Search Results (12,534)

Sirtuins are conserved proteins regulating oxidative stress and lifespan. While they enhance cellular adaptability, the long-term biological consequences of combining bioactive compounds with nanomaterials remain poorly understood. This study examined the effects of combined resveratrol and nanodiamonds (RV+NDs) in two Acheta domesticus strains: wild-type (H) and longevity-selected (D). The impact was assessed across developmental stages, focusing on survival, total sirtuin activity, specific isoforms (SIRT1, SIRT6), oxidative stress, antioxidant enzymes, and DNA damage markers. RV+NDs exposure did not result in consistent lifespan extension or sustained oxidative stress. Molecular responses were strongly dictated by genetic background and age, as reflected by significant survival differences between strains H and D (p < 0.001) Notably, a persistent increase in total sirtuin activity (~60% ↑ across developmental stages) occurred exclusively in the longevity-selected strain, though no stable activation of SIRT1 or SIRT6 was detected. While classical redox parameters showed only transient changes, DNA damage response markers emerged as the most sensitive indicators of RV+NDs exposure. Overall, the findings demonstrate that RV+NDs treatment induces context-dependent, adaptive molecular responses. This highlights the critical role of genetic background and age in shaping ageing-related pathways, suggesting that nanodelivery systems do not produce universal effects across different genotypes. Full article

Background: Primary peritoneal carcinoma (PPC) is an uncommon malignancy typically diagnosed in postmenopausal women, accounting for less than 1% of all gynecologic cancers. Its occurrence in adolescents is extremely rare. We present a case of a 16-year-old female with low-grade serous carcinoma (LGSC) arising from the anterior rectal peritoneum, highlighting diagnostic challenges and therapeutic considerations. Case Presentation: A 16-year-old girl presented with a 7-day history of lower abdominal pain. Ultrasound revealed an 8 cm mixed cystic–solid pelvic mass anterior to the rectum. Laboratory tests showed elevated CA-125 (106 U/mL). Exploratory laparotomy demonstrated an 8 cm solid mass attached to the anterior rectal wall, extending into the right mesorectum with peritoneal nodules at the bladder reflection. The uterus and adnexa appeared grossly normal. Frozen section analysis revealed adenocarcinoma with psammoma body formation. Histopathology and immunohistochemistry confirmed low-grade serous carcinoma: PAX8(+), WT1(+), CK7(+), ER(60%), PR(40%), CK20(–), and P53 wild-type. Peritoneal washings contained rare malignant cells. Postoperatively, the patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. Final pathology confirmed low-grade serous carcinoma involving the anterior rectal wall, bilateral adnexal surfaces, and peritoneum. She completed six cycles of adjuvant chemotherapy (paclitaxel + carboplatin, TC regimen). No recurrence was observed during follow-up. Conclusions: This case underscores the importance of considering PPC in the differential diagnosis of pelvic masses in young females, even when the ovaries appear normal. Full article

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder characterized by hyperphosphatemia and ectopic calcifications. Mutations in GALNT3, which encodes a key enzyme responsible for O-glycosylation of FGF23, represent a major genetic cause of HFTC. This modification is essential for the stability and secretion of FGF23. We investigated a 4-year and 6-month-old Chinese girl with HFTC to characterize the clinical features, identify the causative variants, and explore the underlying pathogenic mechanism. Whole-exome sequencing followed by Sanger validation identified novel compound heterozygous variants in GALNT3 (c.659T>A, p.Ile220Asn and c.1850C>A, p.Ser617*). The patient exhibited hyperphosphatemia with a biochemical profile consistent with FGF23 deficiency, including extremely low intact FGF23 and elevated C-terminal fragments. Functional studies using Western blotting and wheat germ agglutinin affinity chromatography demonstrated that the mutant GALNT3 caused a severe defect in FGF23 O-glycosylation, leading to impaired secretion of intact FGF23. Glycosylated FGF23 was detected only in the medium of cells expressing wild-type GALNT3. These findings indicate that defective O-glycosylation results in failure of FGF23 secretion and functional inactivation. This study expands the mutational spectrum of GALNT3 and provides mechanistic insight into the role of GALNT3 in phosphate homeostasis. Full article

Tendon-derived stem cells (TDSCs) are a unique cell population found in tendons, exhibiting both mesenchymal stem cell (MSC)-like phenotypes and tendon-specific markers. They have emerged as a promising research tool in tendon-related tissue engineering studies. However, there is currently no well-characterized TDSC line with MSC-related phenotypes for investigating tendon biology or developing therapeutics. Here, we established an immortalized monoclonal TDSC, named iTDSC#6, from the Achilles tendon of an adult male Sprague-Dawley rat. Cell clones were characterized for MSC-associated cell surface markers, colony formation capacity, and trilineage differentiation potentials, tenogenic potential and SV40LT expression at both early (passage < 10) and late (passage > 30) stages. iTDSC#6 showed stable expression of Simian virus 40 large T antigen (SV40LT) and demonstrated similar MSC-like phenotypes as its wild-type counterpart at both early and late passages, including colony formation capability and multi-lineage differentiation potentials. iTDSC#6 was positive for the MSC markers CD90, CD44, CD29 and CD73 (≥95%) and negative for the hematopoietic markers CD34 and CD45 (<1%). Regarding its utility for basic research and therapeutic development, iTDSC#6 showed potential for modelling cells with increased levels of senescence-associated beta-galactosidase activity in response to hydrogen peroxide and for bioengineering scaffold-free, tendon-like 3D constructs as evidenced by its upregulation of tendon-related markers, high nuclear aspect ratio, and aligned collagen organization. In conclusion, an immortalized TDSC line was successfully established that shows promise as a useful research tool to study tendon biology and aid the development of therapeutics for tissue engineering and regenerative medicine. 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

Single nucleotide polymorphisms (SNPs), as common genetic variations, can influence biological processes. Identifying these variations is crucial for recognizing high-risk subgroups, guiding preventive strategies, and enabling personalized management. Objective: This study aimed to determine the relationship between SNPs and survival, thereby identifying genetic profiles associated with increased risk. Methods: We included seropositive patients with Chagas disease who had a disease duration of >20 years and no comorbidities. DNA was extracted. A SNP panel focusing on genes involved in cardiac structure was created from the GnomAD database. Patients were followed for 8 years to assess survival. The association between SNPs and survival was evaluated, and a genetic risk score was generated. Univariate and multivariate Cox regression models assessed the association between SNPs (coded as ordinal variables) and survival time. SNPs with p < 0.05 were selected to construct a risk score, which was then assessed using Kaplan–Meier curves and median survival times. Results: A total of 182 patients were included, with 96.7% completing follow-up for a median of 5.1 years (interquartile range: 3.4–6.5). The median age was 62 years; 39.6% of patients were male, and 31% had reduced left ventricular ejection fraction. Univariate analysis showed that 3 of the 68 SNPs studied were associated with survival. Variant rs3755863 (PPARGC1A gene) was significantly associated with an increased risk of death (hazard ratio, HR = 1.94; p = 0.022). Conversely, two variants, rs7310615 (SH2B3 gene) and rs7405731 (JUP gene), showed a protective effect with significantly reduced mortality risk (HR = 0.45; p = 0.006 and HR = 0.48; p = 0.006, respectively). In multivariate analysis, rs7310615 and rs7405731 remained significantly associated with survival. A genetic risk score was constructed, assigning 0 points for homozygous wild-type, 1 point for heterozygotes, and 2 points for homozygous alternative alleles. Individual scores were calculated, and survival was estimated for each score category using Kaplan–Meier analysis and median survival times. Conclusions: Two SNPs were identified as significantly associated with survival. These findings require confirmation in larger and more diverse populations. Their validation could enable the identification of a subgroup of patients at particularly high risk. Full article

Cadmium (Cd) pollution has caused severe environmental hazards and human health risks. Phytoremediation, a green and sustainable approach, has emerged as a promising solution for Cd-contaminated soil remediation. Sedum plumbizincicola, a typical Cd hyperaccumulator, can efficiently uptake Cd from soil and translocate it to above-ground tissues, making it an ideal model for studying Cd tolerance mechanisms. Our preliminary studies demonstrated that the Rubber elongation factor (SpREFl) enhances Cd tolerance in S. plumbizincicola, and yeast one-hybrid screening identified SpNAC089 (NCBI accession number: PV553670.1) as a potential upstream transcription factor of SpREFl. In this study, we systematically investigated the regulatory mechanism of the SpNAC089 transcription factor on SpREFl. Subcellular localization assays showed that SpNAC089 is exclusively localized in the cell nucleus, and yeast transcriptional activation experiments confirmed its intrinsic transcriptional autoactivation activity. Transgenic S. alfredii overexpressing SpNAC089 exhibited significantly enhanced cadmium tolerance—with milder leaf yellowing and growth inhibition under Cd stress—and reduced Cd accumulation in roots, stems, and leaves compared to wild-type (WT) plants. Further mechanistic analyses revealed that SpNAC089 directly binds to the 1901–1950 bp region of the SpREFl promoter, which contains cis-acting elements (MBS and TCA motifs). This binding activates SpREFl transcription, thereby upregulating the activities of antioxidant enzymes (superoxide dismutase, SOD; peroxidase, POD) and reducing malondialdehyde (MDA) content under Cd stress, ultimately mitigating oxidative damage. These findings uncover a novel transcriptional regulatory pathway (SpNAC089-SpREFl) underlying Cd tolerance in S. plumbizincicola and highlight SpNAC089 as a candidate gene for optimizing phytoremediation strategies of Cd-polluted soils. Full article

Vibrio alginolyticus is a foodborne pathogen commonly found in seafood and freshwater products, causing human illness through the consumption of tainted seafood. Small non-coding RNAs (sRNAs) take effect on the stability and translation of their target mRNAs by base-pairing, thereby quickly altering bacterial physiology and pathogenicity at the post-transcriptional level. This work constructed a label-free in-frame deletion mutant and a complement strain of micX, a cell-density-associated sRNA in V. alginolyticus. The ΔmicX mutant exhibited reduced growth and a reduction in the synthesis of exopolysaccharides, biofilm, and alkaline serine protease. A TMT-based quantitative proteomic analysis comparing ΔmicX with the wild-type strain identified 900 differentially expressed proteins, comprising 376 that were upregulated and 524 that were downregulated. The upregulated proteins are primarily associated with porin activity, transmembrane signaling receptor function, and the two-component system. The downregulated proteins are mainly engaged in processes including biofilm formation, cellular communication, and transmembrane transport activity. Of note, the expression levels of proteins involved in the type VI secretion system, exopolysaccharide synthesis, mannose-sensitive hemagglutinin type IV pili (MSHA), and biofilm formation were significantly reduced in the absence of micX. Furthermore, the expression levels of proteins associated with quorum sensing (particularly LuxR and AphA) changed significantly in the ΔmicX vs. WT comparison. These findings strengthened comprehension of the novel sRNA regulatory network and established a theoretical foundation for additional investigations into the virulence of V. alginolyticus. Full article

Background: G_M1-gangliosidosis (G_M1) is a lysosomal storage disorder caused by mutations in the Glb1 gene, resulting in reduced β-galactosidase activity and accumulation of G_M1 gangliosides in neuronal lysosomes. Effective therapeutic strategies for this disease remain limited. Substrate reduction therapy using small molecules targeting glucosylceramide synthase (GCS) and non-lysosomal glucosylceramidase (GBA2), such as sinbaglustat, represents a promising approach. Methods: Structural and electrophysiological properties of principal neurons of the medial nucleus of the trapezoid body (MNTB) were investigated in 7-month-old Glb1^−/− mice. Animals received long-term treatment with either low (LD; 10 mg/kg) or high (HD; 300 mg/kg) doses of sinbaglustat and were compared with untreated Glb1^−/− (KO) and untreated wild-type (WT) mice. Results: Sinbaglustat treatment reduced lysosomal storage material in MNTB neurons. Basal membrane properties were largely unchanged across groups. However, action potential halfwidth was significantly increased in untreated KO and LD mice compared to untreated WT animals but was normalized in HD mice. After-hyperpolarization duration was prolonged in Glb1^−/− mice relative to WT. Temporal precision during high-frequency stimulation was reduced in untreated KO mice and improved following sinbaglustat treatment. Conclusions: These findings indicate that G_M1-gangliosidosis is associated with functional alterations in MNTB neurons and suggest that long-term sinbaglustat treatment can partially restore neuronal electrophysiological properties, supporting its therapeutic potential in G_M1. Full article

During the last few decades, an urgent need for sustainable and health-promoting food products has been witnessed. In this vein, the development of functional foods enriched with probiotics has gained considerable interest from both the food industry and consumers. However, the maintenance of high cell viability until the time of consumption remains a significant challenge. In this study, freeze-dried immobilized Lacticaseibaciilus paracasei FBM_1327 cells on sunflower seeds were evaluated as a functional food ingredient, and their ability to survive during simulated digestion and storage at ambient and refrigerated temperatures in comparison to free cells was assessed. Cell immobilization resulted in higher survival rates (>70%) after in vitro digestion compared to free cells (<40%), while the freeze-dried immobilized cells maintained in cell levels >7.5 log cfu/g during storage for 6 months at 4 °C. In the next step, freeze-dried free or immobilized cells were incorporated in cream cheese (CCF and CCI samples, respectively) at a concentration of >8 log cfu/g. Cell viability of the immobilized cells remained stable (>8.1 log cfu/g) during storage, while live cell counts of free cells dropped to 7.51 ± 0.11 log cfu/g after 28 days. The fortification of cream cheese with immobilized L. paracasei FBM_1327 cells on sunflower seeds improved the volatile compounds profile, while all samples were accepted by the panel during the sensory evaluation. Full article

Lacticaseibacillus rhamnosus CRL1505 enhances antiviral immunity at mucosal sites, but its capacity to modulate liver immune responses remains unclear. Therefore, this study evaluated whether this immunomodulatory bacterium protects against Toll-like receptor 3 (TLR3)-mediated acute hepatitis induced by poly(I:C), and whether this effect depends on mucosal adhesion. BALB/c mice received the wild-type CRL1505 strain or the Δmbf CRL1505 mutant lacking the mucus-binding factor gene prior to poly(I:C) challenge. Liver injury, serum transaminases, and hepatic expression of interferons (IFNs), antiviral factors, inflammatory mediators, and regulatory cytokines were evaluated 48 h later. Poly(I:C) challenge induced acute hepatitis characterized by increased ALT/AST levels, leukocyte infiltration, and elevated hepatic IFNs and proinflammatory cytokines. The CRL1505 strain administration significantly reduced TNF-α, IL-1β, and IL-6 while enhancing IFNs, antiviral factors, and the regulatory cytokines IL-10 and IL-27, resulting in improved transaminase levels and attenuated liver damage. Notably, the Δmbf CRL1505 mutant conferred protection comparable to the wild-type strain. These findings demonstrate that L. rhamnosus CRL1505 exerts immunomodulatory and hepatoprotective effects during TLR3-driven hepatitis and that mbf-mediated adhesion is not required for this protection. Overall, CRL1505 emerges as a promising preventive strategy to enhance antiviral defenses and limit inflammation-associated liver injury. Full article

Glial brain tumours, including astrocytoma IDH (Isocitrate Dehydrogenase) mutant and glioblastoma IDH wild-type, are highly malignant brain tumours with poor clinical outcomes. Genomic instability, encompassing microsatellite (MIN) and chromosomal instability (CIN), drives tumour heterogeneity and evolution. In this study, genomic instability was analysed in 85 patients using AP-PCR (Arbitrarily Primed Polymerase Chain Reaction) by comparing tumour and normal tissue (blood) DNA profiles of the same patient. Both types of alterations were present in all analysed samples, contributing almost equally to the total level of genomic instability. The dominant pattern of genomic instability in our cohort was low overall instability, predominantly manifesting as low-degree microsatellite instability. A general decrease in genomic instability was observed with increasing tumour grade. Glioblastoma IDH wild-type was more prevalent in older patients, whereas astrocytoma IDH mutant predominated in younger individuals. Notably, low genomic instability (both MIN and CIN) was associated with poorer survival in patients over 50 years of age. Females, compared to males, exhibited higher MIN in grade 2 tumours and elevated CIN in grade 4 tumours. Our results confirm that genomic instability contributes to tumour progression, MIN being the pivotal factor, and could serve as a prognostic biomarker in malignant gliomas. Full article

Natural killer (NK) cells, key effectors of innate immunity, are classically categorized into CD56^dim and CD56^bright subsets in humans. While murine NK cell heterogeneity has become increasingly recognized, the classification of mature NK cell subsets remains incompletely defined. Here, we comprehensively characterized CD127⁺ NK cells in mice and identified them as a distinct, mature subset, developing independently of the thymus and interleukin (IL)-15 signaling. Flow cytometric analyses revealed that CD127⁺ NK cells are broadly distributed across lymphoid and non-lymphoid tissues—including in C57BL/6 wild-type and athymic Foxn1^−/− mice—and exhibit a surface phenotype distinct from CD127⁻ NK and thymus-derived CD127⁺ NK cells. Functional assays demonstrated that CD127⁺ NK cells produce interferon-γ and exert cytotoxic activity, despite expressing markers typically associated with immature NK cells. CD127⁺ NK cells were absent in IL-7Rα^−/− mice but present in IL-15^−/− and IL-15Rα^−/− mice, indicating a selective dependence on IL-7 signaling. IL-7 promoted their proliferation and activation both in vitro and in vivo. These findings revise current models of NK cell development by identifying a novel, IL-7-responsive, IL-15-independent, thymus-independent, and functionally competent CD127⁺ NK cell subset that is phenotypically distinct from helper-like innate lymphoid cells (ILCs). This study provides a framework for future investigations on NK cell heterogeneity, tissue specialization, and cytokine-mediated regulation. Full article

Species of the genus Thunbergia, native to Africa, Asia, and Australia, are widely cultivated as ornamental plants; however, their ability to escape cultivation and establish themselves in novel environments poses a growing threat to tropical forests. Here, we provide the first nationwide assessment of Thunbergia species occurring in Ecuador, integrating data from citizen science platforms, herbarium collections, and field surveys. We analyzed spatiotemporal patterns of occurrence, evaluated invasion status based on wild persistence and spread, and assessed environmental preferences using climatic niche analyses. Species distributions were further examined across land-cover types, conservation areas, and forest–non-forest interfaces. We confirmed the presence of five Thunbergia species in Ecuador, two of which also occur in the Galapagos Islands. All species were recorded both in cultivation and in the wild, indicating ornamental horticulture as the main introduction pathway for the genus, and occurrences were documented within 24 conservation areas. Thunbergia alata, T. fragrans, and T. grandiflora were categorized as invasive in Ecuador. Among them, T. fragrans exhibited broad environmental tolerance across bioregions. Wild occurrences were predominantly associated with human-modified landscapes but frequently occurred near forest edges, indicating ongoing encroachment into natural forests. These findings highlight the urgent need for preventive and targeted management strategies, particularly against T. alata, which represents an emerging threat to Andean forest ecosystems. Full article

The adhesion G protein-coupled receptor F5 (ADGRF5) has been implicated in modulating immune responses in cancer; however, its role in inflammatory bowel diseases (IBDs), particularly colitis, remains largely unexplored. In this study, we aimed to design and characterize novel peptide agonists derived from the ADGRF5 Stachel sequence, as well as to evaluate their therapeutic potential in preclinical colitis models. In silico analysis and single amino acid substitutions within the ADGRF5 tethered agonist sequence, combined with functional assays in ADGRF5-overexpressing cells, including calcium mobilization and inositol phosphate production, were employed to assess the activity of novel ADGRF5 agonists. Western blot technique and murine model of colitis were used to evaluate downstream signaling pathways and immunomodulatory effects of ADGRF5 ligands. We identified a series of peptides exhibiting significantly enhanced ADGRF5 agonist activity, achieving up to a 6-fold increase in potency over the wild-type version. We identified critical substitutions within the Stachel sequence, namely S11N and D13S, as essential for improving agonistic activity. Finally, using these novel ADGRF5 agonists, we demonstrated their potent anti-inflammatory effects in vivo, showing that ADGRF5 activation ameliorates experimental colitis, as evidenced by reduced macroscopic damage scores and improved colon architecture. These findings establish ADGRF5 as a potential therapeutic target for colitis and highlight the promise of Stachel-derived peptide agonists for the development of novel anti-inflammatory therapies. Full article