Search Results (89)

This review systematically evaluates research on self-assembling protein nanoparticles (SPNPs)-based vaccine, focusing on three major categories: virus-like particles (VLPs), natural protein nanoparticles (e.g., ferritin and encapsulin), and computationally designed protein nanoparticles—with comparative analyses of their design strategies, immunogenicity, and applicability in next-generation vaccines. VLPs can elicit robust humoral and cellular immune responses due to their virus-mimetic structures. Natural protein nanoparticles provide excellent biocompatibility and controllable self-assembly for multivalent antigen presentation. Artificially designed protein nanoparticles allow precise structural optimization to facilitate tailored antigen display and immune modulation. Overall, SPNPs constitute a versatile and powerful platform for vaccine development. By integrating natural and engineered design principles, they offer new opportunities for rational vaccine design and the development of safer and more effective immunization strategies. Full article

Ferritin, a natural cage-like protein, can be applied as a nanomaterial to encapsulate and deliver bioactive ingredients, while challenges remain when using ferritin to deliver multiple bioactive ingredients. In this study, a ferritin–zinc ion–alginate oligosaccharide (AOS) core–shell complex (FZA) and hydrophobic astaxanthin (AST) were applied as the water and oil phase to prepare oil-in-water emulsions simultaneously containing mineral element and hydrophobic AST. The ferritin works as a multicompartment carrier to encapsulate the Zn²⁺ ions and bind with the AOS. This emulsion exhibited smaller particle size and higher apparent viscosity, elastic modulus, and anti-delamination stability. After heat treatment, natural light irradiation, and ultraviolet irradiation, the retention rates of AST in FZA-stabilized emulsion were increased by 23.09%, 18.25%, and 19.24%, respectively, compared with AST dissolved in oil. The release rate of AST in FZA-stabilized emulsion was increased by 26.97% compared with that dissolved in oil in vitro digestion simulation, and release rate of Zn²⁺ ions in FZA-stabilized emulsion improved by 20.38% relative to the control. This study provides experimental evidence for the emulsion stabilized by the AOS and ferritin multi-interface, which achieves dual co-delivery and protection of mineral and hydrophobic molecules. Full article

Background: Brucellosis is a globally distributed zoonotic disease characterized by highly variable clinical manifestations that may mimic systemic autoimmune and inflammatory disorders. In Europe, where the incidence of brucellosis is relatively low, limited clinical awareness may contribute to delayed diagnosis and inappropriate management. In addition to zoonotic transmission, Brucella species are a well-recognized cause of laboratory-acquired infections (LAIs) among microbiology laboratory personnel. Methods: We report a case of laboratory-acquired Brucella abortus infection in a young woman presenting with undulant fever, arthralgia, systemic inflammation, elevated ferritin levels, and antinuclear antibody (ANA) positivity. Microbiological confirmation was achieved through serological testing (ELISA), repeat blood cultures, species-specific quantitative PCR, and whole-genome sequencing (WGS) followed by core genome multilocus sequence typing (cgMLST). Results: Initial laboratory evaluation revealed elevated C-reactive protein, mildly increased ferritin levels (146 ng/mL), abnormal liver enzyme levels, and rising ANA titers (from 1:160 to 1:320), raising suspicion of a systemic autoimmune disorder and prompting consideration of corticosteroid therapy. Although the initial blood culture was negative, subsequent molecular diagnostics and repeat cultures confirmed B. abortus infection. Epidemiological investigation suggested a possible occupational exposure in a diagnostic microbiology laboratory, consistent with a laboratory-acquired infection. Genomic analysis classified the isolate as sequence type 1 (ST1) and demonstrated zero allelic differences compared with the ST1 reference strain. Targeted antimicrobial therapy resulted in complete clinical recovery, supporting an infection-triggered immune response rather than primary autoimmunity. Conclusions: Acute brucellosis should be considered in the differential diagnosis of febrile syndromes accompanied by autoimmune-like laboratory abnormalities, even in low-incidence regions. This case highlights the diagnostic challenges posed by laboratory-acquired brucellosis and underscores the importance of early microbiological investigation and strict biosafety awareness in laboratory settings. Full article

Background/Objectives: Ferritins are key iron-sequestering proteins that maintain cellular homeostasis by storing iron in a bioavailable and nontoxic form. They also contribute to innate immunity, cellular proliferation and differentiation, shell formation, and protection against oxidative stress. In this study, we identified and characterized the M-type subunit of ferritin (Mbi-Fer) from the Indian backwater oyster, Magallana bilineata (Röding, 1798). Methods: A full-length cDNA of Mbi-Fer was sequenced and analyzed, and its gene expression was quantified in oysters collected from their natural habitat. Additionally, the coding region of Mbi-Fer was transformed and expressed in Escherichia coli, and the recombinant protein was purified and analyzed. Results: Mbi-Fer exhibited all the typical features of M-type ferritins, including the ferroxidation site of the H subunit and the nucleation core of the L subunit. The amino acid sequence alignment and phylogenetic analysis showed high similarity to the M-type ferritin subunits of Magallana gigas (Thunberg, 1793). A putative iron-responsive element was identified in the 5′ UTR, indicating potential post-transcriptional regulation. Mbi-Fer expression in wild oysters was increased by more than fourfold, relative to laboratory-maintained control oysters. The recombinant expression result revealed a unique protein band that was specific to a ferritin M-like subunit, with an approximately molecular weight of 20 kDa. Conclusions: Our findings suggest that Mbi-Fer may play a role in both the iron storage and shell formation of backwater oysters and may serve as a valuable molecular marker of oxidative and environmental stress responses in estuarine bivalves. Full article

The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on public health. In the present study, we aimed to analyze the association of certain inflammatory biomarkers with severe COVID-19 and to explore the role of diabetes mellitus (DM) and vaccination status in relation to COVID-19 severity, intensive care need and mortality. Associated comorbidities (DM, obesity, cardiovascular, neurological, endocrine, hepatic, renal, pulmonary, rheumatological, psychiatric, hematological diseases, cancer and HIV), as well as inflammatory biomarkers, like ferritin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were analyzed in 866 subjects, according to vaccination status. In unvaccinated subjects, the highest AUROC curve for severe COVID-19 was recorded for CRP (0.668), and in the vaccinated group, the highest was recorded for SII (0.694). In age- and comorbidity-adjusted analyses, diabetes mellitus was associated with higher odds of severe COVID-19, ICU admission, and mortality among unvaccinated patients. This analysis was not feasible in the vaccinated group because of the very low number of unfavorable outcomes. These findings emphasize the potential role of vaccination in attenuating the excess risk linked to comorbidities—particularly diabetes mellitus—and support the use of accessible inflammatory biomarkers for early risk stratification. The results should be interpreted within the specific epidemiological phases of the pandemic and in the context of the observational study design. Full article

Background and Objectives: Neutrophil extracellular traps (NETs) have been linked to hypercoagulability, immunothrombosis, and organ injury in COVID-19. Digital morphology of peripheral blood smears enables the identification of NET-compatible appearances (NET-like) in circulation, and associations between NET-like derived indices and clinical outcomes have been reported. However, evidence at hospital admission that relates smear NET-like burden to systemic inflammation and clinical severity remains limited. We therefore aimed to compare the burden of NET-like structures on admission smears according to disease severity and systemic inflammatory markers. Materials and Methods: We included 50 consecutively enrolled adults hospitalized for COVID-19; samples were obtained within 24 h of admission. Severity was defined by the World Health Organization Clinical Progression Scale and grouped as moderate or severe. C-reactive protein (CRP), ferritin, and complete blood counts were measured; the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated. Digital morphology assessed 200 leukocytes per patient; the presence of morphological abnormalities, including NET-like events per patient, was recorded. We additionally quantified NET-like events per 100 white blood cells (NET-like/100 WBC) and the neutrophil extracellular trap–segmented neutrophil ratio (NNSR). Results: At admission, CRP, ferritin, NLR, and PLR of patients were above method-specific reference intervals. NET-like events were identified in 66% of patients. NET-like/100 WBC correlated positively with NLR (r = 0.312; p < 0.05). Patients with severe COVID-19 had higher NET-like/100 WBC than those with moderate disease (5.8 ± 7.34 vs. 14.14 ± 15.12; p = 0.0294). Conclusions: Digital morphological identification of NET-like structures on peripheral blood smears is frequent at admission and is associated with systemic inflammatory burden and with greater COVID-19 severity. These findings support the potential complementary value of reporting NET-like events for initial risk stratification in the clinical laboratory. Full article

Objective: The optimal patient subgroup that derives substantial benefit from triplet chemotherapy (FOLFOXIRI/FOLFIRINOX) as first-line treatment for metastatic colorectal cancer (mCRC), and the clinical scenarios in which its increased toxicity is justified, remain uncertain. This study employed a machine learning–based approach to develop a predictive biomarker capable of identifying patients most likely to benefit from triplet therapy. Methods: Clinical data from 136 patients in the Ankara University de novo mCRC cohort were retrospectively reviewed. 66 clinical and biochemical variables were analyzed. Consistent with the existing literature, progression-free survival (PFS) ≥ 270 days was selected as the primary outcome. Individual treatment effect (ITE) estimation was performed using the T-Learner method with separate regression models for each treatment arm (μ1 − μ0). Model performance was evaluated using leave-one-out cross-validation (LOOCV). Feature importance was assessed using SHAP analysis, after which a reduced model was constructed using only the most influential variables. Results: The model incorporating all features demonstrated the highest predictive performance, with a ROC AUC of 0.919. SHAP analysis identified the top 10 predictive variables: primary tumor localization, ferritin, CA19-9, CRP, uric acid, TSH, triglycerides, total protein, LDL, and platelet count. The reduced model built using only these 10 features achieved an AUC of 0.869 for predicting PFS ≥270 days. Conclusion: This machine learning–based model presents a promising framework for improving patient selection for triplet chemotherapy in mCRC. Prospective validation in larger cohorts will be essential to support its integration into clinical decision making. Full article

Pearl color is the primary determinant of its value, and the mantle donor tissue (saibo) used in pearl culture plays a critical role in color formation. To elucidate the molecular mechanisms underlying nacre color, we performed comparative transcriptomic analyses of saibo tissues from Sinohyriopsis cumingii displaying three representative phenotypes: white (W), purple (P), and golden (G). A total of 364 differentially expressed genes (DEGs) (102 upregulated and 162 downregulated genes) were identified in W vs. P. A total of 770 DEGs (467 upregulated and 303 downregulated genes) were identified in W vs. G. KEGG pathway analysis revealed significant differences in the expression of genes mainly involved in pigment-based and structural coloration, including amino sugar and nucleotide sugar metabolism (ko00520), cell adhesion molecules (ko04514), tyrosine metabolism (ko00350), ECM-receptor interaction (ko04512), and PI3K-Akt signaling pathway (ko04151). Subsequent integrative analyses across W vs. P and W vs. G groups identified 45 key regulatory genes, which were classified into four functional categories: extracellular matrix protein synthesis and biomineralization (e.g., chit, silkmaxin, bmp2/7, profilin, perlucin2), organic pigment metabolism (e.g., tyr, typ, dbh, bco2, gst5, ldlr, cpox, pks-like 1, pks15), metal ion metabolism and accumulation (e.g., hip-like, fcr1, ferritin 2), and epigenetic regulation (e.g., metK, mbd4/6, mettl24/27, alkbh6). Taken together, our findings reaffirm the complex nature of pearl coloration and reveal that structural coloration, pigment biosynthesis, and epigenetic modulation collectively shape nacre color formation, which paves the way for further functional elucidation of color-related genes and facilitates selective breeding practices in S. cumingii. Full article

Background: Anemia and iron deficiency (ID) affect children and are regarded as a major public health problem in developing countries. This study aimed to evaluate the prevalences of anemia and ID in Tunisian children aged 6 to 12 years and to identify their associated risk factors. Methods: A nationwide cross-sectional survey was conducted across the seven major regions of Tunisia. A total of 2610 schoolchildren were selected using a two-stage random sampling method. Venous blood was collected to measure hemoglobin and ferritin for iron status determination. C-reactive protein (CRP) and Alpha-1-acid glycoprotein (AGP) were also measured to establish the inflammatory status of children. Multivariable logistic regression models were performed to identify factors associated with anemia and ID. Results: Anemia affected 5.7% of children, similarly between girls and boys. A quarter of children had ID and iron deficiency anemia (IDA) was diagnosed in 42% of the anaemic schoolchildren. In rural areas, girls were more affected by ID than boys whereas no significant difference was observed for anemia between both genders. Multivariate analysis revealed that insufficient consumption of iron-rich foods significantly increased the risk of ID (OR = 1.40; 95% CI [1.05–1.85]; p = 0.021). Children in public schools were 1.74 times more likely to be at risk of ID (95% CI [1.34–2.21]; p = 0.004) than those in private schools. Conclusions: To alleviate the burden of ID, national interventions should focus on iron supplementation, food diversification, nutritional education and regular longitudinal studies. Full article

Background/Objectives: Maternal nutrition and pregestational BMI are critical determinants of pregnancy outcomes. This prospective multicenter observational study investigated the interplay between prepregnancy BMI, dietary patterns, and oxidative/inflammatory status in 153 Italian healthy pregnant women with normal weight (NW), overweight (OW), or obesity (OB). Methods: Detailed clinical, biochemical, placental, and neonatal data were measured at third trimester and delivery. Dietary intake was assessed via a validated questionnaire, and dietary patterns were derived using principal component analysis. Results: OW and OB women had significantly higher levels of inflammatory (CRP, hepcidin) and oxidative stress biomarkers (DNA/RNA damage, catalase activity) than NW. Multivariate models confirmed independent associations between BMI and these biomarkers (CRP: β = 0.297, p = 0.000; hepcidin: β = 1.419, p = 0.006; DNA/RNA damage: β = 409.9, p = 0.000; catalase activity: β = 1.536, p = 0.000). Superoxide dismutase activity and total antioxidant capacity were not associated with BMI. Nutritional intake across BMI groups was largely suboptimal relative to national recommendations, with insufficient levels of polyunsaturated fats and key micronutrients. Four dietary patterns were identified, with adherence varying by BMI. A “prudent-style” pattern (high plant, low animal) was positively associated with gestational age (β = 0.243, p = 0.033) and inversely with neonatal head circumference (β = −0.414, p = 0.050). A “Western-like” pattern (high sugars, snacks, animal fats) was linked to reduced maternal ferritin (β = −2.093, p = 0.036) and increased neonatal head circumference (β = 0.403, p = 0.036). However, not all deviations from the “prudent-style” pattern were metabolically equivalent: while Pattern 3 (high-protein, carbohydrate) may offer partial protective effects, Pattern 4 (moderate protein/plant/sugar) displayed elements of nutritional imbalance with signs of placental inefficiency (β = −0.384, p = 0.023). Conclusions: These findings underscore the dual impact of maternal BMI and diet quality on oxidative-inflammatory balance and perinatal outcomes, supporting the need for early, individualized nutritional strategies in pregnancy. This is further emphasized by the variability in dietary adherence across BMI categories. Full article

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the aberrant expression of the double homeobox 4 (DUX4) gene. In this study, an analysis of human FSHD muscle biopsies revealed differential expressions of six m6A regulators, including writers, readers and eraser proteins. In immortalized human FSHD myoblasts, we found higher levels of mRNA and protein expression of a major m6A regulator, methyltransferase-like protein 3 (METTL3), in comparison with myoblasts from unaffected siblings (UASbs). Quantification of the overall RNA m6A levels in the FSHD myoblasts revealed significant elevation compared with their UASb, which was reversed to UASb levels following treatment with an antisense oligonucleotide targeting the DUX4 mRNA. Using Oxford Nanopore direct-RNA sequencing, we mapped m6A across the transcriptome and identified genes harboring differential methylated m6A sites, including several involved in iron homeostasis. Western blot protein quantification showed that FSHD myoblasts had higher levels of ferritin-heavy chain-207 isoform and mitoferrin-1. In addition, our data showed elevation in mitochondrial ferrous iron in FSHD myoblasts. Our findings suggest that m6A RNA modifications play a pivotal role in FSHD pathophysiology and may serve as biomarker for this disease. Full article

Ferritin, an emerging protein resource, has garnered significant attention in scientific research due to its biocompatibility and unique cavity structure capable of encapsulating bioactive compounds. This study aimed to optimize ultrasound-assisted extraction (UAE) for enhancing ferritin yield from northern pike liver byproducts and evaluate its potential as a nanocarrier for chlorogenic acid (CA). Through response surface methodology (RSM), the optimal UAE parameters were established as 200 W ultrasonic power, 1:3 solid–liquid ratio, and 25 min extraction time. Under these conditions, the ferritin extraction yield reached 139.46 mg/kg, representing a 4.02-fold increase compared to conventional methods (34.65 mg/mL). Electrophoretic analysis confirmed the electrophoretic purity of the extracted liver ferritin. Comprehensive characterization using UV-vis spectroscopy, FTIR, and fluorescence spectroscopy revealed preserved structural integrity of UAE-extracted ferritin. Homology modeling provided molecular insights into the ferritin architecture. Successful encapsulation of CA was achieved with an encapsulation efficiency of 13.25%, as quantified by HPLC. Analysis by DLS and ζ potential as well as TG and DSC showed that not only the thermal stability of CA was enhanced after ferritin encapsulation, but also that the ferritin remained stable with a cage-like structure. This investigation establishes UAE as an effective strategy for valorizing fish processing byproducts through high-yield ferritin extraction while demonstrating the protein’s functional capacity as a nanocarrier for bioactive compound delivery. The findings highlight the dual advantage of sustainable resource utilization and advanced delivery system development through this biotechnological approach. Full article

Ferritins are globular proteins that, upon self-assembly in nanocages, are capable of bio-safely storing huge concentrations of bioavailable iron. They are present in most cell types and organisms; one of the exceptions is yeast. Heterologous expression of either human or vegetal ferritins in Saccharomyces cerevisiae revealed new and unknown functions for soya bean ferritins; validated this model by confirming previously characterized functions in human ferritins and also demonstrated that, like human H chain, vegetal H1, and H2 chains also shown a tendency to localize in the nucleus when expressed in an eukaryotic cell model lacking plastids and chloroplasts. Furthermore, when expressed in the system budding yeast, the four ferritins (human H and L and soya bean H1 and H2 chains) present equivalent and relevant functions as protectors against oxidative damage and against the accumulation of double-strand breaks in the DNA. We present evidence demonstrating that these effects are exclusively observed with oxidative agents that operate through the Fenton reaction, such as H₂O₂. Here, we also discuss the ferritin requirement for N-glycosylation to exert these functions. We believe that our approach might contribute to extending the knowledge around ferritin function and its consequent relevance to human health. Full article

Background: Elite-neutralizer-derived HIV-1 envelopes (Envs), which induce broadly neutralizing antibodies (bnAbs), can inform HIV-1 vaccine design by serving as templates for bnAb-eliciting vaccines. Since single Env-based immunizations are insufficient to induce bnAb responses, sequential regimens using multivalent immunogens or Env cocktails hold greater promise. This underscores the need to develop stable Env trimers from diverse HIV-1 strains, particularly clade-C, which accounts for 50% of global infections and over 90% in India and South Africa. While various platforms exist to stabilize soluble Env trimers for use as antigenic baits and vaccines, stabilizing clade C trimers remains challenging. Methods: We stabilized an HIV-1 clade C trimer based on an Env isolated from a pediatric elite neutralizer (AIIMS_329) using multiple platforms, including SOSIP.v8.2, ferritin nanoparticles (NPs) and I53-50 two-component NPs, followed by characterization of their biophysical, antigenic, and immunogenic properties. Results: The stabilized 329 Envs showed binding to multiple HIV-1 bnAbs, with negligible binding to non-neutralizing antibodies. Negative-stain electron microscopy confirmed the native-like conformation of the Envs. Multimerization of 329 SOSIP.v8.2 on ferritin and two-component I53-50 NPs improved the affinity to HIV-1 bnAbs and showed higher immunogenicity in rabbits. Conclusions: The soluble 329 Env protein could serve as an antigenic bait, and multimeric 329 NP Envs are potential vaccine candidates. Full article

Rhodopseudomonas palustris (RP) are known anaerobic bacteria with probiotic properties containing several bioactive compounds and enzymes that benefit aquatic animals. However, studies on the use of RP on aquatic animal species are limited. This study investigated the effects of dietary supplementation with RP formulation on the growth, non-specific immunity, and disease resistance of juvenile ivory shells (Babylonia areolata). The experiment was conducted for 8 weeks, with B. areolata fed a control diet (RP0) and four diets containing four different RP formulations, with doses of 1 (RP1), 5 (RP2), 10 (RP3), and 20 (RP4) g/kg, respectively. Higher levels of R. palustris in the formulation led to increased final weight, weight gain, and specific growth rate in B. areolata. The crude protein content was significantly higher in the RP4 group compared to the RP0 group. However, there was no significant difference in the crude lipid content. Higher levels of R. palustris in the RP4 formulation group increased the trypsin and lipase activities. Dietary supplementation with RP significantly increased the total antioxidant capacity, superoxide dismutase, and catalase activities and decreased the malondialdehyde content in B. areolata. Acid phosphatase and alkaline phosphatase activities were significantly increased in the RP4 group compared to the RP0 group. Dietary RP significantly increased the expression levels of antioxidant-related (superoxide dismutase, Cu/Zn-superoxide dismutase, glutathione S-transferase A-like, ferritin) and immune-related (acid phosphatase, cytochrome c) genes. Higher levels of R. palustris in the formulations RP3 and RP4 increased the survival rate of B. areolata challenged with Vibrio parahaemolyticus. These findings indicate that R. palustris preparation could improve growth performance, muscle composition, and digestive capacity and may act as an immune booster for preventing disease in B. areolata. Full article