Search Results (2,031)

This study investigated the incorporation of Salicornia perennans powder as a natural antioxidant and functional ingredient in cooked sausages, with the aim of improving product quality and promoting sustainable production strategies. The inclusion of 3% Salicornia perennans resulted in a nutritionally favorable shift in the fatty acid profile, with a 1.5-fold increase in α-linolenic acid ALA and the presence of long-chain ω-3 fatty acids EPA and DHA, along with improved PUFA/SFA and ω-6/ω-3 ratios. Lipid and protein oxidation were significantly suppressed during refrigerated storage, as evidenced by the reduced peroxide value of 10.6 vs. 12.8 meq/kg, thiobarbituric acid-reactive substance value of 0.158 vs. 0.210 mg MDA/kg, acid value of 4.6 vs. 5.5 mg KOH/g, and carbonyl compound value of 101.9 vs. 112.3 nmol/mg protein compared to the control. Color stability was enhanced, with ΔE* values remaining below perceptible thresholds in Salicornia perennans-supplemented sausages, highlighting its role in preserving visual quality. Antioxidant capacity was markedly higher, with FRAP values of 14.5 mg GAE/g undetected in the control and improved DPPH radical-scavenging activity of 22.6% vs. 12.5%. These findings demonstrate that Salicornia perennans not only enriches meat products with bioactive compounds and health-promoting lipids but also reduces oxidative spoilage, thereby extending shelf life. The results emphasize the potential of halophyte-based ingredients to support technological innovation, environmental impact reduction, and the development of clean-label functional meat products aligned with sustainable production strategies. Full article

Bothrops species are responsible for the majority of envenomations in Argentina. In particular, Bothrops diporus is among the main species responsible for the majority of envenomations in Argentina and causes significant injury and coagulopathy. Given the significance of this venom, the authors sought to define the toxin responsible for coagulopathy with specialized spectrophotometric and thromboelastographic methods. Utilizing clotting time, spectrophotometry, and thromboelastography, it was determined that B. diporus venom has potent, procoagulant activity in human plasma and buffer milieu. Calcium-dependent and -independent activities consistent with serine protease activity were identified. The activity included both thrombin-generating and thrombin-like enzymatic activity. The venom cleaved the serine protease-specific chromogenic substrate β-Ala-Gly-Arg-p-nitroanilide diacetate, and its activity was inhibited in plasma by antithrombin after addition of heparin. Further, venom exposed in isolation to RuCl₃, a known inhibitor of serine protease-containing venoms, demonstrated decreased activity in human plasma. In conclusion, the present study contributes to a better understanding of B. diporus venom and may have implications for the rational design of inhibitors, antivenom formulations, or preclinical models to study venom-induced coagulopathies. Full article

5-Aminolevulinic acid (5-ALA) is used clinically for photodynamic therapy and fluorescence-guided diagnosis and surgery due to its selective accumulation in malignant cells, where it is converted into photoactive protoporphyrin IX (PpIX) via the heme biosynthesis pathway. The resulting buildup allows for selective visualization or destruction of the tissue under specific light exposure, particularly in pre-malignant and malignant skin lesions, brain tumors, and bladder cancer. More recently, 5-ALA and 5-ALA-induced PpIX have attracted interest for emerging diagnostic and therapeutic approaches. For instance, PpIX is being investigated as a potential marker for liquid biopsy. PpIX-mediated photodynamic therapy also shows promise for targeting specific cancer cell populations, including dormant cancer cells and cancer stem cells. In addition, the benefits of 5-ALA in neurological and mental health are under investigation, as disruptions in heme biosynthesis are increasingly linked to neurodegenerative diseases, chronic fatigue, and mood and sleep disorders. This review highlights these expanding research directions, discusses current challenges, and explores potential opportunities for 5-ALA-based applications. Full article

Background: Chronic and acute wounds are often colonized by polymicrobial biofilms, delaying healing and complicating treatment. Rapid, non-invasive detection of pathogenic bacteria is therefore crucial for timely and targeted therapy. This study investigated porphyrin-producing bacterial species using the handheld cureVision imaging system. Methods: In this study, 20 clinically relevant, porphyrin-producing bacterial species were cultured on δ-aminolevulinic acid (ALA)-supplemented agar and analyzed using the handheld cureVision imaging system under 405 nm excitation. Both Red-Green-Blue (RGB) and fluorescence images were acquired under ambient daylight conditions, and fluorescence signals were quantified by grayscale intensity analysis. Results: All tested species exhibited measurable red porphyrin-associated fluorescence, with the highest intensities observed in Klebsiella pneumoniae, Klebsiella oxytoca, Veillonella parvula, and Alcaligenes faecalis. A standardized detectability threshold of 0.25, derived from negative controls, enabled semi-quantitative comparison across species. Statistical analysis confirmed that the fluorescence intensities of all bacterial samples were significantly elevated compared to the control (Wilcoxon signed-rank test and sign test, both p < 0.001; median intensity = 0.835, IQR: 0.63–0.975). Conclusions: These results demonstrate that the cureVision system enables robust and reliable detection of porphyrin-producing wound bacteria, supporting its potential as a rapid, non-invasive diagnostic method for assessing wound colonization and guiding targeted clinical interventions. Full article

Background: Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) enables the intraoperative visualization of glioma. However, its effectiveness varies based on tumor subtype and molecular profile, posing challenges for achieving complete resection. Our systematic review aims to explore the relationship between IDH mutation status and intraoperative fluorescence visualization. Importantly, this is the first study to propose that vorasidenib, an emerging IDH-targeting agent, could enhance 5-ALA-guided surgery, marking a novel direction for translational research. Methods: A systematic literature search was conducted using the PubMed, Cochrane Library, Scopus and Web of Science databases up to May 2025, following PRISMA guidelines. The primary outcomes included fluorescence detection rates across different glioma subtypes and their correlation with IDH mutation status. Secondary outcomes comprised surgical efficacy measures such as gross total resection (GTR), overall survival (OS), and progression-free survival (PFS). Additionally, we analyzed the metabolic consequences of IDH mutations and evaluated the potential role of vorasidenib in enhancing 5-ALA-induced fluorescence. Results: Seven studies including 621 patients included in the final analysis. Fluorescence detection was nearly universal in WHO grade 4 gliomas (94–100%), but lower in grade 3 (43–85%) and rare in grade 2 (7–26%). Several cohorts reported reduced fluorescence in IDH-mutant gliomas, although this was not consistent across all studies. In high-grade gliomas, visible fluorescence correlated with higher GTR rates and, in some series, longer OS. Conversely, in lower-grade IDH-mutant gliomas, fluorescence did not increase GTR and was associated with worse PFS and OS. Conclusions: The effectiveness of 5-ALA-guided fluorescence in glioma surgery is significantly influenced by both tumor grade and IDH mutation status. Vorasidenib may represent a potential avenue for modulating tumor metabolism and enhancing intraoperative fluorescence in IDH-mutant gliomas, a hypothesis that warrants further experimental validation. Full article

5-aminolevulinic acid (5-ALA) is a heme precursor involved in mitochondrial activation. A clinical study suggested that 5-ALA supplementation alleviates fatigue in healthy individuals who experience chronic physical tiredness. However, the detailed mechanisms are unknown. Therefore, we investigated the mechanism underlying the antifatigue effect of 5-ALA using fatigue mouse models. C57BL/6N mice were orally administered 5-ALA hydrochloride or distilled water for 8 weeks. Fatigue mouse models were developed by housing the mice in a cage filled with water for 4 days. Fatigue was evaluated through running distance via a treadmill test. The decrease in the running distance in female mice significantly recovered after 5-ALA administration. 5-ALA administration ameliorated the decreased blood glucose levels in fatigue mouse models. These results suggest that 5-ALA improves fatigue-induced hypoglycemia by promoting the use of fatty acids. PpIX’s concentration in the FCX of the fatigue mouse models significantly increased after 5-ALA treatment. Decreased levels of 3-methoxy-4-hydroxyphenylglycol and noradrenaline (NA) turnover ratio in the FCX recovered to non-fatigue levels after 5-ALA treatment. Therefore, the antifatigue effect of 5-ALA in mice could be related to the activation of the NA neuronal systems in the FCX and the increase in energy production via glycogenesis activation from peripheral adipose tissue. Full article

Background/Objectives: This study explores the potential of the inducible G protein-coupled kinin B1 receptor (B1R) as a target for the diagnosis and treatment of prostate cancer (PCa) and aims to develop the first theranostic agent targeting hB1R for both molecular imaging and radionuclide therapy. Methods: B1R expression was analyzed via qPCR and immunohistochemistry in human PCa cells and tissues specimens. A novel ⁶⁴Cu/NOTA-conjugated peptide analog of the potent B1R antagonist R954 was synthetized and evaluated in vitro and in vivo. Results: B1R was confirmed to be expressed (RNA, protein) by varying degrees in all PCa cell lines and tissues investigated, with protein level significantly correlating with tumor grades. This finding was supported by similar analyses from the TCGA and MSKCC databases. In vitro, the ⁶⁴Cu/NOTA-βAla-R954 conjugate showed nanomolar affinity/potency at hB1R, complete plasma stability over 24 h, significant cellular uptake (up to 33% of ID at 24 h), and dose-dependent anti-clonal growth effects. In vivo, the radioconjugate remained stable in circulation for up to 90 min and was primarily excreted intact via the kidneys following IV administration. Intravenous ⁶⁴Cu/NOTA-βAla-R954 (7.5 MBq) effectively detected subcutaneous PCa xenografts via µPET imaging in male athymic nude mice. At a single higher dose (65 MBq; 50 µg/kg), it significantly reduced tumor growth without observable toxicity. This antitumor effect was associated with increased apoptosis (active caspase-3) and reduced proliferation (Ki67), as shown by immunohistochemistry. In contrast, the nonradioactive ^NatCu/NOTA-βAla-R954 had no therapeutic effect at the same dose. Conclusions: Our findings provide proof-of-concept for the potential theranostic use of ⁶⁴Cu/NOTA-R954 in PCa, and potentially other types of B1R-positive solid cancers. Full article

Pigeon meat is gaining increasing popularity due to its high nutritional value and desirable sensory qualities. This study aimed to comprehensively evaluate the quality-related components of pigeon meat by analyzing conventional nutritional indicators—including amino acids, fatty acids, and flavor nucleotides—in combination with multi-omics approaches. The results indicated that pigeon meat contains high levels of arginine (Arg), alanine (Ala), linoleic acid, and glycerophospholipids (GPs), which contribute significantly to its flavor profile. Additionally, several lipids, namely, PS (18:0/20:4), PE (16:2; O/2:0), HexCer (9:0;2O/42:11), Hex2Cer (38:1;2O), PS (16:0; O/21:0), and PE (42:9), were identified as potential characteristic markers of pigeon meat. A comparative analysis among three breeds—White King, Shiqi, and Tarim pigeons—revealed breed-specific differences in endogenous compounds, with each breed exhibiting distinct compositional traits. This study provides a comprehensive dataset for quality assessment and offers critical insights for the authenticity verification of pigeon meat. Full article

Background: Fragility fractures of the pelvis (FFP) are an increasing challenge in aging societies. Among these, FFP type 4B (“H-shaped” sacral fractures) represent the most unstable subtype, characterized by bilateral sacral ala fractures with transverse dissociation. Optimal fixation strategies remain debated, as spinopelvic fixation provides maximal stability but is invasive, while iliosacral screws often fail in osteoporotic bone. Trans-sacral bar (TSB) fixation has been proposed as a less invasive alternative, though evidence for its use in FFP 4B remains limited. Methods: We conducted a retrospective single-center study of 31 elderly patients (mean age 77.9 years; 87.1% female) with CT-confirmed FFP type 4B fractures treated between 2015 and 2022 using navigation-guided TSB constructs. Surgical configurations included hybrid fixation (TSB + bilateral iliosacral screws, n = 25) and dual-bar fixation (n = 6). Outcomes included perioperative complications, implant survival, radiographic healing, pain, and mobility at 3 and 12 months. Opportunistic CT-derived Hounsfield units (HU) were used to assess bone quality. Results: All patients had severe osteoporosis (mean HU 75.8 ± 30.1). Mean operative time was 71 min, and mean hospitalization was 9.1 days. No intraoperative or postoperative complications occurred, and no implant loosening, migration, or revision surgeries were required. At 3 months, mean pain score was 1.9, further decreasing to 1.1 at 12 months; 60.9% of patients reported complete pain resolution. Mobility improved in most cases, with 80.6% discharged with a walker or crutches. Radiographic follow-up confirmed stable healing in all patients. Conclusions: Navigation-guided TSB-based fixation provided stable osteosynthesis with excellent implant survival, significant pain relief, and early mobilization in elderly patients with FFP type 4B fractures. Hybrid and dual-bar constructs both achieved reliable outcomes. TSB fixation thus represents a safe and effective alternative to spinopelvic fixation in this fragile population. Larger multicenter prospective studies are warranted to confirm these findings and refine fixation strategies. Full article

Animal and cellular models harboring SNCA gene mutations have been instrumental in synucleinopathy, but faithful human brain models remain limited. Here, we report the development of a human cerebral organoid (CO) model of synucleinopathy carrying the Ala53Thr mutation in SNCA (SNCA^A53T). Using a human embryonic stem cell (hESC) line overexpressing SNCA^A53T (A53T hESC line), we generated COs (A53T COs) that recapitulate hallmark features of synucleinopathy. These A53T COs exhibited elevated α-synuclein (α-Syn) expression, the increased phosphorylation of α-Syn, and Lewy body-like aggregations. Notably, we also observed the increased expression of phosphorylated tau and neurofibrillary tangle-like silver deposits, although amyloid β expression and accumulation remained unchanged. To evaluate the utility of this model in drug screening, we treated A53T COs with synuclean D (SynD), an inhibitor of α-Syn aggregation, which significantly reduced both α-Syn and tau phosphorylation without affecting total α-Syn levels. Together, our findings establish a robust hESC-derived synucleinopathy CO model harboring the SNCA^A53T mutation, demonstrating its potential as a valuable tool for therapeutic drug screening. Full article

Glioblastoma (GB) is one of the most aggressive brain tumors, characterized by high infiltrative capacity that enables tumor cells to invade healthy brain tissue and evade complete surgical resection. This invasiveness contributes to resistance against conventional therapies and a high recurrence rate. Strategies capable of eliminating residual tumor cells are urgently needed. Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA), an FDA- and EMA-approved compound, induces selective accumulation of the photosensitizer protoporphyrin IX (PpIX) in metabolically active tumor cells, enabling targeted cytotoxicity through light activation. A major limitation to its clinical application is the unclear variation in the cytotoxic effect of PDT according to individual tumoral differences. In this study, we propose and validate an in vivo model of patient-derived GB initiating cells (GICs) and brain organoids to test the effects of PDT. First, patient-derived GICs were molecularly characterized by flow cytometry and copy number variation profiling using OncoScan CNV Assays, then co-cultured with human brain organoids to generate a hybrid model recapitulating key aspects of the tumor microenvironment. 5-ALA photodynamic therapy (PDT) efficacy was assessed in vitro by GFP-based viability measurements, LDH release assays, and TUNEL staining. Then, a murine model was generated to study PDT in vivo, based on a heterotopic (renal subcapsular engraftment) xenograft of the GICs-human brain organoid co-culture. PDT was tested in the model; in each subject, one kidney tumoral engraftment was treated and the contralateral served as a control. Immunofluorescence analysis was used to study the cell composition of the brain organoid-tumoral engraftment after PDT, and the effects on non-GIC cells. The antitumoral effect was determined by the degree of cell death analysis with the TUNEL technique. The GICs-brain organoid co-culture resulted in tumoral growth and infiltration both in vitro and in vivo. The pattern of growth and infiltration varied according to the tumoral genetic profile. 5-ALA PDT resulted in a reduction in the number of GICs and an increase in apoptotic cells in all four lines tested in vitro. A correlation was found between the induced phototoxicity in vivo with the molecular typification of GICs cell lines in vitro. There were no changes in the number or distribution of neuronal cells after the application of PDT, while a reduction in active astrocytes was observed. 5-ALA PDT could be effective in eradicating GICs with a heterogeneous molecular profile. The hybrid human-murine model presented here could be useful in investigating adjuvant therapies in GB, under the concept of personalized medicine. Full article

Approximately half of the world population is infected with the human pathogen Helicobacter pylori, which causes gastric inflammation, chronic gastritis, or peptide ulceration. A significant factor in the colonization of the upper digestive system is the helical shape of H. pylori. This helical form is maintained by a complex network of peptidoglycan (PG)-modifying enzymes and cytoskeletal proteins. Among these, the D,D-endopeptidase Csd2 plays a central role, working in conjunction with other cell shape-determining (Csd) proteins. Csd1 and Csd2 have been categorized as members of the M23B metallopeptidase family. These enzymes are classified as D,D-endopeptidases, and their function involves the cleavage of the D-Ala4-mDAP3 bond, which is present in the cross-linked di-mer muropeptides. Despite the fact that the structure of the Csd1:Csd2 complex has been examined via biochemical methods, information on the in vivo localization and dynamics of D,D-endopeptidases is still missing. Here, we use an approach that employs sophisticated different microscopy methods to visualize the spatial temporal localization and dynamics of Csd2, involving both structured illumination microscopy and single-molecule tracking. Our findings thus contribute to refining the existing model for this cellular complex by revealing curvature-dependent spatial organization and temporal dynamics underlying peptidoglycan remodeling processes essential for helical cell shape formation and maintenance. Understanding the dynamics provides insight into the mechanisms that maintain bacterial morphology and potential targets for therapeutic intervention. Full article

Background/Objectives: Early parenting can influence child self-regulatory skills, which are in turn linked to allostatic load (AL)—a predictor of future morbidity and mortality. However, this mechanistic pathway from early parenting to later AL has not been tested using longitudinal data. Methods: We analyzed longitudinal data (N = 1364) from the Study of Early Child Care and Youth Development to examine relationships between early childhood (ages 2–3) observed parenting behaviors (i.e., autonomy support, supportive presence and hostility) and a comprehensive index of adolescent (age 15) AL, and assessed delay of gratification (at 54 months) as a mediator and moderator of these associations. Results: Maternal supportive presence and hostility in early childhood were directly associated with adolescent AL. All three early childhood parenting behaviors were associated with delay of gratification at 54 months. There was no evidence of mediation or moderation. Conclusions: The findings suggest the important role of early parenting behaviors in predicting long-term AL outcomes. Full article

Background/Objectives: Hemoglobinopathies, including thalassemia and sickle cell disease, are among the most common inherited disorders worldwide. This study aimed to profile hemoglobin variants in the Tharu community of Lakhimpur Kheri, Uttar Pradesh, with particular focus on the rare variant Hb J-Meerut [α 120 (H3) Ala→Glu (α1)]. Methods: A cross-sectional study was conducted during a community health camp in February 2024. Peripheral blood samples were collected from 505 individuals, of which 445 were analyzed using complete blood count (CBC) and high-performance liquid chromatography (HPLC). Suspected variants were confirmed by Sanger sequencing. Results: Hemoglobinopathies were identified in nearly one-fifth of participants. The major variants detected were sickle cell trait, β-thalassemia trait, and Hb J-Meerut. Sequencing confirmed Hb J-Meerut in the majority of suspected cases. HPLC profiles showed clear differences between groups, supporting its role as a reliable screening tool. Conclusions: Community-based screening combining HPLC and sequencing provides an effective approach for identifying both common and rare hemoglobin variants. Early detection of silent carriers such as Hb J-Meerut is essential for targeted genetic counseling and preventive strategies in high-risk populations. Full article

Krabbe disease is a rare and severe lysosomal disorder affecting the white matter of the central and peripheral nervous system. It is characterized by neurodegeneration, with the most common form being infantile Krabbe disease, typically diagnosed within the first year of life. This autosomal-recessive disease is caused by mutations in the GALC gene, which encodes the lysosomal enzyme β-galactocerebrosidase. This study focuses on a β-galactocerebrosidase variant, with Thr112Ala identified as a homozygous mutation in a patient with infantile Krabbe disease. To understand the structural effects of this mutation, we conducted all-atom molecular dynamics simulations of both the mutant and wild-type (wt) enzymes at cytosolic (pH 7.0) and lysosomal pH (pH 4.5), as β-galactocerebrosidase is localized in the lysosome. The results showed differences in protein flexibility, the hydrogen bond network, and the stability of secondary structure elements between the wild type and mutant enzymes. Additionally, the mutation affected the size of the substrate-binding pocket at lysosomal pH, even though the mutation site is not part of the active/binding site of the enzyme. These findings provide valuable insights into how the mutation impacts the structure of β-galactocerebrosidase in the lysosomal environment, contributing to the understanding of Krabbe disease’s molecular mechanisms. Full article