Polyamine homeostasis is tightly regulated by interconversion and catabolic pathways and has been increasingly implicated in neurodegenerative disorders, including Parkinson's disease (PD), where accumulation of α-synuclein (α-Syn) perturbs neuronal homeostasis. Spermidine/spermine N[1]-acetyltransferase 1 (SAT1) occupies a central position in polyamine interconversion, and alterations in SAT1 activity have been linked to α-Syn toxicity and PD-related neuropathology. To investigate how SAT1 activity influences α-Syn-associated neurodegeneration, we employed a Drosophila model of neuronal α-Syn expression. SAT1 overexpression reduced α-Syn protein levels, altered its subcellular distribution within the brain, and mitigated α-Syn-induced lifespan shortening. Transcriptomic analyses showed that SAT1 modulates stress-associated gene expression in the α-Syn background, including attenuation of chaperone and ubiquitin-related responses and coordinated changes in pathways linked to mitochondrial function and amino acid metabolism. SAT1 co-expression partially restored α-Syn-associated alterations in genes involved in mitochondrial quality control, including USP30, Uch-L5R, RNF185, and the mitochondrial ornithine carrier SLC25A15. At the protein level, SAT1 increased mitochondrial-associated signal, enhanced LC3 association with mitochondrial compartments, restored LC3-II/LC3-I ratios in mitochondrial fractions, and reduced mitochondrial accumulation of α-Syn. Functional analyses further showed that SAT1 increased steady-state ATP levels and attenuated the ATP depletion induced by α-Syn expression. These findings indicate that SAT1 activity is associated with reduced α-Syn toxicity and preservation of mitochondrial homeostasis during α-Syn-associated stress.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality, and its incidence is rising among individuals, especially young, underscoring the need for novel therapeutic strategies. CRC development is driven by genetic and epigenetic alterations in key oncogenic pathways and is accompanied by profound reprogramming of polyamine metabolism. In this context, spermidine (SPD), a central polyamine produced downstream of the MYC-ODC axis, is regarded as a pro-tumorigenic metabolite that sustains CRC growth by fueling eIF5A hypusination and MYC translation, thereby establishing a feed-forward MYC-ODC-polyamine-eIF5A circuit that promotes tumorigenesis. Recent studies also show that combined inhibition of polyamine biosynthesis and eIF5A hypusination synergistically impairs MYC translation and suppresses CRC growth in preclinical models, outperforming single-agent strategies such as ornithine decarboxylase (ODC) blockade with difluoromethylornithine (DFMO) and highlighting the translational potential of dual targeting of this axis. Conversely, other lines of evidence indicate that excessive SPD or altered flux through the polyamine pathway can be cytotoxic: multiple reports demonstrate that high-dose SPD triggers apoptosis, while experimental models suggest that SPD and epithelial eIF5A hypusination can protect against colitis and colitis-associated cancer by supporting the translation of detoxifying enzymes. Overall, the literature points to a dual role of SPD, and the aim of this review is to dissect the functions of SPD in CRC, to summarize and critically discuss the potential benefits of this polyamine, and to evaluate how it might be rationally exploited as a therapeutic agent in cancer.

Breast cancer (BRCA) is a major health threat to women and often carries a poor prognosis. Succinylation is closely associated with cancer metabolism; however, research on succinylation-related genes (SRGs) in BRCA remains relatively limited. This study first identified differentially expressed genes between normal and BRCA groups in the TCGA cohort and intersected them with known SRGs to obtain differentially expressed SRGs (DE-SRGs). Univariate Cox and LASSO Cox regression analyses were used to screen the DE-SRGs, followed by multivariate Cox regression to develop a succinylation-related prognostic model. Subsequently, patients were categorized into high and low succinylation-related risk score (SRS) groups according to the median score. Two groups were then compared for differences in immune microenvironment characteristics, somatic mutation burden, and drug sensitivity. Additionally, the expression levels of the signature genes were validated via qRT-PCR. This study developed a prognostic risk model for BRCA patients based on 13 SRGs (ACOT4, ALDH3A1, B3GALT1, IFNG, MMP1, NFKB2, PCSK6, PTK2, SERPINA1, SHMT2, SIRT7, ST3GAL1, and SUCLA2). A markedly elevated infiltration of immune cells was observed in the low-SRS group, including B cells, Mast cells, and Macrophages. The tumor mutational burden was notably lower in the low-SRS group. Drug sensitivity analysis suggested that the high-SRS BRCA patients might be more susceptible to FTI-277 and GNF-2. qRT‑PCR results showed that ACOT4, IFNG, MMP1, NFKB2, PCSK6, PTK2, SHMT2, SIRT7, and ST3GAL1 were significantly upregulated in human BRCA cell lines, while ALDH3A1, B3GALT1, and SUCLA2 were significantly downregulated. Our findings highlight the prognostic value of SRGs in BRCA, laying the groundwork for its potential use in guiding personalized treatment.

This study investigated the effects of proline on intestinal injury in piglets infected with porcine epidemic diarrhea virus (PEDV). Twenty-eight 7-day-old piglets were assigned to four groups: control (CON), proline (Pro), PEDV, and Pro + PEDV. Piglets in the Pro and Pro + PEDV groups received oral proline (500 mg/kg body weight) for 7 days. During the last 3 days, piglets in the PEDV and Pro + PEDV groups were inoculated with PEDV. Under PEDV infection, proline administration increased villus height and the villus height/crypt depth ratio in both the jejunum and ileum, and villus width and villus surface area in the ileum. Proline increased PEDV N protein abundance and interferon β (IFN-β) mRNA level in both intestinal segments, suppressed downstream antiviral genes in infected piglets, but upregulated these genes in the jejunum of uninfected piglets. Proline further increased interleukin 1β (IL-1β) concentrations and the expression of inflammation-related genes in the jejunum of infected piglets. Under PEDV infection, proline increased superoxide dismutase (SOD) activity in serum and jejunum, while reducing jejunal H2O2 concentration. Furthermore, proline downregulated genes related to lipid synthesis and ion transport in the jejunum of infected piglets. Transcriptomic and RT-qPCR analyses supported these findings, indicating that proline enhanced immune defense while suppressing lipid metabolism. In conclusion, proline alleviated PEDV-induced intestinal injury by improving villus morphology and enhancing antiviral and antioxidant defenses. However, it promoted viral replication and inflammation, while suppressing lipid metabolism. The multifaceted effects of proline on PEDV infection indicate its practical use warrants careful consideration.

Postmenopausal women face increased risks of vascular dysfunction, loss of lean muscle mass, and reduced physical performance due to age-related hormonal and metabolic changes. These factors contribute to heightened cardiovascular risk and physical frailty. L-citrulline, a non-essential amino acid and precursor to nitric oxide (NO), has emerged as a potential therapeutic agent for improving vascular and muscular health. When combined with structured exercise, L-citrulline may enhance NO bioavailability, improve endothelial function, increase muscle perfusion, and potentiate exercise-induced adaptations. This review synthesizes current evidence on the combined impact of L-citrulline supplementation and exercise on endothelial function, arterial stiffness, leg muscle function, lean mass, and strength in postmenopausal women. Findings from preclinical and clinical studies suggest that this combined intervention can reduce arterial stiffness, enhance leg muscle strength, increase lean body mass, and improve overall physical function, potentially via NO-mediated vasodilation, the mechanistic target of rapamycin signaling, improved mitochondrial function, and reduced oxidative stress. These effects are especially relevant in postmenopausal populations at risk for cardiovascular disease and sarcopenia. While early results are promising, further high-quality randomized controlled trials are needed to confirm these benefits, establish optimal dosing strategies, and determine long-term clinical relevance.

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.

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.

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.

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.

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 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.

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[6] cells) are homogenized, and cytosolic fractions are prepared by centrifugation. These fractions are incubated with d7-ornithine under 37 °C conditions, and the produced d7-putrescine is derivatized with dansyl chloride and quantified by LC-MS analysis. Reaction samples showed a distinct peak corresponding to d7-putrescine, whereas negative control displayed negligible signals. Moreover, d7-spermidine and d7-spermine were not detectable under these conditions, indicating d7-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.

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.

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.