCTs that assessed the effect of glutamine supplementation on inflammation and oxidative stress markers were included in the study. In these studies, glutamine was administered to the participants through oral or parenteral routes. In three studies improve inflammation via significant reductions in CRP were observed. However, in three studies that examined TNF-α as an inflammatory marker, only one study found its levels to be significantly reduced. Also, of the two studies that examined oxidative stress levels, only one study significantly decreased the MDA and increased SOD levels, and in the other study, glutamine supplementation had no significant effect on glutathione levels. Our findings showed that glutamine supplementation might have a positive effect on inflammation and oxidative stress indices such as TNF-α, CRP, MDA, and SOD in some chronic diseases, however, these effects have not been shown in all studies, so more carefully designed clinical trial studies with different doses of glutamine on inflammation and oxidative stress in chronic diseases are needed. PROSPERO Code: This study was registered in the PROSPERO international prospective register of systematic reviews registration number: CRD420251049112.
Reprogramming parasitic signatures into anticancer peptide candidates: in silico discovery of Leishmania major-derived peptides.
Dehghanian A, Izadi M, Minaei Z … +6 more , Cheshrokh M, Fathi Tadavani F, Masoudi A, Bagherzadeh MA, Mofazzal Jahromi MA, Pirestani M
Amino Acids · 2026 Jun · PMID 42366251 · Publisher ↗
This study aims to computationally identify and prioritize anticancer peptide (ACP) candidate sequences derived from the Leishmania major proteins KMP11 and GP63 using an integrated bioinformatics framework that incorpor...
This study aims to computationally identify and prioritize anticancer peptide (ACP) candidate sequences derived from the Leishmania major proteins KMP11 and GP63 using an integrated bioinformatics framework that incorporates peptide design, safety assessment, multi-criteria decision-making, and membrane-oriented evaluation. Amino acid sequences of KMP11 and GP63 were obtained from the NCBI database. Peptide fragments ranging from 5 to 25 residues were computationally generated and initially screened for anticancer potential using AntiCP 2.0 and MLACP prediction tools. Candidate peptides were subsequently subjected to systematic amino acid substitutions followed by iterative re-evaluation to optimize predicted anticancer properties. Toxicity, allergenicity, and antigenicity were assessed using TOXINPRED2, ALGPRED2, and VAXIJEN2, respectively. Peptides meeting safety and functional criteria were prioritized using the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS). Structural modeling, exploratory molecular docking, and membrane interaction analyses were then performed to provide comparative mechanistic insights into membrane association and potential receptor accessibility, rather than to predict specific target binding. Reference datasets of experimentally validated ACPs and non-ACPs were compiled, and motif analysis using MERCI identified sequence patterns associated with anticancer activity, with enriched motifs most frequently observed in the 12-13 residue range. Following iterative screening and safety evaluation, subsets of peptides derived from KMP11 and GP63 were identified as non-toxic and non-allergenic according to in silico prediction tools. These peptides were subsequently prioritized using the TOPSIS multi-criteria decision-making model. The top-ranked candidates were further subjected to exploratory molecular docking against selected cancer-associated receptors and coarse-grained membrane interaction analysis to provide comparative mechanistic context regarding membrane interaction propensity and potential receptor accessibility. Based on integrated computational scoring, ten peptides were prioritized as candidate sequences for further experimental validation. This study demonstrates the feasibility of computationally deriving and prioritizing anticancer peptide candidates from L. major proteins KMP11 and GP63. The proposed framework provides a structured, hypothesis-generating strategy for ACP candidate prioritization, emphasizing comparative evaluation rather than direct prediction of therapeutic efficacy or specific molecular targets. By leveraging evolutionary and physicochemical features associated with host-pathogen interactions, this approach enables systematic exploration of parasite-derived peptide sequence space. Experimental validation will be essential to determine the biological activity, selectivity, and translational relevance of the identified candidates.
Effects of taurine on skeletal muscle in senescence-accelerated mice and C2C12 myoblasts and myotubes.
Huang Y, Kobayashi H, Zhou X … +7 more , Matsuoka K, Kawanokuchi J, Midorikawa K, Oikawa S, Zhang Z, Ma N, Murata M
Amino Acids · 2026 Jun · PMID 42360509 · Publisher ↗
Taurine is a semi-essential amino acid with diverse cytoprotective effects and is associated with anti-aging. This study explores the role and molecular mechanism of taurine in muscle aging. Senescence-accelerated mouse...
Taurine is a semi-essential amino acid with diverse cytoprotective effects and is associated with anti-aging. This study explores the role and molecular mechanism of taurine in muscle aging. Senescence-accelerated mouse prone 8 (SAMP8) and its resistant (senescence-accelerated mouse resistant 1, SAMR1) mice were given 1% taurine water from 5 to 10 months of age, while control mice were given distilled water (DW). At 10 months of age, a rotarod test was performed to assess muscle endurance. SAMP8 mice had a shorter running time on the rotarod test than SAMR1 mice. Taurine significantly extended running time compared with that of DW-drinking group in SAMP8 mice, a similar trend was observed in SAMR1 mice. The gastrocnemius muscle was used for the RNA-sequencing analysis. Among differentially expressed genes between taurine and DW, Tbx5 and Alb showed some significant differences between the treatment by RT-qPCR. Myoblast C2C12 cells underwent cellular senescence induction with D-galactose (D-gal), which was detected by SA-β-gal staining. Taurine reduced SA-β-gal-positive area induced by D-gal, suggesting its protective effect against cellular senescence. Myotube induction was inhibited by D-gal treatment and restored by taurine, as detected by immunocytochemistry of myosin heavy chain (MHC) and Western blot of myogenin. D-gal-induced decrease trend in protein level of TBX5 was significantly increased in C2C12 myotubes treated with taurine. Taurine may have a protective effect on muscle senescence and myotube regeneration.
Dual functions of thermospermine in plant growth and stress responses.
Foschi V, D'Incà R, Saraumi M … +2 more , Tavladoraki P, Takahashi T
Amino Acids · 2026 Jun · PMID 42360390 · Publisher ↗
In seed plants, putrescine, spermidine, and spermine are ubiquitously present, whereas a structural isomer of spermine, thermospermine (TSpm), is synthesized mainly in the vascular tissue. Initially identified in the bac...
In seed plants, putrescine, spermidine, and spermine are ubiquitously present, whereas a structural isomer of spermine, thermospermine (TSpm), is synthesized mainly in the vascular tissue. Initially identified in the bacterium Thermus thermophilus, TSpm was later shown to be synthesized in Arabidopsis thaliana by ACAULIS5 (ACL5). ACL5 gene homologs may have been acquired early in plant evolution via endosymbiotic gene transfer from a cyanobacterial ancestor. Loss-of-function acl5 mutants exhibit a dwarf phenotype and excessive vascular xylem formation. Subsequent studies, including analysis of suppressor-of-acl5 (sac) mutants, revealed that TSpm exerts a critical role in the repression of vascular xylem proliferation by acting in upstream open-reading-frame (uORF)-dependent translational regulation of specific mRNAs. A recent study revealed functional TSpm binding to the peptidyl transferase center of 25 S rRNA promoted by methylation of residue U2952. Like other polyamines, TSpm has also been shown to participate in stress responses, enhancing tolerance to salt, drought, heat, and pathogen challenges in multiple species. Collectively, TSpm represents a unique polyamine with dual roles in xylem development and stress adaptation, whose evolutionary origin and molecular mechanisms provide insights into the specialization of polyamine biology. Further studies in nonvascular plants and algae are needed to elucidate the ancestral functions of TSpm.
Zinc finger protein-associated gene signature serves as a potential predictor for prognosis and therapeutic response in lung adenocarcinoma.
Zou M, Zheng G, Bao Y
Amino Acids · 2026 Jun · PMID 42360372 · Publisher ↗
Zinc finger proteins (ZNFs), characterized by zinc ion-binding domains, participate in cell proliferation, differentiation, and metastasis in lung adenocarcinoma (LUAD). However, associations between ZNFs-related genes a...
Zinc finger proteins (ZNFs), characterized by zinc ion-binding domains, participate in cell proliferation, differentiation, and metastasis in lung adenocarcinoma (LUAD). However, associations between ZNFs-related genes and clinical outcomes, immune cell infiltration, and immunotherapy remain unclear. To explore feasibility of using ZNFs-related genes as prognostic tools for LUAD risk stratification. Retrospective analyses were conducted utilizing data from TCGA and GSE26939. After screening differentially expressed ZNFs, regression analyses were performed to construct prognostic signature. Enrichment analysis identified biological processes and pathways involved in signature genes, while immune landscape was examined by multiple algorithms. The drug sensitivity analysis identified potential candidate drugs related to the signature genes. Cell experiments indicated the function of the key risk gene CTCFL in promoting the malignant behavior of LUAD cells. A prognostic signature comprising 12 ZNFs-related genes (CBFA2T3, CTCFL, GFI1B, IGF2BP1, RIMS2, TRIM29, TRIML2, ZIC2, ZNF208, KLF10, ZNF750, and ZNF257) stratified LUAD patients into two risk groups, demonstrating robust performance in predicting clinical outcomes. These genes were significantly enriched in epidermal development, intermediate filament cytoskeleton, endopeptidase inhibitor activity, hormone activity, and neuroactive ligand-receptor interactions. Low-risk patients exhibited higher levels of immune cell infiltration (e.g., DCs, B cells, and neutrophils) and superior responses to immunotherapy (anti-CTLA-4 and PD-1/CTLA-4 dual blockade). Possible therapeutic compounds for LUAD patients included SHP-099, Dimethylfasudil, EMD-534085, and PF-2771. The expression of CTCFL enhanced the malignant cellular behavior in LUAD. ZNFs-related gene signature provides predictive insights into LUAD patient survival, immune cell infiltration, and immune checkpoint blockade therapy, serving as a valuable tool to guide clinical decision-making.
LC-MS assay for quantifying ornithine decarboxylase activity in the biological matrix and cultured cells using stable isotope‑labeled ornithine.
Shiomi Y, Ogawa N, Takahama K … +2 more , Murai A, Furukawa K
Amino Acids · 2026 Jun · PMID 42323767 · Publisher ↗
Polyamines (putrescine, spermidine, and spermine) are essential for animal health and development, and their intracellular levels must be tightly regulated to maintain normal cellular functions. Ornithine decarboxylase (...
Polyamines (putrescine, spermidine, and spermine) are essential for animal health and development, and their intracellular levels must be tightly regulated to maintain normal cellular functions. Ornithine decarboxylase (ODC) catalyzes the rate-limiting decarboxylation step in polyamine biosynthesis, and thus accurate assessment of its activity is vital for studies of polyamine metabolism. However, conventional ODC assays rely on radiolabeled substrates and require specialized facilities for radioactive handling. To overcome these limitations, we developed a sensitive and non-radioactive ODC assay using stable isotope-labeled ornithine in combination with liquid chromatography-mass spectrometry (LC-MS). In this protocol, animal tissues (e.g., 0.5 g) or cultured cells (e.g., 2.0 × 10 cells) are homogenized, and cytosolic fractions are prepared by centrifugation. These fractions are incubated with d-ornithine under 37 °C conditions, and the produced d-putrescine is derivatized with dansyl chloride and quantified by LC-MS analysis. Reaction samples showed a distinct peak corresponding to d-putrescine, whereas negative control displayed negligible signals. Moreover, d-spermidine and d-spermine were not detectable under these conditions, indicating d-putrescine production directly reflects ODC activity. We optimized reaction time and substrate concentrations to ensure linearity and precision, and confirmed that the assay responds appropriately to pharmacological inhibition of ODC. Collectively, this protocol provides a practical, sensitive, and non-radioactive method for quantifying ODC activity in both animal tissues and cultured cells, and it offers an accessible tool for polyamine metabolism research.
Deciphering the molecular heterogeneity of HER2-positive breast cancer: the critical interplay of hormone receptor status and transcriptomic landscapes.
Sengul I, Sengul D, Akalin C
Amino Acids · 2026 Jun · PMID 42301336 · Publisher ↗
The clinical management of HER2-positive breast cancer is undergoing a paradigm shift, recognizing that hormone receptor (HR) co-expression defines a fundamental biological dichotomy rather than a minor clinical variatio...
The clinical management of HER2-positive breast cancer is undergoing a paradigm shift, recognizing that hormone receptor (HR) co-expression defines a fundamental biological dichotomy rather than a minor clinical variation. This perspective evaluates the profound heterogeneity within the HER2-positive subclass, where HR status acts as a master regulator of genomic landscapes and patient outcomes. Evidence from large-scale database analyses reveals that HR+/HER2 + malignancies are associated with a significant survival advantage, contrasting with the heightened phenotypic aggression and advanced staging characteristic of HR-negative disease. At the molecular level, this divergence is underpinned by distinct transcriptomic profiles; specifically, the enrichment of drug-metabolizing pathways-including cytochrome P450 and retinol metabolism involving CYP2A6 and UGT2B7-suggests a mechanism for superior endocrine sensitivity and modulated apoptotic signaling in the double-positive cohort. Furthermore, the tumor microenvironment reflects this biological disparity, with HR status potentially governing local immune responses, as evidenced by the differential infiltration of resting mast cells versus plasma cells. Of note, while somatic mutations in TP53 and PIK3CA persist across both cohorts, the unique metabolic and immunological milieus confirm that these subtypes represent biologically discrete entities. Moving forward, the "HER2-positive" designation must be refined through integrated, biomarker-driven frameworks. Incorporating these molecular nuances into prospective clinical trials is essential for optimizing therapeutic de-escalation and overcoming the persistent challenges of resistance in HER2-targeted care.
Computational identification of antigens and development of a multi-epitope vaccine for bacterial vaginosis caused by Gardnerella vaginalis.
Niknezhad MA, Doosti A, Shakhsi-Niaei M
Amino Acids · 2026 Jun · PMID 42289006 · Publisher ↗
Bacterial vaginosis (BV), a prevalent form of vaginal dysbiosis, is primarily caused by Gardnerella vaginalis. The increasing prevalence of BV has raised global health concerns, prompting the need for a vaccine that can...
Bacterial vaginosis (BV), a prevalent form of vaginal dysbiosis, is primarily caused by Gardnerella vaginalis. The increasing prevalence of BV has raised global health concerns, prompting the need for a vaccine that can enhance human immunity and mitigate BV transmission. The study developed a multi-epitope vaccine for BV infection using immunoinformatic methodologies. B-cell and T-cell epitopes were identified using the IEDB recommended server and NetCTL. Specifically, HTL epitopes were predicted against HLA-DR alleles (including DRB101:01, DRB103:05, and DRB104:04), while CTL epitopes were predicted against HLA class I supertypes (including HLA-A02:01 and HLA-A*01:01). The selected epitopes were fused using adjuvants and linkers. The peptide sequence MSPSVRHSPSVRH, derived from the heat shock protein 60 (HSP60) of Mycobacterium tuberculosis, was incorporated as an adjuvant to activate innate immunity via TLR2/4 and enhance dendritic cell maturation. The B-cell and (CTL or HTL) epitopes were connected using GGGS linkers, whereas the CTL + HTL epitopes were connected using HEYGAEALERAG linkers. Additional epitopes were chosen based on antigenicity, allergenicity, and immunological features. TLR2 recognizes bacterial lipoproteins and peptidoglycan. TLR2 and TLR-4 showed robust interactions in molecular docking. The results of the present study demonstrate that the produced vaccine displayed stability, shown by a molecular weight of 49924.79 Da and an antigenicity value of 1.37. The Vaccine Construct demonstrated stability and basicity, shown by an instability score of 32.65 and a projected isoelectric point (pI) of 5.09. The expected secondary structure of the vaccine construct consisted of 94.57% random coil, and 5.43% extended strand. The suggested vaccine demonstrated efficient binding to its TLR2 and TLR4 receptors, yielding the maximum Van der Waals energy of (-97.2 +/- 5.9) and (-67.6 +/- 7.3) kcal/mol, respectively. The polypeptide vaccine's stability and compactness were assessed using molecular dynamics simulations. The vaccine showed favorable stability, expression, immunostimulatory properties, and solubility.
L-Proline protects human sperm from heat stress-induced oxidative damage.
Moradi M, Shayestehyekta M, Hashemian AH … +1 more , Faramarzi A
Amino Acids · 2026 Jun · PMID 42283890 · Publisher ↗
L-proline, an amino acid with antioxidant properties, has demonstrated significant potential in counteracting oxidative stress and preserving sperm quality. This study evaluated the protective effects of L-proline agains...
L-proline, an amino acid with antioxidant properties, has demonstrated significant potential in counteracting oxidative stress and preserving sperm quality. This study evaluated the protective effects of L-proline against heat stress-induced damage during sperm preparation incubation, a critical step in assisted reproductive technologies (ART). Semen samples from 30 normozoospermic men were divided into two groups: a control group and a treatment group supplemented with 2 mmol/L L-proline. Following initial incubation at 37 °C for 30 min, samples were further subdivided and subjected to controlled thermal exposures at 25 °C, 37 °C, and 42 °C for both short-term (3 h) and long-term (24 h) incubation periods, simulating physiological and heat-stress conditions. Sperm parameters, including motility, viability, morphology, and biochemical markers of oxidative stress, including catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), malondialdehyde (MDA), and nitric oxide (NO), were comprehensively assessed. Results indicated that heat stress exposure significantly impaired sperm function and disrupted redox homeostasis. Supplementation with 2 mmol/L L-proline significantly preserved sperm motility and viability during heat stress conditions compared to the control group (p < 0.05). However, no significant protective effect on sperm morphology was observed. Additionally, L-proline enhanced antioxidant defenses by improving CAT, SOD, and TAC levels while concurrently modulating MDA and NO levels under heat stress conditions (p < 0.05). In conclusion, these findings highlight the potential of L-proline as a protective supplement to ameliorate the detrimental effects of heat stress on human sperm quality and oxidative status, suggesting that incorporating L-proline into sperm preparation protocols may offer a promising strategy to enhance clinical outcomes.
Assessment of molecular interactions and anti-inflammatory activity of fermented camel milk-derived peptides in RAW macrophages.
Padhiyar PN, Basaiawmoit B, Mankad PM … +8 more , Sakure AA, Bhattacharya A, Kondepudi KK, Tiwary BK, Sarkar P, Koringa P, Adil S, Hati S
Amino Acids · 2026 Jun · PMID 42262414 · Publisher ↗
Fermented camel milk is gaining attention as a functional food due to the formation of bioactive peptides during microbial fermentation. This study aimed to investigate the generation of bioactive peptides and their asso...
Fermented camel milk is gaining attention as a functional food due to the formation of bioactive peptides during microbial fermentation. This study aimed to investigate the generation of bioactive peptides and their associated antidiabetic, antioxidant, and anti-inflammatory activities in camel milk fermented using Lacticaseibacillus rhamnosus M9 and Saccharomyces cerevisiae WBS2A. The in vitro fermentation process was evaluated in relation to proteolytic activity and peptide formation under varying fermentation times and inoculum concentrations. Antidiabetic activity was assessed using α-amylase and α-glucosidase inhibition assays, while antioxidant potential was determined using the ABTS assay. Peptide profiles and metabolite changes were characterized using RP-HPLC, SDS-PAGE, and 2D electrophoresis, and structural modifications were analysed through FTIR and CLSM. Fermentation significantly enhanced proteolytic activity, leading to the release of low-molecular-weight peptides (3-10 kDa) associated with improved bioactivity. Fermented samples exhibited notable α-amylase (70.68%) and α-glucosidase (59.18%) inhibition, along with maximum antioxidant activity (54.97%) after 48 h. In addition, fermented camel milk reduced intracellular ROS, pro-inflammatory cytokines, and apoptosis in LPS-stimulated RAW 264.7 macrophages. Molecular docking analysis further suggested potential interactions between identified peptides and target enzymes, supporting the observed in vitro activities.These findings demonstrate that fermentation-derived peptides contribute to the functional properties of camel milk; however, further in vivo studies are required to confirm their bioavailability and therapeutic relevance.
Taurine reduces intracellular glucose accumulation in fructose-treated Caenorhabditis elegans.
Machado JC, Vidal BA, Sant'Ana BH … +7 more , Viçozzi GP, de Oliveira Pereira FS, Laurentino AO, Picada JN, Leal MB, Garcia SC, Gomez R
Amino Acids · 2026 Jun · PMID 42223754 · Publisher ↗
Regulation of glucose homeostasis is a central feature of antidiabetic drugs such as metformin. However, a subset of individuals exhibited limited therapeutic response, highlighting the need for complementary treatment s...
Regulation of glucose homeostasis is a central feature of antidiabetic drugs such as metformin. However, a subset of individuals exhibited limited therapeutic response, highlighting the need for complementary treatment strategies. Taurine, a semi-essential amino acid, has been reported to improve glycemic control in mammalian models, supporting its potential as an adjuvant therapy for metabolic disorders. In this study, we established a fructose-induced metabolic dysfunction model in Caenorhabditis elegans (C. elegans), characterized by increased intracellular glucose accumulation, and evaluated the effects of taurine. A metabolic dysfunction state was induced in L1-stage N2 Bristol worms by exposing them to 500 mM fructose for 48 h. Metformin (25, 50, and 100 µM) was initially used to establish an effective pharmacological control, and the optimal dose (50 µM) was subsequently employed as a positive control to assess the effects of taurine (10, 50, and 100 µM) under fructose-induced conditions. Fructose exposure significantly increased intracellular glucose levels. Metformin reduced intracellular glucose at all concentrations tested and improved survival at the lowest dose, without affecting morphological parameters. Taurine reduced intracellular glucose accumulation only at the highest concentration tested (100 µM), whereas lower concentrations selectively increased survival, indicating dose-dependent and functionally distinct effects on glucose regulation and organismal viability. These findings show that taurine modulates intracellular glucose accumulation and survival in fructose-treated C. elegans. Given the evolutionary conservation of key pathways involved in glucose metabolism, this model provides a simple and reproducible platform to investigate mechanisms of glucose dysregulation and to screen compounds with potential metabolic or antidiabetic activity.
Computational identification and characterization of noncoding RNA-encoded peptides: tools, databases, and in silico strategies.
Shenoy N, Karkare A, Gangadhar V … +7 more , Padubidri SR, Rao S, Dsouza LA, Joshi MB, Damerla RR, Gandhi NS, Mallya S
Amino Acids · 2026 May · PMID 42171789 · Publisher ↗
Once dismissed as transcriptional artifacts, noncoding RNAs (ncRNAs) have gained recognition in recent years for their ability to participate in gene regulation, as well as their ability to encode functional molecules re...
Once dismissed as transcriptional artifacts, noncoding RNAs (ncRNAs) have gained recognition in recent years for their ability to participate in gene regulation, as well as their ability to encode functional molecules referred to as ncRNA-encoded peptides (ncPEPs). The discovery of ncPEPs has opened new avenues in proteomics and genomics research, revealing biological mechanisms that were previously unexplored. This review presents an extensive overview of the computational tools, databases, and in silico strategies used to identify ncRNA-encoded peptides across all major ncRNA classes, including long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and primary microRNAs (pri-miRNAs). Furthermore, we outline publicly available databases that compile experimentally validated and computationally predicted ncPEPs across multiple species, enabling systematic annotation and cross-referencing of candidate peptides. By highlighting the current challenges and emerging methodologies, we emphasize how computational methods continue to advance our ability to uncover hidden functional peptides within the noncoding transcriptome. These developments provide a framework for validating ncPEPs and elucidating their biological significance across diverse systems.
Methionine concentration regulates LSD1 acetylation in glioma cells.
Chang J, Wang L, Pan Y … +2 more , Lou Q, Xu W
Amino Acids · 2026 May · PMID 42156569 · Publisher ↗
Glioma is a highly aggressive brain cancer with poor prognosis, characterized by vigorous methionine metabolism. While methionine restriction demonstrates broad anticancer effects, its mechanistic relationship with epige...
Glioma is a highly aggressive brain cancer with poor prognosis, characterized by vigorous methionine metabolism. While methionine restriction demonstrates broad anticancer effects, its mechanistic relationship with epigenetic regulators in glioma remains inadequately understood. This study reveals the molecular mechanism by which methionine restriction (0.1 mM) modulates the epigenetic regulator LSD1. Restricting methionine to 0.1 mM induced site-specific acetylation at LSD1 lysine residues K6 and K359, promoting its ubiquitin-proteasome-dependent degradation independently of transcriptional alterations. Multi-omics analysis revealed that LSD1 inhibition induced dual reprogramming: transcriptomic activation of the p38MAPK and ubiquitin-proteasome pathways, coupled with metabolomic suppression of the TCA cycle with accumulation of L-proline and other amino acid metabolites. The HDAC inhibitor TSA synergized with methionine restriction to enhance LSD1 acetylation and degradation, whereas K6R/K359R mutations stabilized LSD1, confirming the role of acetylation in proteasomal targeting. Functional validation via colony formation identified LSD1 as a key mediator of methionine restriction; LSD1 knockdown mimicked the growth inhibition of methionine starvation, while its overexpression partially restored proliferation. Collectively, these results establish the methionine-LSD1 axis as a crucial nutrient-sensing mechanism that drives glioma adaptation via epigenetic-metabolic crosstalk. This highlights potential combinatorial therapeutic strategies involving dietary methionine limitation and LSD1 acetylation-targeted therapy to disrupt tumor survival pathways.
Efficient acrylamide adduct formation suggests dual applications of ReAIV L-asparaginase.
Sliwiak J, Grzechowiak M, Worsztynowicz P … +4 more , Pokrywka K, Ruszkowski M, Gilski M, Jaskolski M
Amino Acids · 2026 May · PMID 42113412 · Publisher ↗
Isothermal titration calorimetry (ITC) studies of the enzyme kinetics and substrate specificity of Rhizobium etli Class 3 L-asparaginases, ReAIV (constitutive) and ReAV (inducible), showed that despite highly conserved c...
Isothermal titration calorimetry (ITC) studies of the enzyme kinetics and substrate specificity of Rhizobium etli Class 3 L-asparaginases, ReAIV (constitutive) and ReAV (inducible), showed that despite highly conserved catalytic site, the two isoforms differ significantly in thermostability, zinc affinity, and biochemical properties. As part of a wider investigation of potential non-natural substrates, acrylamide was tested, revealing a pronounced heat effect with ReAIV but none with ReAV. Crystallographic analysis showed the formation of a Michael adduct between acrylamide and a surface-exposed cysteine 183 in ReAIV, while the catalytic activity toward L-asparagine hydrolysis remained unaffected. These findings highlight the unique and multimodal reactivity of ReAIV, suggesting its potential dual application in the food industry: in selective removal of L-asparagine and in covalent sequestration of acrylamide under mild conditions. The acrylamide modification improved crystal morphology of ReAIV, offering practical advantages for structural studies. Additionally, a covalent modification of the catalytic Ser47 residue was observed in the presented crystal structure. Based on B-factor analysis, literature data, and detection of borate contamination in the laboratory water, this modification was interpreted as an orthoborate ester.
Analysis of total and free amino acid compositions of fishery byproducts from three commonly consumed fish species in South Korea.
Han J, Hyeon JY, Lee YJ … +3 more , Kim HJ, Lee E, Choi YU
Amino Acids · 2026 May · PMID 42105107 · Full text
Largehead hairtail (Trichiurus japonicus), kwangtung skate (Dipturus kwangtungensis), and mottled skate (Raja pulchra) are the most popular aquatic products in Korea. In the present study, total and free amino acid analy...
Largehead hairtail (Trichiurus japonicus), kwangtung skate (Dipturus kwangtungensis), and mottled skate (Raja pulchra) are the most popular aquatic products in Korea. In the present study, total and free amino acid analyses were performed to confirm the usability of byproducts from largehead hairtail (head and fins) and skates (skin and liver). Amino acid contents were determined using specific methods and high-performance liquid chromatography. Notably, 18 types of total amino acids and 19 free amino acids were identified in the byproducts of largehead hairtail, kwangtung skate, and mottled skate. Among the amino acids, the total amino acids glycine and glutamate/glutamine and the free amino acids leucine, alanine, and glycine exhibited the highest contents in the byproducts of the three species, indicating that the byproducts contained high-quality proteins. Conclusively, these results suggest that the byproducts are potential materials for producing nutritious foods, protein supplements, cosmetics, functional materials, and nutraceuticals. Overall, these data indicate that fishery byproducts can be used as recyclable resources.
PCLPred: identifying plant chloride transport-related proteins using reduced amino acid alphabets and N-peptide composition.
Bai G, Liu L, Zhang H … +9 more , Geng R, Li Y, Yang D, Fei M, Pang T, Wang H, Yang A, Xie H, Eang H
Amino Acids · 2026 May · PMID 42101708 · Full text
Chloride transport-related proteins play critical roles in coordinating ion cycling, maintaining cellular homeostasis, and enabling plants to dynamically adapt to environmental changes, particularly under salt stress con...
Chloride transport-related proteins play critical roles in coordinating ion cycling, maintaining cellular homeostasis, and enabling plants to dynamically adapt to environmental changes, particularly under salt stress conditions. Given the rapid accumulation of protein sequence data, the experimental identification of proteins is time-consuming and expensive. Therefore, efficient computational methods are urgently needed as a practical supplement to experimental research. Here, we present PCLPred, an SVM-based predictor that integrates reduced amino acid alphabets with N-peptide composition to represent protein sequences. We systematically evaluated 673 reduction schemes and selected an optimal encoding strategy for model training. PCLPred demonstrated superior performance compared to baseline models, achieving an overall accuracy of 95.10% and an AUC of 0.981 in nested cross-validation. Altogether, PCLPred provides an efficient and reliable tool for high-throughput screening of candidate plant chloride transport-related proteins, facilitating functional annotation and experimental validation.
Targeting the amino acid metabolic axis: the Achilles' heel of tumor cells.
Hu Z, Wang Y, Ma Q
Amino Acids · 2026 Apr · PMID 41995885 · Full text
Cancer is characterized by profound reprogramming of its metabolic programs, with the unending demand for exogenous amino acids by tumor cells serving as a hallmark manifestation. While this high dependency supports rapi...
Cancer is characterized by profound reprogramming of its metabolic programs, with the unending demand for exogenous amino acids by tumor cells serving as a hallmark manifestation. While this high dependency supports rapid proliferation, it exposes a critical vulnerability: disruption of amino acid supply can specifically trigger metabolic catastrophe in cancer cells. Furthermore, tumor cells exploit this metabolic reprogramming to deplete key amino acids in the microenvironment, thereby suppressing T-cell function and facilitating immune evasion. This review systematically elucidates therapeutic strategies targeting four critical amino acid metabolic axes (glutamine, arginine, tryptophan, and methionine). We delve into how inhibition of glutamine metabolism disrupts tumor bioenergetics, how arginine deprivation selectively targets cells with synthetic defects, and how methionine restriction interferes with key epigenetic regulation. Additionally, we explore interventions for these four amino acid metabolic axes to reverse immunosuppression. Convincing preclinical and clinical evidence demonstrates that these strategies, whether as monotherapy or rational combinations with conventional treatments, exhibit significant antitumor efficacy and substantial clinical translation potential. By integrating metabolic and immunological perspectives and critically assessing translational challenges, this review aims to provide a roadmap for future development of precision combination strategies capable of overcoming drug resistance and reshaping the immune microenvironment.
Revisiting the antizyme 1 - ODC interaction reveals low-nanomolar affinity.
Bereta GP, Wątor-Wilk E, Kochanowski P … +3 more , Nowak J, Kantyka T, Grudnik P
Amino Acids · 2026 Apr · PMID 41989609 · Full text
Ornithine decarboxylase (ODC) catalyzes the rate-limiting step in polyamine biosynthesis and is one of the shortest-lived mammalian proteins. Its activity and proteasomal degradation are controlled by antizyme (AZ), whic...
Ornithine decarboxylase (ODC) catalyzes the rate-limiting step in polyamine biosynthesis and is one of the shortest-lived mammalian proteins. Its activity and proteasomal degradation are controlled by antizyme (AZ), which disrupts the active ODC homodimer and exposes proteasome-interacting surfaces. Disturbance of the polyamine biosynthesis pathway and their overproduction is associated with multiple diseases, including cancers. We employed activity assays and direct interaction analysis methods to quantify ODC-AZ interaction. Fluorometric activity assay, surface plasmon resonance, microscale thermophoresis and spectral shift assays allowed consistent determination of AZ-ODC binding with previously unavailable sensitivity. Contrary to former studies of this interaction, we show that binding of AZ to ODC occurs with a single-digit nanomolar affinity. Collectively, our orthogonal assays converge on a low-nanomolar interaction (apparent K 1-4 nM in solution), affinity substantially stronger than previous estimates in the 200-700 nM range. Our results provide new insight into the functioning of the ODC regulatory network, which affects the downstream polyamine synthesis pathway. Such sensitive tools are needed for screening compound libraries and characterizing promising candidates that could affect ODC activity and consequently, polyamine levels.
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